20 research outputs found
Cardiac q-space trajectory imaging by motion-compensated tensor-valued diffusion encoding in human heart in vivo
No full textPurpose: Tensor-valued diffusion encoding can probe more specific features of tissue microstructure than what is available by conventional diffusion weighting. In this work, we investigate the technical feasibility of tensor-valued diffusion encoding at high b-values with q-space trajectory imaging (QTI) analysis, in the human heart in vivo. Methods: Ten healthy volunteers were scanned on a 3T scanner. We designed time-optimal gradient waveforms for tensor-valued diffusion encoding (linear and planar) with second-order motion compensation. Data were analyzed with QTI. Normal values and repeatability were investigated for the mean diffusivity (MD), fractional anisotropy (FA), microscopic FA (μFA), isotropic, anisotropic and total mean kurtosis (MKi, MKa, and MKt), and orientation coherence (Cc). A phantom, consisting of two fiber blocks at adjustable angles, was used to evaluate sensitivity of parameters to orientation dispersion and diffusion time. Results: QTI data in the left ventricular myocardium were MD = 1.62 ± 0.07 μm2/ms, FA = 0.31 ± 0.03, μFA = 0.43 ± 0.07, MKa = 0.20 ± 0.07, MKi = 0.13 ± 0.03, MKt = 0.33 ± 0.09, and Cc = 0.56 ± 0.22 (mean ± SD across subjects). Phantom experiments showed that FA depends on orientation dispersion, whereas μFA was insensitive to this effect. Conclusion: We demonstrated the first tensor-valued diffusion encoding and QTI analysis in the heart in vivo, along with first measurements of myocardial μFA, MKi, MKa, and Cc. The methodology is technically feasible and provides promising novel biomarkers for myocardial tissue characterization.</p
A comprehensive mouse kidney atlas enables rare cell population characterization and robust marker discovery
No full textThe kidney's cellular diversity is on par with its physiological intricacy; yet identifying cell populations and their markers remains challenging. Here, we created a comprehensive atlas of the healthy adult mouse kidney (MKA: Mouse Kidney Atlas) by integrating 140.000 cells and nuclei from 59 publicly available single-cell and single-nuclei RNA-sequencing datasets from eight independent studies. To harmonize annotations across datasets, we built a hierarchical model of the cell populations. Our model allows the incorporation of novel cell populations and the refinement of known profiles as more datasets become available. Using MKA and the learned model of cellular hierarchies, we predicted previously missing cell annotations from several studies. The MKA allowed us to identify reproducible markers across studies for poorly understood cell types and transitional states, which we verified using existing data from micro-dissected samples and spatial transcriptomics.</p
The link between diffusion MRI and tumor heterogeneity: Mapping cell eccentricity and density by diffusional variance decomposition (DIVIDE)
No full textAbstractThe structural heterogeneity of tumor tissue can be probed by diffusion MRI (dMRI) in terms of the variance of apparent diffusivities within a voxel. However, the link between the diffusional variance and the tissue heterogeneity is not well-established. To investigate this link we test the hypothesis that diffusional variance, caused by microscopic anisotropy and isotropic heterogeneity, is associated with variable cell eccentricity and cell density in brain tumors. We performed dMRI using a novel encoding scheme for diffusional variance decomposition (DIVIDE) in 7 meningiomas and 8 gliomas prior to surgery. The diffusional variance was quantified from dMRI in terms of the total mean kurtosis (MKT), and DIVIDE was used to decompose MKT into components caused by microscopic anisotropy (MKA) and isotropic heterogeneity (MKI). Diffusion anisotropy was evaluated in terms of the fractional anisotropy (FA) and microscopic fractional anisotropy (μFA). Quantitative microscopy was performed on the excised tumor tissue, where structural anisotropy and cell density were quantified by structure tensor analysis and cell nuclei segmentation, respectively. In order to validate the DIVIDE parameters they were correlated to the corresponding parameters derived from microscopy. We found an excellent agreement between the DIVIDE parameters and corresponding microscopy parameters; MKA correlated with cell eccentricity (r=0.95, p<10−7) and MKI with the cell density variance (r=0.83, p<10−3). The diffusion anisotropy correlated with structure tensor anisotropy on the voxel-scale (FA, r=0.80, p<10−3) and microscopic scale (μFA, r=0.93, p<10−6). A multiple regression analysis showed that the conventional MKT parameter reflects both variable cell eccentricity and cell density, and therefore lacks specificity in terms of microstructure characteristics. However, specificity was obtained by decomposing the two contributions; MKA was associated only to cell eccentricity, and MKI only to cell density variance. The variance in meningiomas was caused primarily by microscopic anisotropy (mean±s.d.) MKA=1.11±0.33 vs MKI=0.44±0.20 (p<10−3), whereas in the gliomas, it was mostly caused by isotropic heterogeneity MKI=0.57±0.30 vs MKA=0.26±0.11 (p<0.05). In conclusion, DIVIDE allows non-invasive mapping of parameters that reflect variable cell eccentricity and density. These results constitute convincing evidence that a link exists between specific aspects of tissue heterogeneity and parameters from dMRI. Decomposing effects of microscopic anisotropy and isotropic heterogeneity facilitates an improved interpretation of tumor heterogeneity as well as diffusion anisotropy on both the microscopic and macroscopic scale
Elective Cancer Surgery in COVID-19–Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study
No full textPURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.No Full Tex
The impact of immune response on endochondral bone regeneration
No full textTissue engineered cartilage substitutes, which induce the process of endochondral ossification, represent a regenerative strategy for bone defect healing. Such constructs typically consist of multipotent mesenchymal stromal cells (MSCs) forming a cartilage template in vitro, which can be implanted to stimulate bone formation in vivo. The use of MSCs of allogeneic origin could potentially improve the clinical utility of the tissue engineered cartilage constructs in three ways. First, ready-to-use construct availability can speed up the treatment process. Second, MSCs derived and expanded from a single donor could be applied to treat several patients and thus the costs of the medical interventions would decrease. Finally, it would allow more control over the quality of the MSC chondrogenic differentiation. However, even though the envisaged clinical use of allogeneic cell sources for bone regeneration is advantageous, their immunogenicity poses a significant obstacle to their clinical application. The aim of this review is to increase the awareness of the role played by immune cells during endochondral ossification, and in particular during regenerative strategies when the immune response is altered by the presence of implanted biomaterials and/or cells. More specifically, we focus on how this balance between immune response and bone regeneration is affected by the implantation of a cartilaginous tissue engineered construct of allogeneic origin
Role of variant allele fraction and rare SNP filtering to improve cellular DNA repair endpoint association
No full textBackground Large cancer genome studies continue to reveal new players in treatment response and tumorigenesis. The discrimination of functional alterations from the abundance of passenger genetic alterations still poses challenges and determines DNA sequence variant selection procedures. Here we evaluate variant selection strategies that select homozygous variants and rare SNPs and assess its value in detecting tumor cells with DNA repair defects. Methods To this end we employed a panel of 29 patient-derived head and neck squamous cell carcinoma (HNSCC) cell lines, of which a subset harbors DNA repair defects. Mitomycin C (MMC) sensitivity was used as functional endpoint of DNA crosslink repair deficiency. 556 genes including the Fanconi anemia (FA) and homologous recombination (HR) genes, whose products strongly determine MMC response, were capture-sequenced. Results We show a strong association between MMC sensitivity, thus loss of DNA repair function, and the presence of homozygous and rare SNPs in the relevant FA/HR genes. Excluding such selection criteria impedes the discrimination of crosslink repair status by mutation analysis. Applied to all KEGG pathways, we find that the association with MMC sensitivity is strongest in the KEGG FA pathway, therefore also demonstrating the value of such selection strategies for exploratory analyses. Variant analyses in 56 clinical samples demonstrate that homozygous variants occur more frequently in tumor suppressor genes than oncogenes further supporting the role of a homozygosity criterion to improve gene function association or tumor suppressor gene identification studies. Conclusion Together our data show that the detection of relevant genes or of repair pathway defected tumor cells can be improved by the consideration of allele zygosity and SNP allele frequencies.Pattern Recognition and Bioinformatic
Pedological characterization and soil classification of selected soil units of Morogoro District, Tanzania
No full textInternational Journal of Plant & Soil Science 16(1): 1-12, 2017; Article no.IJPSS.32681
This work was carried out in collaboration between both authors. Author SML designed the study,
performed the statistical analysis, wrote the protocol, managed the literature searches and wrote the
first draft of the manuscript. Author BMM managed the site selection of the study, edited the data,
reviewed and edited the protocol and manuscript. Both authors read and approved the final
manuscriptThe study aimed at provision of research information by pedological characterization of soil units of
Morogoro District, Tanzania. Three soil units were selected coupled with field reconnaissance
survey. Soil pedons were characterized at Kiziwa (KZW-P1), Mkambarani (MKA-P1) and Fulwe
(FUL-P1). Pedons were observed to be formed from in-situ weathering of granitic rocks under ustic
moisture and iso-hyperthermic temperature regimes. Thirteen soil samples were described and
analyzed for physica-chemical and mineralogical properties. KZW-P1 and FUL-P1 had red dark
brown sandy clay and gravely clay (MKA-P1) top soils overlaying mainly clayey subsoil. Both
pedons indicate clay eluviation-illuviation as a dominant pedogenic process with slightly acidic
condition and P<7 except FUL-P1 with 23.8 mg/kg P in top soils. Organic carbon is low in both
pedons while total N is low to very low. CEC values for both pedons are 33.8, 26.4 and 27
cmol(+)/kg respectively. CIA values indicates intermediate to strong level of weathering. In USDA
Soil Taxonomy and the FAO-UNESCO soil classification system, Soils were classified as: Kiziwa.
Ultisols (Alisols), and Inceptisols (Cambisols) for Fulwe and Mkambarani, reflecting their differences
in potentials and constraints and hence use and management. The results reflects variations in soil
characteristics both vertically and laterally so as to account for spatial linkages within the
landscape
Pedological characterization and soil classification of selected soil units of Morogoro District, Tanzania
No full textInternational Journal of Plant & Soil Science 16(1): 1-12, 2017; Article no.IJPSS.32681
This work was carried out in collaboration between both authors. Author SML designed the study,
performed the statistical analysis, wrote the protocol, managed the literature searches and wrote the
first draft of the manuscript. Author BMM managed the site selection of the study, edited the data,
reviewed and edited the protocol and manuscript. Both authors read and approved the final
manuscriptThe study aimed at provision of research information by pedological characterization of soil units of
Morogoro District, Tanzania. Three soil units were selected coupled with field reconnaissance
survey. Soil pedons were characterized at Kiziwa (KZW-P1), Mkambarani (MKA-P1) and Fulwe
(FUL-P1). Pedons were observed to be formed from in-situ weathering of granitic rocks under ustic
moisture and iso-hyperthermic temperature regimes. Thirteen soil samples were described and
analyzed for physica-chemical and mineralogical properties. KZW-P1 and FUL-P1 had red dark
brown sandy clay and gravely clay (MKA-P1) top soils overlaying mainly clayey subsoil. Both
pedons indicate clay eluviation-illuviation as a dominant pedogenic process with slightly acidic
condition and P<7 except FUL-P1 with 23.8 mg/kg P in top soils. Organic carbon is low in both
pedons while total N is low to very low. CEC values for both pedons are 33.8, 26.4 and 27
cmol(+)/kg respectively. CIA values indicates intermediate to strong level of weathering. In USDA
Soil Taxonomy and the FAO-UNESCO soil classification system, Soils were classified as: Kiziwa.
Ultisols (Alisols), and Inceptisols (Cambisols) for Fulwe and Mkambarani, reflecting their differences
in potentials and constraints and hence use and management. The results reflects variations in soil
characteristics both vertically and laterally so as to account for spatial linkages within the
landscape
Knowledge about oral leukoplakia for use at different levels of expertise, including patients
No full textObjective: The purpose of this contribution is to discuss how the subject of oral leukoplakia might be communicated among the various healthcare workers and also among patients. Material and Methods: The discussion is based on the available literature and on many decades of clinical and histopathological experience of the author. Results: The literature does not contain guidelines on what level of expertise can be expected from the various dental and medical healthcare workers in the field of oral leukoplakia, nor on how to communicate this disorder with patients. Based on personal experience, a number of suggestions have been proposed to overcome this shortcoming. Conclusion: Knowledge about oral leukoplakia varies among the various healthcare workers, depending on their level of expertise. Communication on this subject with patients should be in easy to understand wording, avoiding professional terminology as much as possible
A comparison of torque forces used to apply intermaxillary fixation screws
No full textPurpose When establishing intermaxillary fixation (IMF) using bone screws, fracture of a screw is a potential complication. This study was conducted to investigate the forces that arise at bone screw insertion and to determine safety margins between torque for manually tightened insertion and torque until breakage for 3 different IMF screw systems, which could ultimately favor the use of 1 IMF screw system based on decreased risk of complications. Materials and Methods IMF screws were placed into porcine mandibles by 3 oral and maxillofacial surgeons. The porcine mandibles were evaluated for cortical thickness and suitable insertion sites by cone-beam computed tomography. Measurements of torque until failure were performed on predrilled aluminum plates by the primary author. A digital torque screwdriver measured 180 data points per second as continuous data and recorded the measurements. Results Measurements indicated clear differences in torsion forces between manually tightened insertions and torque until breakage for all 3 IMF screw systems. No statistical difference in safety margins was found among the IMF screw systems. Conclusions Because no statistical differences in safety margins were found among the IMF screw systems, this study indicates that IMF screw selection should be based on other clinical factors, such as ease of use or economic factors. Future prospective studies are necessary to fully determine evidence-based criteria for IMF screw selection
