Diagnosis of Coronavirus Disease 2019 Pneumonia by Using Chest Radiography: Value of Artificial Intelligence.

Background Radiologists are proficient in differentiating between chest radiographs with and without symptoms of pneumonia but have found it more challenging to differentiate coronavirus disease 2019 (COVID-19) pneumonia from non-COVID-19 pneumonia on chest radiographs. Purpose To develop an artificial intelligence algorithm to differentiate COVID-19 pneumonia from other causes of abnormalities at chest radiography. Materials and Methods In this retrospective study, a deep neural network, CV19-Net, was trained, validated, and tested on chest radiographs in patients with and without COVID-19 pneumonia. For the chest radiographs positive for COVID-19, patients with reverse transcription polymerase chain reaction results positive for severe acute respiratory syndrome coronavirus 2 with findings positive for pneumonia between February 1, 2020, and May 30, 2020, were included. For the non-COVID-19 chest radiographs, patients with pneumonia who underwent chest radiography between October 1, 2019, and December 31, 2019, were included. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated to characterize diagnostic performance. To benchmark the performance of CV19-Net, a randomly sampled test data set composed of 500 chest radiographs in 500 patients was evaluated by the CV19-Net and three experienced thoracic radiologists. Results A total of 2060 patients (5806 chest radiographs; mean age, 62 years ± 16 [standard deviation]; 1059 men) with COVID-19 pneumonia and 3148 patients (5300 chest radiographs; mean age, 64 years ± 18; 1578 men) with non-COVID-19 pneumonia were included and split into training and validation and test data sets. For the test set, CV19-Net achieved an AUC of 0.92 (95% CI: 0.91, 0.93). This corresponded to a sensitivity of 88% (95% CI: 87, 89) and a specificity of 79% (95% CI: 77, 80) by using a high-sensitivity operating threshold, or a sensitivity of 78% (95% CI: 77, 79) and a specificity of 89% (95% CI: 88, 90) by using a high-specificity operating threshold. For the 500 sampled chest radiographs, CV19-Net achieved an AUC of 0.94 (95% CI: 0.93, 0.96) compared with an AUC of 0.85 (95% CI: 0.81, 0.88) achieved by radiologists. Conclusion CV19-Net was able to differentiate coronavirus disease 2019-related pneumonia from other types of pneumonia, with performance exceeding that of experienced thoracic radiologists. © RSNA, 2021 Online supplemental material is available for this article.

Limb functional recovery is impaired in fibroblast growth factor-2 (FGF2) deficient mice despite chronic ischaemia-induced vascular growth.

FGF2 is a potent stimulator of vascular growth; however, even with a deficiency of FGF2 (Fgf2-/-), developmental vessel growth or ischaemia-induced revascularization still transpires. It remains to be elucidated as to what function, if any, FGF2 has during ischaemic injury. Wildtype (WT) or Fgf2-/- mice were subjected to hindlimb ischaemia for up to 42 days. Limb function, vascular growth, inflammatory- and angiogenesis-related proteins, and inflammatory cell infiltration were assessed in sham and ischaemic limbs at various timepoints. Recovery of ischaemic limb function was delayed in Fgf2-/- mice. Yet, vascular growth response to ischaemia was similar between WT and Fgf2-/- hindlimbs. Several angiogenesis- and inflammatory-related proteins (MCP-1, CXCL16, MMPs and PAI-1) were increased in Fgf2-/- ischaemic muscle. Neutrophil or monocyte recruitment/infiltration was elevated in Fgf2-/- ischaemic muscle. In summary, our study indicates that loss of FGF2 induces a pro-inflammatory microenvironment in skeletal muscle which exacerbates ischaemic injury and delays functional limb use.

Transarterial radioembolization with yttrium-90 of unresectable primary hepatic malignancy in children.

BACKGROUND: Primary malignant liver tumors are rare, accounting for 1% to 2% of all childhood cancers. When chemotherapy fails, transarterial radioembolization with yttrium-90 (TARE-Y90) may offer an alternative therapy as a bridge to surgical resection or liver transplant or for palliation. METHODS: We conducted a retrospective review of 10 pediatric patients with histologically confirmed primary liver malignancy who received treatment with TARE-Y90. RESULTS: The median age at treatment was 5.5 years (range, 2-18 years). Median patient survival from initial diagnosis was 12.5 months (range, 10-28 months), and median patient survival after TARE-Y90 was 4 months (range, 2-20 months). Retreatment was well tolerated in three of 10 patients, with these patients demonstrating the longest survival times (range, 17-20 months). One patient was transplanted 6 weeks after TARE-Y90. By RECIST 1.1 criteria of all target lesions, eight of nine patients had stable disease, and one of nine had progressive disease. By mRECIST criteria (requiring postcontrast arterial phase imaging), two of seven patients had a partial response, four of seven had stable disease, and one of seven had progressive disease. CONCLUSION: TARE-Y90 of unresectable primary liver malignancy is both technically feasible and demonstrates an anticancer effect, and retreatment is well tolerated. TARE-Y90 could be considered as adjunctive therapy in pediatric patients with unresectable hepatic malignancies and could be used as a bridge to surgical resection or liver transplant. More research is required to determine the efficacy of this treatment in children and to define the clinical scenarios where benefit is likely to be optimized.

Radiation dose reduction through combining positron emission tomography/computed tomography (PET/CT) and diagnostic CT in children and young adults with lymphoma.

BACKGROUND: Both [F-18]2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and diagnostic CT are at times required for lymphoma staging. This means some body segments are exposed twice to X-rays for generation of CT data (diagnostic CT + localization CT). OBJECTIVE: To describe a combined PET/diagnostic CT approach that modulates CT tube current along the z-axis, providing diagnostic CT of some body segments and localization CT of the remaining body segments, thereby reducing patient radiation dose. MATERIALS AND METHODS: We retrospectively compared total patient radiation dose between combined PET/diagnostic CT and separately acquired PET/CT and diagnostic CT exams. When available, we calculated effective doses for both approaches in the same patient; otherwise, we used data from patients of similar size. To confirm image quality, we compared image noise (Hounsfield unit [HU] standard deviation) as measured in the liver on both combined and separately acquired diagnostic CT images. We used t-tests for dose comparisons and two one-sided tests for image-quality equivalence testing. RESULTS: Mean total effective dose for the CT component of the combined and separately acquired diagnostic CT exams were 6.20±2.69 and 8.17±2.61 mSv, respectively (P<0.0001). Average dose savings with the combined approach was 24.8±17.8% (2.60±2.51 mSv [range: 0.32-4.72 mSv]) of total CT effective dose. Image noise was not statistically significantly different between approaches (12.2±1.8 HU vs. 11.7±1.5 HU for the combined and separately acquired diagnostic CT images, respectively). CONCLUSION: A combined PET/diagnostic CT approach as described offers dose savings at similar image quality for children and young adults with lymphoma who have indications for both PET and diagnostic CT examinations.

Recombinant covalently closed circular hepatitis B virus DNA induces prolonged viral persistence in immunocompetent mice.

It remains crucial to develop a laboratory model for studying hepatitis B virus (HBV) chronic infection. We hereby produced a recombinant covalently closed circular DNA (rcccDNA) in view of the key role of cccDNA in HBV persistence. A loxP-chimeric intron was engineered into a monomeric HBV genome in a precursor plasmid (prcccDNA), which was excised using Cre/loxP-mediated DNA recombination into a 3.3-kb rcccDNA in the nuclei of hepatocytes. The chimeric intron was spliced from RNA transcripts without interrupting the HBV life cycle. In cultured hepatoma cells, cotransfection of prcccDNA and pCMV-Cre (encoding Cre recombinase) resulted in accumulation of nuclear rcccDNA that was heat stable and epigenetically organized as a minichromosome. A mouse model of HBV infection was developed by hydrodynamic injection of prcccDNA. In the presence of Cre recombinase, rcccDNA was induced in the mouse liver with effective viral replication and expression, triggering a compromised T-cell response against HBV. Significant T-cell hyporesponsiveness occurred in mice receiving 4 µg prcccDNA, resulting in prolonged HBV antigenemia for up to 9 weeks. Persistent liver injury was observed as elevated alanine transaminase activity in serum and sustained inflammatory infiltration in the liver. Although a T-cell dysfunction was induced similarly, mice injected with a plasmid containing a linear HBV replicon showed rapid viral clearance within 2 weeks. Collectively, our study provides an innovative approach for producing a cccDNA surrogate that established HBV persistence in immunocompetent mice. It also represents a useful model system in vitro and in vivo for evaluating antiviral treatments against HBV cccDNA. Importance: (i) Unlike plasmids that contain a linear HBV replicon, rcccDNA established HBV persistence with sustained liver injury in immunocompetent mice. This method could be a prototype for developing a mouse model of chronic HBV infection. (ii) An exogenous intron was engineered into the HBV genome for functionally seamless DNA recombination. This original approach could be also extended to other viral studies. (iii) rcccDNA was substantially induced in the nuclei of hepatocytes and could be easily distinguished by its exogenous intron using PCR. This convenient model system affords the opportunity to test antivirals directly targeting HBV cccDNA.

Training certified detectives to track down the intrinsic shortcuts in COVID-19 chest x-ray data sets.

Deep learning faces a significant challenge wherein the trained models often underperform when used with external test data sets. This issue has been attributed to spurious correlations between irrelevant features in the input data and corresponding labels. This study uses the classification of COVID-19 from chest x-ray radiographs as an example to demonstrate that the image contrast and sharpness, which are characteristics of a chest radiograph dependent on data acquisition systems and imaging parameters, can be intrinsic shortcuts that impair the model's generalizability. The study proposes training certified shortcut detective models that meet a set of qualification criteria which can then identify these intrinsic shortcuts in a curated data set.

Training certified detectives to track down the intrinsic shortcuts in COVID-19 chest x-ray data sets.

Deep learning faces a significant challenge wherein the trained models often underperform when used with external test data sets. This issue has been attributed to spurious correlations between irrelevant features in the input data and corresponding labels. This study uses the classification of COVID-19 from chest x-ray radiographs as an example to demonstrate that the image contrast and sharpness, which are characteristics of a chest radiograph dependent on data acquisition systems and imaging parameters, can be intrinsic shortcuts that impair the model's generalizability. The study proposes training certified shortcut detective models that meet a set of qualification criteria which can then identify these intrinsic shortcuts in a curated data set.

A quality-checked and physics-constrained deep learning method to estimate material basis images from single-kV contrast-enhanced chest CT scans.

BACKGROUND: Single-kV CT imaging is one of the primary imaging methods in radiology practices. However, it does not provide material basis images for some subtle lesion characterization tasks in clinical diagnosis. PURPOSE: To develop a quality-checked and physics-constrained deep learning (DL) method to estimate material basis images from single-kV CT data without resorting to dual-energy CT acquisition schemes. METHODS: Single-kV CT images are decomposed into two material basis images using a deep neural network. The role of this network is to generate a feature space with 64 template features with the same matrix dimensions of the input single-kV CT image. These 64 template image features are then combined to generate the desired material basis images with different sets of combination coefficients, one for each material basis image. Dual-energy CT image acquisitions with two separate kVs were curated to generate paired training data between a single-kV CT image and the corresponding two material basis images. To ensure the obtained two material basis images are consistent with the encoded spectral information in the actual projection data, two physics constraints, that is, (1) effective energy of each measured projection datum that characterizes the beam hardening in data acquisitions and (2) physical factors of scanners such as detector and tube characteristics, are incorporated into the end-to-end training. The entire architecture is referred to as Deep-En-Chroma in this paper. In the application stage, the generated material basis images are sent to a deep quality check (Deep-QC) network to assess the quality of estimated images and to report the pixel-wise estimation errors for users. The models were developed using 5592 training and validation pairs generated from 48 clinical cases. Additional 1526 CT images from another 13 patients were used to evaluate the quantitative accuracy of water and iodine basis images estimated by Deep-En-Chroma. RESULTS: For the iodine basis images estimated by Deep-En-Chroma, the mean difference with respect to dual-energy CT is -0.25 mg/mL, and the agreement limits are [-0.75 mg/mL, +0.24 mg/mL]. For the water basis images estimated by Deep-En-Chroma, the mean difference with respect to dual-energy CT is 0.0 g/mL, and the agreement limits are [-0.01 g/mL, 0.01 g/mL]. Across the test cohort, the median [25th, 75th percentiles] root mean square errors between the Deep-En-Chroma and dual-energy material images are 14 [12, 16] mg/mL for the water images and 0.73 [0.64, 0.80] mg/mL for the iodine images. When significant errors are present in the estimated material basis images, Deep-QC can capture these errors and provide pixel-wise error maps to inform users whether the DL results are trustworthy. CONCLUSIONS: The Deep-En-Chroma network provides a new pathway to estimating the clinically relevant material basis images from single-kV CT data and the Deep-QC module to inform end-users of the accuracy of the DL material basis images in practice.

Multicontrast x-ray computed tomography imaging using Talbot-Lau interferometry without phase stepping.

PURPOSE: The purpose of this work is to demonstrate that multicontrast computed tomography (CT) imaging can be performed using a Talbot-Lau interferometer without phase stepping, thus allowing for an acquisition scheme like that used for standard absorption CT. METHODS: Rather than using phase stepping to extract refraction, small-angle scattering (SAS), and absorption signals, the two gratings of a Talbot-Lau interferometer were rotated slightly to generate a moiré pattern on the detector. A Fourier analysis of the moiré pattern was performed to obtain separate projection images of each of the three contrast signals, all from the same single-shot of x-ray exposure. After the signals were extracted from the detector data for all view angles, image reconstruction was performed to obtain absorption, refraction, and SAS CT images. A physical phantom was scanned to validate the proposed data acquisition method. The results were compared with a phantom scan using the standard phase stepping approach. RESULTS: The reconstruction of each contrast mechanism produced the expected results. Signal levels and contrasts match those obtained using the phase stepping technique. CONCLUSIONS: Absorption, refraction, and SAS CT imaging can be achieved using the Talbot-Lau interferometer without the additional overhead of long scan time and phase stepping.

Extraction of tumor motion trajectories using PICCS-4DCBCT: a validation study.

PURPOSE: As a counterpart of 4DCT in the treatment planning stage of radiotherapy treatment, 4D cone beam computed tomography (4DCBCT) method has been proposed to verify tumor motion trajectories before radiation therapy treatment delivery. Besides 4DCBCT acquisition using slower gantry rotation speed or multiple rotations, a new method using the prior image constrained compressed sensing (PICCS) image reconstruction method and the standard 1-min data acquisition were proposed. In this paper, the PICCS-4DCBCT method was combined with deformable registration to validate its capability in motion trajectory extraction using physical phantom data, simulated human subject data from 4DCT and in vivo human subject data. METHODS: Two methods were used to validate PICCS-4DCBCT for the purpose of respiratory motion delineation. The standard 1-min gantry rotation Cone Beam CT acquisition was used for both methods. In the first method, 4DCBCT projection data of a physical motion phantom were acquired using an on-board CBCT acquisition system (Varian Medical Systems, Palo Alto, CA). Using a deformable registration method, the object motion trajectories were extracted from both FBP and PICCS reconstructed 4DCBCT images, and compared against the programmed motion trajectories. In the second method, using a clinical 4DCT dataset, Cone Beam CT projections were simulated by forward projection. Using a deformable registration method, the tumor motion trajectories were extracted from the reconstructed 4DCT and PICCS-4DCBCT images. The performance of PICCS-4DCBCT is assessed against the 4DCT ground truth. The breathing period was varied in the simulation to study its effect on motion extraction. For both validation methods, the root mean square error (RMSE) and the maximum of the errors (MaxE) were used to quantify the accuracy of the extracted motion trajectories. After the validation, a clinical dataset was used to demonstrate the motion delineation capability of PICCS-4DCBCT for human subjects. RESULTS: In both validation studies, the RMSEs of the extracted motion trajectories from PICCS-4DCBCT images are less than 0.7 mm, and their MaxEs are less than 1 mm, for all three directions. In comparison, FBP-4DCBCT shows considerably larger RMSEs in the physical phantom based validation. PICCS-4DCBCT also shows insensitivity to the breathing period in the 4DCT based validation. For the in vivo human subject study, high quality 3D motion trajectory of the tumor was obtained from PICCS-4DCBCT images and showed consistency with visual observation. CONCLUSIONS: These results demonstrate accurate delineation of tumor motion trajectory can be achieved using PICCS-4DCBCT and the standard 1-min data acquisition.

Scaling law for noise variance and spatial resolution in differential phase contrast computed tomography.

PURPOSE: The noise variance versus spatial resolution relationship in differential phase contrast (DPC) projection imaging and computed tomography (CT) are derived and compared to conventional absorption-based x-ray projection imaging and CT. METHODS: The scaling law for DPC-CT is theoretically derived and subsequently validated with phantom results from an experimental Talbot-Lau interferometer system. RESULTS: For the DPC imaging method, the noise variance in the differential projection images follows the same inverse-square law with spatial resolution as in conventional absorption-based x-ray imaging projections. However, both in theory and experimental results, in DPC-CT the noise variance scales with spatial resolution following an inverse linear relationship with fixed slice thickness. CONCLUSIONS: The scaling law in DPC-CT implies a lesser noise, and therefore dose, penalty for moving to higher spatial resolutions when compared to conventional absorption-based CT in order to maintain the same contrast-to-noise ratio.

Quantitative lung perfusion blood volume using dual energy CT-based effective atomic number (Zeff ) imaging.

BACKGROUND: Iodine material images (aka iodine basis images) generated from dual energy computed tomography (DECT) have been used to assess potential perfusion defects in the pulmonary parenchyma. However, iodine material images do not provide the needed absolute quantification of the pulmonary blood pool, as materials with effective atomic numbers (Zeff ) different from those of basis materials may also contribute to iodine material images, thus confounding the quantification of perfusion defects. PURPOSE: (i) To demonstrate the limitations of iodine material images in pulmonary perfusion defect quantification and (ii) to develop and validate a new quantitative biomarker using effective atomic numbers derived from DECT images. METHODS: The quantitative relationship between the perfusion blood volume (PBV) in pulmonary parenchyma and the effective atomic number (Zeff ) spatial distribution was studied to show that the desired quantitative PBV maps are determined by the spatial maps of Zeff as PB V Z eff ( x ) = a Z eff ß ( x ) + b , where a, b, and ß are three constants. Namely, quantitative PB V Z eff is determined by Zeff images instead of the iodine basis images. Perfusion maps were generated for four human subjects to demonstrate the differences between conventional iodine material image-based PBV (PBViodine ) derived from two-material decompositions and the proposed PB V Z eff method. RESULTS: Among patients with pulmonary emboli, the proposed PB V Z eff maps clearly show the perfusion defects while the PBViodine maps do not. Additionally, when there are no perfusion defects present in the derived PBV maps, no pulmonary emboli were diagnosed by an experienced thoracic radiologist. CONCLUSION: Effective atomic number-based quantitative PBV maps provide the needed sensitive and specific biomarker to quantify pulmonary perfusion defects.

Small-angle scattering computed tomography (SAS-CT) using a Talbot-Lau interferometerand a rotating anode x-ray tube:theory and experiments.

X-ray differential phase contrast imaging methods, including projection imaging and the corresponding computed tomography (CT), have been implemented using a Talbot interferometer and either a synchrotron beam line or a low brilliance x-ray source generated by a stationary-anode x-ray tube. From small-angle scattering events which occur as an x-ray propagates through a medium, a signal intensity loss can be recorded and analyzed for an understanding of the micro-structures in an image object. This has been demonstrated using a Talbot-Lau interferometer and a stationary-anode x-ray tube. In this paper, theoretical principles and an experimental implementation of the corresponding CT imaging method are presented. First, a line integral is derived from analyzing the cross section of the small-angle scattering events. This method is referred to as small-angle scattering computed tomography (SAS-CT). Next, a Talbot-Lau interferometer and a rotating-anode x-ray tube were used to implement SAS-CT. A physical phantom and human breast tissue sample were used to demonstrate the reconstructed SAS-CT image volumes.

Radiation dose efficiency comparison between differential phase contrast CT and conventional absorption CT.

PURPOSE: The superior radiation dose efficiency of a newly implemented differential phase contrast CT imaging method compared to the conventional absorption CT method is demonstrated. METHODS: A differential phase contrast CT imaging method has recently been implemented using conventional x-ray sources with a grating interferometer consisting of three gratings. This approach offers the possibility of simultaneous reconstruction of both attenuation contrast and phase contrast images from a single acquisition. This enables a direct comparison of radiation dose efficiency of both types of reconstructed images under identical conditions. Radiation dose efficiency was studied by measuring the change in contrast-to-noise ratio (CNR) with different exposure levels. A physical phantom of 28.5 mm diameter was constructed and used for measurement of CNR in both the absorption and phase contrast CT images, which were reconstructed from the same data set. RESULTS: For three of the four materials studied, at any given exposure level, the CNR of the differential phase contrast CT images was superior to that of the corresponding absorption contrast CT images. The most dramatic improvement was noted in the contrast between PMMA and water, where the CNR was improved by a factor of approximately 5.5 in the differential phase contrast CT images. Additionally, the CNR of phase contrast CT is empirically shown to have the same square root dependence on exposure, as is the case for absorption contrast CT. CONCLUSIONS: The differential phase contrast CT method provided higher CNR than conventional absorption CT at equivalent dose levels for most of the materials studied, and so may enable achievement of the same object visibility as conventional absorption CT methods at a lower exposure level.

Role of CT imaging in left atrial appendage occlusion for the WATCHMAN™ device.

Computed tomography (CT) plays a key role in the peri-procedural planning of left atrial appendage occlusion (LAAO) device placement and post-procedural evaluation. The geometric variability of the interatrial septum, left atrium, and the left atrial appendage morphology can be fully visualized and intuitively appreciated through CT-derived, patient-specific 3D model unique to each individual's anatomy. This review further defines the strengths and limitations of CT peri-procedural imaging in the planning of LAAO.

Purified PEGylated human glucagon-like peptide-2 reduces the severity of irradiation-induced acute radiation enteritis in rats.

Radiation-induced acute intestinal injury after abdominal and pelvic irradiation is a common and serious problem in the clinical setting. Glucagon-like peptide-2 (GLP-2), a 33-amino acid peptide, exerts diverse effects related to the regulation of gastrointestinal growth and function. However, GLP-2 is relatively unstable in vivo. The aim of the present study was to improve GLP-2 stability in vivo and to evaluate its therapeutic effect on acute radiation enteritis. We generated long-lasting intestinal protection peptides by conjugating human GLP-2 (hGLP-2) peptides to polyethyleneglycol (PEG) to produce mPEGylation hGLP-2 (Mono-PEG-hGLP-2) through an enzymatic site-specific transglutamination reaction. Mono-PEG-hGLP-2 synthesized under optimal reaction conditions and separated by one-step ion-exchange chromatography was found to be resistant to degradation in vitro. Pretreatment with Mono-PEG-hGLP-2 reduced the severity of radiation-induced intestinal injury, oxidative stress, and the expression of NF-κB in rats with irradiation-induced acute radiation enteritis. The enhanced biological potency of Mono-PEG-hGLP-2 highlights its potential as a therapeutic agent for intestinal diseases.

Image reconstruction for fan-beam differential phase contrast computed tomography.

Recently, x-ray differential phase contrast computed tomography (DPC-CT) has been experimentally implemented using a conventional tube combined with gratings. Images were reconstructed using a parallel-beam reconstruction formula. However, parallel-beam reconstruction formulae are not applicable when the parallel-beam approximation fails. In this paper, we present a new image reconstruction formula for fan-beam DPC-CT. There are several novel features of the new image reconstruction formula: (i) when the scanning angular range of data acquisition is larger than pi + gamma(m) (gamma(m) is the full fan angle), the entire field of view can be exactly reconstructed; (ii) when the scanning angular range is smaller than pi + gamma(m), a local region of interest (ROI) can be exactly reconstructed; (iii) it enables an exact reconstruction for a local ROI when the projection data are truncated at some view angles; (iv) it enlarges the imaging field of view when the detector is asymmetrically placed. In this last case, the data are truncated from every view angle. Numerical simulations have been conducted to validate the new reconstruction formula.

A locus on chromosome 5 shows African ancestry-limited association with alloimmunization in sickle cell disease.

Red blood cell (RBC) transfusion remains a critical therapeutic intervention in sickle cell disease (SCD); however, the apparent propensity of some patients to regularly develop RBC alloantibodies after transfusion presents a significant challenge to finding compatible blood for so-called alloimmunization responders. Predisposing genetic loci have long been thought to contribute to the responder phenomenon, but to date, no definitive loci have been identified. We undertook a genome-wide association study of alloimmunization responder status in 267 SCD multiple transfusion recipients, using genetic estimates of ancestral admixture to bolster our findings. Analyses revealed single nucleotide polymorphisms (SNPs) on chromosomes 2 and 5 approaching genome-wide significance (minimum P = 2.0 × 10-8 and 8.4 × 10-8, respectively), with local ancestry analysis demonstrating similar levels of admixture in responders and nonresponders at implicated loci. Association at chromosome 5 was nominally replicated in an independent cohort of 130 SCD transfusion recipients, with meta-analysis surpassing genome-wide significance (rs75853687, P meta = 6.6 × 10-9), and this extended to individuals forming multiple (>3) alloantibodies (P meta = 9.4 × 10-5). The associated variant is rare outside of African populations, and orthogonal genome-wide haplotype analyses, contingent on local ancestry, revealed genome-wide significant sharing of a ∼60-kb haplotype of African ancestry at the chromosome 5 locus (Bayes Factor = 4.95). This locus overlaps a putative cis-acting enhancer predicted to regulate transcription of ADRA1B and the lncRNA LINC01847, both members of larger ontologies associated with immune regulation. Our findings provide potential insights to the pathophysiology underlying the development of alloantibodies and implicate non-RBC ancestry-limited loci in the susceptibility to alloimmunization.

A local region of interest image reconstruction via filtered backprojection for fan-beam differential phase-contrast computed tomography.

Recently, x-ray differential phase contrast computed tomography (DPC-CT) has been experimentally implemented using a conventional source combined with several gratings. Images were reconstructed using a parallel-beam reconstruction formula. However, parallel-beam reconstruction formulae are not directly applicable for a large image object where the parallel-beam approximation fails. In this note, we present a new image reconstruction formula for fan-beam DPC-CT. There are two major features in this algorithm: (1) it enables the reconstruction of a local region of interest (ROI) using data acquired from an angular interval shorter than 180 degrees + fan angle and (2) it still preserves the filtered backprojection structure. Numerical simulations have been conducted to validate the image reconstruction algorithm.

Nitrogen loss and oxygen paradox in full-scale biofiltration for drinking water treatment.

The nitrogen loss and DO paradox in full-scale biofiltration for drinking water treatment and the possible pathway responsible for them were investigated. A highly contaminated source water was treated at Pinghu Surface Water Plant using four biofilters, which resulted in a steady removal of NH(4)(+)-N (2.67mg/L), a great DO consumption (8.86 mg/L) and an increase in the concentration of NO(3)(-)-N (1.77mg/L). The nitrogen and DO balances indicated that about 13 NH(4)(+)-N was lost and the actual DO consumption was about 30% lower than the theoretical DO demand if nitrification was regarded as the only pathway to remove NH(4)(+)-N. The analysis of correlation coefficients analysis between several factors and the nitrogen loss suggested that "Aerobic deammonification", the coupling of shortcut nitrification and the anaerobic ammonia oxidation (Anammox) in an aerobic environment, might be the most probable pathways to explain the occurrence of these phenomena. According to this mechanism, about 57% NH(4)(+)-N was removed through complete nitrification and about 21.5% NH(4)(+)-N was incompletely nitrified into NO(2)(-)-N. The latter then involved in Anammox as the electron acceptor with the remaining NH(4)(+)-N as the electron donor. Since the Anammox reaction is anaerobic, the nitrogen loss and DO paradox can be justified.