Metapaths: similarity search in heterogeneous knowledge graphs via meta-paths.

SUMMARY: Heterogeneous knowledge graphs (KGs) have enabled the modeling of complex systems, from genetic interaction graphs and protein-protein interaction networks to networks representing drugs, diseases, proteins, and side effects. Analytical methods for KGs rely on quantifying similarities between entities, such as nodes, in the graph. However, such methods must consider the diversity of node and edge types contained within the KG via, for example, defined sequences of entity types known as meta-paths. We present metapaths, the first R software package to implement meta-paths and perform meta-path-based similarity search in heterogeneous KGs. The metapaths package offers various built-in similarity metrics for node pair comparison by querying KGs represented as either edge or adjacency lists, as well as auxiliary aggregation methods to measure set-level relationships. Indeed, evaluation of these methods on an open-source biomedical KG recovered meaningful drug and disease-associated relationships, including those in Alzheimer's disease. The metapaths framework facilitates the scalable and flexible modeling of network similarities in KGs with applications across KG learning. AVAILABILITY AND IMPLEMENTATION: The metapaths R package is available via GitHub at https://github.com/ayushnoori/metapaths and is released under MPL 2.0 (Zenodo DOI: 10.5281/zenodo.7047209). Package documentation and usage examples are available at https://www.ayushnoori.com/metapaths.

Syndecan-2 enriches for hematopoietic stem cells and regulates stem cell repopulating capacity.

The discovery of novel hematopoietic stem cell (HSC) surface markers can enhance understanding of HSC identity and function. We have discovered a population of primitive bone marrow (BM) HSCs distinguished by their expression of the heparan sulfate proteoglycan Syndecan-2, which serves as both a marker and a regulator of HSC function. Syndecan-2 expression was increased 10-fold in CD150+CD48-CD34-c-Kit+Sca-1+Lineage- cells (long-term HSCs [LT-HSCs]) compared with differentiated hematopoietic cells. Isolation of BM cells based solely on syndecan-2 surface expression produced a 24-fold enrichment for LT-HSCs and sixfold enrichment for α-catulin+c-kit+ HSCs, and yielded HSCs with superior in vivo repopulating capacity compared with CD150+ cells. Competitive repopulation assays revealed the HSC frequency to be 17-fold higher in syndecan-2+CD34-KSL cells compared with syndecan-2-CD34-KSL cells and indistinguishable from CD150+CD34-KSL cells. Syndecan-2 expression also identified nearly all repopulating HSCs within the CD150+CD34-KSL population. Mechanistically, syndecan-2 regulates HSC repopulating capacity through control of expression of Cdkn1c (p57) and HSC quiescence. Loss of syndecan-2 expression caused increased HSC cell cycle entry, downregulation of Cdkn1c, and loss of HSC long-term repopulating capacity. Syndecan-2 is a novel marker of HSCs that regulates HSC repopulating capacity via control of HSC quiescence.

Postoperative anemia in cardiac surgery patients: a narrative review.

PURPOSE: Anemia reduces the blood's ability to carry and deliver oxygen. Following cardiac surgery, anemia is very common and affects up to 90% of patients. Nevertheless, there is a paucity of data examining the prognostic value of postoperative anemia. In this narrative review, we present findings from the relevant literature on postoperative anemia in cardiac surgery patients, focusing on the incidence, risk factors, and prognostic value of postoperative anemia. We also explore the potential utility of postoperative anemia as a therapeutic target to improve clinical outcomes. SOURCE: We conducted a targeted search of MEDLINE, Embase, and the Cochrane Database of Systematic Reviews up to September 2022, using a combination of search terms including postoperative (post-operative), perioperative (peri-operative), anemia (anaemia), and cardiac surgery. PRINCIPAL FINDINGS: The reported incidence of postoperative anemia varied from 29% to 94% across the studies, likely because of variations in patient inclusion criteria and classification of postoperative anemia. Nonetheless, the weight of the evidence suggests that postoperative anemia is common and is an independent risk factor for adverse postoperative outcomes such as acute kidney injury, stroke, mortality, and functional outcomes. CONCLUSIONS: In cardiac surgery patients, postoperative anemia is a common and prognostically important risk factor for postoperative morbidity and mortality. Nevertheless, there is a lack of data on whether active management of postoperative anemia is feasible or effective in improving patient outcomes.

RéSUMé: OBJECTIF: L'anémie réduit la capacité du sang à transporter et à fournir de l'oxygène. Suite à une chirurgie cardiaque, l'anémie est très fréquente et touche jusqu'à 90 % des patient·es. Néanmoins, il existe peu de données examinant la valeur pronostique de l'anémie postopératoire. Dans ce compte rendu narratif, nous présentons les résultats de la littérature pertinente sur l'anémie postopératoire chez les patient·es ayant bénéficié d'une chirurgie cardiaque, en mettant l'accent sur l'incidence, les facteurs de risque et la valeur pronostique de l'anémie postopératoire chez les personnes ayant bénéficié d'une chirurgie cardiaque. Nous explorons également l'utilité potentielle de l'anémie postopératoire en tant que cible thérapeutique pour améliorer les devenirs cliniques. SOURCES: Nous avons réalisé une recherche ciblée dans MEDLINE, Embase et la base de données des revues systématiques Cochrane jusqu'en septembre 2022, en utilisant une combinaison de termes de recherche, notamment postopératoire (postoperative/post-operative), périopératoire (perioperative/peri-operative), anémie (anemia/anaemia) et chirurgie cardiaque (cardiac surgery). CONSTATATIONS PRINCIPALES: L'incidence rapportée de l'anémie postopératoire variait de 29 % à 94 % d'une étude à l'autre, probablement en raison des variations dans les critères d'inclusion des patient·es et la classification de l'anémie postopératoire. Néanmoins, le poids de la preuve suggère que l'anémie postopératoire est courante et constitue un facteur de risque indépendant pour les devenirs postopératoires indésirables tels que l'insuffisance rénale aiguë, les accidents vasculaires cérébraux, la mortalité et les devenirs fonctionnels. CONCLUSION: Chez la patientèle en chirurgie cardiaque, l'anémie postopératoire est un facteur de risque commun et pronostiquement important de morbidité et de mortalité postopératoires. Néanmoins, il y a un manque de données sur la faisabilité ou l'efficacité de la prise en charge active de l'anémie postopératoire pour améliorer les devenirs des patient·es.

Holmium laser enucleation of the prostate for a case of transition zone prostate cancer.

Standard treatment approaches for localized prostate cancer remain limited to active surveillance, radiotherapy, and radical prostatectomy. We present a case of transition zone prostate cancer that was treated with holmium laser enucleation of the prostate, a procedure that is normally reserved for the management of benign prostatic hyperplasia.

Exploring and engineering PAM-diverse Streptococci Cas9 for PAM-directed bifunctional and titratable gene control in bacteria.

The RNA-guided Cas9s serve as powerful tools for programmable gene editing and regulation; their targeting scopes and efficacies, however, are always constrained by the PAM sequence stringency. Most Streptococci Cas9s, including the prototype SpCas9 from S. pyogenes, specifically recognize a canonical NGG PAM via a conserved RxR PAM-binding motif within the PAM-interaction (PI) domain. Here, SpCas9-based mining unveils three distinct and rarely presented PAM-binding motifs (QxxxR, QxQ and RxQ) among Streptococci Cas9 orthologs. With the catalytically-dead QxxxR-containing SedCas9 from S. equinus, we dissect its NAG PAM specificity and elucidate its underlying recognition mechanism via computational prediction and mutagenesis analysis. Replacing the SedCas9 PI domain with alternate PAM-binding motifs rewires its PAM specificity to NGG or NAA. Moreover, a semi-rational design with minimal mutation creates a SedCas9-NQ variant showing robust activity towards expanded NNG and NAA PAMs, based upon which we engineered a compact ω-SedCas9-NQ transcriptional regulator for PAM-directed bifunctional and titratable gene control. The ω-SedCas9-NQ mediated metabolic reprogramming of endogenous genes in Escherichia coli affords a 2.6-fold increase of 4-hydroxycoumarin production. This work reveals new Cas9 scaffolds with distinct PAM-binding motifs for PAM relaxation and creates a new PAM-diverse Cas9 variant for versatile gene control in bacteria.

Multiple courses of intralesional collagenase injections for Peyronie disease: a retrospective analysis.

BACKGROUND: In the original clinical trials evaluating intralesional collagenase Clostridium histolyticum for Peyronie disease (PD), treatment protocols were limited to 8 injections. AIM: We sought to describe our single-center experience with the use of multiple rounds (>8 injections) of intralesional collagenase in patients with PD. METHODS: We conducted a retrospective analysis of all patients with PD receiving intralesional collagenase injections at our institution from October 2015 through December 2020. Some patients who completed 1 round of treatment elected to undergo additional rounds (16 or 24 injections) based on persistent curvature and presence of penile plaque. Clinical improvement was defined as a 20% reduction in penile curvature from the start of a given round of treatment to the end of that round of treatment. We measured erect penile curvature before and after each round and collected demographics, medical and surgical history, curvature outcomes, and treatment-related adverse events. OUTCOME: The primary outcome was the reduction in penile curvature after multiple rounds of treatment with intralesional collagenase injections in patients with PD. RESULTS: A total of 330 patients underwent intralesional collagenase injections for PD, of whom 229 completed at least 8 injections and underwent pre- and posttreatment erect penile goniometry. An overall 42.8% (98/229), 38.6% (22/57), and 12.5% (1/8) of patients achieved clinical improvement after 1 round of therapy (8 injections), 2 rounds (16 injections), and 3 rounds (24 injections), respectively. Mean degree and mean percentage improvement of penile curvature for the start and end of each round of treatment were 8.3° and 16.4% (after 1 round), 7.2° and 16.8% (after 2 rounds), and 3.3° and 8.1% (after 3 rounds). Bruising was the most common complication, with an incidence of at least 50% in each round. CLINICAL IMPLICATIONS: Knowledge of patient responses to multiple rounds of intralesional collagenase injections may help guide physicians in management and counseling of patients regarding PD treatment options. STRENGTHS AND LIMITATIONS: This is the first study to evaluate multiple rounds (>8 injections) of intralesional collagenase for PD. Limitations include retrospective analysis and smaller sample size among patients undergoing 3 rounds (24 injections). CONCLUSION: For patients who did not achieve clinical improvement after 1 round of treatment, an additional round may be beneficial. However, no real improvement was observed for patients undergoing a third round.

Examining a Hypothesized Causal Chain for the Effects of the 2007 Repeal of the Permit-to-Purchase Licensing Law in Missouri: Homicide Guns Recovered in State and within a Year of Purchase.

Firearm-related deaths are a leading cause of death in the USA. Webster et al. (2014) found an association between Missouri's repeal of a permit-to-purchase handgun licensing law and an increase in firearm-related homicides. The evidence for causality of this association would be strengthened by finding that the increase occurred through the hypothesized mechanism of increasing the ease with which those with violent intent could obtain guns. This study examines two measures: (1) proportion of guns recovered and purchased in-state and (2) time between firearm purchase and recovery by police following criminal use. The repeal was associated from 2008 to 2019 with a 0.05 increase in the proportion own-state gun trace (p < 0.0001, 95% confidence interval: 0.08,0.13) and a 0.10 increase in the proportion of guns recovered prior to 1 year after purchase (p = 0.01, 95% confidence interval: 1.20, 1.90). Our study provides supportive evidence for the repeal increasing firearm-related homicides.

Mutant combinations of lycopene ɛ-cyclase and ß-carotene hydroxylase 2 homoeologs increased ß-carotene accumulation in endosperm of tetraploid wheat (Triticum turgidum L.) grains.

Grains of tetraploid wheat (Triticum turgidum L.) mainly accumulate the non-provitamin A carotenoid lutein-with low natural variation in provitamin A ß-carotene in wheat accessions necessitating alternative strategies for provitamin A biofortification. Lycopene ɛ-cyclase (LCYe) and ß-carotene hydroxylase (HYD) function in diverting carbons from ß-carotene to lutein biosynthesis and catalyzing the turnover of ß-carotene to xanthophylls, respectively. However, the contribution of LCYe and HYD gene homoeologs to carotenoid metabolism and how they can be manipulated to increase ß-carotene in tetraploid wheat endosperm (flour) is currently unclear. We isolated loss-of-function Targeting Induced Local Lesions in Genomes (TILLING) mutants of LCYe and HYD2 homoeologs and generated higher order mutant combinations of lcye-A, lcye-B, hyd-A2, and hyd-B2. Hyd-A2 hyd-B2, lcye-A hyd-A2 hyd-B2, lcye-B hyd-A2 hyd-B2, and lcye-A lcye-B hyd-A2 hyd-B2 achieved significantly increased ß-carotene in endosperm, with lcye-A hyd-A2 hyd-B2 exhibiting comparable photosynthetic performance and light response to control plants. Comparative analysis of carotenoid profiles suggests that eliminating HYD2 homoeologs is sufficient to prevent ß-carotene conversion to xanthophylls in the endosperm without compromising xanthophyll production in leaves, and that ß-carotene and its derived xanthophylls are likely subject to differential catalysis mechanisms in vegetative tissues and grains. Carotenoid and gene expression analyses also suggest that the very low LCYe-B expression in endosperm is adequate for lutein production in the absence of LCYe-A. These results demonstrate the success of provitamin A biofortification using TILLING mutants while also providing a roadmap for guiding a gene editing-based approach in hexaploid wheat.

Acute Lower Back Pain after Intralesional Injection of Collagenase Clostridium histolyticum for Peyronie's Disease.

PURPOSE: The safety label for collagenase Clostridium histolyticum was updated to include postinjection acute lower back pain as an adverse event observed with intralesional therapy for Peyronie's disease. Incidence and causality are unknown. We assessed frequencies and temporal associations for this adverse event in a large cohort. MATERIALS AND METHODS: Data on all men undergoing collagenase injections for Peyronie's disease at our institution from October 2015 through December 2020 were retrospectively assessed. The study included 330 patients, 300 completing at least 1 full course (8 injections). Measured outcomes included incidence and timing of back pain, and associations with demographics and comorbidities. RESULTS: Of 330 patients, 19 (5.8%) experienced at least 1 episode of postinjection acute lower back pain. Of 300 who completed at least 1 full course of 8 injections, 4 (1.3%) reported back pain within the 8-injection course. A subset underwent additional rounds (16 or 24 injections). Back pain increased to 8.7% (13/149) during a second round, 6.9% (3/43) during a third. No association was found with age, diabetes or back pain history. Most cases occurred shortly after injection; all were self-limited or resolved with a single dose of ketorolac. CONCLUSIONS: This single-center, retrospective analysis suggests that intralesional collagenase injections for Peyronie's disease may cause acute lower back pain in up to 6% of patients. Patients may benefit from counseling regarding this risk. Incidence rises with additional rounds of treatment. Prospective safety data regarding >8 injections do not exist. No patient had long-term sequelae of back pain.

The relative contributions of adiposity and activity levels to physical performance in children with excess weight.

OBJECTIVE: This study examined predictors of physical performance, a key aspect of quality of life, in children with excess weight. METHODS: Participants were 269 children aged 6-12 years with a body mass index above the 85th percentile. Children completed a standardized physical performance task capturing lower extremity strength, balance, and gait speed. Height, weight, and waist circumference were objectively measured, and daily moderate-vigorous physical activity (min/day) and sedentary time (% of day) were assessed with a 7-day accelerometer protocol. RESULTS: Physical performance task completion averaged 15.0 (SD = 2.5) seconds. Children with higher body mass index z-scores and waist circumferences had significantly longer task completion times. The task took 1.8 additional seconds per 1.0 body mass index z-score (p < .001), and 1.2 additional seconds for every 20 cm higher waist circumference (p < .001). Daily moderate-vigorous physical activity and sedentary time were unrelated to physical performance, and did not moderate its associations with the adiposity measures. CONCLUSION: Among children with excess weight, physical performance declines with increasing levels of total and central adiposity. Daily activity levels do not moderate this association. Interventions that directly target weight reduction would likely yield the greatest improvement in physical performance in children with overweight or obesity.

A sciatic nerve gap-injury model in the rabbit.

There has been an increased number of studies of nerve transection injuries with the sciatic nerve gap-injury model in the rabbit in the past 2 years. We wanted to define in greater detail what is needed to test artificial nerve guides in a sciatic nerve gap-injury model in the rabbit. We hope that this will help investigators to fully exploit the robust translational potential of the rabbit sciatic nerve gap-injury model in its capacity to test devices whose diameter and length are in the range of those commonly applied in hand and wrist surgery (diameter ranging between 2 and 4 mm; length up to 30 mm). We suggest that the rabbit model should replace the less translational rat model in nerve regeneration research. The rabbit sciatic model, however, requires an effective strategy to prevent and control self-mutilation of the foot in the postoperative period, and to prevent pressure ulcers.

Application of deep learning image reconstruction algorithm to improve image quality in CT angiography of children with Takayasu arteritis.

BACKGROUND: The inflammatory indexes of children with Takayasu arteritis (TAK) usually tend to be normal immediately after treatment, therefore, CT angiography (CTA) has become an important method to evaluate the status of TAK and sometime is even more sensitive than laboratory test results. OBJECTIVE: To evaluate image quality improvement in CTA of children diagnosed with TAK using a deep learning image reconstruction (DLIR) in comparison to other image reconstruction algorithms. METHODS: hirty-two TAK patients (9.14±4.51 years old) underwent neck, chest and abdominal CTA using 100 kVp were enrolled. Images were reconstructed at 0.625 mm slice thickness using Filtered Back-Projection (FBP), 50%adaptive statistical iterative reconstruction-V (ASIR-V), 100%ASIR-V and DLIR with high setting (DLIR-H). CT number and standard deviation (SD) of the descending aorta and back muscle were measured and contrast-to-noise ratio (CNR) for aorta was calculated. The vessel visualization, overall image noise and diagnostic confidence were evaluated using a 5-point scale (5, excellent; 3, acceptable) by 2 observers. RESULTS: There was no significant difference in CT number across images reconstructed using different algorithms. Image noise values (in HU) were 31.36±6.01, 24.96±4.69, 18.46±3.91 and 15.58±3.65, and CNR values for aorta were 11.93±2.12, 15.66±2.37, 22.54±3.34 and 24.02±4.55 using FBP, 50%ASIR-V, 100%ASIR-V and DLIR-H, respectively. The 100%ASIR-V and DLIR-H images had similar noise and CNR (all P > 0.05), and both had lower noise and higher CNR than FBP and 50%ASIR-V images (all P < 0.05). The subjective evaluation suggested that all images were diagnostic for large arteries, however, only 50%ASIR-V and DLIR-H met the diagnostic requirement for small arteries (3.03±0.18 and 3.53±0.51). CONCLUSION: DLIR-H improves CTA image quality and diagnostic confidence for TAK patients compared with 50%ASIR-V, and best balances image noise and spatial resolution compared with 100%ASIR-V.

Evaluating the biocontrol potential of Canadian strain Bacillus velezensis 1B-23 via its surfactin production at various pHs and temperatures.

BACKGROUND: Microorganisms, including Bacillus species are used to help control plant pathogens, thereby reducing reliance on synthetic pesticides in agriculture. Bacillus velezensis strain 1B-23 has been shown to reduce symptoms of bacterial disease caused by Clavibacter michiganensis subsp. michiganensis in greenhouse-grown tomatoes, with in vitro studies implicating the lipopeptide surfactin as a key antimicrobial. While surfactin is known to be effective against many bacterial pathogens, it is inhibitory to a smaller proportion of fungi which nonetheless cause the majority of crop diseases. In addition, knowledge of optimal conditions for surfactin production in B. velezensis is lacking. RESULTS: Here, B. velezensis 1B-23 was shown to inhibit in vitro growth of 10 fungal strains including Candida albicans, Cochliobolus carbonum, Cryptococcus neoformans, Cylindrocarpon destructans Fusarium oxysporum, Fusarium solani, Monilinia fructicola, and Rhizoctonia solani, as well as two strains of C. michiganensis michiganensis. Three of the fungal strains (C. carbonum, C. neoformans, and M. fructicola) and the bacterial strains were also inhibited by purified surfactin (surfactin C, or [Leu7] surfactin C15) from B. velezensis 1B-23. Optimal surfactin production occurred in vitro at a relatively low temperature (16 °C) and a slightly acidic pH of 6.0. In addition to surfactin, B. velenzensis also produced macrolactins, cyclic dipeptides and minor amounts of iturins which could be responsible for the bioactivity against fungal strains which were not inhibited by purified surfactin C. CONCLUSIONS: Our study indicates that B. velezensis 1B-23 has potential as a biocontrol agent against both bacterial and fungal pathogens, and may be particularly useful in slightly acidic soils of cooler climates.

Application of a deep learning image reconstruction (DLIR) algorithm in head CT imaging for children to improve image quality and lesion detection.

BACKGROUND: To evaluate the performance of a Deep Learning Image Reconstruction (DLIR) algorithm in pediatric head CT for improving image quality and lesion detection with 0.625 mm thin-slice images. METHODS: Low-dose axial head CT scans of 50 children with 120 kV, 0.8 s rotation and age-dependent 150-220 mA tube current were selected. Images were reconstructed at 5 mm and 0.625 mm slice thickness using Filtered back projection (FBP), Adaptive statistical iterative reconstruction-v at 50% strength (50%ASIR-V) (as reference standard), 100%ASIR-V and DLIR-high (DL-H). The CT attenuation and standard deviation values of the gray and white matters in the basal ganglia were measured. The clarity of sulci/cisterns, boundary between white and gray matters, and overall image quality was subjectively evaluated. The number of lesions in each reconstruction group was counted. RESULTS: The 5 mm FBP, 50%ASIR-V, 100%ASIR-V and DL-H images had a subjective score of 2.25 ± 0.44, 3.05 ± 0.23, 2.87 ± 0.39 and 3.64 ± 0.49 in a 5-point scale, respectively with DL-H having the lowest image noise of white matter at 2.00 ± 0.34 HU; For the 0.625 mm images, only DL-H images met the diagnostic requirement. The 0.625 mm DL-H images had similar image noise (3.11 ± 0.58 HU) of the white matter and overall image quality score (3.04 ± 0.33) as the 5 mm 50% ASIR-V images (3.16 ± 0.60 HU and 3.05 ± 0.23). Sixty-five lesions were recognized in 5 mm 50%ASIR-V images and 69 were detected in 0.625 mm DL-H images. CONCLUSION: DL-H improves the head CT image quality for children compared with ASIR-V images. The 0.625 mm DL-H images improve lesion detection and produce similar image noise as the 5 mm 50%ASIR-V images, indicating a potential 85% dose reduction if current image quality and slice thickness are desired.

Performance evaluation of a deep learning image reconstruction (DLIR) algorithm in "double low" chest CTA in children: a feasibility study.

BACKGROUND: Chest CT angiography (CTA) is a convenient clinical examination for children with an increasing need to reduce both radiation and contrast medium doses. Iterative Reconstruction algorithms are often used to reduce image noise but encounter limitations under low radiation dose and conventional 100 kVp tube voltage may not provide adequate enhancement under low contrast dose. PURPOSE: To evaluate the performance of a deep learning image reconstruction (DLIR) algorithm in conjunction with lower tube voltage in chest CTA in children under reduced radiation and contrast medium (CM) dose. MATERIALS AND METHODS: 46 Children (age 5.9 ± 4.2 years) in the study group underwent chest CTA with 70 kVp and CM dose of 0.8-1.2 ml/kg. Images were reconstructed at 0.625 mm using a high setting DLIR (DLIR-H). The control group consisted of 46 age-matching children scanned with 100 kVp, CM dose of 1.3-1.8 ml/kg and images reconstructed with 50% and 100% adaptive statistical iterative reconstruction-V. Two radiologists evaluated images subjectively for overall image noise, vessel contrast and vessel margin clarity separately on a 5-point scale (5, excellent and 1, not acceptable). CT value and image noise of aorta and erector spinae muscle were measured. RESULTS: Compared to the control group, the study group reduced the dose-length-product by 11.2% (p = 0.01) and CM dose by 24% (p < 0.001), improved the enhancement in aorta (416.5 ± 113.1HU vs. 342.0 ± 57.6HU, p < 0.001) and reduced noise (15.1 ± 3.5HU vs. 18.6 ± 4.4HU, p < 0.001). The DLIR-H images provided acceptable scores on all 3 aspects of the qualitative evaluation. CONCLUSION: "Double low" chest CTA in children using 70 kVp and DLIR provides high image quality with reduced noise and improved vessel enhancement for diagnosis while further reduces radiation and CM dose.

Application of 70 kVp in abdominal CT angiography to reduce both radiation and contrast dosage and improve patient comfort for children.

BACKGROUND: Low-tube voltage scanning improves CT attenuation value of contrast medium (CM). Thus, we hypothesized that 70 kVp in pediatric abdominal CT angiography (CTA) could be used to reduce both radiation and CM dose and improve patient comfort at the same time. OBJECTIVE: To evaluate the feasibility of using 70 kVp in pediatric abdominal CTA to reduce radiation dose and CM dose and improve patient care for children. MATERIALS AND METHODS: Forty-six children needing abdominal CTA were enrolled in the study group using low-dose scanning protocol with 70 kVp and 0.7-1.1 ml/kg contrast dose, and reconstructed with 50%ASIR-V. They were compared with other 46 children in control group with matching body weight and underwent conventional CT scans with 100 kVp, 1.2-1.8 ml/kg contrast dose and reconstructed using 50%ASIR. Image quality of large vessels was evaluated using a 5-point scale. CT value and standard deviation of descending aorta (Ao) was measured, and signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Radiation dose, contrast dose, the maximum injection pressure between the two groups were also compared. RESULTS: Score for displaying large vessels by 70 kVp images was 3.91±0.28, lower than that (4.17±0.38) of the control group (p < 0.05), but fully met the diagnostic requirements. CT value of Ao was 390.87±86.79HU in study group, which is higher than 343.93±49.94HU in control group, while there was no difference in SNR and CNR between two groups; the radiation dose, contrast dosage and injection pressure of the study group were 1.23±0.39mGy, 12.67±7.27 ml and 43.83±17.16psi, respectively, which are significantly lower than the 1.95±0.37mGy, 22.67±7.39 ml, and 77.59±19.68psi of control group. CONCLUSION: Use of 70 kVp in pediatric abdominal CTA provides diagnostic quality images while significantly reduce radiation and contrast dose, as well as injection pressure to improve patient comfort for children.

Characterization and genomic analysis of a diesel-degrading bacterium, Acinetobacter calcoaceticus CA16, isolated from Canadian soil.

BACKGROUND: With the high demand for diesel across the world, environmental decontamination from its improper usage, storage and accidental spills becomes necessary. One highly environmentally friendly and cost-effective decontamination method is to utilize diesel-degrading microbes as a means for bioremediation. Here, we present a newly isolated and identified strain of Acinetobacter calcoaceticus ('CA16') as a candidate for the bioremediation of diesel-contaminated areas. RESULTS: Acinetobacter calcoaceticus CA16 was able to survive and grow in minimal medium with diesel as the only source of carbon. We determined through metabolomics that A. calcoaceticus CA16 appears to be efficient at diesel degradation. Specifically, CA16 is able to degrade 82 to 92% of aliphatic alkane hydrocarbons (CnHn + 2; where n = 12-18) in 28 days. Several diesel-degrading genes (such as alkM and xcpR) that are present in other microbes were also found to be activated in CA16. CONCLUSIONS: The results presented here suggest that Acinetobacter strain CA16 has good potential in the bioremediation of diesel-polluted environments.

RNA markers for ultra-rapid molecular antimicrobial susceptibility testing in fluoroquinolone-treated Klebsiella pneumoniae.

OBJECTIVES: Traditional antimicrobial susceptibility testing (AST) is growth dependent and time-consuming. With rising rates of drug-resistant infections, a novel diagnostic method is critically needed that can rapidly reveal a pathogen's antimicrobial susceptibility to guide appropriate treatment. Recently, RNA sequencing has been identified as a powerful diagnostic tool to explore transcriptional gene expression and improve AST. METHODS: RNA sequencing was used to investigate the potential of RNA markers for rapid molecular AST using Klebsiella pneumoniae and ciprofloxacin as a model. Downstream bioinformatic analysis was applied for optimal marker selection. Further validation on 11 more isolates of K. pneumoniae was performed using quantitative real-time PCR. RESULTS: From RNA sequencing, we identified RNA signatures that were induced or suppressed following exposure to ciprofloxacin. Significant shifts at the transcript level were observed as early as 10 min after antibiotic exposure. Lastly, we confirmed marker expression profiles with concordant MIC results from traditional culture-based AST and validated across 11 K. pneumoniae isolates. recA, coaA and metN transcripts harbour the most sensitive susceptibility information and were selected as our top markers. CONCLUSIONS: Our results suggest that RNA signature is a promising approach to AST development, resulting in faster clinical diagnosis and treatment of infectious disease. This approach is potentially applicable in other models including other pathogens exposed to different classes of antibiotics.

Reducing both radiation and contrast doses in coronary CT angiography in lean patients on a 16-cm wide-detector CT using 70 kVp and ASiR-V algorithm, in comparison with the conventional 100-kVp protocol.

OBJECTIVE: To investigate the value of prospectively ECG-triggered coronary CT angiography (CCTA) for lean patients with body mass index (BMI) ≤ 23 kg/m2 using 70 kVp and high-level volume-based adaptive statistical iterative reconstruction (ASiR-V) algorithm on a 16-cm wide-detector CT system for reducing both radiation and contrast doses in comparison with the conventional 100-kVp protocol. MATERIALS AND METHODS: Thirty patients (group A) were prospectively enrolled to undergo 70-kVp CCTA on a 16-cm wide-detector CT scanner with noise index (NI) of 36 HU and at weight-dependent contrast dose rate of 16 mg I/kg/s for 9-s injection. Images were reconstructed with 80% ASiR-V. Radiation dose, contrast dose, and image quality were statistically compared with 30 patients (group B) in database with matching BMI who underwent conventional 100-kVp CCTA with NI of 25 HU, and at 25 mg I/kg/s rate for 10-s injection and reconstructed with 60% ASiR-V. RESULTS: There was no significant difference in patient demographics between the two groups (all p > 0.05). The two groups also had similar mean CT values and contrast-noise ratio (CNR) and subjective image quality (all p > 0.05). However, group A with 70 kVp reduced the effective dose by 75.3% compared with group B (0.43 ± 0.20 mSv vs. 1.74 ± 1.01 mSv, p < 0.001), and required 42.4% less contrast dose than group B (22.46 ± 2.94 ml vs. 38.99 ± 5.10 ml, p < 0.001). CONCLUSIONS: Prospectively ECG-triggered CCTA using 70 kVp and high-level ASiR-V on a 16-cm wide-detector CT system provides diagnostic images with substantial reduction in both radiation and contrast doses for patients with BMI ≤ 23 kg/m2 compared to the conventional 100-kVp protocol. KEY POINTS: • 70-kVp CCTA produces excellent images at sub-millisievert radiation. • 70-kVp CCTA reduces both radiation and contrast doses over conventional protocol. • Achieving low-dose CCTA with combined low kVp and high-level ASIR-V.

Human CLEC16A regulates autophagy through modulating mTOR activity.

CLEC16A is genetically linked with multiple autoimmune disorders but its functional relevance in autoimmunity remains obscure. Recent evidence has signposted the emerging role of autophagy in autoimmune disease development. Here, by ectopic expression and siRNA silencing, we show that CLEC16A has an inhibitory role in starvation-induced autophagy in human cells. Combining quantitative proteomics and immunoblotting analyses, we found that CLEC16A likely regulates autophagy by activating mTOR pathway. Overexpression of CLEC16A was found to sensitize cells towards the availability of nutrients, resulting in a heightened mTOR activity, which in turn diminished LC3 autophagic activity following nutrient deprivation. CLEC16A deficiency, on the other hand, delayed mTOR activity in response to nutrient sensing, thereby resulted in an augmented autophagic response. CLEC16A was found residing in cytosolic vesicles and the Golgi, and nutrient removal promoted a stronger clustering within the Golgi, where it was possibly in a vantage position to activate mTOR upon nutrient replenishment. These findings suggest that Golgi-associated CLEC16A negatively regulates autophagy via modulation of mTOR activity, and may provide support for a functional link between CLEC16A and autoimmunity.