Nevin Manimala

J Microbiol. 2022 Apr 18. doi: 10.1007/s12275-022-1661-7. Online ahead of print.

ABSTRACT

Adjuvants are substances added to vaccines to enhance antigen-specific immune responses or to protect antigens from rapid elimination. As pattern recognition receptors, Toll-like receptors 7 (TLR7) and 8 (TLR8) activate the innate immune system by sensing endosomal single-stranded RNA of RNA viruses. Here, we investigated if a 2,4-diaminoquinazoline-based TLR7/8 agonist, (S)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexan-1-ol (named compound 31), could be used as an adjuvant to enhance the serological and mucosal immunity of an inactivated influenza A virus vaccine. The compound induced the production of proinflammatory cytokines in macrophages. In a dose-response analysis, intranasal administration of 1 µg compound 31 together with an inactivated vaccine (0.5 µg) to mice not only enhanced virus-specific IgG and IgA production but also neutralized influenza A virus with statistical significance. Notably, in a virus-challenge model, the combination of the vaccine and compound 31 alleviated viral infection-mediated loss of body weight and increased survival rates by 40% compared with vaccine only-treated mice. We suggest that compound 31 is a promising lead compound for developing mucosal vaccine adjuvants to protect against respiratory RNA viruses such as influenza viruses and potentially coronaviruses.

PMID:35437625 | DOI:10.1007/s12275-022-1661-7

J Cardiovasc Transl Res. 2022 Apr 18. doi: 10.1007/s12265-022-10255-8. Online ahead of print.

ABSTRACT

The ABCD-GENE score was constructed to identify patients with high platelet reactivity (HPR) after 30 days of clopidogrel treatment. In our study, 1297 eligible patients with acute coronary syndrome (ACS) were included, and 44 (3.4%) major adverse cardiovascular events (MACEs) occurred during the 12-month clopidogrel treatment. The score with a cutoff of ≥ 10 was independently associated with the risk of 5-day HPR (adjusted HR: 1.73, 95% CI: 1.09-2.74, P = 0.020) and MACEs (adjusted HR: 2.25, 95% CI: 1.19-4.25, P = 0.013). The risk of MACEs increased when the multivariable model with the score (≥ 10) plus 5-day HPR was used (adjusted HR: 4.37, 95% CI: 1.90-10.10, P = 0.001). The c-statistic for MACEs was 0.60 when using the score threshold of ≥ 10 and 0.63 when using the model with the score plus 5-day HPR. As a simple tool, the ABCD-GENE score could identify clopidogrel-treated Chinese patients with ACS who are at increased risk of MACEs. The addition of 5-day HPR could slightly improve the diagnostic ability of the score.

PMID:35437618 | DOI:10.1007/s12265-022-10255-8

Eur Radiol. 2022 Apr 18. doi: 10.1007/s00330-022-08750-2. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the role of apparent diffusion coefficient (ADC) histogram analysis in the identification of MYCN-amplification status in neuroblastomas.

METHODS: We retrospectively evaluated imaging records from 62 patients with neuroblastomas (median age: 15 months (interquartile range (IQR): 7-24 months); 38 females) who underwent magnetic resonance imaging at our institution before the initiation of any therapy or biopsy. Fourteen patients had MYCN-amplified (MYCNA) neuroblastoma. Histogram parameters of ADC maps from the entire tumour was obtained from the baseline images and the normalised images. The Mann-Whitney U test was used to compare the absolute and normalised histogram parameters amongst neuroblastomas with and without MYCN-amplification. Receiver operating characteristic (ROC) curves and area under the curves (AUC) were generated for the statistically significant histogram parameters. Cut-offs obtained from the ROC curves were evaluated on an external validation set (n-15, MYCNA-6, F-7, age 24 months (10-60)). A logistic regression model was trained to predict MYCNA by combining statistically significant histogram parameters and was evaluated on the validation set.

RESULTS: MYCN-amplified neuroblastomas had statistically significant higher maximum ADC and lower minimum ADC than non-amplified neuroblastomas. They also demonstrated higher entropy, variance, energy, and lower uniformity than non-amplified neoplasms (p > 0.05). Energy, entropy, and maximum ADC had AUC of 0.85, 0.79, and 0.82, respectively.

CONCLUSIONS: Whole tumour ADC histogram analysis of neuroblastomas can differentiate between tumours with and without MYCN-amplification. These parameters can help identify areas for targeted biopsies or can be used to predict subtypes of these high-risk tumours before biopsy results are available.

KEY POINTS: • MYCN-amplification significantly affects treatment decisions in neuroblastomas. • MYCN-amplified neuroblastomas had significantly different ADC histogram metrics as compared to tumours without amplification. • ADC histogram metrics can be used to predict MYCN-amplification status based on imaging.

PMID:35437614 | DOI:10.1007/s00330-022-08750-2

Knee Surg Sports Traumatol Arthrosc. 2022 Apr 18. doi: 10.1007/s00167-022-06979-4. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the intra/inter-rater and diagnostic reliability of the sagittal plane adjusted patellar instability ratios (PIRs) compared to tibial tubercle-trochlear groove (TT-TG) distance alone while employing a matched case-control analysis for age and sex to minimize a potential confounding effect.

METHODS: A retrospective case-control study was performed of all knee MRI studies of patients diagnosed with patellar instability, between 2005 and 2020 at a regional tertiary medical centre. Using a 1:1 case-control matching of sex and age at the time of the diagnosis, one control subject was assigned to each case of patellar instability. Measurements of TT-TG distance, sagittal patellar length (PL), sagittal patellar tendon length (PTL), TT-TG/PL ratio, and TT-TG/PTL ratio were conducted. Two orthopaedic surgery residents and a senior musculoskeletal radiologist were assigned to assess the intra- and inter-rater reliability. Inter-class coefficients were calculated (ICC). The receiver operating characteristic (ROC) curve and area under curve (AUC) for each parameter were compared to evaluate for diagnostic reliability. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated and a multivariable logistic regression model was performed to control for possible confounders.

RESULTS: The study included 324 individuals (162 case-control matched pairs). In terms of intra- and inter-rater reliability, TT-TG/PL and TT-TG/PTL ratios showed an excellent correlation within and between readers (TT-TG/PL; intra-rater ICC 0.94 and inter-rater ICC 0.92, TT-TG/PTL; intra-rater ICC 0.91 and inter-rater ICC 0.88). The ROC curve showed a slightly greater AUC of the TT-TG/PL ratio compared to TT-TG distance alone (0.75 vs 0.73, p < 0.001). When applying the pathologic cutoff of TT-TG ≥ 20 mm and TT-TG/PL ≥ 0.5; the calculated odds ratios for the above cutoff were as follows; TT-TG distance alone had an OR of 14 (95% CI 1.8-106.5, p = 0.011) and OR for TT-TG/PL ratio was 23 (95% CI 3.1-170.3, p = 0.002). In the multivariable analysis, while controlling for height and weight, only the association between TT-TG/PL ratio and patellar dislocation remained statistically significant with an adjusted OR of 2.7 (CI 1.3-5.4, p = 0.006), compared to TTTG distance alone (OR = 1.9, n.s.).

CONCLUSIONS: Patellar instability ratios are significantly more reliable compared to TT-TG distance alone for the evaluation of patellar instability. Patellar instability ratios present superior diagnostic reliability, sensitivity and specificity, and intrainter rater reliability. Thus, patellar instability ratios could function as a valuable diagnostic tool for the evaluation of patellar instability.

LEVEL OF EVIDENCE: III.

PMID:35437608 | DOI:10.1007/s00167-022-06979-4

Brief Bioinform. 2022 Apr 18:bbac132. doi: 10.1093/bib/bbac132. Online ahead of print.

ABSTRACT

Each type of cancer usually has several subtypes with distinct clinical implications, and therefore the discovery of cancer subtypes is an important and urgent task in disease diagnosis and therapy. Using single-omics data to predict cancer subtypes is difficult because genomes are dysregulated and complicated by multiple molecular mechanisms, and therefore linking cancer genomes to cancer phenotypes is not an easy task. Using multi-omics data to effectively predict cancer subtypes is an area of much interest; however, integrating multi-omics data is challenging. Here, we propose a novel method of multi-omics data integration for clustering to identify cancer subtypes (MDICC) that integrates new affinity matrix and network fusion methods. Our experimental results show the effectiveness and generalization of the proposed MDICC model in identifying cancer subtypes, and its performance was better than those of currently available state-of-the-art clustering methods. Furthermore, the survival analysis demonstrates that MDICC delivered comparable or even better results than many typical integrative methods.

PMID:35437603 | DOI:10.1093/bib/bbac132

J Natl Cancer Inst. 2022 Apr 19:djac085. doi: 10.1093/jnci/djac085. Online ahead of print.

ABSTRACT

BACKGROUND: Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systemic mechanisms modulated by HP are involved in this more favorable outcome.

METHODS: A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1), and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors.

RESULTS: Among 491 cases that were analyzed, 175 (36%) and 316 (64%) cases were HP+ and HP⁻, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 dose (Pinteraction=0.0487) and PD-L1 (P = .016). HP+ patients in the PD-L1⁻ group had significantly higher five-year OS and RFS than HP- patients (81% vs. 68%; P = .0011; HR 0.477; 95% CI, 0.303-0.751 and 76% vs. 63% P = .0011; HR 0.508; 95% CI, 0.335-0.771, respectively). The five-year OS and RFS was also significantly higher for HP+ compared to HP- patients in the PD-L1-/S-1-reduced group (86% vs. 46%; P = .0014; HR 0.205; 95% CI, 0.07-0.602 and 83% vs. 34%; P = .001; HR 0.190; 95% CI, 0.072-0.498, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival.

CONCLUSION: This retrospective study suggests that an HP-modulated host immune system may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.

PMID:35437596 | DOI:10.1093/jnci/djac085

Health Promot Int. 2022 Apr 19:daac042. doi: 10.1093/heapro/daac042. Online ahead of print.

ABSTRACT

The progression of diabetes-related complications can be delayed with multifactorial interventions that support healthy behaviours. However, many initiatives have focused on educational or individual-level activities and observed limited or modest sustained improvements in healthy behaviours. A multicomponent approach to behaviour change, which simultaneously considers numerous social determinants of health across multiple socio-ecological model levels, may be required to achieve meaningful health outcomes for people with Type 2 diabetes. Applying a multicomponent method of inquiry, this integrative review aimed to synthesize the evidence on interventions using multifactorial interventions to promote healthy behaviours in adults with Type 2 diabetes. Interventions promoting healthy behaviours in adults with Type 2 diabetes were considered for the review. A total of 7205 abstracts retrieved from eight databases were screened for inclusion. Thirteen articles were included, of these 11 achieved statistically significant clinical and/or behavioural changes in outcomes such as glycated haemoglobin, blood pressure, cholesterol, diet and physical activity. The multifactorial components utilized included the coordination of multi-disciplinary health care teams, in-person self-care classes, group activities, incorporation of peer-leaders, the development of community partnerships, economic relief and built-environment support. The proportion of included studies published within recent years indicates a trend towards multicomponent interventions and the growing recognition of this approach in promoting public health. Our findings provide early support for the potential of extending intervention components beyond educational, individual-level and health care system-level focus to incorporate multiple socio-ecological model components that contribute to the system of influence affecting the health of people with diabetes.

PMID:35437595 | DOI:10.1093/heapro/daac042

Ann Work Expo Health. 2022 Apr 19:wxac019. doi: 10.1093/annweh/wxac019. Online ahead of print.

ABSTRACT

The factors influencing transfer of chemicals or other contaminants to and from the surface of the skin are often poorly understood. Previous research has indicated that environmental conditions, skin hydration, and repeated contacts may all influence the quantity of dermal transfer. The aim of this analysis was to evaluate the influence of skin hydration and condition on quantitative chemical transfer in a series of systematic measurements using human subjects for 5 and 10 repeated contacts. Elemental metallic lead was used as the exemplar test substance for the measurements collected. Skin hydration index (HI) was assessed using a corneometer and skin condition and barrier function were measured using an open-chamber transepidermal water loss (TEWL) instrument. Results indicated that for the palmar surface of the index finger where sampling was conducted, the relative hydration level of the skin was higher for males (n = 6) versus females (n = 4) (mean HI = 4.0 for females; mean HI = 5.5 for males) but this difference was not statistically significant. Overall, the skin hydration level was not significantly associated with dermal loading for either the 5 contact scenario (Pearson correlation = 0.27; R2 = 0.07; P = 0.45) or the 10 contact scenario (Pearson correlation = 0.26; R2 = 0.07; P = 0.47). When the results were stratified by higher versus lower hydration levels (HI = 1-5 versus HI = 5-10), for the higher hydration levels (HI = 5-10; mean HI = 7), there was a moderately positive association between skin hydration and loading, but this was not statistically significant for either the 5 contact scenario (Pearson correlation = 0.75; R2 = 0.56; P = 0.15) or the 10 contact scenario (Pearson correlation = 0.6; R2 = 0.36; P = 0.28). No clear relationship was observed between the lower hydration levels (HI = 1-5) and dermal loading. For the palmar index finger, there was a negative correlation between the TEWL measurements and both the 5 contact (Pearson correlation = -0.45; R2 = 0.2; P = 0.19) and 10 contact (Pearson correlation = -0.3; R2 = 0.09; P = 0.4) scenarios, but this was not statistically significant. The results of this study are consistent with the limited results of other analyses, which have suggested that there may be nuances with respect to the effects of skin hydration on the quantitative dermal transfer to and from the skin, although additional data are needed to better understand these potential differences.

PMID:35437588 | DOI:10.1093/annweh/wxac019

Zhonghua Yi Xue Za Zhi. 2022 Apr 19;102(15):1100-1107. doi: 10.3760/cma.j.cn112137-20211105-02457.

ABSTRACT

Objectives: To explore the risk factors associated with septic cardiomyopathy and establish a predictive model of the disease based on left ventricular global longitudinal strain (LV GLS). Methods: Data from sepsis patients without a history of cardiac dysfunction who were treated in the Critical Care Department of the Northern Jiangsu People’s Hospital from September, 2019 to January, 2021 were included in the analysis. The LV GLS was measured by echocardiography within 72 hours and the patients were divided into a septic myocardiopathy group (LV GLS>-17%) and a normal cardiac function group (LV GLS≤-17%). Clinical data from two groups of patients were collected for univariate analysis. The receiver operating characteristic (ROC) curves of the factors that were statistically different were drawn for exploring the diagnostic and cut-off values. The continuous variable was converted to a dichotomous variable according to the cut-off value. Multivariate logistic regression analysis of sepsis cardiomyopathy was performed to screen the risk factors and create a predictive model. The predictive model was evaluated by ROC curve analysis and the Bootstrap method and shown as a nomograph. Results: Patients in the sepsis cardiomyopathy group had higher levels of high sensitive troponin I (Hs-TnI), procalcitonin (PCT), lactate (Lac), N-terminal pro-brain atriuretic peptide (NT-proBNP), vasopressor dosing intensity (VDI) and sequential organ failure assessment (SOFA) when compared to those in the normal cardiac function group (all P<0.05). The multivariate logistic regression analysis showed that Hs-TnI≥0.131 μg/L (OR=6.71, 95%CI:2.67-16.88, P<0.001), PCT≥40 μg/L (OR=3.08, 95%CI:1.10-8.59, P=0.032), Lac≥4.2 mmol/L (OR=2.80, 95%CI:1.02-7.69, P=0.045), NT-proBNP≥3 270 ng/L (OR=2.67, 95%CI:1.06-6.74, P=0.038) were independent risk factors for septic myocardiopathy. The area under the ROC curve of the predictive model based on the four indexes up-mentioned was 0.838 (95%CI:0.766-0.910), and the C-index was 0.822 (95%CI:0.750-0.894) which indicated the utility of the nomogram. The model had a good predictive ability, accuracy and discrimination. Conclusions: Hs-TnI≥0.131 μg/L, PCT≥40 μg/L, Lac≥4.2 mmol/L and NT-proBNP≥3 270 ng/L are independent risk factors for septic myocardiopathy, and the septic cardiomyopathy predictive model constructed based on these factors has a good diagnostic performance.

PMID:35436809 | DOI:10.3760/cma.j.cn112137-20211105-02457

Zhonghua Yi Xue Za Zhi. 2022 Apr 19;102(15):1093-1099. doi: 10.3760/cma.j.cn112137-20211018-02304.

ABSTRACT

Objective: To investigate the application value of relaxation time quantitative technique from synthetic magnetic resonance imaging (MRI) in the diagnosis and invasion assessment of prostate cancer. Methods: A total of 119 patients with prostate diseases [122 regions of interest(ROI)] who underwent routine MRI scan and magnetic resonance image compilation (MAGiC) sequence of prostate from March 2020 to March 2021 in General Hospital of Ningxia Medical University were retrospectively collected, they were divided into prostate cancer group(58 cases, 61 ROI) and non-prostate cancer group(61 cases, 61 ROI) according to the pathological results. In the prostate cancer group, those patients with an age of 48 to 85(69.8±5.9) years, and further divided into two subgroups according to the location of occurrence: peripheral zone cancer group (43 cases, 45 ROI) and transitional zone cancer group (15 cases, 16 ROI). The non-prostate cancer group consisted of patients with benign prostatic hyperplasia or complicated with chronic prostatitis, with an age of 41 to 81(68.6±7.0) years, and they were further divided into two subgroups according to the location of occurrence: non-cancerous peripheral zone group (45 cases, 45 ROI) and transitional zone benign prostatic hyperplasia group(16 cases, 16 ROI). Prostate cancer lesions were classified as low risk (Gleason score ≤6) or intermediate/high risk (Gleason score ≥7). After the post-processing of MAGiC images, T₁, T₂ and proton density(PD) values of prostate cancer group and non-prostate cancer group were obtained. At the same time, relevant software were used for image post-processing to generate apparent diffusion coefficient (ADC) value, the data between the two groups were analyzed by the Independent sample t-test or Mann-Whitney U-test, and the diagnostic effectiveness of each quantitative parameter in diagnosing prostate cancer and discriminating low risk prostate cancer from intermediate/high risk prostate cancer was analyzed by using receiver operating characteristic curve (ROC) analysis, the correlation between each quantitative parameter and Gleason score were assessed by Spearman correlation analysis. Results: The T₁ value and T₂ value of the peripheral zone cancer group were lower than those in non-cancerous peripheral zone group [1 201.3 (1 103.5, 1 298.2) ms vs 2 274.0 (1 620.9, 2 776.5) ms; 78.0 (74.0, 83.8) ms vs (160.6±54.9) ms] (all P<0.001), there was no statistically significant in PD value between the two groups (P>0.05). The T₁ value and T₂ value of the transitional zone cancer group were lower than those in transitional zone benign prostatic hyperplasia group [1 073.3 (1 003.9, 1 164.9) ms vs 1 340.8 (1 208.5, 1 502.8) ms; 76.9 (74.8, 82.8) ms vs 95.1(82.8, 103.4) ms] (all P<0.001), there was no statistically significant in PD value between the two groups (P>0.05). The area under the curve (AUC) of T₂ value was similar with the ADC value in discriminating peripheral zone cancer group from non-cancerous peripheral zone group(0.963 vs 0.991, P=0.105), while in discriminating transitional zone cancer group from transitional zone benign prostatic hyperplasia group, the AUC of T₂ value、T₁ value and ADC value were similar(0.867, 0.930 vs 0.938, all P>0.05). ADC value, T₂ value all were negatively correlated with Gleason score (r=-0.747,-0.453, all P<0.001). T₂ value and ADC value demonstrated equivalent diagnostic performance in discriminating low risk from intermediate/high risk prostate cancer, and there were no statistically significant (AUC: 0.787 vs 0.943, P=0.069). Conclusions: Quantitative relaxation time T₁ and T₂ values derived from synthetic MRI can discriminate prostate cancer from other benign pathologies, and T₂ value have the equivalent diagnostic performance compared to ADC value. Synthetic MRI has high clinical application value, and T₂ value can distinguish low risk prostate cancer from intermediate/high risk prostate cancer.

PMID:35436808 | DOI:10.3760/cma.j.cn112137-20211018-02304