Breast cancer (BC) is the most frequent malignant disease in women worldwide and is therefore challenging for the healthcare system. Early BC detection remains a leading factor that improves overall ...outcome and disease management. Aside from established screening procedures, there is a constant demand for additional BC detection methods. Routine BC screening via non-invasive liquid biopsy biomarkers is one auspicious approach to either complete or even replace the current state-of-the-art diagnostics. The study explores the diagnostic potential of urinary exosomal microRNAs with specific BC biomarker characteristics to initiate the potential prospective application of non-invasive BC screening as routine practice.
Based on a case-control study (69 BC vs. 40 healthy controls), expression level quantification and subsequent biostatistical computation of 13 urine-derived microRNAs were performed to evaluate their diagnostic relevance in BC.
Multilateral statistical assessment determined and repeatedly confirmed a specific panel of four urinary microRNA types (miR-424, miR-423, miR-660, and let7-i) as a highly specific combinatory biomarker tool discriminating BC patients from healthy controls, with 98.6% sensitivity and 100% specificity.
Urine-based BC diagnosis may be achieved through the analysis of distinct microRNA panels with proven biomarker abilities. Subject to further validation, the implementation of urinary BC detection in routine screening offers a promising non-invasive alternative in women's healthcare.
In assembly of small-volume products, tasks are still frequently executed manually. However, the lead times foreseen for these tasks, often do not take into account the actual capabilities of the ...employees, which in turn leads to increased workload and the associated stress among the employees. This paper investigates how a commercially available wearable low-cost sensor and two machine learning algorithms can be applied to measure and evaluate heart rate, heart rate variability and respiration rate to establish a relationship with workload. The investigated algorithms, namely Random Forest and K-Nearest-Neighbours are able to distinguish between tasks phases and rest phases as well as between easy and difficult tasks executed by the employee, which is the main novelty of this paper.
•Machine learning is used to evaluate the workload of employees in assembly processes.•The results of machine learning are compared with subjective assessment methods.•In the presented case study, machine learning is suitable for assessing the workload.
Due to the positive association between neoadjuvant chemotherapy (NACT) and the promising early response rates of patients with triple negative breast cancer (TNBC), including probabilities of ...pathological complete response, NACT is increasingly used in TNBC management. Liquid biopsy-based biomarkers with the power to diagnose the early response to NACT may support established monitoring tools, which are to a certain extent imprecise and costly. Simple serum- or urine-based analyses of non-coding RNA (ncRNA) expression may allow for fast, minimally-invasive testing and timely adjustment of the therapy regimen. The present study investigated breast cancer-related ncRNAs microRNA (miR)-7, -9, -15a, -17, -18a, -19b, -21, -30b, -222 and -320c, PIWI-interacting RNA-36743 and GlyCCC2 in triple positive BT-474 cells and three TNBC cell lines (BT-20, HS-578T and MDA-MB-231) treated with various chemotherapeutic agents using reverse transcription-quantitative PCR. Intracellular and secreted microvesicular ncRNA expression levels were analysed using a multivariable statistical regression analysis. Chemotherapy-driven effects were investigated by analysing cell cycle determinants at the mRNA and protein levels. Serum and urine specimens from 8 patients with TNBC were compared with 10 healthy females using two-sample t-tests. Samples from the patients with TNBC were compared at two time points. Chemotherapeutic treatments induced distinct changes in ncRNA expression in TNBC cell lines and the BT-474 cell line in intra- and extracellular compartments. Serum and urine-based ncRNA expression analysis was able to discriminate between patients with TNBC and controls. Time point comparisons in the urine samples of patients with TNBC revealed a general rise in the level of ncRNA. Serum data suggested a potential association between piR-36743, miR-17, -19b and -30b expression levels and an NACT-driven complete clinical response. The present study highlighted the potential of ncRNAs as liquid biopsy-based biomarkers in TNBC chemotherapy treatment. The ncRNAs tested in the present study have been previously investigated for their involvement in BC or TNBC chemotherapy responses; however, these previous studies were restricted to patient tissue or in vitro models. The data from the present study offer novel insight into ncRNA expression in liquid samples from patients with TNBC, and the study serves as an initial step in the evaluation of ncRNAs as diagnostic biomarkers in the monitoring of TNBC therapy. Key words: ncRNA, triple negative breast cancer, liquid biopsy, neoadjuvant chemotherapy, therapy response, biomarker
Rationale
A substantial overlap exists between catatonic phenomena and features of neuroleptic malignant syndrome.
Objectives
The objective of this study is to examine whether catatonia can be ...distinguished from neuroleptic malignant syndrome and to identify symptoms that may have discriminatory power.
Methods
We conducted a literature search to identify relevant studies up to and including the year 2012. A total of 386 studies containing 490 case reports were included. To evaluate the discriminant value of each feature, we performed binominal regression analyses with the diagnosis as the dependent variable. First, all features were entered into the model as independent variables. In a second step, a stepwise backwards analysis was conducted to eliminate criteria with low discriminant value.
Results
The most common symptoms in patients with neuroleptic malignant syndrome were fever (87.7 %), rigor (85.9 %), laboratory evidence of muscle injury (70.5 %), and tachycardia (62.1 %) and in patients with catatonia were mutism (78.0 %), rigor (73.0 %), stupor (54.0 %), and agitation (49.0 %). Eleven variables with statistically significant discriminatory power remained after statistical analysis: diaphoresis (odds ratio (OR) 10.011), rigor (OR 9.550), fever (OR 7.317), tremor (OR 4.064), laboratory evidence of muscle injury (OR 3.542), leukocytosis (OR 3.081), negativism (OR 0.262), posturing (OR 0.241), waxy flexibility (OR 0.223), stupor (OR 0.158), and stereotypy (OR 0.122).
Conclusions
Catatonia and neuroleptic malignant syndrome can be distinguished, at least on a descriptive level. There is a strong syndromal overlap. Our findings might be influenced by the fact that they are based on case reports, which reflect the respective authors’ clinical opinion of the patient’s condition.
Purpose
It is essential to understand the structural dynamic behavior of electrical machines to predict their acoustic and vibrational behavior. Stacking technology, which is used to manufacture soft ...magnetic cores, has a strong influence on the material properties. The purpose of this paper is therefore to research the influence of the stacking technologies welding and bonding with bake varnish on the modal properties of iron cores.
Design/methodology/approach
A finite element simulation model is developed based on homogenization of the stator core. Eigenfrequencies, modeshapes and modal damping ratios are extracted from measurements and are used to validate the simulation model.
Findings
Modal characteristics depend on the participation of certain material layers at a certain mode. Higher amount of shear deformation results in higher modal damping. Bonded stacks exhibit lower shear stiffness and higher damping ratios.
Originality/value
This research paper provides insights to the modal characteristics of iron cores used in electric machine and compares the influence of stacking technologies.
To reduce CO2 emissions, besides the automotive industry, manufacturing industries are increasingly under pressure to optimize processes and procedures for energy efficiency. These optimizations ...mainly involve the production processes, where most energy demand occurs. Alternatively, when most of this energy demand can be determined during the product design phase, the product designer can make energy-efficient decisions in the design phase. Most product designers are unaware of their decisions’ significant impact on a product’s energy demand. Therefore, this paper presents a workflow and novel method for predicting the energy demand of parts of their machining operation during the design phase. For this purpose, 29 energy consumption models for machining processes are examined, and the data published in the literature are summarized. Four resulting comprehensive process maps are derived, which enable the prediction of a part’s energy consumption due to machining, specifically, the milling operation, based on the geometric features of the part. This was further verified on three machined parts. The workflow and methods presented in this paper are some of the first steps to facilitate conscious decisions already in the product design phase. The benefits of the method were demonstrated in a final survey: Both product designers and machine operators showed in this survey that their estimation of the energy consumption of the parts investigated differed by orders of magnitude.
•A workflow was developed to evaluate machined parts concerning their energy consumption in the product design phase.•In this workflow, a novel method is incorporated, which assigns the total energy consumption of a machined part to its geometric features.•For parametrization of this method, 397 different data points were elicited of 29 energy existing consumption models.•The verification of the novel method is based on data generated by edge sensor Simatic IPC227E from Siemens.•The validation of the workflow is based on two surveys, each with product designers and machine operators.
To find dysregulated urinary microRNAs associated with endometrial cancer as a first step in finding a non-invasive new diagnostic biomarker. The second objective is to determine the correlation of ...urinary microRNAs with clinicopathological characteristics.
A prospective cohort study of patients presenting with abnormal bleeding between March and November 2019 was performed at the Royal Cornwall Hospital Trust Truro. Urine samples were obtained from women diagnosed with endometrial cancer and benign endometrial sampling. MicroRNA was isolated and quantitative real time PCR was used to detect expression levels of microRNAs.
A total of 61 women were included in this study: 24 endometrial cancer patients, and 37 controls. Median age was 64 years (range 45-94) and median body mass index was 29 kg/m
(range 17-54). MiR-223 was significantly up-regulated in urine of endometrial cancers patients (p=0.003). Furthermore, let7-i, miR-34a, and miR-200c were significantly down-regulated and miR-424 was up-regulated in obese women. In addition, miR-148a and miR-222 were significantly down-regulated in elderly women, and miR-16, miR-26b, and miR-200c were significantly deregulated in women with multiple comorbidities.
MicroRNA expression levels in urine can potentially be used as a non-invasive diagnostic test for endometrial cancer. Furthermore, aberrant microRNA expression in urine is associated with patient characteristics. Further research in larger trials is needed to validate the potential utility of urinary microRNAs.
Zusammenfassung
Nach dem Stand der Technik ist es nicht möglich, die Geräuschcharakteristik eines elektrischen Antriebsstrangs mit zufriedenstellender Genauigkeit vorherzuberechnen. Eine ...Herausforderung stellt die strukturdynamische Beschreibung und insbesondere die Dämpfungsmodellierung dar. Ursache sind die verschiedenen zum Teil nicht linearen Mechanismen, welche zur Dämpfung beitragen. Unter anderem sind hier die Materialdämpfung, Schallabstrahlung und Fügestellendämpfung zu nennen. In dieser Arbeit werden für eine mögliche EMKS geeignete modale Dämpfungen am Beispiel von Aluminiumkörpern berechnet, indem die Beiträge durch Materialdämpfung und Schallabstrahlung unabhängig betrachtet werden. Auf Herausforderungen der Dämpfungsmessung zur Validierung wird im Detail eingegangen. Der Fehler durch die Modellierung eines nicht proportionalen Systems durch proportionale Dämpfung wird anhand einer berechneten FRF abgeschätzt. Die Methode ist für orthotrope Materialien anwendbar und kann prinzipiell auch Fügestellendämpfung abdecken.
Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of ...mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance.
We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program.
We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests.
Moderate statistical power due to relatively small sample size.
COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders.
•Mitochondria generate energy through oxidative phosphorylation (OXPHOS) pathway.•Variation in mitochondria-related genes can affect key proteins involved in OXPHOS.•The protein COA8 is associated with cognitive performance.•Mitochondrial genetic risk burden has no clear effects on cognitive function.
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