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1.
Neuroradiology ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404789

RESUMO

PURPOSE: Hypertension is a risk factor for cognitive impairment; however, the mechanisms leading to cognitive changes remain unclear. In this cross-sectional study, we evaluate the impact of white matter lesion (WML) burden on brain functional connectivity (FC) and cognition in a large cohort of hypertensive patients from the Systolic Blood Pressure Intervention Trial (SPRINT) at baseline. METHODS: Functional networks were identified from baseline resting state functional MRI scans of 660 SPRINT participants using independent component analysis. WML volumes were calculated from structural MRI. Correlation analyses were carried out between mean FC of each functional network and global WML as well as WML within atlas-defined white matter regions. For networks of interest, voxel-wise-adjusted correlation analyses between FC and regional WML volume were performed. Multiple variable linear regression models were built for cognitive test performance as a function of network FC, followed by mediation analysis. RESULTS: Mean FC of the default mode network (DMN) was negatively correlated with global WML volume, and regional WML volume within the precuneus. Voxel-wise correlation analyses revealed that regional WML was negatively correlated with FC of the DMN's left lateral temporal region. FC in this region of the DMN was positively correlated to performance on the Montreal Cognitive Assessment and demonstrated significant mediation effects. Additional networks also demonstrated global and regional WML correlations; however, they did not demonstrate an association with cognition. CONCLUSION: In hypertensive patients, greater WML volume is associated with lower FC of the DMN, which in turn is related to poorer cognitive test performance. TRIAL REGISTRATION: NCT01206062.

2.
Wiley Interdiscip Rev Cogn Sci ; : e1553, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33470055

RESUMO

Combining transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging offers an unprecedented tool for studying how brain networks interact in vivo and how repetitive trains of TMS modulate those networks among patients diagnosed with affective disorders. TMS compliments neuroimaging by allowing the interrogation of causal control among brain circuits. Together with TMS, neuroimaging can provide valuable insight into the mechanisms underlying treatment effects and downstream circuit communication. Here we provide a background of the method, review relevant study designs, consider methodological and equipment options, and provide statistical recommendations. We conclude by describing emerging approaches that will extend these tools into exciting new applications. This article is categorized under: Psychology > Emotion and Motivation Psychology > Theory and Methods Neuroscience > Clinical Neuroscience.

3.
Inorg Chem ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33470793

RESUMO

Mixed-matrix membranes (MMMs) incorporating metal-organic framework crystalline fillers as heterogeneous catalysts for organic transformation reactions have attracted more attention in catalysis science. Herein, a new 3D cadmium metal-organic framework (H3O)·[Cd(dppa)] (1) was first synthesized using the rigid 4-(3,5-dicarboxylphenyl)picolinic acid (H3dppa) as an organic ligand under solvothermal conditions, exhibiting a novel 6,6-connected network and good tolerance to various solvents. After activation, 1 showed good catalytic reactivity and selectivity for the synthesis of benzimidazole derivatives, affording solvent-dependent catalytic activity. Then, using the microcrystals of 1 and poly(vinylidene fluoride) (PVDF) as raw materials, 1@PVDF MMMs were successfully prepared by polymer solution casting. Notably, the integration of MOF and PVDF endows the mixed-matrix membrane 1@PVDF with great advantages in terms of more dispersive Lewis acid catalytic sites and recyclability. As expected, 1@PVDF not only displays good catalytic activity comparable to that of activated 1 but also exhibits remarkable recyclability and continuous usability for the production of benzimidazole and α- or ß-amino acid derivatives. To the best of our knowledge, this is the first time that a Cd-based MOF and MMMs have been applied as a catalyst for the production of a ß-amino acid. The combination of catalytic MOF and PVDF provides a way to simplify the design of a flow reactor and reduce the costs of manufacturing.

4.
Signal Transduct Target Ther ; 6(1): 5, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33414365

RESUMO

Forkhead box C1 (FOXC1) is required for neural crest and ocular development, and mutations in FOXC1 lead to inherited Axenfeld-Rieger syndrome. Here, we find that FOXC1 and paired box 6 (PAX6) are co-expressed in the human limbus and central corneal epithelium. Deficiency of FOXC1 and alternation in epithelial features occur in patients with corneal ulcers. FOXC1 governs the fate of the corneal epithelium by directly binding to lineage-specific open promoters or enhancers marked by H3K4me2. FOXC1 depletion not only activates the keratinization pathway and reprograms corneal epithelial cells into skin-like epithelial cells, but also disrupts the collagen metabolic process and interferon signaling pathways. Loss of interferon regulatory factor 1 and PAX6 induced by FOXC1 dysfunction is linked to the corneal ulcer. Collectively, our results reveal a FOXC1-mediated regulatory network responsible for corneal epithelial homeostasis and provide a potential therapeutic target for corneal ulcer.

5.
J Orthop Surg Res ; 16(1): 20, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413515

RESUMO

BACKGROUND: Minimally invasive-transforaminal lumbar interbody fusions (MIS-TLIF), in which the nerve root pain is caused by early postoperative edema reaction, is a common clinical complication. However, there is no effective method to solve this problem. We aimed to use gelatin sponge impregnated with mixed anti-inflammatory drugs combined with no drainage after MIS-TLIF to optimize postoperative effect in the treatment of recurrent lumbar disc herniation (LDH). METHODS: From June 2018, the middle-aged patients (45-60 years old) with recurrent LDH were recruited. Included patients were treated with MIS-TLIF surgery, and no drainage tube was placed after surgery. All patients were randomly divided into intervention group (gelatin sponge impregnated with mixed anti-inflammatory drugs) and control group (saline was immersed in gelatin sponge as a control). RESULTS: The intervention group included 63 cases, and the control group included 65 cases. The length of hospital stays and bedridden period in the intervention group were significantly lower than those in the control group (P < 0.05). The VAS score of low back pain in the intervention group was significantly lower than that of the control group at postoperative days 1-6 (P < 0.05, for all). The VAS scores of leg pain in the intervention group at postoperative days 1-9 were statistically lower than the control group (P < 0.05, for all). CONCLUSIONS: Application of gelatin sponge impregnated with mixed anti-inflammatory drugs combined with no drainage after MIS-TLIF can significantly further optimize the surgical effect of recurrent LDH and shorten the bedridden period and hospital stays, to achieve the purpose of early rehabilitation. TRIAL REGISTRATION: China Clinical Trial Registration Center, ChiCTR1800016236. Registered on May 21, 2018, http://www.chictr.org.cn/listbycreater.aspx.

6.
Nat Rev Microbiol ; 19(1): 55-71, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32887946

RESUMO

Observational findings achieved during the past two decades suggest that the intestinal microbiota may contribute to the metabolic health of the human host and, when aberrant, to the pathogenesis of various common metabolic disorders including obesity, type 2 diabetes, non-alcoholic liver disease, cardio-metabolic diseases and malnutrition. However, to gain a mechanistic understanding of how the gut microbiota affects host metabolism, research is moving from descriptive microbiota census analyses to cause-and-effect studies. Joint analyses of high-throughput human multi-omics data, including metagenomics and metabolomics data, together with measures of host physiology and mechanistic experiments in humans, animals and cells hold potential as initial steps in the identification of potential molecular mechanisms behind reported associations. In this Review, we discuss the current knowledge on how gut microbiota and derived microbial compounds may link to metabolism of the healthy host or to the pathogenesis of common metabolic diseases. We highlight examples of microbiota-targeted interventions aiming to optimize metabolic health, and we provide perspectives for future basic and translational investigations within the nascent and promising research field.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33333202

RESUMO

PURPOSE: To predict overall survival of patients receiving stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (ES-NSCLC), we developed a radiomic model that integrates risk of death estimates and changes based on pre- and posttreatment computed tomography (CT) scans. We hypothesize this innovation will improve our ability to stratify patients into various oncologic outcomes with greater accuracy. METHODS AND MATERIALS: Two cohorts of patients with ES-NSCLC uniformly treated with SBRT (a median dose of 50 Gy in 4-5 fractions) were studied. Prediction models were built on a discovery cohort of 100 patients with treatment planning CT scans, and then were applied to a separate validation cohort of 60 patients with pre- and posttreatment CT scans for evaluating their performance. RESULTS: Prediction models achieved a c-index up to 0.734 in predicting survival outcomes of the validation cohort. The integration of the pretreatment risk of survival measures (risk-high vs risk-low) and changes (risk-increase vs risk-decrease) in risk of survival measures between the pretreatment and posttreatment scans further stratified the patients into 4 subgroups (risk: high, increase; risk: high, decrease; risk: low, increase; risk: low, decrease) with significant difference (χ2 = 18.549, P = .0003, log-rank test). There was also a significant difference between the risk-increase and risk-decrease groups (χ2 = 6.80, P = .0091, log-rank test). In addition, a significant difference (χ2 = 7.493, P = .0062, log-rank test) was observed between the risk-high and risk-low groups obtained based on the pretreatment risk of survival measures. CONCLUSION: The integration of risk of survival measures estimated from pre- and posttreatment CT scans can help differentiate patients with good expected survival from those who will do more poorly following SBRT. The analysis of these radiomics-based longitudinal risk measures may help identify patients with early-stage NSCLC who will benefit from adjuvant treatment after lung SBRT, such as immunotherapy.

8.
Biomed Res Int ; 2020: 6131968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33344644

RESUMO

Objective: To evaluate Roux-en-Y and Billroth II reconstruction following pancreaticoduodenectomy (PD). Methods: PubMed, Embase, the Cochrane Library, and the Web of Science were searched to identify randomized controlled trials (RCTs) and controlled clinical trials that compared Roux-en-Y and Billroth II reconstruction following PD up to December 2019. RevMan 5.3 software was used for the statistical analysis. Results: Four RCTs and five controlled clinical trials were included, with a total of 1,072 patients (500 and 572 patients in the Roux-en-Y and Billroth II groups, respectively). No significant differences in delayed gastric emptying (DGE), A-grade DGE, B-grade DGE, or C-grade DGE were observed between the Roux-en-Y and Billroth II reconstruction groups after PD (odds ratio [OR] = 1.01, 95% confidence interval [CI]: 0.50-2.03, P = 0.98; OR = 0.49, 95% CI: 0.17-1.45, P = 0.20; OR = 0.63, 95% CI: 0.29-1.38, P = 0.25; and OR = 2.13, 95% CI: 0.38-11.99, P = 0.39). No significant difference in the incidence of postoperative pancreatic fistula, abscess, bile leaks, infection, postoperative bleeding, or the length of the postoperative hospital stay was observed between the Roux-en-Y and Billroth II groups (P > 0.05), but the operation time was significantly different (mean difference [MD] = 31.65, 95% CI: 7.14-56.17, P = 0.01). Conclusions: Billroth II reconstruction after PD did not significantly reduce the incidence of DGE or other complications but shortened the operation time compared to Roux-en-Y reconstruction. However, the results must be verified by further high-quality, large RCTs or controlled clinical trials.

9.
Aging (Albany NY) ; 122020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33373318

RESUMO

Oxybenzone (OBZ), an ultraviolet light filter that is widely used in sunscreens and cosmetics, is an emerging contaminant found in humans and the environment. Recent studies have shown that OBZ has been detected in women's plasma, urine, and breast milk. However, the effects of OBZ exposure on oocyte meiosis have not been addressed. In this study, we investigated the detrimental effects of OBZ on oocyte maturation and the protective roles of melatonin (MT) in OBZ-exposed mouse models. Our in vitro and in vivo results showed that OBZ suppressed oocyte maturation, while MT attenuated the meiotic defects induced by OBZ. In addition, OBZ facilitated H3K4 demethylation by increasing the expression of the Kdm5 family of genes, elevating ROS levels, decreasing GSH, impairing mitochondrial quality, and disrupting spindle configuration in oocytes. However, MT treatment resulted in significant protection against OBZ-induced damage during oocyte maturation and improved oocyte quality. The mechanisms underlying the beneficial roles of MT involved reduction of oxidative stress, inhibition of apoptosis, restoration of abnormal spindle assembly and up-regulation of H3K4me3. Collectively, our results suggest that MT protects against defects induced by OBZ during mouse oocyte maturation in vitro and in vivo.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33373075

RESUMO

Multiplexed tools allow for simultaneous identification of multiple constituents in one preparation offering the rapid, high through-put method in modern biological analysis. Luminescent materials with engineered optical property have been developed for multiplexed labeling detection, where encoding capacity plays a pivotal role in the efficiency. However, multi-dimensional optical identities are usually not independent which essentially hinder the practical encoding numbers to access theoretical capacity. In this work, we carefully studied the sensitizer gradient doping structure in near-infrared (NIR) excitable upconversion nanoparticles (UCNPs) and managed to achieve independent emission intensity and lifetime tuning. With the orthogonally tunability, it breaks the constraint of intensity (k) and lifetime (n) correlation and expands the practical encoding number to theoretical value as (k+1) n -1 in binary encoding. This method can also be combined with previous lifetime engineering as well to realize high level multiplexing.

11.
Semin Arthritis Rheum ; 51(1): 175-191, 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33383294

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) is the most important prognostic factor for mortality in patients with polymyositis (PM) and dermatomyositis (DM), but the prevalence of ILD in PM/DM may vary between countries. The aim of this study was to determine the overall prevalence of ILD in global patients with PM/DM. METHODS: We performed a systematic literature review of studies published from Jan 1, 2000 to April 30, 2020 on ILD and PM/DM. We extracted data and pooled the prevalence by using a random-effect model due to high heterogeneity. Heterogeneity was assessed by subgroup analysis and sensitivity analysis. RESULTS: A total of 34 studies with 10,130 patients were included in our meta-analysis. Pooled data demonstrated that the global prevalence of ILD in patients with PM/DM was 0.41 (95% confidence interval [CI] 0.35-0.48). However, this prevalence varied with geographical locations and time trends. The prevalence of ILD in PM/DM was 0.5 (95% CI 0.42-0.57) in Asia, 0.23 (95% CI 0.15-0.31) in America, and 0.26 (95% CI 0.18-0.34) in Europe. A higher prevalence of ILD was reported in studies published in 2011-2015 (0.43, 95% CI 0.34-0.52) and 2016-2020 (0.45, 95% CI 0.35-0.54), compared with those published in 2000-2010 (0.27, 95% CI 0.16-0.39). The pooled prevalence of ILD in patients with DM, PM, and clinically amyopathic dermatomyositis subtype was 0.42 (95% CI 0.35-0.49), 0.35 (95% CI 0.27-0.42), and 0.53 (95% CI 0.32-0.74), respectively. Patients with anti-Jo-1 and anti-melanoma differentiation-associated gene 5 antibodies were more likely to develop ILD than other myositis-specific autoantibodies. CONCLUSION: The global prevalence of ILD in patients with PM/DM was approximately 41% and the condition was predominant in Asians. This highlights potential genetic and environmental differences in the pathogenesis of ILD in patients with PM/DM. More studies are required to elucidate the specific associations.

12.
Front Chem ; 8: 766, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134258

RESUMO

This study developed a simple and efficient strategy to stabilize inorganic halide perovskite CsPbX3 at high relative humidity by embedding it into the matrix with elastic and self-healing features. The polymer matrix has a naturally hydrophobic characteristic of n-butyl acrylate segment (n-BA) and cross-linkable and healable moiety from N-(hydroxymethyl) acrylamide segment (NMA). It was chosen due to the provisions of both a surrounding protective layer for inorganic perovskite and elastic, as well as healing ability to the whole organic-inorganic composite. This fabricated CsPbBr3/PBA-co-PNMA composite was demonstrated to stably persist against the suffering from hydrolysis of perovskites when exposed to a high moisture environment. The PL intensity of the composite after crosslinking was found to be relatively stable after 30 days of exposure to air. Upon water immersion, the PL intensity of composite only showed a decrease of 32% after the first 6 h, then remained stable for 6 h afterward. Furthermore, this fabricated composite was not only flexible and relatively transparent but also exhibited excellent self-healing capability in ambient conditions (T = 25°C), in which the self-healing efficiency after 24 h was above 40%. The tensile strength and stretching ability of 5 wt% perovskite content in the random copolymer were observed to be 3.8 MPa and 553.5% respectively. Overall, flexible and self-healing properties combining with high luminescence characteristics are very promising materials for next-generation soft optical devices.

13.
Proc IEEE Int Symp Biomed Imaging ; 2020: 1331-1334, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33250955

RESUMO

Functional connectivity (FC) analysis is an appealing tool to aid diagnosis and elucidate the neurophysiological underpinnings of autism spectrum disorder (ASD). Many machine learning methods have been developed to distinguish ASD patients from healthy controls based on FC measures and identify abnormal FC patterns of ASD. Particularly, several studies have demonstrated that deep learning models could achieve better performance for ASD diagnosis than conventional machine learning methods. Although promising classification performance has been achieved by the existing machine learning methods, they do not explicitly model heterogeneity of ASD, incapable of disentangling heterogeneous FC patterns of ASD. To achieve an improved diagnosis and a better understanding of ASD, we adopt capsule networks (CapsNets) to build classifiers for distinguishing ASD patients from healthy controls based on FC measures and stratify ASD patients into groups with distinct FC patterns. Evaluation results based on a large multi-site dataset have demonstrated that our method not only obtained better classification performance than state-of-the-art alternative machine learning methods, but also identified clinically meaningful subgroups of ASD patients based on their vectorized classification outputs of the CapsNets classification model.

14.
Proc IEEE Int Symp Biomed Imaging ; 2020: 1866-1869, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33250956

RESUMO

Pulmonary nodule detection plays an important role in lung cancer screening with low-dose computed tomography (CT) scans. It remains challenging to build nodule detection deep learning models with good generalization performance due to unbalanced positive and negative samples. In order to overcome this problem and further improve state-of-the-art nodule detection methods, we develop a novel deep 3D convolutional neural network with an Encoder-Decoder structure in conjunction with a region proposal network. Particularly, we utilize a dynamically scaled cross entropy loss to reduce the false positive rate and combat the sample imbalance problem associated with nodule detection. We adopt the squeeze-and-excitation structure to learn effective image features and utilize inter-dependency information of different feature maps. We have validated our method based on publicly available CT scans with manually labelled ground-truth obtained from LIDC/IDRI dataset and its subset LUNA16 with thinner slices. Ablation studies and experimental results have demonstrated that our method could outperform state-of-the-art nodule detection methods by a large margin.

15.
Med Image Comput Comput Assist Interv ; 12267: 479-488, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33251531

RESUMO

Function magnetic resonance imaging (fMRI) data are typically contaminated by noise introduced by head motion, physiological noise, and thermal noise. To mitigate noise artifact in fMRI data, a variety of denoising methods have been developed by removing noise factors derived from the whole time series of fMRI data and therefore are not applicable to real-time fMRI data analysis. In the present study, we develop a generally applicable, deep learning based fMRI denoising method to generate noise-free realistic individual fMRI volumes (time points). Particularly, we develop a fully data-driven 3D convolutional encapsulated Long Short-Term Memory (3DConv-LSTM) approach to generate noise-free fMRI volumes regularized by an adversarial network that makes the generated fMRI volumes more realistic by fooling a critic network. The 3DConv-LSTM model also integrates a gate-controlled self-attention model to memorize short-term dependency and historical information within a memory pool. We have evaluated our method based on both task and resting state fMRI data. Both qualitative and quantitative results have demonstrated that the proposed method outperformed state-of-the-art alternative deep learning methods.

16.
J Electromyogr Kinesiol ; 56: 102487, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33221599

RESUMO

This study compared the effect of local and general fatiguing exercise on disturbed and static postural control performances. Surface electromyography and center of pressure signals were respectively recorded during self-initiated perturbation test and static postural stability test from 7 young male subjects. Local fatiguing exercise was performed using intermittent isometric knee extensions at the level of 40% of maximal voluntary torques. General fatiguing exercise was implemented with rowing ergometer at a speed of 200 ± 5 m/min. Results of disturbed postural tests showed no significant change of anticipatory postural adjustment (APAs) organizations in individual muscles following both fatiguing exercises, but observed larger APAs coactivations in trunk and dorsal muscle pairs following local than general fatiguing exercise, and larger compensatory postural adjustments (CPAs) coactivation in dorsal muscle pair after both fatiguing exercises. In addition, the results of static postural tests indicated efficient static postural stability accompanying the down-weighting of visual input and the up-weighting of vestibular/somatosensory component following both fatiguing exercises. These findings evidenced a general compensation in the central nervous system in response to the neuromuscular deficiencies induced by local fatiguing exercise and put forward the function of sensory recalibration in maintaining postural stability under fatigue conditions.

17.
Autoimmun Rev ; 19(12): 102687, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33131688

RESUMO

INTRODUCTION: Immune checkpoints inhibitors (ICIs) are associated with frequent immune-related adverse events (irAEs), but patients with preexisting autoimmune disease (PAD) have been excluded from clinical trials, leaving serious gaps in knowledge. OBJECTIVE: To evaluate the safety and efficacy of ICIs in PAD patients and cancer and explore the impact of different PAD types and baseline receiving immunosuppressive therapy. METHODS: Systematic searches were performed of PubMed, EMBASE, and the Cochrane library from inception through August 2019 for observational studies reporting safety and efficacy data among ICI-treated patients with cancer and PAD. RESULTS: 619 ICI-treated patients with PAD in 14 publications were finally identified. In the random-effects meta-analysis, pooled incidence of PAD flares, de novo immune-related adverse events (irAEs) or both of any grade was 60% (95%CI = 52%-68%). Separately, there were 219 and 206 patients experiencing PAD exacerbation and de novo irAEs of any grade, yielding a pooled incidence of 35% (95%CI = 29%-41%) and 33% (95%CI = 24%-42%) respectively. Rheumatoid arthritis was associated with a trend toward higher flare occurrence compared with another individual PADs (RR = 1.25-1.88). A total of 136 patients showed complete or partial response, corresponding to a pooled response rates of 30% (95%CI = 22%-39%). There were no statistical differences between patients with and without immunosuppressive therapy at ICI start regarding flare (RR = 1.08, 95%CI = 0.72-1.62), but a trend toward lower response rates was observed in patients with baseline immunosuppressants (RR = 0.58, 95%CI = 0.26-1.33). CONCLUSIONS: Immune toxicities are frequent in ICI-treated patients with PAD but often mild and manageable without discontinuing therapy. ICI treatment are also effective in PAD patients, but close monitoring and multidisciplinary collaboration should be contemplated, especially for those concomitantly receiving immunosuppressant or having rheumatoid arthritis.

18.
J Insect Physiol ; 127: 104160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33137328

RESUMO

Apolipoprotein D (ApoD) is a lipocalin superfamily member that plays important roles in the transport of small hydrophobic molecules, lipid metabolism, and stress resistance. Cuticular hydrocarbons are the principal components of the epicuticular lipid layer and play a critical role in water retention against environmental desiccation stress; however, the mechanism underlying the role of ApoD in insect desiccation tolerance has not yet been elucidated. Here, we report the molecular constitution, functional analysis, and phylogenetic relationship of the ApoD gene in Acyrthosiphon pisum (ApApoD). We found that ApApoD was transcribed throughout the life cycle of A. pisum, but was prominently expressed in the embryonic period and abdominal cuticle. In addition, we optimized the dose and silencing duration of RNAi, observing that RNAi against ApApoD significantly reduced the levels of both internal and cuticular hydrocarbons and adult fecundity. Moreover, cuticular hydrocarbon deficiency increased the sensitivity of aphids to desiccation stress and reduced their survival time, while desiccation stress significantly increased ApApoD expression. Together, it is confirmed that ApApoD participates in regulating cuticular hydrocarbon content of aphids under desiccation stress and is crucial for aphid reproduction. Therefore, the ApApoD gene of A. pisum may be a potential target for RNAi-based insect pest control due to its involvement in cuticular hydrocarbon accumulation and reproduction.

19.
Front Immunol ; 11: 553362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193321

RESUMO

Advancements in science enable researchers to constantly innovate and create novel biologics. However, the use of non-human animal models during the development of biologics impedes identification of precise in vivo interactions between the human immune system and treatments. Due to lack of this understanding, adverse effects are frequently observed in healthy volunteers and patients exposed to potential biologics during clinical trials. In this study, we evaluated and compared the effects of known immunotoxic biologics, Proleukin®/IL-2 and OKT3 in humanized mice (reconstituted with human fetal cells) to published clinical outcomes. We demonstrated that humanized mice were able to recapitulate in vivo pathological changes and human-specific immune responses, such as elevated cytokine levels and modulated lymphocytes and myeloid subsets. Given the high similarities of immunological side effects observed between humanized mice and clinical studies, this model could be used to assess immunotoxicity of biologics at a pre-clinical stage, without placing research participants and/or patients at risk.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33206976

RESUMO

AIMS: We aimed to determine the early changes and predictive value of left ventricular (LV) segmental strain measures in women with breast cancer receiving doxorubicin. METHODS AND RESULTS: In a cohort of 237 women with breast cancer receiving doxorubicin with or without trastuzumab, 1151 echocardiograms were prospectively acquired over a median (Q1-Q3) of 7 (2-24) months. LV ejection fraction (LVEF) and 36 segmental strain measures were core lab quantified. A supervised machine learning (ML) model was then developed using random forest regression to identify segmental strain measures predictive of nadir LVEF post-doxorubicin completion. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥10% absolute LVEF decline pre-treatment to a value <50%. Median (Q1-Q3) baseline age was 48 (41-57) years. Thirty-five women developed CTRCD, and eight of these developed symptomatic heart failure. From pre-treatment to doxorubicin completion, longitudinal strain worsened across the basal and mid-LV segments but not in the apical segments; circumferential strain worsened primarily in the septum; radial strain worsened uniformly and transverse strain remained unchanged across all LV segments. In the ML model, anterolateral and inferoseptal circumferential strain were the most predictive features; longitudinal and transverse strain in the basal inferoseptal, anterior, basal anterolateral, and apical lateral segments were also top predictive features. The addition of predictive segmental strain measures to a model including age, cancer therapy regimen, hypertension, and LVEF increased the area under the curve (AUC) from 0.70 (95% confidence interval (CI) 0.60-0.80) to 0.87 (95% CI 0.81-0.92), ΔAUC = 0.18 (95% CI 0.08-0.27) for the prediction of CTRCD. CONCLUSION: Our findings suggest that segmental strain measures can enhance cardiotoxicity risk prediction in women with breast cancer receiving doxorubicin.

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