The super-resolution reconstruction in diffusion-weighted imaging of preoperative rectal MR using generative adversarial network (GAN): Image quality and T-stage assessment.

AIMS: To assess the feasibility of using a generative adversarial network (GAN) to improve diffusion-weighted imaging (DWI) resolution in rectal MR scans for rectal carcinoma (RC), and to evaluate both the image quality and the diagnostic utility of super-resolution DWI (SR-DWI) in T stage assessment. MATERIALS AND METHODS: In this retrospective investigation, a total of 291 patients diagnosed with RC during the period spanning May 2018 to December 2021 were included. The generated SR-DWI was evaluated against the original DWI using multi-scale structural similarity and peak signal-to-noise ratio. Two radiologists scored the SR-DWI and original DWI using a 4-point Likert scale in image quality. Moreover, both radiologists independently evaluated the T category staging based on T2WI and SR-DWI. Interobserver agreement was assessed using Cohen's kappa. RESULTS: The PSRN and MS-SSIM values of SR-DWI (4 ×) were significantly higher compared to those of SR-DWI (16 ×). Regarding the details of anatomic structures and overall image quality parameters, both radiologists exhibited a preference for SR DWI with 16 × enlargement over SR DWI with 4 × enlargement, yielding significantly superior ratings (both p < 0.001). The T-staging accuracy rates of SR-DWI (16 ×) performed by radiologist 1 and radiologist 2 were significantly superior to those achieved with T2WI (0.621 vs. 0.768, p = 0.027; 0.653 vs 0.810, p = 0.014). CONCLUSIONS: Our study demonstrates that the adapted super-resolution approach can significantly improve the overall image quality and details of anatomic structure of DWI in rectal MR. And SR-DWI offer better diagnostic accuracy in RC T staging when compared with T2WI.

[Risk factors analysis and prediction model establishment of contralateral central lymph node metastasis in intermediate-to-high risk unilateral papillary thyroid carcinoma].

Objective: To explore the risk factors of contralateral central lymph nodes (Cont-CLNs) metastasis in intermediate-to-high risk unilateral papillary thyroid carcinoma and establish a prediction model. Methods: The clinical data of 206 patients receiving thyroid cancer surgery at Nantong University Affiliated Hospital between January 2021 and June 2023 were retrospectively analyzed, including 50 males and 156 females, with an age of [M(Q1, Q3)] 49.0(33.8, 57.0) years old. The risk factors of Cont-CLNs metastasis were screened by univariate analysis and multivariate logistic regression analysis. A nomogram was constructed for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC. The area under the receiver operating characteristic (ROC) curve(AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the model's predictive ability, accuracy, and clinical applicability, respectively. R language was used to randomly select 70% of the patients to establish a validation group for internal validation of the model. Results: Patients were divided into a metastasis group (n=56) and a non-metastasis group (n=150) based on the occurrence of Cont-CLNs metastasis. The ages of the two groups were 39.0 (28.0, 56.8) years and 51.0 (38.8, 57.0) years, respectively. There were statistically significant differences in gender, maximum tumor diameter (>1 cm), ipsilateral central lymph nodes (Ipsi-CLNs) metastasis, number of Ipsi-CLNs metastases (≥4), and lateral lymph node metastasis and Cont-CLNs metastasis between the two groups (all P<0.05). The results of multivariate logistic regression analyses showed that males(OR=2.926, 95%CI: 1.063-8.051), maximum tumor diameter>1 cm(OR=4.471, 95%CI: 1.344-14.877), and number of Ipsi-CLNs metastases≥4 (OR=5.011, 95%CI: 1.815-13.834) were risk factors for Cont-CLNs metastasis (all P<0.05). The AUC of the ROC curve, sensitivity, and specificity for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC by the prediction model in the modeling group were 0.821 (95%CI: 0.744-0.898), 82.5%, and 63.4%, respectively. In the internal validation group, the AUC of the ROC curve, sensitivity, and specificity for predicting Cont-CLNs metastasis in intermediate-to-high risk uPTC by the prediction model were 0.810 (95%CI: 0.717-0.902), 63.3%, and 83.7%, respectively. The calibration curves of the modeling group and the validation group showed that the model had good calibration ability. The DCA curves of the modeling group and the validation group indicated that the prediction model had good clinical adaptability. Conclusions: The prediction model constructed in this study has good predictive performance for Cont-CLNs metastasis in intermediate-to-high uPTC. When patient with intermediate-to-high risk uPTC is male, with maximum tumor diameter>1 cm, and the number of Ipsi-CLNs metastases≥4 should be alert to Cont-CLNs metastasis, and bilateral central lymph node dissection may be considered.

Magnetic hydrogel particles improve nanopore sequencing of SARS-CoV-2 and other respiratory viruses.

Presented here is a magnetic hydrogel particle enabled workflow for capturing and concentrating SARS-CoV-2 from diagnostic remnant swab samples that significantly improves sequencing results using the Oxford Nanopore Technologies MinION sequencing platform. Our approach utilizes a novel affinity-based magnetic hydrogel particle, circumventing low input sample volumes and allowing for both rapid manual and automated high throughput workflows that are compatible with Nanopore sequencing. This approach enhances standard RNA extraction protocols, providing up to 40 × improvements in viral mapped reads, and improves sequencing coverage by 20-80% from lower titer diagnostic remnant samples. Furthermore, we demonstrate that this approach works for contrived influenza virus and respiratory syncytial virus samples, suggesting that it can be used to identify and improve sequencing results of multiple viruses in VTM samples. These methods can be performed manually or on a KingFisher automation platform.

[Differential diagnosis model of benign and malignant breast BI-RADS category 4 nodules based on serum SP70 and conventional laboratory indicators].

Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.

Heterogeneity in the onwards transmission risk between local and imported cases affects practical estimates of the time-dependent reproduction number.

During infectious disease outbreaks, inference of summary statistics characterizing transmission is essential for planning interventions. An important metric is the time-dependent reproduction number (Rt), which represents the expected number of secondary cases generated by each infected individual over the course of their infectious period. The value of Rt varies during an outbreak due to factors such as varying population immunity and changes to interventions, including those that affect individuals' contact networks. While it is possible to estimate a single population-wide Rt, this may belie differences in transmission between subgroups within the population. Here, we explore the effects of this heterogeneity on Rt estimates. Specifically, we consider two groups of infected hosts: those infected outside the local population (imported cases), and those infected locally (local cases). We use a Bayesian approach to estimate Rt, made available for others to use via an online tool, that accounts for differences in the onwards transmission risk from individuals in these groups. Using COVID-19 data from different regions worldwide, we show that different assumptions about the relative transmission risk between imported and local cases affect Rt estimates significantly, with implications for interventions. This highlights the need to collect data during outbreaks describing heterogeneities in transmission between different infected hosts, and to account for these heterogeneities in methods used to estimate Rt. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

[Suppression of HMGB1 inhibits neuronal autophagy and apoptosis to improve neurological deficits in rats following intracerebral hemorrhage].

OBJECTIVE: To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats. METHODS: Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 µL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA. RESULTS: The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05). CONCLUSION: Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.

[Clinical analysis of penetrating keratoplasty for infants with congenital corneal opacity].

Objective: To investigate the corneal graft survival and related risk factors of primary penetrating keratoplasty in congenital corneal opacity infants. Methods: It was a retrospective cohort study. Data were collected from forty-two infants (51 eyes) who were aged ≤12 months and diagnosed with congenital corneal opacity in Beijing Tongren Hospital and Beijing Anzhen Hospital from January 1, 2017 to January 31, 2018. The mean age at surgery was (5.7±2.2) months (3-12 months). The mean follow-up duration was (28.6±2.6) months (24-33 months). All the patients underwent penetrating keratoplasty. The status of the corneal grafts and complications were observed and recorded during the regular follow-up. The survival probabilities were estimated by using the Kaplan-Meier and Log-rank test. The graft survival between different influence factors was analyzed by using the χ2 test. Results: The Kaplan-Meier survival rates for penetrating keratoplasty were 84.3% (43/51) at 6 months, 78.4% (40/51) at 12 months and 60.8% (31/51) at the last follow-up. The presence of corneal neovascularization was significantly correlated with graft failure (χ²=5.264, P=0.022). The graft survival differed between eyes receiving combined surgery and mere penetrating keratoplasty and in eyes with varied surgical indications (P=0.039, <0.01). Increased intraocular pressure (7 eyes, 13.7%) and persistent epithelial defects (7 eyes, 13.7%) were the most common postoperative complications, followed by complicated cataract (4 eyes, 7.8%) and posterior capsule opacification (2 eyes, 3.9%). Conclusions: The graft survival rate was satisfactory following pediatric keratoplasty although it had a tendency to decrease with the follow-up time. Corneal neovascularization was a major risk factor of graft failure. Surgical indications and procedures also had a certain effect on the graft survival.

Laser-cooled 171Yb+ microwave frequency standard with a short-term frequency instability of 8.5 × 10-13/√τ.

We report on the development of a microwave frequency standard based on a laser-cooled 171 Y b + ion trap system. The electronics , lasers, and magnetic shields are integrated into a single physical package. With over 105 ions are stably trapped, the system offers a high signal-to-noise ratio Ramsey line-shape. In comparison with previous work, the frequency instability of a 171 Y b + microwave clock was further improved to 8.5×10-13/τ for averaging times between 10 and 1000 s. Essential systematic shifts and uncertainties are also estimated.

[Progress on clinical trials of common gastrointestinal cancer drugs in China from 2012 to 2021].

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.

Association between low skeletal muscle mass and subclinical coronary atherosclerosis in asymptomatic individuals evaluated by CT.

AIM: To investigate the associations of skeletal muscle area and density with coronary atherosclerotic plaques and significant stenosis in asymptomatic adults. MATERIALS AND METHODS: A total of 243 consecutive subjects who had voluntarily undergone abdominal unenhanced computed tomography (CT) and coronary CT angiography (CCTA) as part of a general health examination were investigated retrospectively. Skeletal muscle area index (SMI) and skeletal muscle density (SMD) was assessed using CT. Coronary atherosclerotic plaques and stenosis on CCTA were evaluated. The associations of low SMI and low SMD with coronary atherosclerotic plaques and significant stenosis were determined by logistic regression analysis. RESULTS: After adjustment for cardiovascular risk factors, there were significant associations of low SMI or low SMD with atherosclerotic plaque, total significant stenosis, and significant stenosis caused by calcified or mixed plaques (for all p<0.05). In addition, multivariate regression analysis also showed that low SMI was independently associated with calcified plaque (p=0.038) and non-calcified plaque (p=0.006), and individuals with low SMD were more likely to have mixed plaque (p=0.001). CONCLUSION: Assessment of the skeletal muscle on CT help to identify asymptomatic adults at risk for coronary atherosclerosis.

Precision determination of the ground-state hyperfine splitting of trapped 113Cd+ ions.

We measured the ground-state hyperfine splitting of trapped 113Cd+ ions to be 15199862855.02799(27) Hz with a fractional uncertainty of 1.8×10-14. The ions were trapped and laser-cooled in a linear quadrupole Paul trap. The fractional frequency stability was measured to be 4.2×10-13/τ, obtained from Ramsey fringes of high signal-to-noise ratios and taken over a measurement time of nearly 5 h, which is close to the short-term stability limit estimated from the Dick effect. Our result is consistent with previously reported values, but the measurement precision is four times better than the best result obtained to date.

Hydrogel particles improve detection of SARS-CoV-2 RNA from multiple sample types.

Here we present a rapid and versatile method for capturing and concentrating SARS-CoV-2 from contrived transport medium and saliva samples using affinity-capture magnetic hydrogel particles. We demonstrate that the method concentrates virus from 1 mL samples prior to RNA extraction, substantially improving detection of virus using real-time RT-PCR across a range of viral titers (100-1,000,000 viral copies/mL) and enabling detection of virus using the 2019 nCoV CDC EUA Kit down to 100 viral copies/mL. This method is compatible with commercially available nucleic acid extraction kits (i.e., from Qiagen) and a simple heat and detergent method that extracts viral RNA directly off the particle, allowing a sample processing time of 10 min. We furthermore tested our method in transport medium diagnostic remnant samples that previously had been tested for SARS-CoV-2, showing that our method not only correctly identified all positive samples but also substantially improved detection of the virus in low viral load samples. The average improvement in cycle threshold value across all viral titers tested was 3.1. Finally, we illustrate that our method could potentially be used to enable pooled testing, as we observed considerable improvement in the detection of SARS-CoV-2 RNA from sample volumes of up to 10 mL.

[Diffusion tensor imaging and visual evoked potentials in pediatric patients with sellar region lesions].

Objiective: To evaluate the prognosis of visual function and the impact of surgery in pediatric patients with sellar mass lesions, as evidenced by diffusion tensor imaging (DTI) and visual evoked potentials. Methods: Twenty patients with sellar mass lesions were included in the study. DTI and visual evoked potentials were obtained before and after surgery. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for both optic nerves. DTI parameters and visual evoked potential amplitudes were compared for all patients to assess the correlation between DTI parameters and visual function. Results: The 20 patients were divided into two groups according the relationship between the lesions and the optic chiasm. The FA values increased significantly after operation, while the ADC values decreased (P<0.05). And the average amplitude of visual evoked potentials after operation was significantly higher than before operation (P<0.05). Conclusions: DTI assessments of the affected sides, with the resulting FA and ADC values, may help to estimate the visual improvement produced by surgical therapy in the early postoperative period. Surgical removal can improve visual function dramatically.

SETD5-AS1 stimulates neuron death in stroke via promoting PTEN expression.

OBJECTIVE: To investigate the specific role of long non-coding RNA (lncRNA) SETD5-AS1 in regulating stroke development, and its underlying mechanism. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) model and OGD/R (oxygen-glucose deprivation/reoxygenation) model were constructed for exploring the mechanism of ischemia-reperfusion injury induced by ischemic stroke. SETD5-AS1 expression in brain tissues of ischemic stroke mice and control mice was detected by quantitative Real-time-polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of N2a cells were detected after transfection of overexpression plasmid or siRNA SETD5-AS1. The downstream gene of SETP5-AS1 was predicted by Starbase and PTEN was screened out. Both mRNA and protein expressions of PTEN in MCAO model and OGD/R model were detected. Furthermore, the binding condition of SETD5-AS1 and PTEN was verified by dual-luciferase reporter gene assay, RNA pull-down assay and RNA binding protein immunoprecipitation (RIP). The regulatory effect of SETD5-AS1 on PI3K/AKT pathway was detected by Western blot. RESULTS: SETD5-AS1 was highly expressed in the ischemia-reperfusion injury model. Overexpression of SETD5-AS1 in N2a cells resulted in increased apoptosis and decreased proliferation. PTEN expression was upregulated in MCAO model and OGD/R model. Dual-luciferase reporter gene assay indicated that SETD5-AS1 can promote PTEN transcription. The binding condition of SETD5-AS1 and PTEN was further verified by RNA pull-down assay and RIP. Overexpression of SETD5-AS1 in N2a cells inhibited PI3K/AKT pathway. CONCLUSIONS: SETD5-AS1 is highly expressed in the ischemia-reperfusion injury model. SETD5-AS1 participates in the development of ischemic stroke by activating PTEN and inhibiting PI3K/AKT pathway.

Development of interface-dominant bulk Cu/V nanolamellar composites by cross accumulative roll bonding.

Traditional nanostructured metals are inherently comprised of a high density of high-energy interfaces that make this class of materials not stable in extreme conditions. Therefore, high performance bulk nanostructured metals containing stable interfaces are highly desirable for extreme environments applications. Here, we reported an attractive bulk Cu/V nanolamellar composite that was successfully developed by integrating interface engineering and severe plastic deformation techniques. The layered morphology and ordered Cu/V interfaces remained stable with respect to continued rolling (total strain exceeding 12). Most importantly, for layer thickness of 25 nm, this bulk Cu/V nanocomposite simultaneously achieves high strength (hardness of 3.68 GPa) and outstanding thermal stability (up to 700 °C), which are quite difficult to realize simultaneously in traditional nanostructured materials. Such extraordinary property in our Cu/V nanocomposite is achieved via an extreme rolling process that creates extremely high density of stable Cu/V heterophase interfaces and low density of unstable grain boundaries. In addition, high temperature annealing result illustrates that Rayleigh instability is the dominant mechanism driving the onset of thermal instability after exposure to 800 °C.

Effect of pregnane X receptor polymorphisms on tacrolimus blood concentrations and the resulting adverse reactions in kidney transplantation recipients.

We investigated the effect of pregnane X receptor (PXR) polymorphisms on tacrolimus (FK506) blood trough concentrations and the associated adverse reactions in kidney transplantation recipients (KTRs). Polymerase chain reaction (PCR)-restriction fragment length polymorphism was used to detect the genotypes of single nucleotide polymorphism loci in 336 KTRs. The PXR six-base deletion mutation was classified using specific allele PCR, and the FK506 blood trough concentration in the KTRs was measured by chemiluminescent microparticle immunoassay. There were significant differences in adverse reactions resulting from FK506 in age, weight, body mass index (BMI) and treatment course (P < 0.05). Logistical regression revealed that the FK506 treatment course and BMI were risk factors for hyperlipidemia, and the risk of hyperlipidemia increased 27.534 times when the BMI was less than 18.5. Moreover, age was also a risk factor leading to hyperglycemia. FK506 blood trough concentration and C0/D value had an impact on adverse reactions induced by hyperglycemia. The KTRs' PXR rs3842689, rs6785049, and rs1523127 mutation frequencies were 26.07, 11.79, and 16.07%, respectively. There was no statistically significant difference in the mutation frequency of each locus between the control group and the adverse reaction groups. Therefore, rs3842689, 7635G>A (rs6785049), and 24381C>A (rs1523127) PXR polymorphisms have no obvious impact on FK506; furthermore, the PXR rs3842689 wild-type homozygous WW genotype is a risk factor of FK506 and results in gastrointestinal reactions.