Regular health screening plays a crucial role in the early detection of common chronic diseases and prevention of their progression. An AI system capable of recapitulating early disease detection, staging and incidence prediction would help to improve healthcare access and delivery, particularly in resource-poor or remote settings. Using a total of 115,344 retinal fundus photographs from 57,672 patients (with data split into mutually exclusive training, internal testing, and external validation sets), we first developed AI models capable of identifying chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) based on fundus images. The AI system was shown to be capable of predicting the clinical indicators of CKD and T2DM (including eGFR and blood glucose levels), which indicates its potential for extracting quantitative clinical metrics embedded subtly within retinal fundus images. We further developed an AI system to predict the risk of disease progression using baseline images of 10,269 patients for whom longitudinal clinical data were available for up to 6 years, which demonstrated potential utility in optimizing health screening intervals and clinical management. The generalizability of the AI system in identifying and predicting the progression of CKD and T2DM was evaluated using population-based external validation cohorts. Moreover, a prospective pilot study with 3,081 patients was also conducted to demonstrate the broader applicability of the AI system at the 'point-of-care' using fundus images captured with smartphones. The results provide proof-of-concept for a reliable and non-invasive AI-based clinical screening tool based on fundus photographs for the early detection and incidence prediction of two common systemic diseases.
We recently identified a locus on the Staphylococcus aureus chromosome, designated sar, for staphylococcal accessory regulator, that is involved in the global regulation of extracellular and cell wall-associated proteins. Previous phenotypic and Southern blot analyses with Tn917 and agr probes indicated that this locus is distinct from agr, a previously described global regulator of exoproteins in S. aureus. To understand the mode of regulatory control of exoprotein synthesis by the sar locus, the sar genotype was transduced from the original sar mutant 11D2 into two prototypic S. aureus strains, RN6390 and RN450, with well-defined geneticbackgrounds. An analysis of extracellular protein profiles by use of silver-stained sodium dodecyl sulfate gels revealed alterations in the pattern of exoprotein production in the late log-early stationary phase in the sar
BackgroundInterleukin (IL)-32 is a recently described pro-inflammatory cytokine that has been reported to be induced by bacteria treatment in culture cells. Little is known about IL-32 production by exogenous pathogens infection in human individuals.Methods and FindingsIn this study, we found that IL-32 level was increased by 58.2% in the serum samples from a cohort of 108 patients infected by influenza A virus comparing to that of 115 healthy individuals. Another pro-inflammatory factor cyclooxygenase (COX)-2-associated prostaglandin E2 was also upregulated by 2.7-fold. Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. Interestingly, we found that COX-2-associate PGE2 production activated by influenza virus infection was significantly suppressed by over-expression of IL-32 but increased by IL-32-specific siRNA, suggesting there was a feedback mechanism between IL-32 and COX-2.ConclusionsIL-32 is induced by influenza A virus infection via COX-2 in the inflammatory cascade. Our results provide that IL-32 is a potential target for anti-inflammatory medicine screening.
Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last followup on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.
BackgroundPrevious studies have reported decreased birth weight associated with increased air pollutant concentrations during pregnancy. However, it is not clear when during pregnancy increases in air pollution are associated with the largest differences in birth weight.ObjectivesUsing the natural experiment of air pollution declines during the 2008 Beijing Olympics, we evaluated whether having specific months of pregnancy (i.e., 1st…8th) during the 2008 Olympics period was associated with larger birth weights, compared with pregnancies during the same dates in 2007 or 2009.MethodsUsing n = 83,672 term births to mothers residing in four urban districts of Beijing, we estimated the difference in birth weight associated with having individual months of pregnancy during the 2008 Olympics (8 August–24 September 2008) compared with the same dates in 2007 and 2009. We also estimated the difference in birth weight associated with interquartile range (IQR) increases in mean ambient particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) concentrations during each pregnancy month.ResultsBabies whose 8th month of gestation occurred during the 2008 Olympics were, on average, 23 g larger (95% CI: 5 g, 40 g) than babies whose 8th month occurred during the same calendar dates in 2007 or 2009. IQR increases in PM2.5 (19.8 μg/m3), CO (0.3 ppm), SO2 (1.8 ppb), and NO2 (13.6 ppb) concentrations during the 8th month of pregnancy were associated with 18 g (95% CI: –32 g, –3 g), 17 g (95% CI: –28 g, –6 g), 23 g (95% CI: –36 g, –10 g), and 34 g (95% CI: –70 g, 3 g) decreases in birth weight, respectively. We did not see significant associations for months 1–7.ConclusionsShort-term decreases in air pollution late in pregnancy in Beijing during the 2008 Summer Olympics, a normally heavily polluted city, were associated with higher birth weight.CitationRich DQ, Liu K, Zhang J, Thurston SW, Stevens TP, Pan Y, Kane C, Weinberger B, Ohman-Strickland P, Woodruff TJ, Duan X, Assibey-Mensah V, Zhang J. 2015. Differences in birth weight associated with the 2008 Beijing Olympics air pollution reduction: results from a natural experiment. Environ Health Perspect 123:880–887; http://dx.doi.org/10.1289/ehp.1408795
CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.
Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. Despite considerable investigation, the pathogenesis of ITP remains incompletely understood, and for many patients, effective therapy is still unavailable. Using murine models and in vitro studies of human blood samples, we recently identified a novel Fc-independent platelet clearance pathway, whereby antibody-mediated desialylated platelets can be cleared in the liver via asialoglycoprotein receptors, leading to decreased response to standard first-line therapies targeting Fc-dependent platelet clearance. Here, we evaluated the significance of this finding in 61 ITP patients through correlation of levels of platelet desialylation with the efficacy of first-line therapies. We found that desialylation levels between different responses to treatment groups were statistically significant (p < 0.01). Importantly, correlation analysis indicated response to treatment and platelet desialylation were related (p < 0.01), whereby non-responders had significantly higher levels of platelet desialylation. Interestingly, we also found secondary ITP and certain non-ITP thrombocytopenias also exhibited significant platelet desialylation compared to healthy controls. These findings designate platelet desialylation as an important biomarker in determining response to standard treatment for ITP. Furthermore, we show for the first time platelet desialylation in other non-ITP thrombocytopenias, which may have important clinical implications and deserve further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0413-3) contains supplementary material, which is available to authorized users.
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