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Nevin Manimala Statistics

Visualization and co-registration of correlative microscopy data with the ImageJ plug-in Correlia

Methods Cell Biol. 2021;162:353-388. doi: 10.1016/bs.mcb.2020.10.001. Epub 2020 Nov 18.

ABSTRACT

Correlative microscopy experiments require the co-registration of the image data acquired by different micro-analytical techniques. Major challenges are the potentially very different fields-of-view and resolutions as well as the multi-modality of the data. To provide microscopists with an easy-to-use software for two-dimensional image co-registration we have developed Correlia, an open source software based on ImageJa/Fiji,b which is fully tailored for the registration of multi-modal microscopy data. It can handle data-sets of in principle arbitrary extent and uses classical approaches, i.e., rigid registration tools or B-spline based deformation models for the correction of both, global and local misalignments, such that a fast registration output is provided. Here we describe some of the basics of Correlia focusing on its application: firstly, registration workflows are outlined on artificial data. In the second part these recipes are applied to register correlative data acquired on an algal biofilm and a soil sample.

PMID:33707019 | DOI:10.1016/bs.mcb.2020.10.001

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Nevin Manimala Statistics

Variation in acute fluid resuscitation among pediatric burn centers

Burns. 2020 May 16:S0305-4179(20)30306-5. doi: 10.1016/j.burns.2020.04.013. Online ahead of print.

ABSTRACT

BACKGROUND: Accurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates.

METHODS: Five pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center’s resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received.

RESULTS: Differences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers’ resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35ml/kg/% TBSA, p<0.001), (4.90 versus 6.35ml/kg/TBSA, p=0.002) and (3.38 versus 6.35ml/kg/TBSA, p<0.0001).

CONCLUSIONS: This variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.

PMID:33707085 | DOI:10.1016/j.burns.2020.04.013

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Nevin Manimala Statistics

Evidence of ordinal position encoding of sequences extracted from continuous speech

Cognition. 2021 Mar 8:104646. doi: 10.1016/j.cognition.2021.104646. Online ahead of print.

ABSTRACT

Infants’ capacity to extract statistical regularities from sequential information is impressive and well documented. However, statistical learning’s underlying mechanism remains mostly unknown, and its role in language acquisition is still under debate. To shed light on these issues, here we address the question of which information human subjects extract and encode after familiarisation with a continuous sequence of stimuli and its dependence on the type of segmentation cues and on the stimuli modality. Specifically, we investigate whether adults and 5-month-old infants learn the syllables’ co-occurrence in the stream or generate a representation of the Words that include syllables’ ordinal position. We test if subtle pauses signalling word boundaries change the encoding and, in adults, if it varies across modalities. In six behavioural experiments, we show that: (i) Adults and infants learn the streams’ statistical structure. (ii) Ordinal encoding emerges in the auditory modality, and pauses enhanced it. However, (iii) ordinal encoding seems to depend on the learning stage and not on pauses marking Words’ edges. Interestingly, (iv) for visual presentation of orthographic syllables, we do not find evidence of ordinal encoding in adults. Our results support the emergence, in the auditory modality, of a Word representation where its constituents are associated with an ordinal position at play already early in life, bringing new insights into speech processing and language acquisition. Additionally, we successfully use for the first time pupillometry in an infant segmentation task.

PMID:33707004 | DOI:10.1016/j.cognition.2021.104646

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Nevin Manimala Statistics

Body Image Dissatisfaction, Eating Disorders, and Associated Factors in Brazilian Professional Ballroom Dancers

J Dance Med Sci. 2021 Mar 15;25(1):18-23. doi: 10.12678/1089-313X.031521c.

ABSTRACT

The search for movement plasticity causes dancers to seek to achieve and maintain low body weight, which can lead to dissatisfaction with their body image and to eating disorders. The purpose of this study was to analyze body image satisfaction and the presence of eating disorders and associated factors in professional ballroom dancers in Brazil. Three hundred and twenty dancers took part via a self-reported questionnaire. The majority of the dancers proved to be dissatisfied with their body image; the increase with age of body mass index (BMI) influenced the dissatisfaction due to excess weight. It is concluded that body image is associated with eating disorders, age, and BMI in ballroom dancers.

PMID:33706851 | DOI:10.12678/1089-313X.031521c

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Nevin Manimala Statistics

A 3D-printed Apparatus for Imaging Multiple Rats Simultaneously

Comp Med. 2021 Mar 11. doi: 10.30802/AALAS-CM-20-000089. Online ahead of print.

ABSTRACT

CT (computerized tomography) is a necessary imaging modality for cancer staging and disease monitoring. Rodent models of cancer are commonly studied prior to human clinical trials, but CT in rodents can be difficult due to their small size and constant movement, which necessitates general anesthesia. Because microCT equipment is not always available, clinical CT may be a viable alternative. Limitations of microCT and clinical CT include biosecurity, anesthesia to limit image distortion due to motion, and cost. To address several of these constraints, we created a 3D-printed apparatus that accommodated simultaneous imaging of as many as 9 rats under gas anesthesia. Rats were anesthetized in series and placed in a 3 × 3 arrangement. To assess differences in attenuation between individual chambers and rows or columns in the device, we first imaged a standardized phantom plug as a control. We hypothesized that attenuation of specific rat organs would not be affected regardless of the location or position in the 3D-printed device. Four organs-liver, kidney, femur, and brain-were evaluated in 9 rats. For both the phantom and kidneys, statistically significant, but clinically negligible, effects on attenuation were noted between rows but not between columns. We attribute this finding to the absence of a top layer of the apparatus, which thus created asymmetric attenuation and beam hardening through the device. This apparatus allowed us to successfully image 9 rats simultaneously in a clinical CT machine, with negligible effects on attenuation. Planned improvements in this apparatus include completely enclosed versions for biosecure imaging.

PMID:33706858 | DOI:10.30802/AALAS-CM-20-000089

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Nevin Manimala Statistics

Tracking SARS-CoV-2 lineage B.1.1.7 dissemination: insights from nationwide spike gene target failure (SGTF) and spike gene late detection (SGTL) data, Portugal, week 49 2020 to week 3 2021

Euro Surveill. 2021 Mar;26(10). doi: 10.2807/1560-7917.ES.2021.26.10.2100130.

ABSTRACT

We show that the SARS-CoV-2 B.1.1.7 lineage is highly disseminated in Portugal, with the odds of B.1.1.7 proportion increasing at an estimated 89% (95% confidence interval: 83-95%) per week until week 3 2021. RT-PCR spike gene target late detection (SGTL) can constitute a useful surrogate to track B.1.1.7 spread, besides the spike gene target failure (SGTF) proxy. SGTL/SGTF samples were associated with statistically significant higher viral loads, but not with substantial shift in age distribution compared to non-SGTF/SGTL cases.

PMID:33706862 | DOI:10.2807/1560-7917.ES.2021.26.10.2100130

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Nevin Manimala Statistics

Growth differentiation factor-15 predicts major adverse cardiac events and all-cause mortality in patients with atrial fibrillation

Eur J Intern Med. 2021 Mar 8:S0953-6205(21)00048-0. doi: 10.1016/j.ejim.2021.02.011. Online ahead of print.

ABSTRACT

BACKGROUND: Growth-differentiation factor-15 (GDF-15) has recently been described as a potential biomarker for predicting risk of mortality and cardiovascular events in patients with atrial fibrillation (AF) but requires validation in clinical practice.

METHODS: The study population consisted of 362 patients (mean age: 71 years, 37% women) with non-valvular AF included in a prospective cohort study. Relationship of GDF-15 with all-cause mortality and major adverse cardiac events (MACE) was analyzed using Cox regression. Survival analysis stratified by GDF-15 was based on national death records, while MACE was recorded at personal follow-up. Further, we evaluated the recently developed GDF-15 based prognostic score towards prediction of all-cause mortality (ABC-death score).

RESULTS: Over a median observation period of 4.3 years, 81 (23.3%) patients died, and over a median personal follow-up of 316 days 47 MACE occurred. GDF-15 was independently associated with all-cause mortality (adjusted HR per double increase 2.33, 95%CI 1.74-3.13) and MACE (adjusted HR per double increase 2.33, 95%CI 1.60-3.39). GDF-15 levels, measured at follow-up, were similarly associated with mortality, and longitudinal measurements of GDF-15 did not significantly differ. Six-year survival probability of patients above vs. below the median GDF-15 level was 44% (95%CI 34-57) and 84% (95%CI 76-93), respectively. The ABC-death score revealed a C-statistic of 0.80.

CONCLUSION: GDF-15 predicts risk of all-cause mortality and MACE in patients with non-valvular AF. Further, the ABC-death score showed good predictive accuracy in a “real-world” cohort. Therefore, introduction of GDF-15 into clinical practice would enhance risk prediction of morbidity and mortality in AF patients.

PMID:33706979 | DOI:10.1016/j.ejim.2021.02.011

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Nevin Manimala Statistics

Explaining decisions of graph convolutional neural networks: patient-specific molecular subnetworks responsible for metastasis prediction in breast cancer

Genome Med. 2021 Mar 11;13(1):42. doi: 10.1186/s13073-021-00845-7.

ABSTRACT

BACKGROUND: Contemporary deep learning approaches show cutting-edge performance in a variety of complex prediction tasks. Nonetheless, the application of deep learning in healthcare remains limited since deep learning methods are often considered as non-interpretable black-box models. However, the machine learning community made recent elaborations on interpretability methods explaining data point-specific decisions of deep learning techniques. We believe that such explanations can assist the need in personalized precision medicine decisions via explaining patient-specific predictions.

METHODS: Layer-wise Relevance Propagation (LRP) is a technique to explain decisions of deep learning methods. It is widely used to interpret Convolutional Neural Networks (CNNs) applied on image data. Recently, CNNs started to extend towards non-Euclidean domains like graphs. Molecular networks are commonly represented as graphs detailing interactions between molecules. Gene expression data can be assigned to the vertices of these graphs. In other words, gene expression data can be structured by utilizing molecular network information as prior knowledge. Graph-CNNs can be applied to structured gene expression data, for example, to predict metastatic events in breast cancer. Therefore, there is a need for explanations showing which part of a molecular network is relevant for predicting an event, e.g., distant metastasis in cancer, for each individual patient.

RESULTS: We extended the procedure of LRP to make it available for Graph-CNN and tested its applicability on a large breast cancer dataset. We present Graph Layer-wise Relevance Propagation (GLRP) as a new method to explain the decisions made by Graph-CNNs. We demonstrate a sanity check of the developed GLRP on a hand-written digits dataset and then apply the method on gene expression data. We show that GLRP provides patient-specific molecular subnetworks that largely agree with clinical knowledge and identify common as well as novel, and potentially druggable, drivers of tumor progression.

CONCLUSIONS: The developed method could be potentially highly useful on interpreting classification results in the context of different omics data and prior knowledge molecular networks on the individual patient level, as for example in precision medicine approaches or a molecular tumor board.

PMID:33706810 | DOI:10.1186/s13073-021-00845-7

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Nevin Manimala Statistics

Effect of infusion irrigation with different irrigating solutions on transient receptor potential vanilloid 5 and intra-articular inflammation in a post-traumatic osteoarthritis rabbit model

Eur J Med Res. 2021 Mar 12;26(1):24. doi: 10.1186/s40001-021-00491-0.

ABSTRACT

BACKGROUND: The incidence of post-traumatic osteoarthritis (PTOA) after anterior cruciate ligament reconstruction (ACLR) is high, but there is still a lack of intra-operative preventive measures. This study aimed to evaluate the effect of different irrigating solutions continuous irrigation on intra-articular inflammation and cartilage degeneration.

METHODS: 66 New Zealand rabbits were randomly divided into normal (N) group, no treatment (NT) group, sodium chloride (NaCl) group, magnesium sulfate (MgSO4) group, and calcium chloride (CaCl2) group. The right knee joint of the experimental group was utilized to construct the model of PTOA, and the left side was utilized as the normal control group. At different time points postoperatively, the blood concentration of hemoglobin and Mg2 + , the synovial fluid concentration of IL-1 β, TNF-α, tartrate-resistant acid phosphatase-5b (TRAP-5b), and Type II Collagen, the gene expression of IL-1 β and MMP-3, and the protein expression of TRPV5 and CaM were detected. Pearson’s linear correlation was employed to identify the possible relationship between the expression of TRAP-5b and the expression of IL-1β, IL-6, TNF-α, and Type II collagen. The hematoxylin and eosin staining (HE), Masson’s trichrome staining, and Alcian blue staining were performed at postoperative 35 days. Osteoarthritis Scoring (OA score) comprised categories including Alcian blue staining, cartilage histology, the cellular density of cartilage, degree of cell disintegration, and formation of chondrocyte cluster were blindly scored by trained researchers at postoperative 35 days.

RESULTS: There was no statistical difference (P > 0.05) in the hemoglobin concentration between different groups. The concentration of serum Mg2+ in the MgSO4 group was higher than that of the other three groups (P < 0.05) on the same day of operation, then gradually decreased. The expression of IL-1 β, IL-6, and TRAP-5b in synovial fluid increased 5 days after the operation, decreased at 15 days, and then increased again with time in the NT group, NaCl group, and NT group and NaCl group. At 35 days after the operation, the expression of IL-1 β, IL-6, TRAP-5b, and type II collagen in the MgSO4 group were lower than that in the other three groups (except group N) (P < 0.05).The correlation analysis results showed that the TRAP-5b levels correlated positively with IL-1 β, IL-6, TNF-α, and type II collagen concentrations. The histological examination revealed that the surface smoothness of cartilage, the morphology of chondrocytes, the arrangement of collagen fibers, and the density of proteoglycan in the MgSO4 group were better than those in other experimental groups. At 35 days postoperatively, the gene expression of IL-1 β and MMP-3 and the protein expression of CaM and TRPV5 in synovium in the MgSO4 group was lower than that in the NaCl group and CaCl2 group.

CONCLUSION: Intra-operative irrigation with magnesium sulfate solution can inhibit the inflammatory factors and the expression of TRPV5, which can also reduce collagen loss and delay cartilage degeneration. Therefore, the use of magnesium sulfate in intra-operative irrigation may be an ideal choice to prevent PTOA.

PMID:33706812 | DOI:10.1186/s40001-021-00491-0

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Nevin Manimala Statistics

Effectiveness of transdiagnostic seminars to support patients with common mental disorders: a multi-service practice research network study

Behav Cogn Psychother. 2021 Mar 12:1-13. doi: 10.1017/S1352465821000114. Online ahead of print.

ABSTRACT

BACKGROUND: This was a multi-site evaluation of psycho-educational transdiagnostic seminars (TDS) as a pre-treatment intervention to enhance the effectiveness and utilisation of high-intensity cognitive behavioural therapy (CBT).

AIMS: To evaluate the effectiveness of TDS combined with high-intensity CBT (TDS+CBT) versus a matched sample receiving CBT only. Second, to determine the consistency of results across participating services which employed CBT+TDS. Finally, to determine the acceptability of TDS across patients with different psychological disorders.

METHOD: 106 patients across three services voluntarily attended TDS while on a waiting list for CBT (TDS+CBT). Individual and pooled service pre-post treatment effect sizes were calculated using measures of depression, anxiety and functional impairment. Effectiveness and completion rates for TDS+CBT were compared with a propensity score matched sample from an archival dataset of cases who received high-intensity CBT only.

RESULTS: Pre-post treatment effect sizes for TDS+CBT were comparable to the matched sample. Recovery rates were greater for the group receiving TDS; however, this was not statistically significant. Greater improvements were observed during the waiting-list period for patients who had received TDS for depression (d = 0.49 compared with d = 0.07) and anxiety (d = 0.36 compared with d = 0.04).

CONCLUSIONS: Overall, this new evidence found a trend for TDS improving symptoms while awaiting CBT across three separate IAPT services. The effectiveness of TDS now warrants further exploration through an appropriately sized randomised control trial.

PMID:33706847 | DOI:10.1017/S1352465821000114