Quantitative study
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OBJECTIVES: T1 relaxometry is a promising tool for the assessment of microstructural changes during brain ageing. Previous cross-sectional studies demonstrated increasing T1 values in white and decreasing T1 values in grey matter over the lifetime. However, these findings have not yet been confirmed on the basis of a longitudinal study. In this longitudinal study over 7 years, T1 relaxometry was used to investigate the dynamics of age-related microstructural changes in older healthy subjects. METHODS: T1 mapping was performed in 17 healthy subjects (range 51-77 years) at baseline and after 7 years. Advanced cortical and white matter segmentation was used to determine mean T1 values in the cortex and white matter. RESULTS: The analysis revealed a decrease of mean cortical T1 values over 7 years, the rate of T1 reduction being more prominent in subjects with higher age. T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. In contrast, mean white matter T1 values remained stable. CONCLUSIONS: T1 mapping is shown to be sensitive to age-related microstructural changes in healthy ageing subjects in a longitudinal setting. Data of a cohort in late adulthood and the senescence period demonstrate a decrease of cortical T1 values over 7 years, most likely reflecting decreasing water content and increased iron concentrations. KEY POINTS: • T1 mapping is sensitive to age-related microstructural changes in a longitudinal setting. • T1 decreases were predominantly localized in the lateral frontal, parietal and temporal cortex. • The rate of T1 reduction was more prominent in subjects with higher age. • These changes most likely reflect decreasing cortical water and increasing iron concentrations.
- Klíčová slova
- Ageing, Cerebral cortex, Quantitative magnetic resonance imaging, T1 relaxation, White matter,
- MeSH
- bílá hmota diagnostické zobrazování patologie MeSH
- hodnotící studie jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- magnetická rezonanční tomografie metody MeSH
- mapování mozku metody MeSH
- mozek diagnostické zobrazování patologie MeSH
- následné studie MeSH
- počítačové zpracování obrazu metody MeSH
- průřezové studie MeSH
- šedá hmota diagnostické zobrazování patologie MeSH
- senioři MeSH
- spánkový lalok diagnostické zobrazování patologie MeSH
- stárnutí patologie fyziologie MeSH
- železo analýza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- Názvy látek
- železo MeSH
A set of 4-benzylsulfanyl derivatives of pyridine-2-carbonitriles and pyridine-2-carbothioamides, previously tested for their antimycobacterial activity, were analysed by quantitative structure-activity relationship (QSAR) techniques, using some physicochemical and quantum-chemical parameters. The resulting QSAR revealed that the activity increases with electron withdrawing substituents in the benzyl moiety of studied compounds. HOMO orbitals can play an important role in the description of the mechanism of interactions at the molecular level. Additionally, the results of multiple linear regression indicate the differences between Mycobacterium tuberculosis and M. avium. The hydrophobicity of studied compounds is important for activity against M. avium.
This paper is an overview of the most significant and impactful interpretation approaches of quantitative structure-activity relationship (QSAR) models, their development, and application. The evolution of the interpretation paradigm from "model → descriptors → (structure)" to "model → structure" is indicated. The latter makes all models interpretable regardless of machine learning methods or descriptors used for modeling. This opens wide prospects for application of corresponding interpretation approaches to retrieve structure-property relationships captured by any models. Issues of separate approaches are discussed as well as general issues and prospects of QSAR model interpretation.
BACKGROUND: The pathophysiology of abnormal temperature sensation in Parkinson's disease (PD) remains unclear. Abnormal thermal detection does not seem to depend on the dopaminergic deficit, suggesting that other systems play a role in these changes, probably both central and peripheral. METHODS: We measured thermal detection thresholds (TDT) using quantitative sensory testing (QST) in 28 patients with PD and compared them with 15 healthy controls. RESULTS: Of 28 patients, 21% had increased TDT according to the normative data. TDT were higher on the dominant side. No correlation between TDT and disease duration, severity of motor impairment, and dopaminergic therapy was observed. 50% of the patients had difficulty differentiating between warm and cold stimuli, as TDT were within the normal range in most of these patients. CONCLUSIONS: Twenty-one percent of the patients in our study had increased TDT according to the normative data. Abnormal thermal detection was more pronounced on the dominant side. Abnormal differentiation between the thermal stimuli suggest impaired central processing of thermal information.
- Klíčová slova
- Parkinson’s disease, cold detection threshold, quantitative sensory testing, warm detection threshold,
- MeSH
- čití, cítění fyziologie MeSH
- lidé MeSH
- nízká teplota MeSH
- Parkinsonova nemoc * diagnóza MeSH
- studie případů a kontrol MeSH
- teplota MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10-10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10-6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.
- MeSH
- alely MeSH
- celogenomová asociační studie * MeSH
- duktální karcinom slinivky břišní genetika MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokus kvantitativního znaku * MeSH
- nádory slinivky břišní genetika MeSH
- proteiny aktivující GTPasu genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- proteiny aktivující GTPasu MeSH
- SRGAP1 protein, human MeSH Prohlížeč
BACKGROUND: Minimal residual disease (MRD) is an important prognostic maker in acute lymphoblastic leukemia (ALL). However, few data comparing the measurement of adult ALL MRD using different methods in daily practice are available. We conducted an analysis comparing the importance of flow cytometry (FCM) and real-time quantitative polymerase chain reaction (PCR) in the assessment of MRD in adult ALL. PATIENTS AND METHODS: Fifty-six consecutive adult patients with both Philadelphia-negative and -positive ALL treated according to an intensive protocol were enrolled in the study. Bone marrow samples were acquired on day 26 and during week 11 of treatment. MRD evaluation was performed using 8-color FCM and PCR of immunoglobulin or T-cell receptor gene clonal rearrangements and BCR-ABL1, KMT2A-AF4 and E2A-PBX1 fusion genes. RESULTS: On day 26, both FCM and PCR seemed to have good discrimination sensitivity for overall survival (P = .001 to .008) and progression-free survival (P = .03 to .04) prediction for both Philadelphia-positive and -negative cases. The most sensitive method in week 11 was PCR including all results > 0 considered to indicate MRD positivity (P = .002 for overall survival and P = .02 for progression-free survival). PCR with other cutoffs was not sufficiently sensitive in week 11. Moreover, no FCM+ samples were found in week 11. The subanalysis of the Philadelphia-negative patients showed similar results. CONCLUSION: Our analysis showed that both FCM and PCR MRD assessment methods are sensitive for survival prediction during induction. However, we believe FCM could not be sufficiently sensitive in later phases of treatment.
- Klíčová slova
- ALL, FCM, MRD, Overall survival, Sensitivity,
- MeSH
- akutní lymfatická leukemie terapie MeSH
- dospělí MeSH
- kostní dřeň MeSH
- kvantitativní polymerázová řetězová reakce metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mladiství MeSH
- mladý dospělý MeSH
- následné studie MeSH
- prognóza MeSH
- průtoková cytometrie metody MeSH
- retrospektivní studie MeSH
- reziduální nádor diagnóza etiologie metabolismus MeSH
- senioři MeSH
- transplantace kmenových buněk škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Lysosomes are the terminal end of catabolic pathways in the cell, as well as signaling centers performing important functions such as the recycling of macromolecules, organelles, and nutrient adaptation. The importance of lysosomes in human health is supported by the fact that the deficiency of most lysosomal genes causes monogenic diseases called as a group Lysosomal Storage Diseases (LSDs). A common phenotypic hallmark of LSDs is the expansion of the lysosomal compartment that can be detected by using conventional imaging methods based on immunofluorescence protocols or overexpression of tagged lysosomal proteins. These methods require the alteration of the cellular architecture (i.e., due to fixation methods), can alter the behavior of cells (i.e., by the overexpression of proteins), and require sample preparation and the accurate selection of compatible fluorescent markers in relation to the type of analysis, therefore limiting the possibility of characterizing cellular status with simplicity. Therefore, a quantitative and label-free methodology, such as Quantitative Phase Imaging through Digital Holographic (QPI-DH), for the microscopic imaging of lysosomes in health and disease conditions may represent an important advance to study and effectively diagnose the presence of lysosomal storage in human disease. Here we proof the effectiveness of the QPI-DH method in accomplishing the detection of the lysosomal compartment using mouse embryonic fibroblasts (MEFs) derived from a Mucopolysaccharidosis type III-A (MSP-IIIA) mouse model, and comparing them with wild-type (WT) MEFs. We found that it is possible to identify label-free biomarkers able to supply a first pre-screening of the two populations, thus showing that QPI-DH can be a suitable candidate to surpass fluorescent drawbacks in the detection of lysosomes dysfunction. An appropriate numerical procedure was developed for detecting and evaluate such cellular substructures from in vitro cells cultures. Results reported in this study are encouraging about the further development of the proposed QPI-DH approach for such type of investigations about LSDs.
- Klíčová slova
- digital holography, intracellular specificity, label‐free imaging, lysosomal storage diseases, lysosomes, quantitative phase imaging,
- MeSH
- fibroblasty metabolismus patologie MeSH
- kvantitativní fázové zobrazování MeSH
- lidé MeSH
- lyzozomální nemoci z ukládání metabolismus patologie genetika diagnóza MeSH
- lyzozomy * metabolismus MeSH
- mukopolysacharidóza III metabolismus patologie genetika MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.
- Klíčová slova
- amniocentesis, amniotic fluid analysis, biomarker, computational methods, diagnostic indices, fetal lung maturity, neonatal respiratory morbidity, predictive values, quantitative texture analysis, respiratory distress syndrome, sonography, transient tachypnea, ultrasound,
- MeSH
- dospělí MeSH
- lidé MeSH
- morbidita MeSH
- novorozenec MeSH
- plíce diagnostické zobrazování embryologie patologie MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- syndrom respirační tísně novorozenců epidemiologie MeSH
- tachypnoe epidemiologie MeSH
- těhotenství MeSH
- ultrasonografie prenatální * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
A comparative study of driving activity between normal subjects and neurological patients was performed. Driving activity was considered as the energy of the visual evoked potentials filtered at the same frequency of stimulation (1, 2, 4, 7, 10, 12 and 15 cps) using a CAT 400 C computer as a digital filter. The hemispheric symmetry of the responses was measured by the Pearson product moment correlation coefficient and the signal energy ratio. Each symmetry measure for every patient was compared with the normal values and considered abnormal when differences were greater than 3 SD from the normal mean. Of 25 patients 14 of them with a normal EEG, 23 presented severe alterations in the symmetry of the filtered visual evoked responses. Each patient showed a peculiar pattern of abnormality. It is concluded that the procedure described is a very powerful method in the discrimination of brain lesions.
- MeSH
- dospělí MeSH
- evokované potenciály * MeSH
- lidé MeSH
- mladiství MeSH
- mozek patofyziologie MeSH
- nemoci mozku patofyziologie MeSH
- zraková percepce * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
A set of 1160 minimum inhibitory concentration (MIC) values evaluating effect of substitution on the antimycobacterial activity of the previously published 2-(substituted benzyl)sulfanyl benzimidazoles, benzoxazoles, and benzothiazoles has been analyzed by the methods of multidimensional analysis (exploratory analysis, 2D-nonlinear mapping (NLM), principal component analysis (PCA), factor analysis (FA), multiple linear regression (MLR)). The antimycobacterial activity of 2-(subst. benzyl)sulfanyl derivatives of benzimidazole (BIM), 5-methylbenzimidazole (5-Me-BIM), benzoxazole (BOZ), and benzothiazole (BTZ) increased in the order of BTZ
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- benzimidazoly chemie farmakologie MeSH
- benzothiazoly chemie farmakologie MeSH
- benzoxazoly chemie farmakologie MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- mikrobiální testy citlivosti metody MeSH
- Mycobacterium avium účinky léků fyziologie MeSH
- Mycobacterium kansasii účinky léků fyziologie MeSH
- Mycobacterium tuberculosis účinky léků fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antibakteriální látky MeSH
- benzimidazoly MeSH
- benzothiazoly MeSH
- benzoxazoly MeSH
