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1.
Malays J Med Sci ; 31(2): 6-17, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38694578

RESUMO

Pregnancy-associated breast cancer (PABC) is a rare type of gestational cancer. It poses a significant challenge in diagnosis and management, especially in Asian countries with limited resources. We carried out a systematic literature review and narrative synthesis to identify survival outcomes for women with PABC in Asia. We searched MEDLINE, PubMed, Cochrane Library and the reference lists of the included English language articles for those conducted between January 2010 and August 2022. The search terms were pregnancy-associated breast cancer, breast cancer AND pregnancy, survival of PABC and prognosis of PABC patients. PABC is defined as breast cancer diagnosed either during pregnancy or 1 year-5 years postpartum. This review included observational studies conducted in Asian countries. The final 11 articles met the selection criteria and were analysed. Five of the studies had high quality methods as assessed using the Joanna Briggs Institute (JBI) checklist. We reported study design, year of diagnosis, country, definition of PABC, control group, age of participants, median follow-up time, survival outcomes and pregnancy as prognostic factors. Only five studies reported that PABC patients had a poor overall or disease-free survival rate compared to the control. Pregnancy was a significant independent prognostic factor of breast cancer in only two studies. This review highlights that pregnancy has an unconfirmed association with breast cancer survival in Asia. Most studies that found a non-significant association had small samples, thus there is a need for large-scale multinational epidemiological studies in Asia to establish the survival outcomes in PABC patients.

2.
Inflamm Bowel Dis ; 30(Supplement_2): S39-S54, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38778628

RESUMO

Precision medicine is part of 5 focus areas of the Challenges in IBD Research 2024 research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and pragmatic clinical research. Building on Challenges in IBD Research 2019, the current Challenges aims to provide a comprehensive overview of current gaps in inflammatory bowel diseases (IBDs) research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient-centric research prioritization. In particular, the precision medicine section is focused on the main research gaps in elucidating how to bring the best care to the individual patient in IBD. Research gaps were identified in biomarker discovery and validation for predicting disease progression and choosing the most appropriate treatment for each patient. Other gaps were identified in making the best use of existing patient biosamples and clinical data, developing new technologies to analyze large datasets, and overcoming regulatory and payer hurdles to enable clinical use of biomarkers. To address these gaps, the Workgroup suggests focusing on thoroughly validating existing candidate biomarkers, using best-in-class data generation and analysis tools, and establishing cross-disciplinary teams to tackle regulatory hurdles as early as possible. Altogether, the precision medicine group recognizes the importance of bringing basic scientific biomarker discovery and translating it into the clinic to help improve the lives of IBD patients.


Precision medicine is the practice of getting the most suitable drug or treatment option to each individual patient at the right time. In Crohn's disease and ulcerative colitis, we need to learn more about the diversity of patients to deliver precision medicine.


Assuntos
Doenças Inflamatórias Intestinais , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Doenças Inflamatórias Intestinais/terapia , Biomarcadores/análise , Pesquisa Biomédica
3.
mSphere ; : e0019624, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742887

RESUMO

Environmental enteric dysfunction (EED) is a subclinical syndrome of altered small intestinal function postulated to be an important contributor to childhood undernutrition. The role of small intestinal bacterial communities in the pathophysiology of EED is poorly defined due to a paucity of studies where there has been a direct collection of small intestinal samples from undernourished children. Sixty-three members of a Pakistani cohort identified as being acutely malnourished between 3 and 6 months of age and whose wasting (weight-for-length Z-score [WLZ]) failed to improve after a 2-month nutritional intervention underwent esophagogastroduodenoscopy (EGD). Paired duodenal luminal aspirates and duodenal mucosal biopsies were obtained from 43 children. Duodenal microbiota composition was characterized by sequencing bacterial 16S rRNA gene amplicons. Levels of bacterial taxa (amplicon sequence variants [ASVs]) were referenced to anthropometric indices, histopathologic severity in biopsies, expression of selected genes in the duodenal mucosa, and fecal levels of an immunoinflammatory biomarker (lipocalin-2). A "core" group of eight bacterial ASVs was present in the duodenal samples of 69% of participants. Streptococcus anginosus was the most prevalent, followed by Streptococcus sp., Gemella haemolysans, Streptococcus australis, Granulicatella elegans, Granulicatella adiacens, and Abiotrophia defectiva. At the time of EGD, none of the core taxa were significantly correlated with WLZ. Statistically significant correlations were documented between the abundances of Granulicatella elegans and Granulicatella adiacens and the expression of duodenal mucosal genes involved in immune responses (dual oxidase maturation factor 2, serum amyloid A, and granzyme H). These results suggest that a potential role for members of the oral microbiota in pathogenesis, notably Streptococcus, Gemella, and Granulicatella species, warrants further investigation.IMPORTANCEUndernutrition among women and children is a pressing global health problem. Environmental enteric dysfunction (EED) is a disease of the small intestine (SI) associated with impaired gut mucosal barrier function and reduced capacity for nutrient absorption. The cause of EED is ill-defined. One emerging hypothesis is that alterations in the SI microbiota contribute to EED. We performed a culture-independent analysis of the SI microbiota of a cohort of Pakistani children with undernutrition who had failed a standard nutritional intervention, underwent upper gastrointestinal tract endoscopy, and had histologic evidence of EED in their duodenal mucosal biopsies. The results revealed a shared group of bacterial taxa in their duodenums whose absolute abundances were correlated with levels of the expression of genes in the duodenal mucosa that are involved in inflammatory responses. A number of these bacterial taxa are more typically found in the oral microbiota, a finding that has potential physiologic and therapeutic implications.

4.
Am J Clin Nutr ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38685382

RESUMO

BACKGROUND: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes. OBJECTIVE: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology. METHODS: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n=69), and those with no pathologic abnormality (NPA; n=8) or celiac disease (n=18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared to NPA or celiac disease, and identify associations between morphometry and histology or immunohistochemistry amongst children with EED. RESULTS: In duodenal biopsies, median EED villus height (248 µm), crypt depth (299 µm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 µm villus height; 246 µm crypt depth; 1.6 V:C ratio) and celiac disease (208 µm villus height; 365 µm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist determined subjective semi-quantitative villus architecture. CONCLUSIONS: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides; although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. While acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED.

5.
Cell Rep Med ; 5(2): 101424, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382470

RESUMO

In the January issue of Cell Reports Medicine, Gerassy-Vainberg et al.1 demonstrate the utility of integrative methods to reveal molecular mechanisms associated with anti-tumor necrosis factor-alpha therapy response in patients with inflammatory conditions.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/complicações , Fator de Necrose Tumoral alfa , Infliximab/uso terapêutico , Biomarcadores
6.
J Clin Transl Sci ; 8(1): e27, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384914

RESUMO

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, and intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This yearlong program provided education, coaching, mentoring, and sponsorship for underrepresented early career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% as Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

7.
medRxiv ; 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37965201

RESUMO

Historically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the "inspiring Diverse Researchers in Virginia" (iDRIV) program. This year-long program provided education, coaching, mentoring, and sponsorship for underrepresented early-career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.

8.
ArXiv ; 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37664408

RESUMO

Introduction: Technical burdens and time-intensive review processes limit the practical utility of video capsule endoscopy (VCE). Artificial intelligence (AI) is poised to address these limitations, but the intersection of AI and VCE reveals challenges that must first be overcome. We identified five challenges to address. Challenge #1: VCE data are stochastic and contains significant artifact. Challenge #2: VCE interpretation is cost-intensive. Challenge #3: VCE data are inherently imbalanced. Challenge #4: Existing VCE AIMLT are computationally cumbersome. Challenge #5: Clinicians are hesitant to accept AIMLT that cannot explain their process. Methods: An anatomic landmark detection model was used to test the application of convolutional neural networks (CNNs) to the task of classifying VCE data. We also created a tool that assists in expert annotation of VCE data. We then created more elaborate models using different approaches including a multi-frame approach, a CNN based on graph representation, and a few-shot approach based on meta-learning. Results: When used on full-length VCE footage, CNNs accurately identified anatomic landmarks (99.1%), with gradient weighted-class activation mapping showing the parts of each frame that the CNN used to make its decision. The graph CNN with weakly supervised learning (accuracy 89.9%, sensitivity of 91.1%), the few-shot model (accuracy 90.8%, precision 91.4%, sensitivity 90.9%), and the multi-frame model (accuracy 97.5%, precision 91.5%, sensitivity 94.8%) performed well. Discussion: Each of these five challenges is addressed, in part, by one of our AI-based models. Our goal of producing high performance using lightweight models that aim to improve clinician confidence was achieved.

9.
Lancet Reg Health Southeast Asia ; 15: 100212, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37614352

RESUMO

Background: Diarrhoea and acute respiratory infections (ARI) are assumed to be major drivers of growth and likely contribute to environmental enteric dysfunction (EED), which is a precursor to childhood malnutrition. In the present study, we checked the correlation between diarrhoeal/ARI burden and EED using a novel duodenal histological index. Methods: Between November 2017 and July 2019, a total of 365 infants with weight-for-height Z scores (WHZ score) of <-2 were enrolled, and 51 infants with WHZ scores of >0 and height-for-age Z scores (HAZ scores) of >-1 were selected as age-matched healthy controls. Morbidity was assessed weekly and categorised as the total number of days with diarrhoea and acute respiratory infection (ARI) from enrolment until two years of age and was further divided into four quartiles in ascending order. Findings: The HAZ declined until two years of age regardless of morbidity burden, and WHZ and weight-for-age Z scores (WAZ scores) were at their lowest at six months. Sixty-three subjects who had a WHZ score <-2 and failed to respond to nutritional and educational interventions were further selected at 15 months to investigate their EED histological scores with endoscopy further. EED histological scores of the subjects were higher with increasing diarrhoeal frequency yet remained statistically insignificant (p = 0.810). Interpretation: There was not a clear correlation between diarrhoea and ARI frequency with growth faltering, however, children with the highest frequency of diarrhoea had the highest EED histological scores and growth faltering. Funding: Bill and Melinda Gates Foundation and The National Institutes of Health.

10.
PLoS One ; 18(7): e0287962, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37437065

RESUMO

BACKGROUND: The reduction in severe and moderate acute malnutrition (SAM and MAM) rates in Pakistan has been sub-optimal compared to other low-and middle-income countries (LMICs). Specially-formulated products have been designed globally to manage SAM and MAM, such as ready-to-use therapeutic food (RUTF) and ready-to-use supplementary food (RUSF), with variable efficacies. RUTF is primarily produced and patented in industrialized countries, raising supply challenges in resource-constrained regions with a high burden of acute malnutrition. RUSF minimizes costs by using locally-available ingredients while providing similar nutritional value. In this study, we compared the efficacy, side effects, and compliance of two months of supplementation with either RUTF or RUSF. METHODS: Children aged nine months in the rural district of Matiari, Pakistan, with a weight-for-height z-score (WHZ) <-2 received either RUTF (500 kcal sachet) for two months in 2015 or RUSF (520 kcal sachet) for two months in 2018. RESULTS: The RUSF group had a higher height gain and mid-upper arm circumferences (MUAC) score. Higher compliance was noted with lower side effects in the RUSF group. A higher compliance rate did correlate with the growth parameters in respective groups. CONCLUSION: Our study found that both RUTF and RUSF partially improve the anthropometric status of acutely malnourished children, with neither being superior to the other.


Assuntos
Alimentos Formulados , Transtornos da Nutrição do Lactente , Desnutrição Aguda Grave , Humanos , Antropometria , Paquistão , População Rural/estatística & dados numéricos , Desnutrição Aguda Grave/dietoterapia , Alimentos Formulados/estatística & dados numéricos , Resultado do Tratamento , Masculino , Feminino , Lactente , Transtornos da Nutrição do Lactente/dietoterapia
11.
Curr Opin Gastroenterol ; 39(4): 294-300, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37144491

RESUMO

PURPOSE OF REVIEW: The Management of inflammatory bowel disease (IBD) has evolved with the introduction and widespread adoption of biologic agents; however, the advent of artificial intelligence technologies like machine learning and deep learning presents another watershed moment in IBD treatment. Interest in these methods in IBD research has increased over the past 10 years, and they offer a promising path to better clinical outcomes for IBD patients. RECENT FINDINGS: Developing new tools to evaluate IBD and inform clinical management is challenging because of the expansive volume of data and requisite manual interpretation of data. Recently, machine and deep learning models have been used to streamline diagnosis and evaluation of IBD by automating review of data from several diagnostic modalities with high accuracy. These methods decrease the amount of time that clinicians spend manually reviewing data to formulate an assessment. SUMMARY: Interest in machine and deep learning is increasing in medicine, and these methods are poised to revolutionize the way that we treat IBD. Here, we highlight the recent advances in using these technologies to evaluate IBD and discuss the ways that they can be leveraged to improve clinical outcomes.


Assuntos
Aprendizado Profundo , Doenças Inflamatórias Intestinais , Humanos , Inteligência Artificial , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Aprendizado de Máquina , Medicina de Precisão
12.
Metabolites ; 13(4)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37110148

RESUMO

Environmental enteric dysfunction (EED) is characterized by intestinal inflammation, malabsorption and growth-faltering in children with heightened exposure to gut pathogens. The aim of this study was to characterize serum non-esterified fatty acids (NEFA), in association with childhood undernutrition and EED, as potential biomarkers to predict growth outcomes. The study comprised a cohort of undernourished rural Pakistani infants (n = 365) and age-matched controls followed prospectively up to 24 months of age. Serum NEFA were quantified at ages 3-6 and 9 months and correlated with growth outcomes, serum bile acids and EED histopathological biomarkers. Serum NEFA correlated with linear growth-faltering and systemic and gut biomarkers of EED. Undernourished children exhibited essential fatty acid deficiency (EFAD), with low levels of linoleic acid and total n-6 polyunsaturated fatty acids, compensated by increased levels of oleic acid and increased elongase and desaturase activities. EFAD correlated with reduced anthropometric Z scores at 3-6 and 9 months of age. Serum NEFA also correlated with elevated BA and liver dysfunction. Essential fatty acid depletion and altered NEFA metabolism were highly prevalent and associated with acute and chronic growth-faltering in EED. The finding suggests that targeting early interventions to correct EFAD and promote FA absorption in children with EED may facilitate childhood growth in high-risk settings.

13.
Am J Trop Med Hyg ; 108(4): 672-683, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36913924

RESUMO

Environmental enteric dysfunction (EED) is a subclinical enteropathy prevalent in resource-limited settings, hypothesized to be a consequence of chronic exposure to environmental enteropathogens, resulting in malnutrition, growth failure, neurocognitive delays, and oral vaccine failure. This study explored the duodenal and colonic tissues of children with EED, celiac disease, and other enteropathies using quantitative mucosal morphometry, histopathologic scoring indices, and machine learning-based image analysis from archival and prospective cohorts of children from Pakistan and the United States. We observed villus blunting as being more prominent in celiac disease than in EED, as shorter lengths of villi were observed in patients with celiac disease from Pakistan than in those from the United States, with median (interquartile range) lengths of 81 (73, 127) µm and 209 (188, 266) µm, respectively. Additionally, per the Marsh scoring method, celiac disease histologic severity was increased in the cohorts from Pakistan. Goblet cell depletion and increased intraepithelial lymphocytes were features of EED and celiac disease. Interestingly, the rectal tissue from cases with EED showed increased mononuclear inflammatory cells and intraepithelial lymphocytes in the crypts compared with controls. Increased neutrophils in the rectal crypt epithelium were also significantly associated with increased EED histologic severity scores in duodenal tissue. We observed an overlap between diseased and healthy duodenal tissue upon leveraging machine learning image analysis. We conclude that EED comprises a spectrum of inflammation in the duodenum, as previously described, and the rectal mucosa, warranting the examination of both anatomic regions in our efforts to understand and manage EED.


Assuntos
Doença Celíaca , Enteropatias , Humanos , Criança , Doença Celíaca/patologia , Estudos Prospectivos , Duodeno/patologia , Enteropatias/patologia , Mucosa Intestinal/patologia , Aprendizado de Máquina
14.
Sci Rep ; 13(1): 203, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604447

RESUMO

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. A clear gap in our existing CD diagnostics and current disease management approaches is the lack of highly specific biomarkers that can be used to streamline or personalize disease management. Comprehensive profiling of metabolites holds promise; however, these high-dimensional profiles need to be reduced to have relevance in the context of CD. Machine learning approaches are optimally suited to bridge this gap in knowledge by contextualizing the metabolic alterations in CD using genome-scale metabolic network reconstructions. Our work presents a framework for studying altered metabolic reactions between patients with CD and controls using publicly available transcriptomic data and existing gene-driven metabolic network reconstructions. Additionally, we apply the same methods to patient-derived ileal enteroids to explore the utility of using this experimental in vitro platform for studying CD. Furthermore, we have piloted an untargeted metabolomics approach as a proof-of-concept validation strategy in human ileal mucosal tissue. These findings suggest that in silico metabolic modeling can potentially identify pathways of clinical relevance in CD, paving the way for the future discovery of novel diagnostic biomarkers and therapeutic targets.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/metabolismo , Biomarcadores/metabolismo , Metabolômica , Redes e Vias Metabólicas , Perfilação da Expressão Gênica
15.
Nat Rev Gastroenterol Hepatol ; 20(4): 223-237, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36526906

RESUMO

Environmental enteric dysfunction (EED) is a subclinical syndrome of intestinal inflammation, malabsorption and barrier disruption that is highly prevalent in low- and middle-income countries in which poverty, food insecurity and frequent exposure to enteric pathogens impair growth, immunity and neurodevelopment in children. In this Review, we discuss advances in our understanding of EED, intestinal adaptation and the gut microbiome over the 'first 1,000 days' of life, spanning pregnancy and early childhood. Data on maternal EED are emerging, and they mirror earlier findings of increased risks for preterm birth and fetal growth restriction in mothers with either active inflammatory bowel disease or coeliac disease. The intense metabolic demands of pregnancy and lactation drive gut adaptation, including dramatic changes in the composition, function and mother-to-child transmission of the gut microbiota. We urgently need to elucidate the mechanisms by which EED undermines these critical processes so that we can improve global strategies to prevent and reverse intergenerational cycles of undernutrition.


Assuntos
Síndromes de Malabsorção , Microbiota , Nascimento Prematuro , Lactente , Recém-Nascido , Feminino , Pré-Escolar , Humanos , Gravidez , Transmissão Vertical de Doenças Infecciosas , Intestino Delgado
17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 4740-4744, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-36086227

RESUMO

Advancements in deep learning techniques have proved useful in biomedical image segmentation. However, the large amount of unlabeled data inherent in biomedical imagery, particularly in digital pathology, creates a semi-supervised learning paradigm. Specifically, because of the time consuming nature of producing pixel-wise annotations and the high cost of having a pathologist dedicate time to labeling, there is a large amount of unlabeled data that we wish to utilize in training segmentation algorithms. Pseudo-labeling is one method to leverage the unlabeled data to increase overall model performance. We adapt a method used for image classification pseudo-labeling to select images for segmentation pseudo-labeling and apply it to 3 digital pathology datasets. To select images for pseudo-labeling, we create and explore different thresholds for confidence and uncertainty on an image level basis. Furthermore, we study the relationship between image-level uncertainty and confidence with model performance. We find that the certainty metrics do not consistently correlate with performance intuitively, and abnormal correlations serve as an indicator of a model's ability to produce pseudo-labels that are useful in training. Clinical relevance - The proposed approach adapts image-level confidence and uncertainty measures for segmentation pseudo-labeling on digital pathology datasets. Increased model performance enables better disease quantification for histopathology.


Assuntos
Algoritmos , Aprendizado de Máquina Supervisionado , Incerteza
18.
Clin Perinatol ; 49(2): 475-484, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35659098

RESUMO

The burden of infant malnutrition is greatest in low- and middle-income countries (LMICs). Infant malnutrition is defined based on distinct subcategories, among them stunting (low-height-for-age) and wasting (low-weight-for-height). Some experts are shifting more toward understanding the interplay between these overlapping phenotypes and other confounding factors such as maternal nutrition and environmental hygiene. Current guidelines emphasize appropriate breastfeeding and nutrition within the 1000 days from conception to a child's second birthday to optimize early development. Future research directed toward better biomarkers of malnutrition before acute clinical symptoms develop will help direct targeted efforts toward at-risk populations.


Assuntos
Transtornos da Nutrição do Lactente , Desnutrição , Países em Desenvolvimento , Transtornos do Crescimento/epidemiologia , Humanos , Lactente , Transtornos da Nutrição do Lactente/epidemiologia , Desnutrição/diagnóstico , Estado Nutricional
19.
Vaccine ; 40(25): 3444-3451, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35534310

RESUMO

BACKGROUND: The underperformance of oral vaccines in children of low- and middle-income countries is partly attributable to underlying environmental enteric dysfunction (EED). METHODOLOGY: We conducted a longitudinal, community-based study to evaluate the association of oral rotavirus vaccine (Rotarix®) seroconversion with growth anthropometrics, EED biomarkers and intestinal enteropathogens in Pakistani infants. Children were enrolled between three to six months of their age based on their nutritional status. We measured serum anti-rotavirus immunoglobulin A (IgA) at enrollment and nine months of age with EED biomarkers and intestinal enteropathogens. RESULTS: A total of 391 infants received two doses of rotavirus (RV) vaccine. 331/391 provided paired blood samples. Of these 331 children, 45% seroconverted at 9 months of age, 35% did not seroconvert and 20% were seropositive at baseline. Non-seroconverted children were more likely to be stunted, wasted and underweight at enrollment. In univariate analysis, insulin-like growth factor (IGF) concentration at 6 months were higher in seroconverters, median (25th, 75th percentile): 26.3 (16.5, 43.5) ng/ml vs. 22.5 (13.6, 36.3) ng/ml for non-seroconverters, p-value = 0.024. At nine months, fecal myeloperoxidase (MPO) concentrations were significantly lower in seroconverters, 3050(1250, 7587) ng/ml vs. 4623.3 (2189, 11650) ng/ml in non-seroconverted children, p-value = 0.017. In multivariable logistic regression analysis, alpha-1 acid glycoprotein (AGP) and IGF-1 concentrations were positively associated with seroconversion at six months. The presence of sapovirus and rotavirus in fecal samples at the time of rotavirus administration, was associated with non-seroconversion and seroconversion, respectively. CONCLUSION: We detected high baseline RV seropositivity and impaired RV vaccine immunogenicity in this high-risk group of children. Healthy growth, serum IGF-1 and AGP, and fecal shedding of rotavirus were positively associated with RV IgA seroconversion following immunization, whereas the presence of sapovirus was more common in non-seroconverters. TRIAL REGISTRATION: Clinical Trials ID: NCT03588013.


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Anticorpos Antivirais , Biomarcadores , Criança , Humanos , Imunoglobulina A , Lactente , Fator de Crescimento Insulin-Like I , Paquistão/epidemiologia , Infecções por Rotavirus/prevenção & controle , Soroconversão , Vacinas Atenuadas
20.
Inflamm Bowel Dis ; 28(6): 819-829, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34417815

RESUMO

There is a rising interest in use of big data approaches to personalize treatment of inflammatory bowel diseases (IBDs) and to predict and prevent outcomes such as disease flares and therapeutic nonresponse. Machine learning (ML) provides an avenue to identify and quantify features across vast quantities of data to produce novel insights in disease management. In this review, we cover current approaches in ML-driven predictive outcomes modeling for IBD and relate how advances in other fields of medicine may be applied to improve future IBD predictive models. Numerous studies have incorporated clinical, laboratory, or omics data to predict significant outcomes in IBD, including hospitalizations, outpatient corticosteroid use, biologic response, and refractory disease after colectomy, among others, with considerable health care dollars saved as a result. Encouraging results in other fields of medicine support efforts to use ML image analysis-including analysis of histopathology, endoscopy, and radiology-to further advance outcome predictions in IBD. Though obstacles to clinical implementation include technical barriers, bias within data sets, and incongruence between limited data sets preventing model validation in larger cohorts, ML-predictive analytics have the potential to transform the clinical management of IBD. Future directions include the development of models that synthesize all aforementioned approaches to produce more robust predictive metrics.


Assuntos
Doenças Inflamatórias Intestinais , Viés , Hospitalização , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Aprendizado de Máquina , Prognóstico
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