UNLABELLED: Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. SIGNIFICANCE: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

• MeSH
• celogenomová asociační studie MeSH
• genetická predispozice k nemoci MeSH
• genetické lokusy MeSH
• index tělesné hmotnosti MeSH
• jednonukleotidový polymorfismus MeSH
• kolorektální nádory * genetika   MeSH
• lidé MeSH
• mezibuněčné signální peptidy a proteiny genetika   MeSH
• obezita * komplikace   genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

PURPOSE OF THE STUDY Hip dislocation is one of the major causes of disability in children with cerebral palsy (CP). Surgical treatment can be achieved using different techniques including proximal femoral varus derotation osteotomy (FVDRO), pelvic osteotomies, and open hip reduction (OHR). However, we claim that pathologies originating from extraarticular structures in the dislocated hip in CP can be reconstructed by extraarticular methods and OHR may not always be necessary. Therefore, this study aims to discuss the results of hip reconstruction with extraarticular intervention in patients with CP. MATERIAL AND METHODS In total, 141 hips (95 patients) were included in the study. All patients underwent FVDRO, either with or without a Dega osteotomy. Changes in the Acetabular Index (AI), Migration Index (MI), neck-shaft angle (NSA), and center-edge angle (CEA) were assessed on the preoperative, postoperative, and final follow-up anterior-posterior radiographs of the pelvis. RESULTS Median age was 8 years (range between 4-18 years). The average follow-up duration was 5 years (range between 2-9 years). Changes in AI, MI, NSA and CEA values were statistically significant for postop and follow-up periods when compared to preoperative values. Of the 141 operated hips, 8 (5.6%) hips required revision surgery due to redislocation/resubluxation detected at the follow-ups, and unilateral operation can be accepted as a risk factor for redislocation. CONCLUSIONS Our results demonstrate that reconstructive treatment consisting of FVDRO, medial capsulotomy (in the case of reduction difficulty) and transiliac osteotomy (in the case of acetabular dysplasia) provides satisfactory outcomes in hip dislocation in CP. Key words: hip displacement, cerebral palsy, hip reduction.

• MeSH
• acetabulum MeSH
• dítě MeSH
• kyčelní kloub chirurgie   MeSH
• lidé MeSH
• luxace kyčle * diagnostické zobrazování   etiologie   chirurgie   MeSH
• mladiství MeSH
• mozková obrna * komplikace   chirurgie   MeSH
• následné studie MeSH
• pánev MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH

NMDA receptors (NMDARs) are ionotropic glutamate receptors that play a key role in excitatory neurotransmission. The number and subtype of surface NMDARs are regulated at several levels, including their externalization, internalization, and lateral diffusion between the synaptic and extrasynaptic regions. Here, we used novel anti-GFP (green fluorescent protein) nanobodies conjugated to either the smallest commercially available quantum dot 525 (QD525) or the several nanometer larger (and thus brighter) QD605 (referred to as nanoGFP-QD525 and nanoGFP-QD605, respectively). Targeting the yellow fluorescent protein-tagged GluN1 subunit in rat hippocampal neurons, we compared these two probes to a previously established larger probe, a rabbit anti-GFP IgG together with a secondary IgG conjugated to QD605 (referred to as antiGFP-QD605). The nanoGFP-based probes allowed faster lateral diffusion of the NMDARs, with several-fold increased median values of the diffusion coefficient (D). Using thresholded tdTomato-Homer1c signals to mark synaptic regions, we found that the nanoprobe-based D values sharply increased at distances over 100 nm from the synaptic edge, while D values for antiGFP-QD605 probe remained unchanged up to a 400 nm distance. Using the nanoGFP-QD605 probe in hippocampal neurons expressing the GFP-GluN2A, GFP-GluN2B, or GFP-GluN3A subunits, we detected subunit-dependent differences in the synaptic localization of NMDARs, D value, synaptic residence time, and synaptic-extrasynaptic exchange rate. Finally, we confirmed the applicability of the nanoGFP-QD605 probe to study differences in the distribution of synaptic NMDARs by comparing to data obtained with nanoGFPs conjugated to organic fluorophores, using universal point accumulation imaging in nanoscale topography and direct stochastic optical reconstruction microscopy.SIGNIFICANCE STATEMENT Our study systematically compared the localization and mobility of surface NMDARs containing GFP-GluN2A, GFP-GluN2B, or GFP-GluN3A subunits expressed in rodent hippocampal neurons, using anti-green fluorescent protein (GFP) nanobodies conjugated to the quantum dot 605 (nanoGFP-QD605), as well as nanoGFP probes conjugated with small organic fluorophores. Our comprehensive analysis showed that the method used to delineate the synaptic region plays an important role in the study of synaptic and extrasynaptic pools of NMDARs. In addition, we showed that the nanoGFP-QD605 probe has optimal parameters for studying the mobility of NMDARs because of its high localization accuracy comparable to direct stochastic optical reconstruction microscopy and longer scan time compared with universal point accumulation imaging in nanoscale topography. The developed approaches are readily applicable to the study of any GFP-labeled membrane receptors expressed in mammalian neurons.

• MeSH
• hipokampus metabolismus   MeSH
• imunoglobulin G metabolismus   MeSH
• jednodoménové protilátky * metabolismus   MeSH
• králíci MeSH
• krysa rodu rattus MeSH
• neurony metabolismus   MeSH
• receptory N-methyl-D-aspartátu * metabolismus   MeSH
• savci MeSH
• synapse fyziologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• čištění vody metody   normy   MeSH
• koupele MeSH
• kvalita vody normy   MeSH
• plavecké bazény MeSH
• řízení kvality MeSH
• Publikační typ
• směrnice MeSH

• Konspekt
• Metrologie. Standardizace
• NLK Obory
• technika
• environmentální vědy
• hygiena

The SARS-CoV-2 viral load in a respiratory sample can be inversely quantified using the cycle threshold (Ct), defined as the number of amplification cycles required to detect the viral genome in a quantitative PCR assay using reverse transcriptase (RT-qPCR). It may be classified as high (Ct < 25), intermediate (25-30) and low (Ct > 30). We describe the clinical course of 3 patients with haematological neoplasms who contracted COVID-19. None of them had been vaccinated. Firstly, a 22-year-old male with a refractory acute lymphoblastic leukaemia experienced an oligosymptomatic COVID-19 and had a Ct of 23 with an ascending curve. Another male, aged 23, had recently begun treatment for a promyelocytic leukaemia. He had a subacute course with high oxygen requirements. His Ct dropped from 28, when he only experienced fever, to 14.8, during the most critical period and on the edge of ventilatory support. Viral clearance was documented 126 days after the beginning of the symptoms. Finally, a 60-year-old male had received rituximab as maintenance therapy for a follicular lymphoma 3 months before contracting COVID-19. He had a fulminant course and required mechanical ventilation a few days later. We highlight the association between the course of CoViD-19 and the Ct. Viral shedding was longer than in immunocompetent hosts.

• MeSH
• COVID-19 * MeSH
• dospělí MeSH
• hematologické nádory * komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory * MeSH
• RNA virová analýza   genetika   MeSH
• SARS-CoV-2 MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

COVID-19 has depleted healthcare systems around the world. Extreme conditions must be defined as soon as possible so that services and treatment can be deployed and intensified. Many biomarkers are being investigated in order to track the patient's condition. Unfortunately, this may interfere with the symptoms of other diseases, making it more difficult for a specialist to diagnose or predict the severity level of the case. This research develops a Smart Healthcare System for Severity Prediction and Critical Tasks Management (SHSSP-CTM) for COVID-19 patients. On the one hand, a machine learning (ML) model is projected to predict the severity of COVID-19 disease. On the other hand, a multi-agent system is proposed to prioritize patients according to the seriousness of the COVID-19 condition and then provide complete network management from the edge to the cloud. Clinical data, including Internet of Medical Things (IoMT) sensors and Electronic Health Record (EHR) data of 78 patients from one hospital in the Wasit Governorate, Iraq, were used in this study. Different data sources are fused to generate new feature pattern. Also, data mining techniques such as normalization and feature selection are applied. Two models, specifically logistic regression (LR) and random forest (RF), are used as baseline severity predictive models. A multi-agent algorithm (MAA), consisting of a personal agent (PA) and fog node agent (FNA), is used to control the prioritization process of COVID-19 patients. The highest prediction result is achieved based on data fusion and selected features, where all examined classifiers observe a significant increase in accuracy. Furthermore, compared with state-of-the-art methods, the RF model showed a high and balanced prediction performance with 86% accuracy, 85.7% F-score, 87.2% precision, and 86% recall. In addition, as compared to the cloud, the MAA showed very significant performance where the resource usage was 66% in the proposed model and 34% in the traditional cloud, the delay was 19% in the proposed model and 81% in the cloud, and the consumed energy was 31% in proposed model and 69% in the cloud. The findings of this study will allow for the early detection of three severity cases, lowering mortality rates.

• MeSH
• algoritmy MeSH
• COVID-19 * MeSH
• internet věcí * MeSH
• lidé MeSH
• poskytování zdravotní péče MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Clinical laboratories routinely use formalin-fixed paraffin-embedded (FFPE) tissue or cell block cytology samples in oncology panel sequencing to identify mutations that can predict patient response to targeted therapy. To understand the technical error due to FFPE processing, a robustly characterized diploid cell line was used to create FFPE samples with four different pre-tissue processing formalin fixation times. A total of 96 FFPE sections were then distributed to different laboratories for targeted sequencing analysis by four oncopanels, and variants resulting from technical error were identified. RESULTS: Tissue sections that fail more frequently show low cellularity, lower than recommended library preparation DNA input, or target sequencing depth. Importantly, sections from block surfaces are more likely to show FFPE-specific errors, akin to "edge effects" seen in histology, while the inner samples display no quality degradation related to fixation time. CONCLUSIONS: To assure reliable results, we recommend avoiding the block surface portion and restricting mutation detection to genomic regions of high confidence.

• MeSH
• fixace tkání MeSH
• formaldehyd * MeSH
• lidé MeSH
• sekvenční analýza DNA MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• zalévání tkání do parafínu MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Depression is a major depressive disorder characterized by persistent sadness and a sense of worthlessness, as well as a loss of interest in pleasurable activities, which leads to a variety of physical and emotional problems. It is a worldwide illness that affects millions of people and should be detected at an early stage to prevent negative effects on an individual's life. Electroencephalogram (EEG) is a non-invasive technique for detecting depression that analyses brain signals to determine the current mental state of depressed subjects. In this study, we propose a method for automatic feature extraction to detect depression by first constructing a graph from the dataset where the nodes represent the subjects in the dataset and where the edge weights obtained using the Euclidean distance reflect the relationship between them. The Node2vec algorithmic framework is then used to compute feature representations for nodes in a graph in the form of node embeddings ensuring that similar nodes in the graph remain near in the embedding. These node embeddings act as useful features which can be directly used by classification algorithms to determine whether a subject is depressed thus reducing the effort required for manual handcrafted feature extraction. To combine the features collected from the multiple channels of the EEG data, the method proposes three types of fusion methods: graph-level fusion, feature-level fusion, and decision-level fusion. The proposed method is tested on three publicly available datasets with 3, 20, and 128 channels, respectively, and compared to five state-of-the-art methods. The results show that the proposed method detects depression effectively with a peak accuracy of 0.933 in decision-level fusion, which is the highest among the state-of-the-art methods.

• MeSH
• algoritmy MeSH
• deprese diagnóza   MeSH
• depresivní porucha unipolární * diagnóza   MeSH
• elektroencefalografie MeSH
• lidé MeSH
• rozhraní mozek-počítač * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Electronic brachytherapy (eBT) is considered a safe treatment with good outcomes. However, eBT lacks standardized and independent dose verification, which could impede future use. PURPOSE: To validate the 3D dose-to-water distribution of an electronic brachytherapy (eBT) source using a small-volume plastic scintillation detector (PSD). METHODS: The relative dose distribution of a Papillon 50 (P50) (Ariane Medical Systems, UK) eBT source was measured in water with a PSD consisting of a cylindrical scintillating BCF-12 fiber (length: 0.5 mm, Ø: 1 mm) coupled to a photodetector via an optical fiber. The measurements were performed with the PSD mounted on a motorized stage in a water phantom (MP3) (PTW, Germany). This allowed the sensitive volume of the PSD to be moved to predetermined positions relative to the P50 applicator, which pointed vertically downward while just breaching the water surface. The percentage depth-dose (PDD) was measured from 0 to 50 mm source-to-detector distance (SDD) in 1-3 mm steps. Dose profiles were measured along two perpendicular axes at five different SDDs with step sizes down to 0.5 mm. Characterization of the PSD consisted of determining the energy correction through Monte Carlo (MC) simulation and by measuring the stability and dose rate linearity using a well-type ionization chamber as a reference. The measured PDD and profiles were validated with corresponding MC simulations. RESULTS: The measured and simulated PDD curves agreed within 2% (except at 0 mm and 43 mm depth) after the PSD measurements were corrected for energy dependency. The absorbed dose decreased by a factor of 2 at 7 mm depth and by a factor of 10 at 26 mm depth. The measured dose profiles showed dose gradients at the profile edges of more than 50%/mm at 5 mm depth and 15%/mm at 50 mm depth. The measured profile widths increased 0.66 mm per 1 mm depth, while the simulated profile widths increased 0.74 mm per 1 mm depth. An azimuthal dependency of > 10% was observed in the dose at 10 mm distance from the beam center. The total uncertainty of the measured relative dose is < 2.5% with a positional uncertainty of 0.4 mm. The measurements for a full 3D dose characterization (PDD and profiles) can be carried out within 8 h, the limiting factor being cooling of the P50. CONCLUSION: The PSD and MP3 water phantoms provided a method to independently verify the relative 3D dose distribution in water of an eBT source.

• MeSH
• brachyterapie * MeSH
• elektronika MeSH
• metoda Monte Carlo MeSH
• plastické hmoty MeSH
• radiometrie MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: Časnou diagnostikou komplikovaného hojení kolorektální anastomózy lze zvýšit šanci na její záchranu a snížit celkovou mortalitu. Konfokální laserová endomikroskopie (CLE) umožňuje hodnocení tkáňové perfuze bez narušení její integrity. Práce na experimentálním modelu hodnotí využitelnost CLE k pooperační monitoraci kolorektální anastomózy. Metody: Do studie bylo zařazeno 9 prasat, u kterých byla provedena ručně šitá kolorektální anastomóza. Zvířata byla následně rozdělena do skupin s normální (N=3) a ischemickou anastomózou (N=6). Pomocí CLE byly pooperačně v pravidelných intervalech hodnoceny mikroskopické známky hypoperfuze. Výsledky: Ve skupině s ischemickou anastomózou bylo patrné nerovnoměrné sycení obrazu, epitel měl nehomogenní okraje a bylo viditelné četnější větvení krypt. Při hodnocení edému (počet krypt na zorné pole) byly rozdíly mezi skupinami signifikantní již při prvním měření po vyvolání ischemie. Signifikantní rozdíl byl i mezi hodnotami naměřenými před a 10 minut po ischemizaci – 8,7±1,9 vs. 6,0±1,1 (p=0,013). Závěr: Pooperační monitorace kolorektální anastomózy pomocí CLE umožňuje rychlé zachycení poruchy perfuze.

Introduction: Early diagnosis of complicated healing of colorectal anastomosis can increase the chance for salvage surgery and thus reduce overall morbidity. Confocal laser endomicroscopy (CLE) enables in vivo assessment of tissue perfusion without disturbing its integrity. This experimental study evaluates the potential of CLE for postoperative monitoring of colorectal anastomosis. Methods: A hand-sewn colorectal anastomosis was performed in 9 pigs. The animals were subsequently divided into groups with normal (N=3) and ischemic anastomosis (N=6). Microscopic signs of hypoperfusion were evaluated postoperatively at regular intervals using CLE. Results: Uneven saturation of the images was evident in the group with ischemic anastomosis. The epithelium had inhomogeneous edges and more numerous crypt branching was visible. Tissue oedema quantified as the number of crypts per visual field was already more extensive at the first measurement after induction of ischemia. There was also a significant difference between the values measured before and 10 minutes after ischemia – 8.7±1.9 vs. 6.0±1.1 (p=0.013). Conclusion: Postoperative monitoring of the colorectal anastomosis using CLE enables prompt detection of perfusion disorders.

• Klíčová slova
• konfokální laserová endomikroskopie,
• MeSH
• anastomóza chirurgická * MeSH
• kolorektální chirurgie veterinární   MeSH
• kolorektální nádory * chirurgie   veterinární   MeSH
• konfokální mikroskopie metody   veterinární   MeSH
• modely nemocí na zvířatech MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH