Nevin Manimala

Brain Behav. 2021 Dec 4:e2449. doi: 10.1002/brb3.2449. Online ahead of print.

ABSTRACT

BACKGROUND: Synthetic MRI (SyMRI) is a quantitative technique that allows measurements of T1 and T2 relaxation times (RTs). Brain RT evolution across lifespan is well described for the younger population. The aim was to study RTs of brain parenchyma in a healthy geriatric population in order to define the normal value of structures in this group population. Normal values for geriatric population could help find biomarker for age-related brain disease.

MATERIALS AND METHODS: Fifty-four normal-functioning individuals (22 females, 32 males) with mean age of 83 years (range 56-98) underwent SyMRI. RT values in manually defined ROIs (centrum semiovale, middle cerebellar peduncles, thalamus, and insular cortex) and in segmented whole-brain components (brain parenchyma, gray matter, white matter, myelin, CSF, and stromal structures) were extracted from the SyMRI segmentation software. Patients’ results were combined into the group age. Main ROI-based and whole-brain results were compared for the all dataset and for age group results as well.

RESULTS: For white matter, RTs between ROI-based analyses and whole-brain results for T2 and for T1 were statistically different and a trend of increasing T1 in centrum semiovale and cerebellar peduncle was observed. For gray matter, thalamic T1 was statistically different from insular T1. A difference was also found between left and right insula (p < .0001). T1 RTs of ROI-based and whole-brain-based analyses were statistically different (p < .0001). No significant difference in T1 and T2 was found between age groups on ROI-based analysis, but T1 in centrum semiovale and thalamus increased with age. No statistical difference between age groups was found for the various segmented volumes except for myelin between 65-74 years of age and the 95-105 years of age groups (p = .038).

CONCLUSIONS: SyMRI is a new tool that allows faster imaging and permits to obtain quantitative T1 and T2. By defining RT values of different brain components of normal-functioning elderly individuals, this technique may be used as a biomarker for clinical disorders like dementia.

PMID:34862855 | DOI:10.1002/brb3.2449

Autism Res. 2021 Dec 4. doi: 10.1002/aur.2650. Online ahead of print.

ABSTRACT

Findings on age-related cognitive effects in autism in adulthood are inconsistent across studies. As these studies substantially differ in their methodology, replication studies are needed. In this replication study frequentist (i.e., null-hypothesis significance testing), and Bayesian statistics were used to investigate the hypothesis that in autistic adults compared to non-autistic adults mostly parallel, but also protective age-related cognitive effects can be observed. Participants were 88 autistic adults, and 88 non-autistic matched comparisons (age range: 30-89 years, mean age: 55 years). Cognitive measures were administered on the following six domains: verbal memory, visual memory, working memory, Theory of Mind (ToM), verbal fluency, and processing speed, and self-reported cognitive failures. Non-autistic adults outperformed autistic adults on ToM, verbal fluency, and verbal memory, but only the first two were confirmed with Bayesian replication analyses. Also, more cognitive failures were reported by autistic adults. No interactions between group and age were observed, suggesting a parallel age-related effect on all cognitive domains. In sum, previously observed difficulties in ToM and verbal fluency were replicated which seem to persist at older age. Previously reported parallel age-related cognitive patterns were replicated, yet no evidence for protective age-related patterns was found. LAY SUMMARY: We investigated whether our previous findings on cognitive aging in autism could be confirmed in a new study measuring the cognitive effects of age in autistic and non-autistic adults. As expected, tasks that younger autistic adults had difficulties with (theory of mind, fluency) were also difficult for older autistic adults, and the effect of age itself was similar in autistic and non-autistic adults. Unexpectedly, we observed no protective effects (less cognitive aging) in autism.

PMID:34862853 | DOI:10.1002/aur.2650

Health Serv Res. 2021 Dec 4. doi: 10.1111/1475-6773.13921. Online ahead of print.

ABSTRACT

OBJECTIVE: To establish a case-adjusted hospital-specific performance evaluation tool using machine learning methodology for cesarean delivery.

DATA SOURCES: Secondary data were collected from patients between 1/1/2015-2/28/2018 using a hospital’s “Electronic Data Warehouse” database from Illinois, USA.

STUDY DESIGN: The machine learning methodology of Optimal Classification Trees (OCT’s) was used to predict cesarean delivery rate by physician group, thereby establishing the case-adjusted benchmarking standards in comparison to the overall hospital cesarean delivery rate. Outcomes of specific patient populations of each participating practice were predicted, as if each were treated in the overall hospital environment. The resulting OCTs estimate physician group expected cesarean delivery outcomes, both aggregate and in specific clinical situations.

DATA COLLECTION/EXTRACTION METHODS: 12,841 singleton, vertex, term deliveries, cared for by practices with ≥50 births.

PRINCIPAL FINDINGS: The overall rate of cesarean delivery was 18.6% (n = 2384), with a range of 13.3%-33.7% amongst 22 physician practices. An optimal decision tree was used to create a prediction model for the overall hospital which defined 23 patient cohorts, divided by 46 nodes. The model’s performance for prediction of cesarean delivery is as follows: area under the curve- 0.73, sensitivity- 98.4%, specificity- 16.1%, positive predictive value 83.7%, negative predictive value 70.6%. Comparisons with the overall hospital’s specific-case adjusted benchmark groups revealed that several groups outperformed the overall hospital and some practice groups underperformed in comparison to the overall hospital.

CONCLUSIONS: OCT benchmarking can assess physician practice specific case-adjusted performance, both overall and clinical situation specific, and can serve as a valuable tool for hospital self-assessment and quality improvement. This article is protected by copyright. All rights reserved.

PMID:34862801 | DOI:10.1111/1475-6773.13921

Clin Pharmacol Ther. 2021 Dec 4. doi: 10.1002/cpt.2504. Online ahead of print.

ABSTRACT

Coronavirus disease 2019 (Covid-19) is associated with a hypercoagulable state. It has been hypothesized that higher-dose anticoagulation, including therapeutic-dose and intermediate-dose anticoagulation, is superior to prophylactic-dose anticoagulation in the treatment of Covid-19. This meta-analysis evaluated the efficacy and safety of higher-dose anticoagulation compared with prophylactic-dose anticoagulation in patients with Covid-19. Ten randomized controlled open-label trials with a total of 5,753 patients were included. The risk of death and net adverse clinical events (including death, thromboembolic events, and major bleeding) were similar between higher-dose and prophylactic-dose anticoagulation (risk ratio (RR) 0.96, 95%CI, 0.79-1.16, P=0.66 and RR 0.87, 95%CI, 0.73-1.03, P=0.11, respectively). Higher-dose anticoagulation, compared with prophylactic-dose anticoagulation, decreased the risk of thromboembolic events (RR 0.63, 95%CI, 0.47-0.84, P=0.002) but increased the risk of major bleeding (RR 1.76, 95%CI, 1.19-2.62, P=0.005). The risk of death showed no statistically significant difference between higher-dose anticoagulation and prophylactic-dose anticoagulation in non-critically ill patients (RR 0.87, 95%CI, 0.50-1.52, P=0.62) and in critically ill patients with Covid-19 (RR 1.04, 95%CI, 0.93-1.17, P=0.5). The risk of death was similar between therapeutic-dose versus prophylactic-dose anticoagulation (RR 0.92, 95%CI 0.69-1.21, P=0.54) and between intermediate-dose versus prophylactic-dose anticoagulation (RR 1.01, 95%CI 0.63-1.61, P=0.98). In patients with markedly increased d-dimer levels, higher-dose anticoagulation was also not associated with a decreased risk of death as compared with prophylactic-dose anticoagulation (RR 0.86, 95%CI, 0.64-1.16, P=0.34). Without any clear evidence of survival benefit, these findings do not support the routine use of therapeutic-dose or intermediate-dose anticoagulation in critically or non-critically ill patients with Covid-19.

PMID:34862791 | DOI:10.1002/cpt.2504

Zhongguo Yi Liao Qi Xie Za Zhi. 2021 Nov 30;45(6):645-649.

ABSTRACT

In order to solve the problem of continuous monitoring and automatic regulation of patient airbag pressure in intensive care unit, the study designed an intelligent management system of artificial airway airbag pressure. It can realize real-time monitoring and automatic control of airbag pressure. Its pressure data was sent to the PC in real time by the serial port. It can realize the display, store, review and analysis of pressure data. Its clinical application effect was discussed. Experiments showed that the system can monitor airbag pressure in real time and control the pressure to stabilize at 25~30 cmH₂O. Compared with the control group, the experimental group had a statistically significant difference in the operation time of monitoring patients’ airbag pressure, changes in airbag pressure, the instantaneous maximum value during nursing operation, and the number of aspiration and reflux cases. The clinical application of the system can reduce the workload of medical staff greatly, effectively reduce the number of patients with aspiration and reflux, reduce the incidence of ventilator pneumonia.

PMID:34862778

Zhongguo Yi Liao Qi Xie Za Zhi. 2021 Nov 30;45(6):628-635.

ABSTRACT

Combined with the clinical use condition of MR in use in Shanghai Sixth People’s Hospital, MR components are divided into scanning type I and scanning type II. At the same time, combined with the main loss force of MR components, the research divides MR components into dynamic components and electric thermal components. In this study, a complete set of MR system reliability indexes and implementation methods are given, including system reliability index determination, system reliability allocation, component reliability index realization, system reliability prediction and system reliability verification. At the same time, this study also gives the methods of reliability prediction and reliability verification, and gives the MTBF calculation method of MR system based on clinical use data statistics.

PMID:34862775

Cancer Med. 2021 Dec 4. doi: 10.1002/cam4.4472. Online ahead of print.

ABSTRACT

PURPOSE: Protein tyrosine phosphatase receptor type T (PTPRT), which is a well-known phosphatase and mutates frequently in melanoma and non-small cell lung cancer (NSCLC). Our research aims to elucidate its mutation association with immune checkpoint inhibitors (ICI) efficacy.

METHODS: We integrated whole-exome sequencing (WES)-based somatic mutation profiles and clinical characteristics of 631 melanoma samples received ICI agents from eight studies and 109 NSCLC samples from two studies. For validation, 321 melanoma and 350 NSCLC immunotherapy samples with targeted next-generation sequencing (NGS) were employed. Besides, an independent NSCLC cohort contained 240 samples was also collected for further corroboration. Distinct immune infiltration was evaluated according to the PTPRT mutational status.

RESULTS: In the WES melanoma cohort, patients with PTPRT mutations harbored a significantly elevated ICI response rate (40.5% vs. 28.6%, p = 0.036) and a prolonged survival outcome (35.3 vs. 24.9 months, p = 0.006). In the WES NSCLC cohort, the favorable response and immunotherapy survival were also observed in PTPRT-mutated patients (p = 0.036 and 0.019, respectively). For the validation cohorts, the associations of PTRPT mutations with better prognoses were identified in melanoma, NSCLC, and pan-cancer patients with targeted-NGS (all p < 0.05). Moreover, immunology analyses showed the higher mutation burden, increased lymphocyte infiltration, decreased- activated-stroma, and immune response pathways were detected in patients with PTPRT mutations.

CONCLUSION: Our investigation indicates that PTPRT mutations may be considered as a potential indicator for assessing ICI efficacy in melanoma and NSCLC, even across multiple cancers. Further prospective validation cohorts are warranted.

PMID:34862763 | DOI:10.1002/cam4.4472

Hum Brain Mapp. 2021 Dec 4. doi: 10.1002/hbm.25711. Online ahead of print.

ABSTRACT

Multiscale integration of gene transcriptomic and neuroimaging data is becoming a widely used approach for exploring the molecular underpinnings of large-scale brain organization in health and disease. Proper statistical evaluation of determined associations between imaging-based phenotypic and transcriptomic data is key in these explorations, in particular to establish whether observed associations exceed “chance level” of random, nonspecific effects. Recent approaches have shown the importance of statistical models that can correct for spatial autocorrelation effects in the data to avoid inflation of reported statistics. Here, we discuss the need for examination of a second category of statistical models in transcriptomic-neuroimaging analyses, namely those that can provide “gene specificity.” By means of a couple of simple examples of commonly performed transcriptomic-neuroimaging analyses, we illustrate some of the potentials and challenges of transcriptomic-imaging analyses, showing that providing gene specificity on observed transcriptomic-neuroimaging effects is of high importance to avoid reports of nonspecific effects. Through means of simulations we show that the rate of reported nonspecific effects (i.e., effects that cannot be specifically linked to a specific gene or gene-set) can run as high as 60%, with only less than 5% of transcriptomic-neuroimaging associations observed through ordinary linear regression analyses showing both spatial and gene specificity. We provide a discussion, a tutorial, and an easy-to-use toolbox for the different options of null models in transcriptomic-neuroimaging analyses.

PMID:34862695 | DOI:10.1002/hbm.25711

Rapid Commun Mass Spectrom. 2021 Dec 3:e9230. doi: 10.1002/rcm.9230. Online ahead of print.

ABSTRACT

RATIONALE: Recycled plastics are increasingly used for packaging of fast-moving consumer goods (FMCG). Compared to packaging made from virgin polymers, there is greater risk of taints entering product due to prior use of the polymers and incomplete cleaning. Increased quality assurance testing of polymer feedstock is required for recycled packaging. Selected ion flow tube mass spectrometry (SIFT-MS) analysis coupled with multivariate statistical data processing can provide high-throughput untargeted screening of recycled polymers at low cost per sample.

METHODS: SIFT-MS is a direct-injection MS technique that provides high-throughput automated headspace analysis of polymer samples when coupled with a syringe-injection autosampler (12 incubated samples per hour). Full-scan SIFT-MS data were processed using multivariate statistical analysis (specifically, the soft independent modeling by class analogy (SIMCA) algorithm.

RESULTS: SIFT-MS full-scan data were acquired for ten replicates each of ten recycled and four virgin high-density polyethylene (HDPE) pellet products from multiple manufacturers. The samples varied approximately 20-fold in terms of total volatile residue, while showing very high repeatability across replicates. SIFT-MS scan data were dominated by aliphatic and monoterpene hydrocarbon residues, and – to a lesser extent – alcohols. Application of the SIMCA algorithm to the data resulted in successful classification by both individual samples and manufacturers.

CONCLUSIONS: Automated, untargeted SIFT-MS analysis coupled with multivariate statistical data analysis has potential to provide rapid, effective screening of recycled polymer products, which would provide increased quality assurance of recycled polymers used for FMCG.

PMID:34862682 | DOI:10.1002/rcm.9230

APMIS. 2021 Dec 4. doi: 10.1111/apm.13195. Online ahead of print.

ABSTRACT

BACKGROUND: Primary central nervous system-diffuse large B-cell lymphoma (PCNS-DLBCL) is a rare, extranodal malignant lymphoma carrying poor prognosis. The prognostic impact of tumor microenvironment (TME) composition and PD-1/PD-L1 immune checkpoint pathway are still undetermined in PCNS-DLBCL. We aimed to quantify the tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and PD-L1 expression in the PCNSL and evaluated their prognostic significance.

MATERIALS AND METHODS: All patients with histopathologically diagnosed PCNS-DLBCL over a period of 7 years were recruited. Immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, PD-1 and PD-L1 was performed on tissue microarray.

RESULT: Forty-four cases of PCNS-DLBCL, who satisfied the selection criteria, were included with mean age of 55 ± 12.3 years and male-to-female ratio of 0.91:1. The mean overall survival (OS) and disease-free survival (DFS) was 531.6 days and 409.8 days, respectively. Among TILs, increased number of CD3+ T cells showed better OS and DFS, without achieving statistical significance. CD4 positive T-cells was significantly associated with the longer OS (p=0.037) and DFS (p=0.023). TAMs (68CD and CD163 positive) showed inverse relationship with OS and DFS but didn’t reach statistical significance (p>0.05). Increased PD-L1 expression in immune cells, but not in tumor cells, was associated with significantly better DFS (p=0.037).

CONCLUSION: TME plays significant role in the prognosis of PCNS-DLBCL. Increased number of CD4+ T cells and PD-L1 expressing immune cells are associated with better prognosis in PCNS-DLBCL. Further studies with larger sample size are required to evaluate the role of targeted therapy against TME and immune check point inhibitors in this disease.

PMID:34862664 | DOI:10.1111/apm.13195