Introduction to biomedical statistics
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INTRODUCTION: Determining the number of expressed receptors per cell (NRPC) in cell lines is an important prerequisite for many experimental procedures in biomedical research. This paper focuses on the comparison of a newly developed method of determining NRPC - the Kinetic extrapolation method (KEX) - with the standard saturation method. These two methods, both based on radiolabeled ligand-receptor binding, were compared with the data on receptor expression found using quantified western blotting. METHODS: Four cell lines with different expressions of epidermal growth factor receptor (EGFR) were chosen for the experiment: A431, HaCaT, HCT116 and HepG2. Two radiolabeled monoclonal antibodies specific for EGFR were used as ligands: [(131)I]-cetuximab and [(131)I]-panitumumab. The classic manual technique based on the saturation of cell receptors was performed on cells seeded in 24-well plates. The KEX method uses the LigandTracer, a special instrument which detects ligand retention in real time from seeded cells onto a rotating Petri dish. The western blot analysis was performed according to the routinely used procedure. RESULTS: A very close accordance between the manual saturation technique and the KEX method was found in all four cell lines used. The NRPC in the cell lines follows the same order using both ligands: A431>HaCaT>HCT116≈HepG2. Similarly, consistent data on EGFR expression in the studied cell lines were obtained using western blot analysis and the radiolabeled ligand binding assays. CONCLUSIONS: The KEX method could be as similarly useful for determining receptor expression as is the classic saturation method and western blotting.
- MeSH
- buněčné linie MeSH
- erbB receptory metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- regulace genové exprese * MeSH
- statistika jako téma metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- erbB receptory MeSH
- ligandy MeSH
INTRODUCTION: In post-stroke spasticity, functional imaging may uncover modulation in the central sensorimotor networks associated with botulinum toxin type A (BoNT) therapy. Investigations were performed to localize brain activation changes in stroke patients treated with BoNT for upper limb spasticity using functional magnetic resonance imaging (fMRI). METHODS: Seven ischemic stroke patients (4 females; mean age 58.86) with severe hand paralysis and notable spasticity were studied. Spasticity was scored according to the modified Ashworth scale (MAS). fMRI examination was performed 3 times: before (W0) and 4 (W4) and 11weeks (W11) after BoNT. The whole-brain fMRI data were acquired during paced repetitive passive movements of the plegic hand (flexion/extension at the wrist) alternating with rest. Voxel-by-voxel statistical analysis using the General Linear Model (GLM) implemented in FSL (v6.00)/FEAT yielded group session-wise statistical maps and paired between-session contrasts, thresholded at the corrected cluster-wise significance level of p<0.05. RESULTS: As expected, BoNT transiently lowered MAS scores at W4. Across all the sessions, fMRI activation of the ipsilesional sensorimotor cortex (M1, S1, and SMA) dominated. At W4, additional clusters transiently emerged bilaterally in the cerebellum, in the contralesional sensorimotor cortex, and in the contralesional occipital cortex. Paired contrasts demonstrated significant differences W4>W0 (bilateral cerebellum and contralesional occipital cortex) and W4>W11 (ipsilesional cerebellum and SMA). The remaining paired contrast (W0>W11) showed activation decreases mainly in the ipsilesional sensorimotor cortex (M1, S1, and SMA). CONCLUSIONS: The present study confirms the feasibility of using passive hand movements to map the cerebral sensorimotor networks in patients with post-stroke arm spasticity and demonstrates that BoNT-induced spasticity relief is associated with changes in task-induced central sensorimotor activation, likely mediated by an altered afferent drive from the spasticity-affected muscles.
- Klíčová slova
- Botulinum toxin, Functional magnetic resonance imaging, Hand weakness, Neuronal plasticity, Spasticity, Stroke,
- MeSH
- botulotoxiny typu A terapeutické užití MeSH
- cévní mozková příhoda komplikace MeSH
- elektromyografie MeSH
- kinestezie MeSH
- kvadruplegie diagnostické zobrazování farmakoterapie etiologie MeSH
- kyslík krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozková kůra diagnostické zobrazování MeSH
- následné studie MeSH
- neparametrická statistika MeSH
- neurologické vyšetření MeSH
- neurotoxiny terapeutické užití MeSH
- počítačové zpracování obrazu MeSH
- senioři 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
- botulotoxiny typu A MeSH
- kyslík MeSH
- neurotoxiny MeSH
The aim of the study was a quantitative comparison of relative renal uptake and both the whole-kidney and the parenchymal transit time derived from factor analysis of image sequences and provided by standard clinical procedues. In order to extract the stable, well-interpretable factors, factor analysis was performed locally in the problem-specific time and spatial windows and the resulting factor images either evaluated directly as functional images or used as fuzzy regions of interest (ROIs) for the subsequent extraction of time-activity curves from the analysed data. The values of relative renal uptake of the left kidney measured in the functional factor images, which demonstrate the initial accumulation of activity in renal parenchyma (mean 51.0%), did not differ significantly from the values obtained by a standard method (mean 51.5%, r = 0.98, P<0.001). Whole-kidney transit time calculated using fuzzy ROI curves correlated well with the reference values (r = 0.84, P<0.001); however, both its mean value (336.5 s) and the standard deviation (151.5 s) were substantially greater than those of the values provided by a standard procedure (262.8+/-86.9 s). Parenchymal transit time calculated using ROI curves correlated better with the transit time through a wider corticomedullary region rather than through a narrow cortical region, which is decisive in a differential diagnosis of renal disorders. In general, values of transit times provided by factor analysis correlated well with those provided by reference methods but with a shift towards the higher numerical values. This may have been a consequence of a greater extent of the automatically extracted fuzzy ROIs, or of occasionally delayed accumulation in the upper calyces. Results of the study provide quantitative evidence that the factor analysis of dynamic data, even without the introduction of prior physiological information, may yield clinically relevant information. However, some basic requirements, such as sufficiently high sampling frequency and count rate, adaption of the method to a specific clinical task, and proper selection of time and spatial windows for locally performed analysis, have to be fullfilled if the method is to be successfully applied clinically.
- MeSH
- algoritmy MeSH
- biologické modely MeSH
- faktorová analýza statistická MeSH
- fuzzy logika MeSH
- ledviny diagnostické zobrazování metabolismus MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- organotechneciové sloučeniny MeSH
- počítačové zpracování obrazu statistika a číselné údaje MeSH
- radiofarmaka MeSH
- radioisotopová scintigrafie MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- monoklonální protilátky MeSH
- organotechneciové sloučeniny MeSH
- radiofarmaka MeSH
- technetium-99m-MAG3-dsFV MeSH Prohlížeč
INTRODUCTION: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD), characterized by abnormal movements during REM sleep, is a prodromal stage of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). While iRBD shows emerging brain changes, their impact on structural connectivity and network efficiency, and their predictive value, remain poorly characterized. METHODS: In this international prospective study, 198 polysomnography-confirmed iRBD patients and 174 controls underwent diffusion magnetic resonance imaging and were analyzed. Cutting-edge diffusion tractography and network-based statistics were applied to reconstruct individual connectomes and assess network properties predicting DLB or PD. RESULTS: Structural architecture was already disrupted in iRBD, with both reduced and compensatory increased connections. Global efficiency was decreased. Local efficiency in motor regions was altered and associated with early clinical symptoms. Altered local efficiency in the supramarginal gyrus predicted DLB only. DISCUSSION: Early disruption of brain architecture in iRBD predicts progression to synucleinopathy-related dementia, offering a novel potential prognostic biomarker. HIGHLIGHTS: Isolated rapid eye movement sleep behavior disorder (iRBD) patients show significant alterations in inter-regional structural connectivity. Global efficiency is reduced in iRBD compared to controls. Areas with increased local efficiency contribute to decreased global efficiency. Altered network efficiency is associated with emerging Parkinsonian features. Higher supramarginal efficiency predicts dementia with Lewy bodies in iRBD.
- Klíčová slova
- dementia with Lewy bodies, diffusion magnetic resonance imaging, graph theory, parasomnias, sleep, structural connectivity, synucleinopathies,
- MeSH
- demence s Lewyho tělísky * diagnostické zobrazování patofyziologie MeSH
- difuzní magnetická rezonance MeSH
- konektom MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek * diagnostické zobrazování patologie MeSH
- nervová síť * diagnostické zobrazování MeSH
- Parkinsonova nemoc diagnostické zobrazování patofyziologie MeSH
- polysomnografie MeSH
- porucha chování v REM spánku * diagnostické zobrazování patofyziologie patologie MeSH
- prospektivní studie MeSH
- senioři MeSH
- zobrazování difuzních tenzorů MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
INTRODUCTION: The aim of this study was to determine the reproducibility and accuracy of linear measurements on 2 types of dental models derived from cone-beam computed tomography (CBCT) scans: CBCT images, and Anatomodels (InVivoDental, San Jose, Calif); these were compared with digital models generated from dental impressions (Digimodels; Orthoproof, Nieuwegein, The Netherlands). The Digimodels were used as the reference standard. METHODS: The 3 types of digital models were made from 10 subjects. Four examiners repeated 37 linear tooth and arch measurements 10 times. Paired t tests and the intraclass correlation coefficient were performed to determine the reproducibility and accuracy of the measurements. RESULTS: The CBCT images showed significantly smaller intraclass correlation coefficient values and larger duplicate measurement errors compared with the corresponding values for Digimodels and Anatomodels. The average difference between measurements on CBCT images and Digimodels ranged from -0.4 to 1.65 mm, with limits of agreement values up to 1.3 mm for crown-width measurements. The average difference between Anatomodels and Digimodels ranged from -0.42 to 0.84 mm with limits of agreement values up to 1.65 mm. CONCLUSIONS: Statistically significant differences between measurements on Digimodels and Anatomodels, and between Digimodels and CBCT images, were found. Although the mean differences might be clinically acceptable, the random errors were relatively large compared with corresponding measurements reported in the literature for both Anatomodels and CBCT images, and might be clinically important. Therefore, with the CBCT settings used in this study, measurements made directly on CBCT images and Anatomodels are not as accurate as measurements on Digimodels.
- MeSH
- kefalometrie statistika a číselné údaje MeSH
- lidé MeSH
- počítačová tomografie s kuželovým svazkem statistika a číselné údaje MeSH
- počítačové zpracování obrazu statistika a číselné údaje MeSH
- povrchové vlastnosti MeSH
- reprodukovatelnost výsledků MeSH
- software MeSH
- zobrazování trojrozměrné statistika a číselné údaje MeSH
- zubní korunka (anatomie) anatomie a histologie MeSH
- zubní modely * MeSH
- zubní oblouk anatomie a histologie MeSH
- zubní technika otisková statistika a číselné údaje MeSH
- zuby anatomie a histologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
INTRODUCTION: The aim of our study was to search for new, readily available and statistically reliable cytological markers for differentiating benign and malignant follicular thyroid neoplasms pre-operatively. METHODS: Cohesiveness of tumour cells in cytology slides from a series of 58 follicular tumours diagnosed between 1998 and 2004 inclusive was studied, including 48 follicular adenomas, and eight minimally invasive and two widely invasive follicular carcinomas. Photomicrographs of the cytology slides were taken and the digital images were analysed using computer image analysis software. We evaluated the relative proportions of cells arranged in groups of various sizes. The cohesiveness of the cells in cytological smears was then correlated with the immunohistochemical expression of E-cadherin in corresponding histological slides. RESULTS: Cases from 15 men (26%) and 43 women (74%) with a mean age of 50 years (range, 19-79) were analysed. In follicular adenomas and carcinomas, respectively, isolated cells were seen in 16.8% and 24.7% (P = 0.028), groups of two to five cells in 9.7% and 11.5% (P = 0.145) and groups of more than five cells in 73.5% and 63.8% (P = 0.041). The mean cell count in groups with more than five cells was 46.5 and 27.0 in adenomas and carcinomas, respectively (P < 0.001). Cell cohesiveness, either as percentage of cells in groups of more than five (R(2) = 0.026) or as mean cell count per group of more than five (R(2) = 0.005), was not found to be dependent on the expression of E-cadherin. Using a threshold of 13% isolated tumour cells in cytological smears, follicular adenomas and carcinomas could be distinguished with 90% sensitivity and 41% specificity. CONCLUSIONS: Although we demonstrated a statistically significant difference in cell cohesion between follicular adenomas and carcinomas, these could not be distinguished in the clinical setting by evaluation of the percentage of isolated cells in cytological smears because the specificity was too low. The absence of correlation of cellular cohesiveness with E-cadherin expression indicates that other factors are probably responsible for the loss of cohesiveness observed in follicular thyroid malignancy.
- MeSH
- adenom chemie patologie MeSH
- buněčná adheze MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- folikulární adenokarcinom chemie patologie MeSH
- imunohistochemie MeSH
- kadheriny analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- počítačové zpracování obrazu MeSH
- senioři MeSH
- tenkojehlová biopsie MeSH
- uzly štítné žlázy chemie patologie MeSH
- Check Tag
- dospělí MeSH
- 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
- kadheriny MeSH
- nádorové biomarkery MeSH
INTRODUCTION AND AIMS: Multiple myeloma (MM) is the second most common hematooncological disease. Patient survival has been greatly improved by the introduction of new drugs into clinical practice, but survival is negatively affected by the so-called extramedullary relapse (EM), caused by the loss of plasma cell dependence on the bone marrow microenvironment and their migration out of the bone marrow. The nature and causes of this process are currently unclear. MicroRNAs (miRNAs) are short, non-coding RNA molecules involved in many physiological and pathological processes. Their significance in the pathogenesis of MM has been demonstrated by several studies. We assume that they are also involved in the development of the EM. The aim of this study was to analyze different miRNA expression between MM and EM patients. MATERIAL AND METHODS: Using next generation sequencing, we analyzed 39 samples of bone marrow cells from MM patients at diagnosis and 9 bone marrow plasma samples of EM patients. RESULTS: In total, 2,278 miRNA were sequenced, but only 658 miRNAs were analyzed as they were expressed in all samples and had at least 20 reads. Expression data were generated using the Chimira tool from fastq data. All sequences were mapped using miRBase v20. Further analyses were performed using the R/Bioconductor package. The Bayesian procedure was used for normalization of expression. P values were adjusted using the Benjamini-Hochberg method. Analysis found 10 miRNA (p < 0.0005) that are statistically significantly expressed in EM vs. MM patients - these are miR-26a-5p, miR-26b-5p, miR-30e-5p, miR-424-3p, miR-503-5p, miR-767-5p, miR-105-5p, miR-5695-5p, miR-450b-5p and miR-92b-3p. These miRNAs will be further verified by qPCR method on a larger set of MM and EM patients. CONCLUSION: Our pilot study has shown that there are differentially expressed miRNAs between MM and EM patients.Key words: multiple myeloma - microRNA - carcinogenesis - next generation sequencing The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papersThis work was supported by grant MZ ČR AZV 17- 29343A. Submitted: 17. 3. 2018Accepted: 20. 3. 2018.
- MeSH
- Bayesova věta MeSH
- buňky kostní dřeně metabolismus MeSH
- lidé MeSH
- lokální recidiva nádoru genetika MeSH
- mikro RNA * MeSH
- mnohočetný myelom genetika MeSH
- pilotní projekty MeSH
- recidiva MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA * MeSH
INTRODUCTION: The incidence of malignant tumors of the uterine body is increasing in the Czech Republic. Endometrial adenocarcinoma is one of the most frequent morphological types. Obesity or even overweight is a risk factor for the development of this disease. More accurate stratification of risk relative to body mass index (BMI) has not yet been determined in the Czech Republic, although the risk of overweight (BMI 25-29.9) has been reported in one study as comparable to that of first or second degree obesity (BMI 30-30.9). PATIENTS AND METHODS: The study population included 376 women of Caucasian race diagnosed with endometrial adenocarcinoma, with BMI measured simultaneously, in 2005-2017. A control group consisted of an equal number of age-matched women not diagnosed with any oncological or gynecological disease. These two files were statistically processed. RESULTS: Odds (OR, 95% CI) relative to normal weight women, overweight women were at 2.26-times higher odds of endometrial adenocarcinoma, and women with obesity were at 5.18-8.67-, and 24.70-times higher odds, depending on the severity of obesity. CONCLUSION: The hypothesis that overweight represents same risk for the development of endometrial adenocarcinoma, as lower degrees of obesity was not verified. However overweight is serious risk for endometrial adenocarcinoma development. The odds of endometrial adenocarcinoma is correlated with increasing BMI and in the population studied is higher than reported previously for all endometrial carcinoma subtypes. This work was carried out with the support of an internal grant of Krajská zdravotní, a.s., for the years 2017-2019: IGA217129002. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 29. 4. 2019 Accepted: 22. 7. 2019.
- Klíčová slova
- Body Mass Index, czech women, endometrial (endometrioid) adenocarcinoma, endometrial (endometrioid) carcinoma, obesis, odds, overweight,
- MeSH
- adenokarcinom etiologie MeSH
- index tělesné hmotnosti * MeSH
- lidé MeSH
- nádory endometria etiologie MeSH
- nadváha komplikace MeSH
- obezita komplikace MeSH
- odds ratio MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
INTRODUCTION: Severe forms of psoriasis are indicated for systemic treatment with conventional and biological preparations. The former includes methotrexate, cyclosporin, acitretin and narrow-band ultraviolet B phototherapy but toxicity may limit the dose and duration of treatment. Currently used less toxic biological preparations include inhibitors of TNF-alpha (etanercept, adalimumab, infliximab) and the monoclonal antibody against IL 12/23 ustekinumab. We present our own more than five-year experience with the systemic treatment of severe forms of psoriasis using these preparations. METHODS: A total of 66 patients treated with systemic therapy (except for phototherapy) were divided into groups based on treatment. Therapeutic doses were administered according to the recommendations of the manufacturer and dermatological societies. Standard PASI and BSA indexes were used to evaluate clinical condition at weeks 0, 12 and 24. RESULTS: Differences in PASI score reduction and BSA index between patient groups treated with different preparations were statistically significant at monitored intervals. At week 12, PASI score was reduced by 75% or more in a significantly greater number of patients treated with infliximab + methotrexate than those treated with acitretin. At week 24, identical comparison showed a significantly greater number of patients treated with etanercept or adalimumab than those receiving methotrexate. For BSA index reduction by 50% or more, no statistically significant differences were found between patient groups during the follow-up period. CONCLUSION: Systemic therapy provides a significant benefit to patients with severe psoriasis. Biological preparations are more effective than conventional medications which are often limited by severe side-effects and generally less tolerated than biological treatments.
- MeSH
- adalimumab MeSH
- etanercept MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- imunoglobulin G terapeutické užití MeSH
- infliximab MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- psoriáza farmakoterapie patologie MeSH
- receptory TNF terapeutické užití MeSH
- TNF-alfa antagonisté a inhibitory MeSH
- ustekinumab MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- Názvy látek
- adalimumab MeSH
- etanercept MeSH
- humanizované monoklonální protilátky MeSH
- imunoglobulin G MeSH
- infliximab MeSH
- monoklonální protilátky MeSH
- receptory TNF MeSH
- TNF-alfa MeSH
- ustekinumab MeSH
INTRODUCTION: Acute kidney injury (AKI) following surgical myocardial revascularization is associated with high mortality and morbidity. The aim of this study was to evaluate the risk of acute kidney injury in a population of very old patients following different surgical techniques. PATIENTS AND METHODS: A retrospective study of 310 consecutive patients aged 78 to 93 years, mean 80.5±2.2, who underwent surgery at one cardiac surgery centre. Based on the surgical technique used the patients were divided into: Group I. CABG (n=134) - surgical myocardial revascularization using extracorporeal circulation and arterial and venous grafts. Group II. OPCABG (n=55) - surgical revascularization without extracorporeal circulation but using arterial and venous grafts. Group III. NOTOUCH (n=121) - no handling with the ascending aorta was performed at all. RESULTS: A statistically insignificant renoprotective trend was found in patients who underwent surgery without extracorporeal circulation regardless of technique. Comparing groups II and III vs. group I, a significantly poorer renal functioning (median difference in creatinine was 10.0 (32.9) vs 17.5 (35.0), P=0.05) was shown for patients in group I. CONCLUSION: Surgical myocardial revascularization without extracorporeal circulation in very old patients is safe. The results of this study show a renoprotective trend.
- Klíčová slova
- acute kidney injury, coronary artery bypass grafting, octogenarians,
- MeSH
- akutní poškození ledvin epidemiologie etiologie MeSH
- hodnocení rizik * MeSH
- incidence MeSH
- koronární bypass bez mimotělního oběhu škodlivé účinky MeSH
- koronární bypass škodlivé účinky MeSH
- lidé MeSH
- nemoci koronárních tepen chirurgie MeSH
- pooperační komplikace epidemiologie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH