Cervical vertebral Hounsfield units are a better predictor of Zero-P subsidence than the T-score of DXA in patients following single-level anterior cervical discectomy and fusion with zero-profile anchored spacer.

OBJECTIVES: To determine the predictive effect of Hounsfield unit (HU) values in the cervical vertebral body measured by computed tomography (CT) and T-scores measured by dual-energy X-ray absorptiometry (DXA) on Zero-P subsidence after anterior cervical discectomy and fusion (ACDF)with Zero-P. In addition, we evaluated the most reliable measurement of cervical HU values. METHODS: We reviewed 76 patients who underwent single-level Zero-P fusion for cervical spondylosis. HU values were measured on CT images according to previous studies. Univariate analysis was used to screen the influencing factors of Zero-P subsidence, and then, logistic regression was used to determine the independent risk factors. The area under the receiver operating characteristic curve (AUC) was used to evaluate the ability to predict Zero-P subsidence. RESULTS: Twelve patients (15.8%) developed Zero-P subsidence. There were significant differences between subsidence group and non-subsidence group in terms of age, axial HU value, and HU value of midsagittal, midcoronal, and midaxial (MSCD), but there were no significant differences in lowest T-score and lowest BMD. The axial HU value (OR = 0.925) and HU value of MSCD (OR = 0.892) were independent risk factors for Zero-P subsidence, and the lowest T-score was not (OR = 1.186). The AUC of predicting Zero-P subsidence was 0.798 for axial HU value, 0.861 for HU value of MSCD, and 0.656 for T-score. CONCLUSIONS: Lower cervical HU value indicates a higher risk of subsidence in patients following Zero-P fusion for single-level cervical spondylosis. HU values were better predictors of Zero-P subsidence than DXA T-scores. In addition, the measurement of HU value in the midsagittal, midcoronal, and midaxial planes of the cervical vertebral body provides an effective method for predicting Zero-P subsidence.

Enhanced magnifying endoscopy for differential diagnosis of superficial gastric lesions identified with white-light endoscopy.

BACKGROUND: Various techniques using magnifying endoscopy (ME) and chromoendoscopy are being developed to enhance images of gastrointestinal tumor. The aim of this study was to evaluate the diagnostic performance of ME enhanced by acetic acid-indigo carmine mixture (ME-AIM) and ME enhanced with narrow-band imaging (ME-NBI) for differential diagnosis of superficial gastric lesions identified with conventional white-light endoscopy (WLE). METHODS: Patients with superficial gastric lesions picked up with WLE were enrolled in the study. ME-NBI and ME-AIM were used to further characterize the lesions. All images of the lesions were evaluated by four skilled endoscopists blinded to the clinical data. The microarchitectural patterns in the lesions were analyzed with reference to the "VS classification" system. RESULTS: A total of 643 lesions (mean diameter, 7 mm) from 508 patients (316 men, 192 women; mean age, 63 years) were evaluated. Pathologically, 24 of the 643 lesions were diagnosed as gastric cancer; the others were noncancerous lesions. For diagnosis of gastric cancer, the negative predictive value of each of the three magnified findings (irregular microvascular pattern, irregular microsurface pattern, and demarcation line) was high (nearly 100 %). According to the "VS classification" system, either ME-NBI or ME-AIM had a higher specificity (99.5 % or 99.4 % vs. 89.5 %, P < 0.001) and accuracy (99.2 % or 98.9 % vs. 89.0 %, P < 0.001) than WLE, and ME-AIM was not superior to ME-NBI for identifying carcinoma. CONCLUSIONS: Enhanced ME is useful for correctly diagnosing early gastric cancer, and in contrast with ME-AIM, ME-NBI is a more feasible and efficient method for clinical practice.

Is smart carbon emission reduction justified in China? Evidence from national big data comprehensive pilot zones.

The intelligent revolution caused by new digital technologies has provided new impetus to reduce carbon emissions. However, the current research on new digital technologies and carbon emissions is still in its infancy and lacks empirical conclusions between them. Therefore, this paper studies the impact of new digital technologies on carbon emissions, identifies its mechanism, and analyzes the regional heterogeneity of its effects. This research treats the National Big Data Comprehensive Pilot Zones pilot in China as a quasi-natural experiment for the development of new digital technologies along with city-level data covering from 2011 to 2019 to conduct a staggered difference-in-difference (DID) model analysis. We find that new digital technologies significantly reduce carbon emissions. This conclusion is still valid after a series of robustness tests such as heterogeneity treatment effect analysis, ex-ante trend test, spillover effect test, and placebo test. Additionally, new digital technologies can reduce carbon emissions by promoting the transformation of industrial structure, improving the level of green technology innovation, and promoting industrial agglomeration. At the same time, the heterogeneity analysis shows that new digital technologies' carbon emission reduction effect is more evident in non-western regions, southern regions, and large cities. To expand the carbon emission reduction effect of new digital technologies, the government should promote the development and application of new digital technologies, and implement differentiated policies based on regional characteristics.

The ctDNA-based postoperative molecular residual disease status in different subtypes of early-stage breast cancer.

Background: Breast cancer is a highly heterogeneous disease. Early-stage, non-metastatic breast cancer is considered curable after definitive treatment. Early detection of tumor recurrence and metastasis through sensitive biomarkers is helpful for guiding clinical decision-making and early intervention in second-line treatment, which could improve patient prognosis and survival. Methods: In this real-world study, we retrospectively analyzed 82 patients with stages I to III breast cancer who had been analyzed by molecular residual disease (MRD) assay. A total of 82 tumor tissues and 224 peripheral blood samples were collected and detected by next-generation sequencing (NGS) based on a 1,021-gene panel in this study. Results: MRD positivity was detected in 18 of 82 patients (22.0%). The hormone receptor-/human epidermal growth factor receptor 2+ (HR-/HER2+) subgroup had the highest postoperative MRD detection rate at 30.8% (4/13). The BRCA2 and SLX4 genes were significantly enriched in all patients in the MRD positive group and FGFR1 amplification was significantly enriched in the MRD negative group with HR+/HER2-. The number of single nucleotide variants (SNVs) in tissue samples of MRD-positive patients was higher than that of MRD-negative patients (11.94 vs. 8.50 SNVs/sample). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that there was a similar biological function of the tumor-mutated genes in the 2 MRD status groups. Conclusions: This real-world study confirmed that patient samples of primary tumor tissue with different MRD status and molecular subtypes had differential genetic features, which may be used to predict patients at high risk for recurrence.

Placing the Blame: What If "They" REALLY Are Responsible?

The new coronavirus pandemic, COVID-19, has resurrected a number of historical and sociological problems associated with naming and blaming collectives for the origin or transmission of infectious disease. The default example of the false accusation in 2020 has been the case of the charge of well poisoning against the Jews of Western Europe causing the pandemic of the Black Death during the fourteenth century. Equally apparent is the wide-spread accusation that Asians are collectively responsible for the spread of the present pandemic. Yet querying group actions in times of pandemics is not solely one of rebutting false attributions. What happens when a collective is at fault, and how does the collective respond to the simultaneous burden of both false, stereotypical accusations and appropriate charges of culpability? The case studies here are of Ultra-Orthodox Jewish (Haredi) communities and the PRC during the 2020 outbreak of COVID-19.

Icaritin enhances the efficacy of cetuximab against triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) has a greater risk of recurrence and metastasis along with a worse prognosis compared with other subtypes of breast cancer. Studies have revealed that mitogenic estrogen signaling is involved in the malignant proliferation of TNBC cells through a novel variant of the estrogen receptor, estrogen receptor α-36 (ER-α36). The results of the present study demonstrated that knockdown of ER-α36 expression in TNBC cells using short hairpin RNA inhibited rapid estrogen signaling bypass activation of the PI3K/AKT signaling pathway. Moreover, the ER-α36 modulator icaritin inhibited the proliferation of TNBC cells both in vitro and in vivo. Here, it was revealed that the combination of icaritin and cetuximab, a therapeutic epidermal growth factor receptor (EGFR) neutralizing antibody, induced apoptosis and inhibited cell proliferation synergistically in TNBC cells. The results of the present study improved the understanding of the underlying mechanisms of TNBC progression and supported the therapeutic potential of combined treatment targeting the ER-α36 and EGFR.

Inhibition of the ALDH18A1-MYCN positive feedback loop attenuates MYCN-amplified neuroblastoma growth.

MYCN-amplified neuroblastoma (NB) is characterized by poor prognosis, and directly targeting MYCN has proven challenging. Here, we showed that aldehyde dehydrogenase family 18 member A1 (ALDH18A1) exerts profound impacts on the proliferation, self-renewal, and tumorigenicity of NB cells and is a potential risk factor in patients with NB, especially those with MYCN amplification. Mechanistic studies revealed that ALDH18A1 could both transcriptionally and posttranscriptionally regulate MYCN expression, with MYCN reciprocally transactivating ALDH18A1 and thus forming a positive feedback loop. Using molecular docking and screening, we identified an ALDH18A1-specific inhibitor, YG1702, and demonstrated that pharmacological inhibition of ALDH18A1 was sufficient to induce a less proliferative phenotype and confer tumor regression and prolonged survival in NB xenograft models, providing therapeutic insights into the disruption of this reciprocal regulatory loop in MYCN-amplified NB.

TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells.

T cell activation is initiated upon ligand engagement of the T cell receptor (TCR) and costimulatory receptors. The CD28 molecule acts as a major costimulatory receptor in promoting full activation of naive T cells. However, despite extensive studies, why naive T cell activation requires concurrent stimulation of both the TCR and costimulatory receptors remains poorly understood. Here, we explore this issue by analyzing calcium response as a key early signaling event to elicit T cell activation. Experiments using mouse naive CD4+ T cells showed that engagement of the TCR or CD28 with the respective cognate ligand was able to trigger a rise in fluctuating calcium mobilization levels, as shown by the frequency and average response magnitude of the reacting cells compared with basal levels occurred in unstimulated cells. The engagement of both TCR and CD28 enabled a further increase of these two metrics. However, such increases did not sufficiently explain the importance of the CD28 pathways to the functionally relevant calcium responses in T cell activation. Through the autocorrelation analysis of calcium time series data, we found that combined but not separate TCR and CD28 stimulation significantly prolonged the average decay time (τ) of the calcium signal amplitudes determined with the autocorrelation function, compared with its value in unstimulated cells. This increasement of decay time (τ) uniquely characterizes the fluctuating calcium response triggered by concurrent stimulation of TCR and CD28, as it could not be achieved with either stronger TCR stimuli or by co-engaging both TCR and LFA-1, and likely represents an important feature of competent early signaling to provoke efficient T cell activation. Our work has thus provided new insights into the interplay between the TCR and CD28 early signaling pathways critical to trigger naive T cell activation.

Effect of Ga2O3 on the spectroscopic properties of erbium-doped boro-bismuth glasses.

The spectroscopic properties and thermal stability of Er3+-doped Bi2O3-B2O3-Ga2O3 glasses are investigated experimentally. The effect of Ga2O3 content on absorption spectra, the Judd-Ofelt parameters Omega t (t=2, 4, 6), fluorescence spectra and the lifetimes of Er3+:4I 13/2 level are also investigated, and the stimulated emission cross-section is calculated from McCumber theory. With the increasing of Ga2O3 content in the glass composition, the Omega t (t=2, 4, 6) parameters, fluorescence full width at half maximum (FWHM) and the 4I 13/2 lifetimes of Er3+ first increase, reach its maximum at Ga2O3=8 mol.%, and then decrease. The results show that Er3+-doped 50Bi2O3-42B2O3-8Ga2O3 glass has the broadest FWHM (81nm) and large stimulated emission cross-section (1.03 x1 0(-20)cm2) in these glass samples. Compared with other glass hosts, the gain bandwidth properties of Er+3-doped Bi2O3-B2O3-Ga2O3 glass is better than tellurite, silicate, phosphate and germante glasses. In addition, the lifetime of 4I 13/2 level of Er(3+) in bismuth-based glass, compared with those in other glasses, is relative low due to the high-phonon energy of the B-O bond, the large refractive index of the host and the existence of OH* in the glass. At the same time, the glass thermal stability is improved in which the substitution of Ga2O3 for B2O3 strengthens the network structure. The suitability of bismuth-based glass as a host for a Er3+-doped broadband amplifier and its advantages over other glass hosts are also discussed.

Aryl[a]pyrrolo[3,4-c]carbazoles as selective cyclin D1-CDK4 inhibitors.

The synthesis of new analogues of Arcyriaflavin A in which one indole ring is replaced by an aryl or heteroaryl ring is described. These new series of aryl[a]pyrrolo[3,4-c]carbazoles were evaluated as inhibitors of Cyclin D1-CDK4. A potent and selective D1-CDK4 inhibitor, 7a (D1-CDK4 IC(50)=45 nM), has been identified. The potency, selectivity profile against other kinases, and structure-activity relationship (SAR) trends of this class of compounds are discussed.