Comparative transcriptomic analysis of soybean cyst nematode inbred populations non-adapted or adapted on soybean rhg1-a/Rhg4-mediated resistance.

Soybean cyst nematode (SCN, Heterodera glycines) is most effectively managed through planting resistant soybean cultivars, but the repeated use of the same resistance sources has led to a widespread emergence of virulent SCN populations that can overcome soybean resistance. Resistance to SCN HG type 0 (Race 3) in soybean cultivar Forrest is mediated by an epistatic interaction between the soybean resistance genes rhg1-a and Rhg4. We previously developed two SCN inbred populations by mass-selecting SCN HG type 0 (Race 3) on susceptible and resistant recombinant inbred lines, derived from a cross between Forrest and the SCN-susceptible cultivar Essex, which differ for Rhg4. To identify SCN genes potentially involved in overcoming rhg1-a/Rhg4-mediated resistance, we conducted RNA-sequencing on early parasitic juveniles of these two SCN inbred populations infecting their respective hosts, only to discover a handful of differentially expressed genes (DEGs). However, in a comparison to early parasitic juveniles of an avirulent SCN inbred population infecting a resistant host, we discovered 59 and 171 DEGs uniquely up- or down-regulated in virulent parasitic juveniles adapted on the resistant host. Interestingly, the proteins coded by these 59 DEGs included vitamin B-associated proteins (reduced folate carrier, biotin synthase, and thiamine transporter) and nematode effectors known to play roles in plant defense suppression, suggesting that virulent SCN may exert a heightened transcriptional response to cope with enhanced plant defenses and an altered nutritional status of a resistant soybean host.

The origin, deployment, and evolution of a plant-parasitic nematode effectorome.

Plant-parasitic nematodes constrain global food security. During parasitism, they secrete effectors into the host plant from two types of pharyngeal gland cells. These effectors elicit profound changes in host biology to suppress immunity and establish a unique feeding organ from which the nematode draws nutrition. Despite the importance of effectors in nematode parasitism, there has been no comprehensive identification and characterisation of the effector repertoire of any plant-parasitic nematode. To address this, we advance techniques for gland cell isolation and transcriptional analysis to define a stringent annotation of putative effectors for the cyst nematode Heterodera schachtii at three key life-stages. We define 717 effector gene loci: 269 "known" high-confidence homologs of plant-parasitic nematode effectors, and 448 "novel" effectors with high gland cell expression. In doing so we define the most comprehensive "effectorome" of a plant-parasitic nematode to date. Using this effector definition, we provide the first systems-level understanding of the origin, deployment and evolution of a plant-parasitic nematode effectorome. The robust identification of the effector repertoire of a plant-parasitic nematode will underpin our understanding of nematode pathology, and hence, inform strategies for crop protection.

[Expert recommendations for magnetic resonance imaging of muscle disorders]. / Expertenempfehlung zur Magnetresonanztomographie bei Muskelerkrankungen.

BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.

[Expert recommendations for magnetic resonance imaging of muscle disorders]. / Expertenempfehlung zur Magnetresonanztomographie bei Muskelerkrankungen.

BACKGROUND: Magnetic resonance (MRI) imaging of the skeletal muscles (muscle MRI for short) is increasingly being used in clinical routine for diagnosis and longitudinal assessment of muscle disorders. However, cross-centre standards for measurement protocol and radiological assessment are still lacking. OBJECTIVES: The aim of this expert recommendation is to present standards for the application and interpretation of muscle MRI in hereditary and inflammatory muscle disorders. METHODS: This work was developed in collaboration between neurologists, neuroradiologists, radiologists, neuropaediatricians, neuroscientists and MR physicists from different university hospitals in Germany. The recommendations are based on expert knowledge and a focused literature search. RESULTS: The indications for muscle MRI are explained, including the detection and monitoring of structural tissue changes and oedema in the muscle, as well as the identification of a suitable biopsy site. Recommendations for the examination procedure and selection of appropriate MRI sequences are given. Finally, steps for a structured radiological assessment are presented. CONCLUSIONS: The present work provides concrete recommendations for the indication, implementation and interpretation of muscle MRI in muscle disorders. Furthermore, it provides a possible basis for the standardisation of the measurement protocols at all clinical centres in Germany.

CT image-based biomarkers for opportunistic screening of osteoporotic fractures: a systematic review and meta-analysis.

The use of opportunistic computed tomography (CT) image-based biomarkers may be a low-cost strategy for screening older individuals at high risk for osteoporotic fractures and populations that are not sufficiently targeted. This review aimed to assess the discriminative ability of image-based biomarkers derived from existing clinical routine CT scans for hip, vertebral, and major osteoporotic fracture prediction. A systematic search in PubMed MEDLINE, Embase, Cochrane, and Web of Science was conducted from the earliest indexing date until July 2023. The evaluation of study quality was carried out using a modified Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. The primary outcome of interest was the area under the curve (AUC) and its corresponding 95% confidence intervals (CIs) obtained for four main categories of biomarkers: areal bone mineral density (BMD), image attenuation, volumetric BMD, and finite element (FE)-derived biomarkers. The meta-analyses were performed using random effects models. Sixty-one studies were included in this review, among which 35 were synthesized in a meta-analysis and the remaining articles were qualitatively synthesized. In comparison to the pooled AUC of areal BMD (0.73 [95% CI 0.71-0.75]), the pooled AUC values for predicting osteoporotic fractures for FE-derived parameters (0.77 [95% CI 0.72-0.81]; p < 0.01) and volumetric BMD (0.76 [95% CI 0.71-0.81]; p < 0.01) were significantly higher, but there was no significant difference with the pooled AUC for image attenuation (0.73 [95% CI 0.66-0.79]; p = 0.93). Compared to areal BMD, volumetric BMD and FE-derived parameters may provide a significant improvement in the discrimination of osteoporotic fractures using opportunistic CT assessments.

Longitudinal MR-based proton-density fat fraction (PDFF) and T2* for the assessment of associations between bone marrow changes and myelotoxic chemotherapy.

OBJECTIVES: MR imaging-based proton density fat fraction (PDFF) and T2* imaging has shown to be useful for the evaluation of degenerative changes in the spine. Therefore, the aim of this study was to investigate the influence of myelotoxic chemotherapy on the PDFF and T2* of the thoracolumbar spine in comparison to changes in bone mineral density (BMD). METHODS: In this study, 19 patients were included who had received myelotoxic chemotherapy (MC) and had received a MR imaging scan of the thoracolumbar vertebrates before and after the MC. Every patient was matched for age, sex, and time between the MRI scans to two controls without MC. All patients underwent 3-T MR imaging including the thoracolumbar spine comprising chemical shift encoding-based water-fat imaging to extract PDFF and T2* maps. Moreover, trabecular BMD values were determined before and after chemotherapy. Longitudinal changes in PDFF and T2* were evaluated and compared to changes in BMD. RESULTS: Absolute mean differences of PDFF values between scans before and after MC were at 8.7% (p = 0.01) and at -0.5% (p = 0.57) in the control group, resulting in significantly higher changes in PDFF in patients with MC (p = 0.008). BMD and T2* values neither showed significant changes in patients with nor in those without myelotoxic chemotherapy (p = 0.15 and p = 0.47). There was an inverse, yet non-significant correlation between changes in PDFF and BMD found in patients with myelotoxic chemotherapy (r = -0.41, p = 0.12). CONCLUSION: Therefore, PDFF could be a useful non-invasive biomarker in order to detect changes in the bone marrow in patients receiving myelotoxic therapy. CLINICAL RELEVANCE STATEMENT: Using PDFF as a non-invasive biomarker for early bone marrow changes in oncologic patients undergoing myelotoxic treatment may help enable more targeted countermeasures at commencing states of bone marrow degradation and reduce risks of possible fragility fractures. KEY POINTS: Quantifying changes in bone marrow fat fraction, as well as T2* caused by myelotoxic pharmaceuticals using proton density fat fraction, is feasible. Proton density fat fraction could potentially be established as a non-invasive biomarker for early bone marrow changes in oncologic patients undergoing myelotoxic treatment.

Long-term reproducibility of opportunistically assessed vertebral bone mineral density and texture features in routine clinical multi-detector computed tomography using an automated segmentation framework.

Background: To investigate reproducibility of texture features and volumetric bone mineral density (vBMD) extracted from trabecular bone in the thoracolumbar spine in routine clinical multi-detector computed tomography (MDCT) data in a single scanner environment. Methods: Patients who underwent two routine clinical thoraco-abdominal MDCT exams at a single scanner with a time interval of 6 to 26 months (n=203, 131 males; time interval mean, 13 months; median, 12 months) were included in this observational study. Exclusion criteria were metabolic and hematological disorders, bone metastases, use of bone-active medications, and history of osteoporotic vertebral fractures (VFs) or prior diagnosis of osteoporosis. A convolutional neural network (CNN)-based framework was used for automated spine labeling and segmentation (T5-L5), asynchronous Hounsfield unit (HU)-to-BMD calibration, and correction for the intravenous contrast medium phase. Vertebral vBMD and six texture features [varianceglobal, entropy, short-run emphasis (SRE), long-run emphasis (LRE), run-length non-uniformity (RLN), and run percentage (RP)] were extracted for mid- (T5-T8) and lower thoracic (T9-T12), and lumbar vertebrae (L1-L5), respectively. Relative annual changes were calculated in texture features and vBMD for each vertebral level and sorted by sex, and changes were checked for statistical significance (P<0.05) using paired t-tests. Root mean square coefficient of variation (RMSCV) and root mean square error (RMSE) were calculated as measures of variability. Results: SRE, LRE, RLN, and RP exhibited substantial reproducibility with RMSCV-values below 2%, for both sexes and at all spine levels, while vBMD was less reproducible (RMSCV =11.9-16.2%). Entropy showed highest variability (RMSCV =4.34-7.69%) due to statistically significant increases [range, mean ± standard deviation: (4.40±5.78)% to (8.36±8.66)%, P<0.001]. RMSCV of varianceglobal ranged from 1.60% to 3.03%. Conclusions: Opportunistic assessment of texture features in a single scanner environment using the presented CNN-based framework yields substantial reproducibility, outperforming vBMD reproducibility. Lowest scan-rescan variability was found for higher-order texture features. Further studies are warranted to determine, whether microarchitectural changes to the trabecular bone may be assessed through texture features.

Cost-effectiveness of opportunistic QCT-based osteoporosis screening for the prediction of incident vertebral fractures.

Objectives: Opportunistic quantitative computed tomography (oQCT) derived from non-dedicated routine CT has demonstrated high accuracy in diagnosing osteoporosis and predicting incident vertebral fractures (VFs). We aimed to investigate the cost-effectiveness of oQCT screening compared to dual-energy X-ray absorptiometry (DXA) as the standard of care for osteoporosis screening. Methods: Three screening strategies ("no osteoporosis screening", "oQCT screening", and "DXA screening") after routine CT were simulated in a state-transition model for hypothetical cohorts of 1,000 patients (women and men aged 65 years) over a follow-up period of 5 years (base case). The primary outcomes were the cumulative costs and the quality-adjusted life years (QALYs) estimated from a U.S. health care perspective for the year 2022. Cost-effectiveness was assessed based on a willingness-to-pay (WTP) threshold of $70,249 per QALY. The secondary outcome was the number of prevented VFs. Deterministic and probabilistic sensitivity analyses were conducted to test the models' robustness. Results: Compared to DXA screening, oQCT screening increased QALYs in both sexes (additional 2.40 per 1,000 women and 1.44 per 1,000 men) and resulted in total costs of $3,199,016 and $950,359 vs. $3,262,934 and $933,077 for women and men, respectively. As a secondary outcome, oQCT screening prevented 2.6 and 2.0 additional VFs per 1,000 women and men, respectively. In the probabilistic sensitivity analysis, oQCT screening remained cost-effective in 88.3% (women) and 90.0% (men) of iterations. Conclusion: oQCT screening is a cost-effective ancillary approach for osteoporosis screening and has the potential to prevent a substantial number of VFs if considered in daily clinical practice.

Computed Tomography of the Head : A Systematic Review on Acquisition and Reconstruction Techniques to Reduce Radiation Dose.

In 1971, the first computed tomography (CT) scan was performed on a patient's brain. Clinical CT systems were introduced in 1974 and dedicated to head imaging only. New technological developments, broader availability, and the clinical success of CT led to a steady growth in examination numbers. Most frequent indications for non-contrast CT (NCCT) of the head include the assessment of ischemia and stroke, intracranial hemorrhage and trauma, while CT angiography (CTA) has become the standard for first-line cerebrovascular evaluation; however, resulting improvements in patient management and clinical outcomes come at the cost of radiation exposure, increasing the risk for secondary morbidity. Therefore, radiation dose optimization should always be part of technical advancements in CT imaging but how can the dose be optimized? What dose reduction can be achieved without compromising diagnostic value, and what is the potential of the upcoming technologies artificial intelligence and photon counting CT? In this article, we look for answers to these questions by reviewing dose reduction techniques with respect to the major clinical indications of NCCT and CTA of the head, including a brief perspective on what to expect from current and future developments in CT technology with respect to radiation dose optimization.

Impact of radiation dose reduction and iterative image reconstruction on CT-guided spine biopsies.

This study aimed to systematically evaluate the impact of dose reduction on image quality and confidence for intervention planning and guidance regarding computed tomography (CT)-based intervertebral disc and vertebral body biopsies. We retrospectively analyzed 96 patients who underwent multi-detector CT (MDCT) acquired for the purpose of biopsies, which were either derived from scanning with standard dose (SD) or low dose (LD; using tube current reduction). The SD cases were matched to LD cases considering sex, age, level of biopsy, presence of spinal instrumentation, and body diameter. All images for planning (reconstruction: "IMR1") and periprocedural guidance (reconstruction: "iDose4") were evaluated by two readers (R1 and R2) using Likert scales. Image noise was measured using attenuation values of paraspinal muscle tissue. The dose length product (DLP) was statistically significantly lower for LD scans regarding the planning scans (SD: 13.8 ± 8.2 mGy*cm, LD: 8.1 ± 4.4 mGy*cm, p < 0.01) and the interventional guidance scans (SD: 43.0 ± 48.8 mGy*cm, LD: 18.4 ± 7.3 mGy*cm, p < 0.01). Image quality, contrast, determination of the target structure, and confidence for planning or intervention guidance were rated good to perfect for SD and LD scans, showing no statistically significant differences between SD and LD scans (p > 0.05). Image noise was similar between SD and LD scans performed for planning of the interventional procedures (SD: 14.62 ± 2.83 HU vs. LD: 15.45 ± 3.22 HU, p = 0.24). Use of a LD protocol for MDCT-guided biopsies along the spine is a practical alternative, maintaining overall image quality and confidence. Increasing availability of model-based iterative reconstruction in clinical routine may facilitate further radiation dose reductions.

Computed Tomography of the Spine : Systematic Review on Acquisition and Reconstruction Techniques to Reduce Radiation Dose.

The introduction of the first whole-body CT scanner in 1974 marked the beginning of cross-sectional spine imaging. In the last decades, the technological advancement, increasing availability and clinical success of CT led to a rapidly growing number of CT examinations, also of the spine. After initially being primarily used for trauma evaluation, new indications continued to emerge, such as assessment of vertebral fractures or degenerative spine disease, preoperative and postoperative evaluation, or CT-guided interventions at the spine; however, improvements in patient management and clinical outcomes come along with higher radiation exposure, which increases the risk for secondary malignancies. Therefore, technical developments in CT acquisition and reconstruction must always include efforts to reduce the radiation dose. But how exactly can the dose be reduced? What amount of dose reduction can be achieved without compromising the clinical value of spinal CT examinations and what can be expected from the rising stars in CT technology: artificial intelligence and photon counting CT? In this article, we try to answer these questions by systematically reviewing dose reduction techniques with respect to the major clinical indications of spinal CT. Furthermore, we take a concise look on the dose reduction potential of future developments in CT hardware and software.

Associations of incidental vertebral fractures and longitudinal changes of MR-based proton density fat fraction and T2* measurements of vertebral bone marrow.

Background: Quantitative magnetic resonance imaging (MRI) techniques such as chemical shift encoding-based water-fat separation techniques (CSE-MRI) are increasingly applied as noninvasive biomarkers to assess the biochemical composition of vertebrae. This study aims to investigate the longitudinal change of proton density fat fraction (PDFF) and T2* derived from CSE-MRI of the thoracolumbar vertebral bone marrow in patients that develop incidental vertebral compression fractures (VCFs), and whether PDFF and T2* enable the prediction of an incidental VCF. Methods: In this study we included 48 patients with CT-derived bone mineral density (BMD) measurements at baseline. Patients that presented an incidental VCF at follow up (N=12, mean age 70.5 ± 7.4 years, 5 female) were compared to controls without incidental VCF at follow up (N=36, mean age 71.1 ± 8.6 years, 15 females). All patients underwent 3T MRI, containing a significant part of the thoracolumbar spine (Th11-L4), at baseline, 6-month and 12 month follow up, including a gradient echo sequence for chemical shift encoding-based water-fat separation, from which PDFF and T2* maps were obtained. Associations between changes in PDFF, T2* and BMD measurements over 12 months and the group (incidental VCF vs. no VCF) were assessed using multivariable regression models. Mixed-effect regression models were used to test if there is a difference in the rate of change in PDFF, T2* and BMD between patients with and without incidental VCF. Results: Prior to the occurrence of an incidental VCF, PDFF in vertebrae increased in the VCF group (ΔPDFF=6.3 ± 3.1%) and was significantly higher than the change of PDFF in the group without VCF (ΔPDFF=2.1 ± 2.5%, P=0.03). There was no significant change in T2* (ΔT2*=1.7 ± 1.1ms vs. ΔT2*=1.1 ± 1.3ms, P=0.31) and BMD (ΔBMD=-1.2 ± 11.3mg/cm3 vs. ΔBMD=-11.4 ± 24.1mg/cm3, P= 0.37) between the two groups over 12 months. At baseline, no significant differences were detected in the average PDFF, T2* and BMD of all measured vertebrae (Th11-L4) between the VCF group and the group without VCF (P=0.66, P=0.35 and P= 0.21, respectively). When assessing the differences in rates of change, there was a significant change in slope for PDFF (2.32 per 6 months, 95% confidence interval (CI) 0.31-4.32; P=0.03) but not for T2* (0.02 per 6 months, CI -0.98-0.95; P=0.90) or BMD (-4.84 per 6 months, CI -23.4-13.7; P=0.60). Conclusions: In our study population, the average change of PDFF over 12 months is significantly higher in patients that develop incidental fractures at 12-month follow up compared to patients without incidental VCF, while T2* and BMD show no significant changes prior to the occurrence of the incidental vertebral fractures. Therefore, a longitudinal increase in bone marrow PDFF may be predictive for vertebral compression fractures.

The genome and lifestage-specific transcriptomes of a plant-parasitic nematode and its host reveal susceptibility genes involved in trans-kingdom synthesis of vitamin B5.

Plant-parasitic nematodes are a major threat to crop production in all agricultural systems. The scarcity of classical resistance genes highlights a pressing need to find new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality phased genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major parasitism stages. Analysis of the hologenome of the plant-nematode infection site identified metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that a highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is required for full pathogenicity. Knockout of either plant-encoded or now nematode-encoded steps in the pathway significantly reduces parasitic success. Our experiments establish a reference for cyst nematodes, further our understanding of the evolution of plant-parasitism by nematodes, and show that congruent differential expression of metabolic pathways in the infection hologenome represents a new way to find nematode susceptibility genes. The approach identifies genome-editing-amenable targets for future development of nematode-resistant crops.

A novel sugar beet cyst nematode effector 2D01 targets the Arabidopsis HAESA receptor-like kinase.

Plant-parasitic cyst nematodes use a stylet to deliver effector proteins produced in oesophageal gland cells into root cells to cause disease in plants. These effectors are deployed to modulate plant defence responses and developmental programmes for the formation of a specialized feeding site called a syncytium. The Hg2D01 effector gene, coding for a novel 185-amino-acid secreted protein, was previously shown to be up-regulated in the dorsal gland of parasitic juveniles of the soybean cyst nematode Heterodera glycines, but its function has remained unknown. Genome analyses revealed that Hg2D01 belongs to a highly diversified effector gene family in the genomes of H. glycines and the sugar beet cyst nematode Heterodera schachtii. For functional studies using the model Arabidopsis thaliana-H. schachtii pathosystem, we cloned the orthologous Hs2D01 sequence from H. schachtii. We demonstrate that Hs2D01 is a cytoplasmic effector that interacts with the intracellular kinase domain of HAESA (HAE), a cell surface-associated leucine-rich repeat (LRR) receptor-like kinase (RLK) involved in signalling the activation of cell wall-remodelling enzymes important for cell separation during abscission and lateral root emergence. Furthermore, we show that AtHAE is expressed in the syncytium and, therefore, could serve as a viable host target for Hs2D01. Infective juveniles effectively penetrated the roots of HAE and HAESA-LIKE2 (HSL2) double mutant plants; however, fewer nematodes developed on the roots, consistent with a role for this receptor family in nematode infection. Taken together, our results suggest that the Hs2D01-AtHAE interaction may play an important role in sugar beet cyst nematode parasitism.

The Predictive Value of Early Postoperative MRI-Based Bone Marrow Parameters for Mid-Term Outcome after MACI with Autologous Bone Grafting at the Knee.

OBJECTIVE: The aim of this study was to longitudinally determine the prognostic value of early postoperative quantitative 3T-MRI (magnetic resonance imaging) parameters of subchondral bone marrow for 2-year clinical and MRI outcome after matrix-associated autologous chondrocyte implantation (MACI) with autologous bone grafting (ABG) at the knee. DESIGN: Consecutive subjects who received MACI with ABG for treatment of focal osteochondral defects received MRI follow-up 3, 6, 12, and 24 months postoperatively. Quantitative MRI included bone marrow edema-like lesion (BMEL) volume measurements and single-voxel magnetic resonance spectroscopy (MRS; n = 9) of the subchondral bone marrow. At 2-year follow-up, morphological MRI outcome included MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 scores. Clinical outcomes were assessed using Lysholm scores. RESULTS: Among a total of 18 subjects (mean age: 28.7 ± 8.4 years, n = 14 males) with defects at the medial or lateral (n = 15 and n = 3, respectively) condyle, mean BMEL volume decreased from 4.9 cm3 at 3 months to 2.0 cm3 at 2-year follow-up (P = 0.040). MRS-based bone marrow water T2 showed a decrease from 20.7 ms at 1-year follow-up to 16.8 ms at 2-year follow-up (P = 0.040). Higher BMEL volume at 6 months correlated with lower 2-year Lysholm (R = -0.616, P = 0.015) and MOCART 2.0 scores (R = -0.567, P = 0.027). Larger early postoperative BMEL volumes at 3 months (R = -0.850, P = 0.007) and 6 months (R = -0.811, P = 0.008) correlated with lower MRS-based unsaturated lipid fractions at 2-year follow-up. Furthermore, patients with early postoperative bony defects showed worse MOCART 2.0 (P = 0.044) and Lysholm scores (P = 0.017) after 24 months. CONCLUSION: Low subchondral BMEL volume and optimal restoration of the subchondral bone at early postoperative time points predict better 2-year clinical and MRI outcomes after MACI with ABG.

Finite Element Analysis of Osteoporotic and Osteoblastic Vertebrae and Its Association With the Proton Density Fat Fraction From Chemical Shift Encoding-Based Water-Fat MRI - A Preliminary Study.

Purpose: Osteoporosis is prevalent and entails alterations of vertebral bone and marrow. Yet, the spine is also a common site of metastatic spread. Parameters that can be non-invasively measured and could capture these alterations are the volumetric bone mineral density (vBMD), proton density fat fraction (PDFF) as an estimate of relative fat content, and failure displacement and load from finite element analysis (FEA) for assessment of bone strength. This study's purpose was to investigate if osteoporotic and osteoblastic metastatic changes in lumbar vertebrae can be differentiated based on the abovementioned parameters (vBMD, PDFF, and measures from FEA), and how these parameters correlate with each other. Materials and Methods: Seven patients (3 females, median age: 77.5 years) who received 3-Tesla magnetic resonance imaging (MRI) and multi-detector computed tomography (CT) of the lumbar spine and were diagnosed with either osteoporosis (4 patients) or diffuse osteoblastic metastases (3 patients) were included. Chemical shift encoding-based water-fat MRI (CSE-MRI) was used to extract the PDFF, while vBMD was extracted after automated vertebral body segmentation using CT. Segmentation masks were used for FEA-based failure displacement and failure load calculations. Failure displacement, failure load, and PDFF were compared between patients with osteoporotic vertebrae versus patients with osteoblastic metastases, considering non-fractured vertebrae (L1-L4). Associations between those parameters were assessed using Spearman correlation. Results: Median vBMD was 59.3 mg/cm3 in osteoporotic patients. Median PDFF was lower in the metastatic compared to the osteoporotic patients (11.9% vs. 43.8%, p=0.032). Median failure displacement and failure load were significantly higher in metastatic compared to osteoporotic patients (0.874 mm vs. 0.348 mm, 29,589 N vs. 3,095 N, p=0.034 each). A strong correlation was noted between PDFF and failure displacement (rho -0.679, p=0.094). A very strong correlation was noted between PDFF and failure load (rho -0.893, p=0.007). Conclusion: PDFF as well as failure displacement and load allowed to distinguish osteoporotic from diffuse osteoblastic vertebrae. Our findings further show strong associations between PDFF and failure displacement and load, thus may indicate complimentary pathophysiological associations derived from two non-invasive techniques (CSE-MRI and CT) that inherently measure different properties of vertebral bone and marrow.

Level-Specific Volumetric BMD Threshold Values for the Prediction of Incident Vertebral Fractures Using Opportunistic QCT: A Case-Control Study.

Purpose: To establish and evaluate the diagnostic accuracy of volumetric bone mineral density (vBMD) threshold values at different spinal levels, derived from opportunistic quantitative computed tomography (QCT), for the prediction of incident vertebral fractures (VF). Materials and Methods: In this case-control study, 35 incident VF cases (23 women, 12 men; mean age: 67 years) and 70 sex- and age-matched controls were included, based on routine multi detector CT (MDCT) scans of the thoracolumbar spine. Trabecular vBMD was measured from routine baseline CT scans of the thoracolumbar spine using an automated pipeline including vertebral segmentation, asynchronous calibration for HU-to-vBMD conversion, and correction of intravenous contrast medium (https://anduin.bonescreen.de). Threshold values at T1-L5 were calculated for the optimal operating point according to the Youden index and for fixed sensitivities (60 - 85%) in receiver operating characteristic (ROC) curves. Results: vBMD at each single level of the thoracolumbar spine was significantly associated with incident VFs (odds ratio per SD decrease [OR], 95% confidence interval [CI] at T1-T4: 3.28, 1.66-6.49; at T5-T8: 3.28, 1.72-6.26; at T9-T12: 3.37, 1.78-6.36; and at L1-L4: 3.98, 1.97-8.06), independent of adjustment for age, sex, and prevalent VF. AUC showed no significant difference between vertebral levels and was highest at the thoracolumbar junction (AUC = 0.75, 95%-CI = 0.63 - 0.85 for T11-L2). Optimal threshold values increased from lumbar (L1-L4: 52.0 mg/cm³) to upper thoracic spine (T1-T4: 69.3 mg/cm³). At T11-L2, T12-L3 and L1-L4, a threshold of 80.0 mg/cm³ showed sensitivities of 85 - 88%, and specificities of 41 - 49%. To achieve comparable sensitivity (85%) at more superior spinal levels, resulting thresholds were higher: 114.1 mg/cm³ (T1-T4), 92.0 mg/cm³ (T5-T8), 88.2 mg/cm³ (T9-T12). Conclusions: At all levels of the thoracolumbar spine, lower vBMD was associated with incident VFs in an elderly, predominantly oncologic patient population. Automated opportunistic osteoporosis screening of vBMD along the entire thoracolumbar spine allows for risk assessment of imminent VFs. We propose level-specific vBMD threshold at the thoracolumbar spine to identify individuals at high fracture risk.

miR778 mediates gene expression, histone modification, and DNA methylation during cyst nematode parasitism.

Despite the known critical regulatory functions of microRNAs, histone modifications, and DNA methylation in reprograming plant epigenomes in response to pathogen infection, the molecular mechanisms underlying the tight coordination of these components remain poorly understood. Here, we show how Arabidopsis (Arabidopsis thaliana) miR778 coordinately modulates the root transcriptome, histone methylation, and DNA methylation via post-transcriptional regulation of the H3K9 methyltransferases SU(var)3-9 homolog 5 (SUVH5) and SUVH6 upon infection by the beet cyst nematode Heterodera schachtii. miR778 post-transcriptionally silences SUVH5 and SUVH6 upon nematode infection. Manipulation of the expression of miR778 and its two target genes significantly altered plant susceptibility to H. schachtii. RNA-seq analysis revealed a key role of SUVH5 and SUVH6 in reprograming the transcriptome of Arabidopsis roots upon H. schachtii infection. In addition, chromatin immunoprecipitation (ChIP)-seq analysis established SUVH5 and SUVH6 as the main enzymes mediating H3K9me2 deposition in Arabidopsis roots in response to nematode infection. ChIP-seq analysis also showed that these methyltransferases possess distinct DNA binding preferences in that they are targeting transposable elements under noninfected conditions and protein-coding genes in infected plants. Further analyses indicated that H3K9me2 deposition directed by SUVH5 and SUVH6 contributes to gene expression changes both in roots and in nematode feeding sites and preferentially associates with CG DNA methylation. Together, our results uncovered multi-layered epigenetic regulatory mechanisms coordinated by miR778 during Arabidopsis-H. schachtii interactions.

On quantification errors of R2*$$ {R}_2

PURPOSE: To study the effect of field inhomogeneity distributions in trabecularized bone regions on the gradient echo (GRE) signal with short TEs and to characterize quantification errors on R2*$$ {R}_2^{\ast } $$ and proton density fat fraction (PDFF) maps when using a water-fat model with an exponential R2*$$ {R}_2^{\ast } $$ decay model at short TEs. METHODS: Field distortions were simulated based on a trabecular bone micro CT dataset. Simulations were performed for different bone volume fractions (BV/TV) and for different bone-fat composition values. A multi-TE UTE acquisition was developed to acquire multiple UTEs with random order to minimize eddy currents. The acquisition was validated in phantoms and applied in vivo in a volunteer's ankle and knee. Chemical shift encoded MRI (CSE-MRI) based on a Cartesian multi-TE GRE scan was acquired in the spine of patients with metastatic bone disease. RESULTS: Simulations showed that signal deviations from the exponential signal decay at short TEs were more prominent for a higher BV/TV. UTE multi-TE measurements reproduced in vivo the simulation-based predicted behavior. In regions with high BV/TV, the presence of field inhomogeneities induced an R2*$$ {R}_2^{\ast } $$ underestimation in trabecularized bone marrow when using CSE-MRI at 3T with a short TE. CONCLUSION: R2*$$ {R}_2^{\ast } $$ can be underestimated when using short TEs (<2 ms at 3 T) and a water-fat model with an exponential R2*$$ {R}_2^{\ast } $$ decay model in multi-echo GRE acquisitions of trabecularized bone marrow.