Improving image quality consistency and diagnostic accuracy in lower extremity CT angiography using a split-bolus contrast injection protocol.

OBJECTIVES: To evaluate the clinical value of using a split-bolus contrast injection protocol in improving image quality consistency and diagnostic accuracy in lower extremity CT angiography (CTA). METHODS: Fifty (mean age, 66 ± 12 years) and 39 (mean age, 66 ± 11 years) patients underwent CTA in the lower extremity arteries using split-bolus and fixed-bolus injection schemes, respectively. The objective and subjective image quality of the 2 groups were compared and the diagnostic efficacy for the degree of vessel stenosis was compared using digital subtraction angiography as the gold standard. A P < .05 was considered statistically significant. RESULTS: In comparison with the fixed-bolus scheme, the split-bolus scheme greatly improved the consistency of image quality of the low extremities by significantly increasing the arterial enhancement (337.87 ± 64.67HU vs. 254.74 ± 71.58HU, P < .001), signal-to-noise ratio (22.58 ± 11.64 vs. 7.14 ± 1.98, P < .001), and contrast-to-noise ratio (37.21 ± 10.46 vs. 31.10 ± 15.40, P = .041) in the infrapopliteal segment. The subjective image quality was better (P < .001) and the diagnostic accuracy was higher in the split-bolus group than in the fixed-bolus group (96.00% vs. 91.67%, P < .05, for diagnosing >50% stenosis, and 97.00% vs. 89.10%, P < .05, for diagnosing occlusion) for the infrapopliteal segment arteries. CONCLUSIONS: Compared with the fixed-bolus injection scheme, the split-bolus injection scheme improves the image quality consistency and diagnostic accuracy especially for the infrapopliteal segment arteries in lower extremity CTA. ADVANCES IN KNOWLEDGE: (1) The split-bolus injection scheme of CTA of the lower extremity arteries improves the overall image quality, uniformity of contrast enhancement. (2) Compared with the fixed-bolus injection scheme, the split-bolus injection scheme especially improves the infrapopliteal segment arteries image quality and diagnostic efficacy.

Tix+ in-situ intercalation and interlayer modification via titanium foil/vanadium ion solution interface of VO2.375 as sulfur-wrapped matrix enabling long-life lithium sulfur battery.

Lithium sulfur battery (LSB) has great potential as a promising next-generation energy storage system owing to ultra-high theoretical specific capacity and energy density. However, the polysulfide shuttle effect and slow redox kinetics are recognized the most stumbling blocks on the way of commercializing LSB. On this account, for the first time, we use Tix+ in-situ intercalation strategy via titanium foil/vanadium ion (V5+) solution interface to modify the layer of vanadium oxide for long cycle LSB. The inserted Tix+ strengthens interlayer interaction and enhances lithium-ion mobility rate. Meanwhile, based on density functional theory (DFT) calculation, the mixed valence of V5+/V4+ in the vanadium oxide structure reduces the stress and strain of lithium-ion intercalation through the interlayer support of titanium ions (Tix+). Also, Tix+ refines the structural stability of the sulfur wrapped composite matrix so as to facilitate the LiPSs transformation, and improve the electrochemical performances. Consequently, the Ti-VO2.375/S cathode delivers a lower capacity decay of 0.037 % per cycle over 1500 cycles with a stable coulombic efficiency around 100 %.

Alternate-day fasting ameliorated anxiety-like behavior in high-fat diet-induced obese mice.

Alternate-day fasting (ADF) has been reported to reduce body weight, neuroinflammation, and oxidative stress damage. However, it is not known whether ADF affects obesity-induced anxiety-like behavior. Here, male C57BL/6 mice were given an alternate fasting and high-fat diet (HFD) or standard chow diet (SD) every other day for 16 or 5 weeks. After the intervention, the degree of anxiety of the mice was evaluated by the open field test (OFT) and the elevated plus maze (EPM) test. Pathological changes in the hippocampus, the expression of Sirt1 and its downstream protein monoamine oxidase A (MAO-A) in the hippocampus, and the expression of 5-hydroxytryptamine (5-HT) were detected. Compared with HFD-fed mice, HFD-fed mice subjected to ADF for 16 weeks had a lower body weight but more brown adipose tissue (BAT), less anxiety behavior, and less pathological damage in the hippocampus, and lower expression of Sirt1 and MAO-A protein and higher 5-HT levels in the hippocampus could be observed. In addition, we noted that long-term ADF intervention could cause anxiety-like behavior in SD mice. Next, we changed the intervention time to 5 weeks. The results showed that short-term ADF intervention could reduce the body weight and increase the BAT mass of SD mice, but it did not affect anxiety. These results indicated that long-term ADF ameliorated obesity-induced anxiety-like behavior and hippocampal damage, but caused anxiety in normal-weight mice. Short-term ADF did not produce adverse emotional reactions in normal-weight mice. Here, we might provide new ideas for the treatment of obesity-induced anxiety.

Characterisation of a Novel Hybrid IncFIIpHN7A8:IncR:IncN Plasmid Co-Harboring blaNDM-5 and blaKPC-2 from a Clinical ST11 Carbapenem-Resistant Klebsiella pneumoniae Strain.

Purpose: We aimed to characterize a novel blaNDM-5 and blaKPC-2 co-carrying hybrid plasmid from a clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) strain. Methods: Antimicrobial susceptibility was determined by the broth microdilution method. Plasmid size and localization were estimated using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Plasmid transfer ability was evaluated by conjugation experiments. Whole genome sequencing (WGS) was performed using Illumina NovaSeq6000 and Oxford Nanopore MinION platforms. Genomic characteristics were analyzed using bioinformatics methods. Results: Strain ZY27320 was a multidrug-resistant (MDR) clinical ST11 K. pneumoniae strain that confers high-level resistance to carbapenems (meropenem, MIC 128 mg/L; imipenem, MIC 64 mg/L) and ceftazidime/avibactam (MIC >128/4 mg/L). Both S1-PFGE-Southern blotting and whole genome sequencing revealed that the carbapenemase genes blaKPC-2 and blaNDM-5 were carried by the same IncFIIpHN7A8:IncR:IncN hybrid plasmid (pKPC2_NDM5). Conjugation experiments indicated that pKPC2_NDM5 was a non-conjugative plasmid. Conclusion: This is the first report of a hybrid plasmid carrying both carbapenemase genes blaNDM-5 and blaKPC-2 in a clinical K. pneumoniae ST11 isolate that confers resistance to both ceftazidime/avibactam and carbapenems, thereby presenting a serious threat to treatment in clinical practice.

Detection and characterization of urinary stones using material-specific images derived from contrast-enhanced dual-energy CT urography.

OBJECTIVE: To determine the accuracy of material-specific images derived from contrast-enhanced dual-energy CT urography (DECTU) in detecting and measuring urinary stones in comparison with that of unenhanced images and its utility in calcified stone differentiation. METHODS: 105 patients with 202 urinary stones (121 had confirmed composition by infrared spectroscopy) underwent triphasic (unenhanced, portal venous (VP) and excretory phase (EP)) DECTU. Material-specific images were derived in VP and EP with calcium-water, calcium-iodine and CaOxalate_Dihydrate (COD)-Hydroxyapatite (HAP) as basis material pairs. Stone number and size were recorded on unenhanced images and VP and EP material-specific images, where stone densities were also measured. Material densities of calcified stones (pure calcium oxalate [pCaO, n = 34], mixed calcium oxalate [mCaO, n = 14], mixed carbonate phosphate [mCaP, n = 70]) were compared and thresholds for differentiating these stones were determined using receiver operating characteristic analysis. RESULTS: All 202 urinary stones were detected on the unenhanced, calcium (water) and calcium (iodine) images in VP. While the detection rate was significantly decreased to 58 and 64% using calcium (water) and calcium (iodine) images in EP, respectively (all p < 0.001). Stone sizes measured on calcium (iodine) images in VP was similar to that of unenhanced images (10.6 vs 10.7 mm, p > 0.05). Significant differences in material densities were found among pCaO, mCaO and mCaP on COD(HAP) images with AUC of 0.72-0.74 for differentiating these stones. CONCLUSION: Material-specific images in VP derived from DECTU allow reliably detecting and measuring urinary tract stones in comparison with unenhanced images and can identify calcified stones with moderate diagnostic performance to provide potential 33% dose reduction. ADVANCES IN KNOWLEDGE: Material-specific images, especially the calcium (iodine) images in VP allow for reliable detection of urinary stones.Stone size measurement should be performed on the calcium (iodine) images in VP.Material density measurements on COD-HAP (VP) material decomposition images can be used to differentiate among pure calcium oxalate, mixed calcium oxalate and mixed carbonate phosphate stones with AUC of 0.72-0.74.

Contribution of microbial necromass to soil organic carbon formation during litter decomposition under incubation conditions.

We conducted a 512-day incubation experiment to study the dynamics of microbial necromass and soil carbon fraction in the 'litter-soil' transformation interface soil layer (TIS) during litter decomposition, using a perennial C3 herb, Stipa bungeana, in the loess hills. The results showed that soil microbial necromass was dominated by fungi in the early and middle stages, and by bacteria in the late stage. The contribution of fungal necromass C to mineral-associated organic C (MAOC) was significantly higher (38.7%-75.8%) than that of bacteria (9.2%-22.5%) and 2-3 times more than the contribution rate of bacterial necromass. Soil organic C (SOC) content was decreasing during litter decomposition. The input of plant C resources stimulated microbial utilization of soil C fractions. The continuous decrease in particulate organic C during the early and late stages of decomposition was directly responsible for the decrease in SOC content. In contrast, the fluctuating changes in microbial necromass C and MAOC played an indirect role in the reduction of SOC. The increase in soil microbial necromass C caused by a single exogenous addition of litter did not directly contribute to SOC accumulation.

Characterization of two novel VIM-type metallo-ß-lactamases, VIM-84 and VIM-85, associated with the spread of IncP-2 megaplasmids in Pseudomonas aeruginosa.

This study aimed to characterize two novel VIM-type metallo-ß-lactamases, VIM-84 and VIM-85, and reveal the important role of the IncP-2 type megaplasmids in the spread of antimicrobial resistance (AMR) genes. VIM-84 and VIM-85 were encoded by two novel genes bla VIM-84 and bla VIM-85 which showed similarity to bla VIM-24. Both bla VIM-84 and bla VIM-85 are harbored into class 1 integrons embedded into the Tn1403 transposon. The bla VIM-85 gene was identified in a megaplasmid, which was related to 17 megaplasmid sequences with sizes larger than 430 kb, deposited previously in Genbank. A comparative analysis of complete plasmid sequences showed highly similar backbone regions and various AMR genes. A phylogenetic tree revealed that these megaplasmids, which were widely distributed globally, were vehicles for the spread of AMR genes. The bla VIM-24, bla VIM-84, and bla VIM-85 genes were cloned into pGK1900, and the recombinant vectors were further transformed into Escherichia coli DH5α and Pseudomonas aeruginosa PAO1. The antimicrobial susceptibility test of the cloning strains showed high levels of resistance to ß-lactams while they remained susceptible to aztreonam. Enzymatic tests revealed that both, VIM-84 and VIM-85, exhibited higher activity in hydrolyzing ß-lactams compared to VIM-24. A D117N mutation found in VIM-24 affected binding to the antibiotics. IMPORTANCE The metallo-ß-lactamases-producing Pseudomonas aeruginosa strains play an important role in hospital outbreaks and the VIM-type enzyme is the most prevalent in European countries. Two novel VIM-type enzymes in our study, VIM-84 and VIM-85, have higher levels of resistance to ß-lactams and greater hydrolytic activities for most ß-lactams compared with VIM-24. Both bla VIM-84 and bla VIM-85 are harbored into class 1 integrons embedded into the Tn1403 transposon. Notably, the genes bla VIM-85 are carried by three different IncP-2-type megaplasmids which are distributed locally and appear responsible for the spread of antimicrobial resistance genes in hospital settings.

Pseudomonas aeruginosa High-Risk Sequence Type 463 Co-Producing KPC-2 and AFM-1 Carbapenemases, China, 2020-2022.

We report the clonal spread and evolution of high-risk Pseudomonas aeruginosa sequence type 463 co-producing KPC-2 and AFM-1 carbapenemases isolated from hospital patients in China during 2020-2022. Those strains pose a substantial public health threat and surveillance and stricter infection-control measures are essential to prevent further infections.

Clinical and microbiological characteristics of carbapenem-resistant Enterobacteriaceae causing post-operative central nervous system infections in China.

OBJECTIVES: Postoperative central nervous system infections (PCNSIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) frequently result in unfavourable outcomes. However, CRE PCNSIs have not been well described from a clinical and microbiological perspective. METHODS: A total of 254 PCNSIs cases were included (January 2017 through June 2020), and clinical features were compared based on pathogenic classification. Cox regression analysis was performed to assess risk factors for mortality. Antibiotic susceptibility testing and whole genome sequencing were conducted on CRE isolates preserved. MLST, cgMLST, resistance genes and virulence genes were further analysed. RESULTS: Among 254 PCNSI cases, 15.4% were caused by Enterobacteriaceae including 28 cases by CRE. The 28-day mortality rates for CRE, CSE and non-Enterobacteriaceae PCNSIs were 50.0%, 27.3%, and 7.4%, respectively. 42.9% (12/28) of the CRE PCNSIs patients achieved clinical cure, with 25.0% achieved microbiological clearance. ST11-KL64 carrying blaKPC-2 was dominant in CRE (17/23, 73.9%), and the 28-day mortality rate of its infection was 58.5%. Most CRKP carried rampA/rampA2 genes (17/23, 73.9%). CONCLUSION: ST11-KL64 CRKP carrying blaKPC-2 dominated among CRE PCNSIs. Targeted anti-infective combination therapy based on ceftazidime/avibactam or amikacin, combined with intrathecal administration of amikacin, was found to be effective. These findings render a new insight into the clinical and microbiological landscape of CRE PCNSIs.

A case report of liver abscesses caused by Fusobacterium necrophorum in immunocompetent patient and review of the literature.

Background: Fusobacterium necrophorum is an anaerobic Gram-negative bacterium that can lead to opportunistic infections, including Lemierre's syndrome and less common presentations of metastatic diseases. However, liver abscesses infected by Fusobacterium necrophorum in clinical settings are rarely reported, particularly in people with normal immune function. Case presentation: A 35-year-old Chinese man was admitted with hyperthermia and abdominal pain that had persisted for three days. The patient continued to have a fever with a maximum temperature of 39.8 °C during hospitalization. Computed Tomography revealed multiple low-density lesions in the liver, which were diagnosed as liver abscesses caused by Fusobacterium necrophorum infection through blood culture and anaerobic liver abscess fluid culture. After simple local percutaneous abscess drainage and effective anti-infective therapy, the patient achieved complete remission. Conclusions: Results of our literature search query revealed rare reports of liver abscesses infected by Fusobacterium necrophorum. We recommend that Fusobacterium necrophorum infection be considered in diagnosis special situations of liver abscess.

Risk factors and outcomes of inpatients with carbapenem-resistant Pseudomonas aeruginosa bloodstream infections in China: a 9-year trend and multicenter cohort study.

Objective: Bacteremia caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) has high mortality, threatening the healthcare quality worldwide. Analysis is required to update the epidemiological data of CRPA bloodstream infections (BSI) and evaluate the prevalent strains in China. Moreover, it is necessary to clarify the risk factors associated with the development and mortality of CRPA bacteremia. Methods: This is a 9-year multicenter retrospective study, enrolling 137 patients with CRPA BSI and 137 carbapenem-susceptible P. aeruginosa (CSPA) BSI during January 2012 and December 2020. Antimicrobials susceptibility between the two groups were compared. Risk factors of CRPA BSI were identified by binary logistic regression for development and cox regression for mortality. The Kaplan-Meier method was used to compare time to mortality. CRPA and difficult-to-treat resistant P. aeruginosa (DTRPA) detection rate was analyzed year-by-year in ZYH. Results: A total of 7,384 P. aeruginosa clinical samples were cultured in ZYH during 9 years, and notable increase of CRPA and DTRPA detection rate in P. aeruginosa BSI was identified (from 17 to 60%; from 2.1 to 25%). Multivariate analysis revealed that prior ICU hospitalization, immunosuppressive therapy and exposure to carbapenems were independent risk factors for development of CRPA BSI. The 30-day crude mortality of 137 CRPA BSI was 39%. A total of 46 DTRPA were identified, and the 30-day mortality for patients infected by DTRPA was 50%. The 30-day crude mortality of CRPA BSI was independently associated with multiple organ failure and higher Pitt bacteremia score, whereas receipt appropriate therapy improved prognosis. Conclusion: A significant increase in the detection rate of CRPA and DTRPA in P. aeruginosa BSI was identified. Strict policies for carbapenems usage, cautious decisions regarding the usage of immunosuppressive agent and standard care for patients with prior ICU hospitalization are necessary for CRPA BSI management.

Emergence of carbapenem-resistant Enterobacter hormaechei ST93 plasmids co-harbouring blaNDM-1, blaKPC-2, and mcr-9 in bloodstream infection.

OBJECTIVES: We isolated a strain of Enterobacter hormaechei, ECC2783, co-harbouring blaNDM-1, blaKPC-2 and mcr-9 plasmids from a bloodstream infection and investigated its biological features. METHODS: The presence of carbapenemase genes and mcr-9 was confirmed by polymerase chain reaction amplification. Whole genome sequencing and genomic analysis were performed on ECC2783. Experiments assessing the conjugation and stability of plasmids carrying the carbapenemase gene were performed. We also performed a colistin resistance induction experiment and studied the fitness cost of transconjugants. RESULTS: ECC2783 has an extensive drug resistance phenotype. Multilocus sequence typing analysis results showed that ECC2783 belongs to sequence type 93. Bioinformatics analysis confirmed that ECC2783 has four plasmids, of which pECC2783_a, carrying mcr-9, is the IncHI2 type, and pECC2783_c, carrying blaNDM-1, is the IncX3 type. pECC2783_d, carrying blaKPC-2, is an unclassified type. We successfully obtained two transconjugants (J53/ECC2783_1, carrying blaNDM-1, and J53/ECC2783_2, carrying blaKPC-2 and blaNDM-1). There was no statistically significant difference in the relative growth rate between J53 and J53/ECC2783_2. CONCLUSION: For the first time, we isolated carbapenem-resistant E. hormaechei plasmids co-harbouring blaNDM-1, blaKPC-2, and mcr-9 from a patient with a blood stream infection. This isolate has a survival advantage in a hospital environment, and its clinical monitoring should be strengthened.

Overexpression of blaGES-1 due to a strong promoter in the class 1 integron contributes to decreased ceftazidime-avibactam susceptibility in carbapenem-resistant Pseudomonas aeruginosa ST235.

Sequence type 235 (ST235) Pseudomonas aeruginosa, harboring so-called international, high-risk, or widespread clones, is associated with relatively high morbidity and mortality, partly due to multiantibiotic and high-level antibiotic resistance. Treatment of infections caused by such strains with ceftazidime-avibactam (CZA) is often successful. However, CZA resistance in carbapenem-resistant P. aeruginosa (CRPA) strains has been consistently reported with the increasing use of this drug. Likewise, we identified thirty-seven CZA-resistant ST235 P. aeruginosa strains from among 872 CRPA isolates. A total of 10.8% of the ST235 CRPA strains were resistant to CZA. Site-directed mutagenesis, cloning, expression, and whole-genome sequencing analysis revealed that overexpression of blaGES-1, which was carried in a class 1 integron of the complex transposon Tn6584, occurred due to a strong promoter, contributing to CZA resistance. Moreover, such overexpression of blaGES-1 combined with an efflux pump resulted in high-level resistance to CZA, considerably reducing the therapeutic options available for treating infections caused by ST235 CRPA. Considering the widespread presence of ST235 P. aeruginosa strains, clinicians should be aware of the risk of CZA resistance development in high-risk ST235 P. aeruginosa. Surveillance initiatives for preventing further dissemination of high-risk ST235 CRPA isolates with CZA resistance are essential.

PCK1 activates oncogenic autophagy via down-regulation Serine phosphorylation of UBAP2L and antagonizes colorectal cancer growth.

Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme in gluconeogenesis. PCK1 is considered an anti-oncogene in several human cancers. In this study, we aimed to determine the functions of PCK1 in colorectal cancer (CRC). PCK1 expression in CRC tissues was tested by western blot and immunohistochemistry analyses and associations of PCK1 level with clinicopathological characteristics and disease survival evaluated. Further, we studied the effect of PCK1 on CRC cell proliferation and the underlying mechanisms. Our results show that PCK1 is expressed at significantly lower levels in CRC than in control tissues. High PCK1 expression was correlated with smaller tumor diameter and less bowel wall invasion (T stage). Overexpression and knockdown experiments demonstrated that PCK1 inhibits CRC cell growth both in vitro and in vivo. Mechanistically, PCK1 antagonizes CRC growth via inactivating UBAP2L phosphorylation at serine 454 and enhancing autophagy. Overall, our findings reveal a novel molecular mechanism involving PCK1 and autophagy, and highlight PCK1 as a promising candidate therapeutic target in CRC.

Re-Exploring the Inflammation-Related Core Genes and Modules in Cerebral Ischemia.

The genetic transcription profile of brain ischemic and reperfusion injury remains elusive. To address this, we used an integrative analysis approach including differentially expressed gene (DEG) analysis, weighted-gene co-expression network analysis (WGCNA), and pathway and biological process analysis to analyze data from the microarray studies of nine mice and five rats after middle cerebral artery occlusion (MCAO) and six primary cell transcriptional datasets in the Gene Expression Omnibus (GEO). (1) We identified 58 upregulated DEGs with more than 2-fold increase, and adj. p < 0.05 in mouse datasets. Among them, Atf3, Timp1, Cd14, Lgals3, Hmox1, Ccl2, Emp1, Ch25h, Hspb1, Adamts1, Cd44, Icam1, Anxa2, Rgs1, and Vim showed significant increases in both mouse and rat datasets. (2) Ischemic treatment and reperfusion time were the main confounding factors in gene profile changes, while sampling site and ischemic time were not. (3) WGCNA identified a reperfusion-time irrelevant and inflammation-related module and a reperfusion-time relevant and thrombo-inflammation related module. Astrocytes and microglia were the main contributors of the gene changes in these two modules. (4) Forty-four module core hub genes were identified. We validated the expression of unreported stroke-associated core hubs or human stroke-associated core hubs. Zfp36 mRNA was upregulated in permanent MCAO; Rhoj, Nfkbiz, Ms4a6d, Serpina3n, Adamts-1, Lgals3, and Spp1 mRNAs were upregulated in both transient MCAO and permanent MCAO; and NFKBIZ, ZFP3636, and MAFF proteins, unreported core hubs implicated in negative regulation of inflammation, were upregulated in permanent MCAO, but not in transient MCAO. Collectively, these results expand our knowledge of the genetic profile involved in brain ischemia and reperfusion, highlighting the crucial role of inflammatory disequilibrium in brain ischemia.

Depletion of PSMD14 suppresses bladder cancer proliferation by regulating GPX4.

Objective: The aim of this study was to investigate the role of deubiquitinase (DUB) 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in patients with bladder cancer. Methods: From 2016 to 2018, 181 patients diagnosed with primary bladder cancer at the Affiliated Hospital of Qingdao University were recruited. The expression of PSMD14 in bladder cancer tissues was tested by immunochemistry. The association between PSMD14 expression and clinical and pathological data and outcomes of bladder cancer patients was determined. Overexpression and knockdown cells were constructed to evaluate the effects of PSMD14 on proliferation of bladder cancer cells. Results: Our results showed that PSMD14 was significantly overexpressed in bladder cancer tissues compared to adjacent non-tumor tissues (76.24% vs 23.76%, P = 0.02). The expression of PSMD14 was significantly higher in patients with larger tumor diameters (85.14% vs 70.09%, P = 0.019) and patients with a family history of cancer (92.16% vs 70.00%, P = 0.002). Patients with high expression of PSMD14 had poor disease-free survival (DFS) (HR = 2.89, 95% CI [1.247-6.711], P = 0.013). Gain and loss of function experiments demonstrated that PSMD14 deficiency inhibited bladder cancer cell proliferation. Additionally, depletion of PSMD14 suppressed bladder cancer cell growth via down-regulation of GPX4, and the promotion of PSMD14-induced cell growth was observably reversed by the GPX4 inhibitor RSL3. Conclusion: We determined that PSMD14 is highly expressed in bladder cancer tissues, and that PSMD14 expression correlated with poor disease-free survival. Depletion of PSMD14 could inhibit the proliferation of bladder cancer cells through the downregulation of GPX4. Therefore, PSMD14 may be an effective target for the treatment of bladder cancer.

Improving spatial resolution and diagnostic confidence with thinner slice and deep learning image reconstruction in contrast-enhanced abdominal CT.

OBJECTIVE: To evaluate image quality and diagnostic confidence improvement using a thin slice and a deep learning image reconstruction (DLIR) in contrast-enhanced abdominal CT. METHODS: Forty patients with hepatic lesions in enhanced abdominal CT were retrospectively analyzed. Images in the portal phase were reconstructed at 5 mm and 1.25 mm slice thickness using the 50% adaptive statistical iterative reconstruction (ASIR-V) (ASIR-V50%) and at 1.25 mm using DLIR at medium (DLIR-M) and high (DLIR-H) settings. CT number and standard deviation of the hepatic parenchyma, spleen, portal vein, and subcutaneous fat were measured, and contrast-to-noise ratio (CNR) was calculated. Edge-rise-slope (ERS) was measured on the portal vein to reflect spatial resolution and the CT number skewness on liver parenchyma was calculated to reflect image texture. Two radiologists blindly assessed the overall image quality including subjective noise, image contrast, visibility of small structures using a 5-point scale, and object sharpness and lesion contour using a 4-point scale. RESULTS: For the 1.25-mm images, DLIR significantly reduced image noise, improved CNR and overall subjective image quality compared to ASIR-V50%. Compared to the 5-mm ASIR-V50% images, DLIR images had significantly higher scores in the visibility and contour for small structures and lesions; as well as significantly higher ERS and lower CT number skewness. At a quarter of the signal strength, the 1.25-mm DLIR-H images had a similar subjective noise score as the 5-mm ASIR-V50% images. CONCLUSION: DLIR significantly reduces image noise and maintains a more natural image texture; image spatial resolution and diagnostic confidence can be improved using thin slice images and DLIR in abdominal CT. KEY POINTS: • DLIR further reduces image noise compared with ASIR-V while maintaining favorable image texture. • In abdominal CT, thinner slice images improve image spatial resolution and small object visualization but suffer from higher image noise. • Thinner slice images combined with DLIR in abdominal CT significantly suppress image noise for detecting low-density lesions while significantly improving image spatial resolution and overall image quality.

Seroprevalence of Toxoplasma gondii infection in women with a gynecological tumor living in eastern China.

The association between Toxoplasma gondii (T. gondii) infection and malignancy has attracted increased attention in recent years, but little is known of T. gondii infection among women diagnosed with a gynecological tumor (GT) in China. We conducted a case-control study involving 460 women diagnosed with a GT and 460 age-matched healthy controls (HCs) to estimate the infection process of T. gondii and understand the risk factors of T. gondii infection in patients with a GT. Levels of anti-T. gondii IgG and IgM were measured by enzyme-linked immunoassays every 12 months. After a median follow-up time of 4.3 years (range 4 to 5 years), 55/460 (11.96%) patients with a GT and 15/460 (3.26%) HCs were seroprevalence for T. gondii antibodies, respectively (P = 0.001). IgG antibodies against T. gondii were found in 54 GT patients (11.74%) and 15 HCs (3.26%), respectively (P = 0.001). The seroprevalence of T. gondii IgM antibodies was similar in patients with a GT and with HCs (2.83% vs 1.3%, P = 0.105). Multivariate stepwise logistic regression analysis revealed contact with cats (OR, 6.67; 95% CI [2.89-10.75]; P = 0.001), exposure to soil (OR, 2.16; 95% CI [1.14-4.10]; P = 0.019), being a farm-worker (OR, 4.17; 95% CI [1.20-11.49]; P = 0.006) and history of chemotherapy (OR, 3.16; 95% CI [1.56-6.45]; P = 0.001) to be independent risk factors for T. gondii infection. Women with an ovarian cancer or endometrial cancer had higher T. gondii seroprevalence than that of HCs. Moreover, T. gondii infection in patients with a GT mostly acquired within two years of diagnosis, but the infection in healthy controls had no obvious time characteristics. Here, we demonstrated that T. gondii infection is significantly higher in patients with a GT (especially in women with an ovarian tumor) compared to HCs. Thus, infection with this parasite should be avoided in patients with a GT, and the causal relationship between T. gondii and GTs should be studied in detail.

Iterative reconstruction vs deep learning image reconstruction: comparison of image quality and diagnostic accuracy of arterial stenosis in low-dose lower extremity CT angiography.

OBJECTIVE: To compare image quality and diagnostic accuracy of arterial stenosis in low-dose lower-extremity CT angiography (CTA) between adaptive statistical iterative reconstruction-V (ASIR-V) and deep learning image reconstruction (DLIR) algorithms. METHODS: 46 patients undergoing low-dose lower-extremity CTA were enrolled. Images were reconstructed using ASIR-V (blending factor of 50% (AV-50) and 100% (AV-100)) and DLIR (medium (DL-M), and high (DL-H)). CT values and standard deviation of the aorta, psoas, popliteal artery, popliteal and ankle muscles were measured. The edge-rise distance and edge-rise slope were calculated. The degrees of granularity and edge blurring were assessed using a 5-point scale. The stenosis degrees were measured on the four reconstructions, and their mean square errors against that of digital subtraction angiography were calculated and compared. RESULTS: For both ASIR-V and DLIR, higher reconstruction intensity generated lower noise and higher signal-to-noise ratio and contrast-to-noise ratio values. The standard deviation values in AV-100 images were significantly lower than other reconstructions. The two DLIR image groups had higher edge-rise slope and lower edge-rise distance (DL-M:1.79 ± 0.37 mm and DL-H:1.82 ± 0.38 mm vs AV-50:1.96 ± 0.39 mm and AV-100:2.01 ± 0.36 mm, p = 0.014) than ASIR-V images. The overall image quality of DLIR was rated higher than ASIR-V (DL-M:0.83 ± 0.61, DL-H:0.41 ± 0.62, AV-50:1.85 ± 0.60 and AV-100:2.37 ± 0.77, p < 0.001), with DL-H having the highest overall image quality score. For stenosis measurement, DL-H had the lowest mean-square-errors compared to digital subtraction angiography among all reconstruction groups. CONCLUSION: DLIR images had higher image quality ratings with lower image noise and sharper vessel walls in low-dose lower-extremity CTA, and DL-H provides the best overall image quality and highest accuracy in diagnosing artery stenoses. ADVANCES IN KNOWLEDGE: DLIR provides high-quality images with sharper edges compared to ASIR-V during low-dose CTA of lower extremity arteries, and DLIR (high) provides the best overall image quality and highest accuracy in diagnosing artery stenoses among all reconstruction algorithms (ASIR-V and DLIR). ASIR-V with blending factor of 100% has the strongest noise reduction ability among all reconstruction algorithms (ASIR-V and DLIR); however, it generates the most blurred images.

Cost Effectiveness of Adding Pembrolizumab to Platinum and Fluoropyrimidine-Based Chemotherapy as First-Line Treatment for Advanced Esophageal Cancer: A US Healthcare Payer's Perspective.

BACKGROUND AND OBJECTIVE: Pembrolizumab plus cisplatin and fluorouracil demonstrated superior efficacy and comparable safety compared with fluorouracil and cisplatin (FP) as first-line treatment for locally advanced unresectable or metastatic carcinoma of the esophagus and gastroesophageal junction adenocarcinoma in a phase III trial (KEYNOTE-590). This study evaluated the cost effectiveness of pembrolizumab plus FP versus FP and versus a blended chemotherapy comparator including FP, carboplatin plus paclitaxel, FOLFOX, FOLFIRI, docetaxel plus FP, trastuzumab plus FP, and trastuzumab plus FOLFOX from a US healthcare payer's perspective. METHODS: A partitioned survival model was developed with three health states (progression-free, progressive disease, and death). Overall survival, progression-free survival, time on treatment, and adverse events were informed by patient-level data from KEYNOTE-590. The blended chemotherapy comparator reflected the current US treatment landscape and was assumed to have similar efficacy and safety as FP. Health utilities were estimated using linear mixed-effects models based on EQ-5D-5L data from the trial. Resource use and cost inputs (2020 US dollars) were based on US standard sources and literature. Costs, life-years, and quality-adjusted life-years (QALYs) discounted at 3.0% per year and incremental cost-effectiveness ratio were outcomes in the model. Sensitivity and scenario analyses were conducted to assess the robustness of base-case results. RESULTS: Compared with FP, pembrolizumab plus FP produced a mean gain of 0.86 life-year and 0.77 QALY with additional costs of $112,630 over 37.6 years, yielding an incremental cost-effectiveness ratio of $147,097 per QALY. Results were similar when the intervention was pembrolizumab plus alternative chemotherapies or when blended chemotherapy became the comparator. Results were most sensitive to different overall survival extrapolation approaches. CONCLUSIONS: Our analysis suggests that pembrolizumab plus chemotherapy extended life-years and QALYs and is cost effective compared with chemotherapy alone as a first-line treatment for advanced esophageal cancer in the USA given a willingness-to-pay threshold of $150,000 per QALY.