RESUMO
BACKGROUND AND AIMS: The prevalence of NAFLD is increasing globally and on a path to becoming the most frequent cause of chronic liver disease. Strategies for the prevention and treatment of NAFLD are urgently needed. APPROACH AND RESULTS: A 6-month prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy of daily NRPT (commercially known as Basis, a combination of nicotinamide riboside and pterostilbene) supplementation in 111 adults with NAFLD. The study consisted of three arms: placebo, recommended daily dose of NRPT (NRPT 1×), and a double dose of NRPT (NRPT 2×). NRPT appeared safe and well tolerated. At the end of the study, no significant change was seen in the primary endpoint of hepatic fat fraction with respect to placebo. However, among prespecified secondary outcomes, a time-dependent decrease in the circulating levels of the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) was observed in the NRPT 1× group, and this decrease was significant with respect to placebo. Furthermore, a significant decrease in the circulating levels of the toxic lipid ceramide 14:0 was also observed in the NRPT 1× group versus placebo, and this decrease was associated with a decrease in ALT in individuals of this group. A dose-dependent effect was not observed with respect to ALT, GGT, or ceramide 14:0 in the NRPT 2× group. CONCLUSIONS: This study demonstrates that NRPT at the recommended dose is safe and may hold promise in lowering markers of hepatic inflammation in patients with NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Prospectivos , gama-Glutamiltransferase , Inflamação/tratamento farmacológico , Inflamação/complicações , Método Duplo-Cego , Alanina TransaminaseRESUMO
Idiopathic pulmonary fibrosis (IPF) is a pathological condition of unknown etiology that results from injury to the lung and an ensuing fibrotic response that leads to the thickening of the alveolar walls and obliteration of the alveolar space. The pathogenesis is not clear, and there are currently no effective therapies for IPF. Small airway disease and mucus accumulation are prominent features in IPF lungs, similar to cystic fibrosis lung disease. The ATP12A gene encodes the α-subunit of the nongastric H+, K+-ATPase, which functions to acidify the airway surface fluid and impairs mucociliary transport function in patients with cystic fibrosis. It is hypothesized that the ATP12A protein may play a role in the pathogenesis of IPF. The authors' studies demonstrate that ATP12A protein is overexpressed in distal small airways from the lungs of patients with IPF compared with normal human lungs. In addition, overexpression of the ATP12A protein in mouse lungs worsened bleomycin induced experimental pulmonary fibrosis. This was prevented by a potassium competitive proton pump blocker, vonoprazan. These data support the concept that the ATP12A protein plays an important role in the pathogenesis of lung fibrosis. Inhibition of the ATP12A protein has potential as a novel therapeutic strategy in IPF treatment.
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Fibrose Cística , Fibrose Pulmonar Idiopática , Camundongos , Animais , Humanos , Fibrose Cística/metabolismo , Bombas de Próton/metabolismo , Bombas de Próton/farmacologia , Bombas de Próton/uso terapêutico , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Bleomicina/farmacologia , Fibrose , ATPase Trocadora de Hidrogênio-Potássio/genética , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/farmacologiaRESUMO
Dietary fibre modulates gastrointestinal (GI) health and function, providing laxation, shifting microbiota, and altering bile acid (BA) metabolism. Fruit juice production removes the polyphenol- and fibre-rich pomace fraction. The effects of orange and apple pomaces on GI outcomes were investigated in healthy, free-living adults. Healthy adults were enrolled in two double-blinded, crossover trials, being randomised by baseline bowel movement (BM) frequency. In the first trial, subjects (n 91) received orange juice (OJ, 0 g fibre/d) or OJ + orange pomace (OJ + P, 10 g fibre/d) for 4 weeks, separated by a 3-week washout. Similarly, in the second trial, subjects (n 90) received apple juice (AJ, 0 g fibre/d) or AJ + apple pomace (AJ + P, 10 g fibre/d). Bowel habit diaries, GI tolerance surveys and 3-d diet records were collected throughout. Fresh faecal samples were collected from a participant subset for microbiota and BA analyses in each study. Neither pomace interventions influenced BM frequency. At Week 4, OJ + P tended to increase (P = 0·066) GI symptom occurrence compared with OJ, while AJ + P tended (P = 0·089) to increase flatulence compared with AJ. Faecalibacterium (P = 0·038) and Negativibacillus (P = 0·043) were differentially abundant between pre- and post-interventions in the apple trial but were no longer significant after false discovery rate (FDR) correction. Baseline fibre intake was independently associated with several microbial genera in both trials. Orange or apple pomace supplementation was insufficient to elicit changes in bowel habits, microbiota diversity or BA of free-living adults with healthy baseline BM. Future studies should consider baseline BM frequency and habitual fibre intake.
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Citrus sinensis , Malus , Microbiota , Humanos , Adulto , Frutas , Ácidos e Sais Biliares , Defecação , Fezes/microbiologia , Fibras na Dieta/farmacologia , HábitosRESUMO
Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale multivariate neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an α brain atlas and a ß brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify and separate mediators that potentially positively and negatively mediate symptoms and psychosis, respectively, and quantify the effect of each neural mediator on disease development. Taken together, these results paint a brain-wide picture of neural markers that are potentially mediating behavioral symptoms and the development of psychotic disorders; additionally, they underscore a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological system.
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Sintomas Comportamentais/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Sintomas Prodrômicos , Transtornos Psicóticos/diagnóstico por imagem , Sintomas Comportamentais/fisiopatologia , Mapeamento Encefálico/métodos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Análise de Mediação , Transtornos Psicóticos/fisiopatologia , Adulto JovemRESUMO
The negatively charged nitrogen-vacancy center in fluorescent nanodiamonds (FNDs) is a point defect with unique magneto-optical properties. It emits far-red fluorescence at â¼700 nm, and its intensity can be magnetically modulated with a depth of more than 10% at a field strength of 30 mT. We have closely examined this property and illustrated its practical use in biomedicine by applying a periodic, time-varying magnetic field to FNDs deposited on a surface or dispersed in a solution with a lock-in detection method. We achieved selective and sensitive detection of 100 nm FNDs on a nitrocellulose membrane at a particle density of 0.04 ng/mm2 (or â¼2 × 104 particles/mm2) and in an aqueous solution with a particle concentration of 1 ng/mL (or â¼1 fM) in 10 s as the detection limits. The utility and versatility of the technique were demonstrated with an application to background-free detection of FNDs as reporters for FND-based lateral flow immunoassays as well as selective quantification of FNDs in tissue digests for in vivo studies.
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Nanodiamantes , Fluorescência , NitrogênioRESUMO
We outline what we believe could be an improvement in future discussions of the brain acting as a Bayesian-Laplacian system. We do so by distinguishing between two broad classes of priors on which the brain's inferential systems operate: in one category are biological priors (ß priors) and in the other artefactual ones (α priors). We argue that ß priors, of which colour categories and faces are good examples, are inherited or acquired very rapidly after birth, are highly or relatively resistant to change through experience, and are common to all humans. The consequence is that the probability of posteriors generated from ß priors having universal assent and agreement is high. By contrast, α priors, of which man-made objects are examples, are acquired post-natally and modified at various stages throughout post-natal life; they are much more accommodating of, and hospitable to, new experiences. Consequently, posteriors generated from them are less likely to find universal assent. Taken together, in addition to the more limited capacity of experiment and experience to alter the ß priors compared with α priors, another cardinal distinction between the two is that the probability of posteriors generated from ß priors having universal agreement is greater than that for α priors. The two categories are distinct at the extremes; there is, however, a middle range where they merge into one another to varying extents, resulting in posteriors that draw upon both categories.
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Encéfalo , Teorema de Bayes , HumanosRESUMO
BACKGROUND: Registry studies have shown that the Endurant stent graft is associated with low rates of all-cause and aneurysm-related mortality when used for the endovascular treatment of abdominal aortic aneurysm (AAA). However, many were limited by length of follow-up and all had a proportion of patients lost to follow-up. The aim of this study is to report results from a large, real-world experience using Endurant, utilizing methods to ensure complete ascertainment of mortality. METHODS: This study describes a large, single vascular unit experience using the Endurant stent graft in consecutive patients treated between August 2008 and March 2019. RESULTS: One-hundred eighty patients (mean age 76.0 ± 8.6 years; 90% male) with mean AAA diameter of 57.5 ± 10.5 mm underwent endovascular aneurysm repair (EVAR). Technical success was achieved in all cases. At median follow-up of 55.0 months (interquartile range 29.8-79.0), 51 (28.3%) patients had died. Kaplan-Meier estimate of 5-year overall survival and freedom from aneurysm-related death was 71.6% and 99.4%, respectively. Lower survival rates were observed in patients who underwent EVAR at age ≥80 years (59.2% vs. 78.3%, P < 0.01) and with aneurysm diameter ≥70 mm (55.6% vs. 73.8%, P = 0.03). Thirteen endoleaks (7.2%; 4 type 1A, 2 type 1B, 7 type 2) were observed during follow-up (mean time from implantation 8.7 ± 4.2, range 1-52 months). Eleven patients (6.1%) required secondary intervention for limb occlusion (n = 7), endoleak (n = 3), and restenosis (n = 1). Patients treated within (n = 104; 57.8%) and outside (n = 76; 42.2%) the manufacturer's instructions for use (IFU) had similar rates of endoleak (7 [6.7%] vs. 6 [7.9%]; P = 0.76), secondary re-intervention (7 [6.7%] vs. 4 [5.3%]; P = 0.74) and overall-survival (72 [69.2%] vs. 55 [72.3%]; P = 0.46). CONCLUSIONS: Results from this real-world study of consecutive patients treated for AAA using the Endurant stent graft demonstrate that it is safe and effective, with excellent long-term outcomes for anatomy that falls both inside and outside IFU recommendations.
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Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Estudos Prospectivos , Desenho de Prótese , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Curcumin exerts a wide range of beneficial physiological and pharmacological activities, including antioxidant, anti-amyloid, anti-inflammatory, anti-microbial, anti-neoplastic, immune-modulating, metabolism regulating, anti-depressant, neuroprotective and tissue protective effects. However, its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites greatly limit its utility as a health-promoting agent and dietary supplement. Recent advances in micro- and nano-formulations of curcumin with greatly enhanced absorption resulting in desirable blood levels of the active forms of curcumin now make it possible to address a wide range of potential applications, including pain management, and as tissue protective. Using these forms of highly bioavailable curcumin now enable a broad spectrum of appropriate studies to be conducted. This review discusses the formulations designed to enhance bioavailability, metabolism of curcumin, relationships between solubility and particle size relative to bioavailability, human pharmacokinetic studies involving formulated curcumin products, the widely used but inappropriate practice of hydrolyzing plasma samples for quantification of blood curcumin, current applications of curcumin and its metabolites and promising directions for health maintenance and applications.
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Células Sanguíneas/química , Curcumina/farmacocinética , Animais , Disponibilidade Biológica , Curcumina/química , Composição de Medicamentos , Humanos , Tamanho da Partícula , Solubilidade , Nanomedicina TeranósticaRESUMO
Mediation analysis is an important tool in the behavioral sciences for investigating the role of intermediate variables that lie in the path between a treatment and an outcome variable. The influence of the intermediate variable on the outcome is often explored using a linear structural equation model (LSEM), with model coefficients interpreted as possible effects. While there has been significant research on the topic, little work has been done when the intermediate variable (mediator) is a high-dimensional vector. In this work, we introduce a novel method for identifying potential mediators in this setting called the directions of mediation (DMs). DMs linearly combine potential mediators into a smaller number of orthogonal components, with components ranked based on the proportion of the LSEM likelihood each accounts for. This method is well suited for cases when many potential mediators are measured. Examples of high-dimensional potential mediators are brain images composed of hundreds of thousands of voxels, genetic variation measured at millions of single nucleotide polymorphisms (SNPs), or vectors of thousands of variables in large-scale epidemiological studies. We demonstrate the method using a functional magnetic resonance imaging study of thermal pain where we are interested in determining which brain locations mediate the relationship between the application of a thermal stimulus and self-reported pain.
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Encéfalo/fisiologia , Neuroimagem Funcional/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Modelos Estatísticos , Nociceptividade/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Temperatura Alta , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVES: To prospectively compare the diagnostic performance of reduced-dose (RD) contrast-enhanced CT (CECT) with standard-dose (SD) CECT for detection of low-contrast liver lesions. METHODS: Seventy adults with non-liver primary malignancies underwent abdominal SD-CECT immediately followed by RD-CECT, aggressively targeted at 60-70 % dose reduction. SD series were reconstructed using FBP. RD series were reconstructed with FBP, ASIR, and MBIR (Veo). Three readers-blinded to clinical history and comparison studies-reviewed all series, identifying liver lesions ≥4 mm. Non-blinded review by two experienced abdominal radiologists-assessing SD against available clinical and radiologic information-established the reference standard. RESULTS: RD-CECT mean effective dose was 2.01 ± 1.36 mSv (median, 1.71), a 64.1 ± 8.8 % reduction. Pooled per-patient performance data were (sensitivity/specificity/PPV/NPV/accuracy) 0.91/0.78/0.60/0.96/0.81 for SD-FBP compared with RD-FBP 0.79/0.75/0.54/0.91/0.76; RD-ASIR 0.84/0.75/0.56/0.93/0.78; and RD-MBIR 0.84/0.68/0.49/0.92/0.72. ROC AUC values were 0.896/0.834/0.858/0.854 for SD-FBP/RD-FBP/RD-ASIR/RD-MBIR, respectively. RD-FBP (P = 0.002) and RD-MBIR (P = 0.032) AUCs were significantly lower than those of SD-FBP; RD-ASIR was not (P = 0.052). Reader confidence was lower for all RD series (P < 0.001) compared with SD-FBP, especially when calling patients entirely negative. CONCLUSIONS: Aggressive CT dose reduction resulted in inferior diagnostic performance and reader confidence for detection of low-contrast liver lesions compared to SD. Relative to RD-ASIR, RD-FBP showed decreased sensitivity and RD-MBIR showed decreased specificity. KEY POINTS: ⢠Reduced-dose CECT demonstrates inferior diagnostic performance for detecting low-contrast liver lesions. ⢠Reader confidence is lower with reduced-dose CECT compared to standard-dose CECT. ⢠Overly aggressive dose reduction may result in misdiagnosis, regardless of reconstruction algorithm. ⢠Careful consideration of perceived risks versus benefits of dose reduction is crucial.
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Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Algoritmos , Protocolos Clínicos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Abdominal/métodos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The purposes of this study were to compare rates of lesion detection at CT colonographic (CTC) screening of adults without symptoms who had and who did not have a family history of colorectal cancer according to American Cancer Society guidelines and to consider the clinical implications. MATERIALS AND METHODS: Over 134 months, consecutively registered CTC cohorts of adults without symptoms who had (n = 156; 88 [56.4%] women; 68 [43.6%] men; mean age, 56.3 years) and who did not have (n = 8857; 4757 [53.7%] women; 4100 [46.3%] men; mean age, 56.6 years) an American Cancer Society-defined family history of colorectal cancer (first-degree relative with diagnosis before age 60 years or two first-degree relatives with diagnosis at any age) were compared for relevant colorectal findings. RESULTS: For the family history versus no family history cohorts, the frequency of all nondiminutive polyps (≥ 6 mm) reported at CTC was 23.7% versus 15.5% (p = 0.007); small polyps (6-9 mm), 13.5% versus 9.1% (p = 0.068); and large polyps (≥ 10 mm), 10.2% versus 6.5% (p = 0.068). The rate of referral for colonoscopy was greater for the family history cohort (16.0% vs 10.5%; p = 0.035). However, the frequencies of proven advanced adenoma (4.5% vs 3.2%; p = 0.357), nonadvanced adenoma (5.1% vs 2.6%; p = 0.070), and cancer (0.0% vs 0.4%; p = 0.999) were not significantly increased. The difference in positive rates between the two cohorts (11.5% vs 4.3%; p < 0.001) was primarily due to nonneoplastic findings of no colorectal cancer relevance, such as small hyperplastic polyps, diverticular disease, and false-positive CTC findings. CONCLUSION: Although the overall CTC-positive and colonoscopy referral rates were higher in the family history cohort, the clinically relevant frequencies of advanced neoplasia and cancer were not sufficiently increased to preclude CTC screening. These findings support the use of CTC as a front-line screening option in adults with a family history of colorectal cancer.
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Colonografia Tomográfica Computadorizada/estatística & dados numéricos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/genética , Detecção Precoce de Câncer/estatística & dados numéricos , Idoso , Colonografia Tomográfica Computadorizada/normas , Colonoscopia/normas , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/normas , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Masculino , Anamnese/estatística & dados numéricos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Wisconsin/epidemiologiaRESUMO
Much of the current understanding of thermal effects in biological systems is based on macroscopic measurements. There is little knowledge about the local thermostability or heat tolerance of subcellular components at the nanoscale. Herein, we show that gold nanorod-fluorescent nanodiamond (GNR-FND) hybrids are useful as a combined nanoheater/nanothermometer in living cells. With the use of a 594â nm laser for both heating and probing, we measure the temperature changes by recording the spectral shifts of the zero-phonon lines of negatively charged nitrogen-vacancy centers in FNDs. The technique allows us to determine the rupture temperatures of individual membrane nanotubes in human embryonic kidney cells, as well as to generate high temperature gradients on the cell membrane for photoporation and optically controlled hyperthermia. Our results demonstrate a new paradigm for hyperthermia research and application.
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Membrana Celular/química , Diamante/química , Ouro/química , Nanopartículas/química , Nanotubos/química , Temperatura , Fluorescência , Células HEK293 , Humanos , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Measuring temperature in nanoscale spatial resolution either at or far from equilibrium is of importance in many scientific and technological applications. Although negatively charged nitrogen-vacancy (NV(-)) centers in diamond have recently emerged as a promising nanometric temperature sensor, the technique has been applied only under steady state conditions so far. Here, we present a three-point sampling method that allows real-time monitoring of the temperature changes over ±100 K and a pump-probe-type experiment that enables the study of nanoscale heat transfer with a temporal resolution of better than 10 µs. The utility of the time-resolved luminescence nanothermometry was demonstrated with 100 nm fluorescent nanodiamonds spin-coated on a glass substrate and submerged in gold nanorod solution heated by a near-infrared laser, and the validity of the measurements was verified with finite-element numerical simulations. The combined theoretical and experimental approaches will be useful to implement time-resolved temperature sensing in laser processing of materials and even for devices in operation at the nanometer scale.
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Depressive symptoms in Schizophrenia Spectrum Disorders (SSDs) negatively impact suicidality, prognosis, and quality of life. Despite this, efficacious treatments are limited, largely because the neural mechanisms underlying depressive symptoms in SSDs remain poorly understood. We conducted a systematic review to provide an overview of studies that investigated the neural correlates of depressive symptoms in SSDs using neuroimaging techniques. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, and Cochrane Library databases from inception through June 19, 2023. Specifically, we focused on structural and functional magnetic resonance imaging (MRI), encompassing: (1) T1-weighted imaging measuring brain morphology; (2) diffusion-weighted imaging assessing white matter integrity; or (3) T2*-weighted imaging measures of brain function. Our search yielded 33 articles; 14 structural MRI studies, 18 functional (f)MRI studies, and 1 multimodal fMRI/MRI study. Reviewed studies indicate potential commonalities in the neurobiology of depressive symptoms between SSDs and major depressive disorders, particularly in subcortical and frontal brain regions, though confidence in this interpretation is limited. The review underscores a notable knowledge gap in our understanding of the neurobiology of depression in SSDs, marked by inconsistent approaches and few studies examining imaging metrics of depressive symptoms. Inconsistencies across studies' findings emphasize the necessity for more direct and comprehensive research focusing on the neurobiology of depression in SSDs. Future studies should go beyond "total score" depression metrics and adopt more nuanced assessment approaches considering distinct subdomains. This could reveal unique neurobiological profiles and inform investigations of targeted treatments for depression in SSDs.
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The impact of Human Immunodeficiency Virus (HIV) infection on the tumor microenvironment (TME) of classic Hodgkin lymphoma (cHL), one of the most common co-morbidities following HIV infection, is not well understood. Here, we have employed multiplexed immunofluorescence (mIF) and spatial transcriptomic analysis to dissect the impact of viral infections (EBV, HIV/EBV) on cHL TME. Compared to HIV-EBV-, HIV-EBV+ cHL TME was characterized by higher cell densities of CD8high T cells co-expressing inhibitory receptors (PD-1, TIGIT), macrophage subsets and an in situ inflammatory molecular profile associated with increased expression of TCR and BCR cell signaling pathways. Compared to HIV-EBV+, HIV+EBV+ cHL TME was characterized by significantly less CD8high T cells co-expressing PD-1 and TIGIT, a profile concomitant with significantly increased cell densities of CD155high neoplastic cells. Significant downregulation of in situ TCR-signaling and upregulation of extracellular matrix reorganization pathways were found in HIV+EBV+ cHL TME, in line with an altered topological organization of CXCL13 and heparan sulfate, an extracellular matrix glycosaminoglycan. Our data reveal the complexity of the cellular and molecular composition of cHL TME in the presence of viral infections, with possible implications for combinatorial immunotherapies. Furthermore, the data suggest specific molecular targets and pathways for further investigation that could improve our understanding of possible mechanistic links between HIV and lymphomagenesis.
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This SIIM-sponsored 2023 report highlights an industry view on artificial intelligence adoption barriers and success related to diagnostic imaging, life sciences, and contrasts. In general, our 2023 survey indicates that there has been progress in adopting AI across multiple uses, and there continues to be an optimistic forecast for the impact on workflow and clinical outcomes. This report, as in prior years, should be seen as a snapshot of the use of AI in imaging. Compared to our 2021 survey, the 2023 respondents expressed wider AI adoption but felt this was behind the potential. Specifically, the adoption has increased as sources of return on investment with AI in radiology are better understood as documented by vendor/client use case studies. Generally, the discussions of AI solutions centered on workflow triage, visualization, detection, and characterization. Generative AI was also mentioned for improving productivity in reporting. As payor reimbursement remains elusive, the ROI discussions expanded to look at other factors, including increased hospital procedures and admissions, enhanced radiologist productivity for practices, and improved patient outcomes for integrated health networks. When looking at the longer-term horizon for AI adoption, respondents frequently mentioned that the opportunity for AI to achieve greater adoption with more complex AI and a more manageable/visible ROI is outside the USA. Respondents focused on the barriers to trust in AI and the FDA processes.
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Alzheimer's Disease (AD) is the leading cause of dementia. It results in cortical thickness changes and is associated with a decline in cognition and behaviour. Such decline affects multiple important day-to-day functions, including memory, language, orientation, judgment and problem-solving. Recent research has made important progress in identifying brain regions associated with single outcomes, such as individual AD status and general cognitive decline. The complex projection from multiple brain areas to multiple AD outcomes, however, remains poorly understood. This makes the assessment and especially the prediction of multiple AD outcomes - each of which may unveil an integral yet different aspect of the disease - challenging, particularly when some are not strongly correlated. Here, uniting residual learning, partial least squares (PLS), and predictive modelling, we develop an explainable, generalisable, and reproducible method called the Residual Partial Least Squares Learning (the re-PLS Learning) to (1) chart the pathways between large-scale multivariate brain cortical thickness data (inputs) and multivariate disease and behaviour data (outcomes); (2) simultaneously predict multiple, non-pairwise-correlated outcomes; (3) control for confounding variables (e.g., age and gender) affecting both inputs and outcomes and the pathways in-between; (4) perform longitudinal AD disease status classification and disease severity prediction. We evaluate the performance of the proposed method against a variety of alternatives on data from AD patients, subjects with mild cognitive impairment (MCI), and cognitively normal individuals (n=1,196) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our results unveil pockets of brain areas in the temporal, frontal, sensorimotor, and cingulate areas whose cortical thickness may be respectively associated with declines in different cognitive and behavioural subdomains in AD. Finally, we characterise re-PLS' geometric interpretation and mathematical support for delivering meaningful neurobiological insights and provide an open software package (re-PLS) available at https://github.com/thanhvd18/rePLS.
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Invasive brain-machine interfaces can restore motor, sensory and cognitive functions. However, their clinical adoption has been hindered by the surgical risk of implantation and by suboptimal long-term reliability. In this Review, we highlight the opportunities and challenges of invasive technology for clinically relevant electrophysiology. Specifically, we discuss the characteristics of neural probes that are most likely to facilitate the clinical translation of invasive neural interfaces, describe the neural signals that can be acquired or produced by intracranial electrodes, the abiotic and biotic factors that contribute to their failure, and emerging neural-interface architectures.
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Interfaces Cérebro-Computador , Reprodutibilidade dos Testes , EletrodosRESUMO
Personalized longitudinal disease assessment is central to quickly diagnosing, appropriately managing, and optimally adapting the therapeutic strategy of multiple sclerosis (MS). It is also important for identifying idiosyncratic subject-specific disease profiles. Here, we design a novel longitudinal model to map individual disease trajectories in an automated way using smartphone sensor data that may contain missing values. First, we collect digital measurements related to gait and balance, and upper extremity functions using sensor-based assessments administered on a smartphone. Next, we treat missing data via imputation. We then discover potential markers of MS by employing a generalized estimation equation. Subsequently, parameters learned from multiple training datasets are ensembled to form a simple, unified longitudinal predictive model to forecast MS over time in previously unseen people with MS. To mitigate potential underestimation for individuals with severe disease scores, the final model incorporates additional subject-specific fine-tuning using data from the first day. The results show that the proposed model is promising to achieve personalized longitudinal MS assessment; they also suggest that features related to gait and balance as well as upper extremity function, remotely collected from sensor-based assessments, may be useful digital markers for predicting MS over time.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Smartphone , MarchaRESUMO
Human sleep is cyclical with a period of approximately 90 minutes, implying long temporal dependency in the sleep data. Yet, exploring this long-term dependency when developing sleep staging models has remained untouched. In this work, we show that while encoding the logic of a whole sleep cycle is crucial to improve sleep staging performance, the sequential modelling approach in existing state-of-the-art deep learning models are inefficient for that purpose. We thus introduce a method for efficient long sequence modelling and propose a new deep learning model, L-SeqSleepNet, which takes into account whole-cycle sleep information for sleep staging. Evaluating L-SeqSleepNet on four distinct databases of various sizes, we demonstrate state-of-the-art performance obtained by the model over three different EEG setups, including scalp EEG in conventional Polysomnography (PSG), in-ear EEG, and around-the-ear EEG (cEEGrid), even with a single EEG channel input. Our analyses also show that L-SeqSleepNet is able to alleviate the predominance of N2 sleep (the major class in terms of classification) to bring down errors in other sleep stages. Moreover the network becomes much more robust, meaning that for all subjects where the baseline method had exceptionally poor performance, their performance are improved significantly. Finally, the computation time only grows at a sub-linear rate when the sequence length increases.