Explore the vast range of titles available.

Background To investigate the prognostic impact of the controlling nutritional status (CONUT) score in non-small-cell lung cancer (NSCLC) patients receiving first-line chemotherapy. Methods We retrospectively reviewed 278 consecutive patients undergoing chemotherapy for stage III-IV NSCLC between May 2012 and July 2020. CONUT score was calculated by incorporating serum albumin, total cholesterol, and total lymphocyte count. The patients were divided into two groups: CONUT ≥ 3 and CONUT < 3, according to receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. Results A high CONUT score was significantly associated with older age( P  = 0.003), worse ECOG-PS( P  = 0.018), advanced clinical stage( P  = 0.006), higher systematic inflammation index (SII) ( P  < 0.001)and lower prognostic nutritional index (PNI) ( P  < 0.001).The high CONUT group had a significantly shorter progression-free survival(PFS) and overall survival(OS) than the low CONUT group. In the univariate analysis, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse PFS ( P all  < 0.05). Worse ECOG-PS, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse OS ( P all  < 0.05). In multivariate analysis, CONUT(HR, 2.487; 95%CI 1.818 ~ 3.403; P  < 0.001) was independently associated with PFS, while PNI(HR, 0.676; 95%CI 0.494 ~ 0.927; P  = 0.015) and CONUT(HR, 2.186; 95%CI 1.591 ~ 3.002; P  < 0.001)were independently associated with OS. In ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 24-month PFS and OS than the SII or PNI. When the time-dependent AUC curve was used to predict PFS and OS, CONUT tended to maintain its predictive accuracy for long-term prognosis at a significantly higher level for an extended period after chemotherapy when compared with the other markers tested. The CONUT score showed better accuracy of predicting OS (C-index: 0.711) and PFS(C-index: 0.753). Conclusion CONUT score is an independent prognostic indicator of poor outcomes for patients with stage III-IV NSCLC and is superior to the SII and PNI in terms of prognostic ability.

As pioneering Fe 3 O 4 nanozymes, their explicit peroxidase (POD)-like catalytic mechanism remains elusive. Although many studies have proposed surface Fe 2+ -induced Fenton-like reactions accounting for their POD-like activity, few have focused on the internal atomic changes and their contribution to the catalytic reaction. Here we report that Fe 2+ within Fe 3 O 4 can transfer electrons to the surface via the Fe 2+ -O-Fe 3+ chain, regenerating the surface Fe 2+ and enabling a sustained POD-like catalytic reaction. This process usually occurs with the outward migration of excess oxidized Fe 3+ from the lattice, which is a rate-limiting step. After prolonged catalysis, Fe 3 O 4 nanozymes suffer the phase transformation to γ-Fe 2 O 3 with depletable POD-like activity. This self-depleting characteristic of nanozymes with internal atoms involved in electron transfer and ion migration is well validated on lithium iron phosphate nanoparticles. We reveal a neglected issue concerning the necessity of considering both surface and internal atoms when designing, modulating, and applying nanozymes. The mechanism of peroxidase-like Fe 3 O 4 nanozymes remains elusive. Here, the authors show the electron transfer mechanism of Fe(II) ions to regenerate surface Fe(II) and the related phase transformation and depletion of activity.

Purpose Rare genetic conditions like Down syndrome (DS) are historically understudied. Infection is a leading cause of mortality in DS, along with cardiac anomalies. Currently, it is unknown how the COVID-19 pandemic affects individuals with DS. Herein, we report an analysis of individuals with DS who were hospitalized with COVID-19 in New York, New York, USA. Methods In this retrospective, dual-center study of 7246 patients hospitalized with COVID-19, we analyzed all patients with DS admitted in the Mount Sinai Health System and Columbia University Irving Medical Center. We assessed hospitalization rates, clinical characteristics, and outcomes. Results We identified 12 patients with DS. Hospitalized individuals with DS are on average ten years younger than patients without DS. Patients with DS have more severe disease than controls, particularly an increased incidence of sepsis and mechanical ventilation. Conclusion We demonstrate that individuals with DS who are hospitalized with COVID-19 are younger than their non-DS counterparts, and that they have more severe disease than age-matched controls. We conclude that particular care should be considered for both the prevention and treatment of COVID-19 in these patients.

Background Systemic inflammation and immune dysfunction has been proved to be significantly associated with cancer progression and metastasis in many cancer types, including colorectal cancer. We examined the prognostic significance of the systemic immune-inflammation index (SII) in patients with metastatic colorectal cancer (mCRC) and the relationship between the lymphocytic response to the tumor and this index. Methods This retrospective study evaluated 240 consecutive patients with newly diagnosed stage IV mCRC who underwent surgical resection. The SII values were calculated based on preoperative laboratory data regarding platelet, neutrophil, and lymphocyte counts. Tumor-infiltrating lymphocytes were evaluated using the surgical specimens. The overall survival and their 95% confidence interval (95% CI) were estimated by regression analyses and the Kaplan–Meier method. Results After a mean follow-up of 26.7 (1.1–92.4) months, 146 patients (60.8%) died. In the univariate analysis, a high SII was significantly associated with poor overall survival ( P  = 0.009). The multivariable analysis also confirmed that a high SII was independently associated with poor overall survival (hazard ratio: 1.462, 95% confidence interval 1.049–2.038, P  = 0.025). The SII value was significantly correlated with the TILs value at the tumor’s center ( P  = 0.04), but not at the invasive margin ( P  = 0.39). When we evaluated overall survival for groupings of the tumor-infiltrating lymphocytes and SII values, we identified three distinct prognostic groups. The group with low tumor-infiltrating lymphocyte values and high SII values had the worst prognosis. Conclusions A high SII value independently predicts poor clinical outcomes among patients with mCRC. In addition, combining the lymphocytic response to the tumor and SII could further enhance prognostication for mCRC.

Due to the small size and low speed of existing vibrating mechanical equipment, the vibrating bodies are often considered rigid, and structural vibrations are neglected. However, with the development of vibrating machinery towards large-scale and high-speed directions, it is difficult to avoid structural vibration. Despite this, there is a lack of investigation into the mechanism of the influence of structural vibration on vibrating machinery. This paper presents a study on the vibration performance and stability behavior of a thin rectangular plate vibration system under three vibrator excitations, considering self-synchronization and the Sommerfeld effect. The theoretical model used is a simple thin rectangular plate structure. Firstly, the modal shape and frequency equations of the thin rectangular plate are obtained using the semi-inverse method. Subsequently, the differential equations of the motion of the system are derived. Moreover, the conditions for synchronization and stability of the vibration system are determined using the average perturbation method. The theoretical results are then compared with simulation and experimental results to verify their correctness. Finally, the effects of unbalance masses and installation positions of vibrators on self-synchronization behavior, the Sommerfeld effect, and the dynamic response of the vibration system are discussed.

Lynch Syndrome (LS) is a common genetic cancer condition that allows for personalized cancer prevention and early cancer detection in identified gene carriers. We used data from the All of Us (AOU) Research Initiative to assess the prevalence of LS in the general U.S. population, and analyzed demographic, personal, and family cancer history, stratified by LS genotype to compare LS and non-LS carriers. The results suggest that population-based germline testing for LS may identify up to 63.2% of carriers who might remain undetected due to lack of personal or family cancer history. LS affects about 1 in 354 individuals in this U.S. cohort, where pathogenic variants in the genes MSH6 and PMS2 account for the majority of cases. These results underscore the need to optimize the identification of LS across diverse populations and population-based germline testing may capture the most individuals who can benefit from precision cancer screening and prevention. Lynch Syndrome results in a predisposition to cancer, however, it is frequently undiagnosed prior to cancer occurrence. Here, the authors use All of Us data to report that 63.2% of Lynch syndrome carriers remain undetected due to lack of personal or family cancer history.

High-fidelity projective readout of a qubit’s state in a single experimental repetition is a prerequisite for various quantum protocols of sensing and computing. Achieving single-shot readout is challenging for solid-state qubits. For Nitrogen-Vacancy (NV) centers in diamond, it has been realized using nuclear memories or resonant excitation at cryogenic temperature. All of these existing approaches have stringent experimental demands. In particular, they require a high efficiency of photon collection, such as immersion optics or all-diamond micro-optics. For some of the most relevant applications, such as shallow implanted NV centers in a cryogenic environment, these tools are unavailable. Here we demonstrate an all-optical spin readout scheme that achieves single-shot fidelity even if photon collection is poor (delivering less than 10 3 clicks/second). The scheme is based on spin-dependent resonant excitation at cryogenic temperature combined with spin-to-charge conversion, mapping the fragile electron spin states to the stable charge states. We prove this technique to work on shallow implanted NV centers, as they are required for sensing and scalable NV-based quantum registers. The NV center in diamond has been used extensively in sensing; however single shot readout of its spin remains challenging, requiring complex optical setups. Here, Irber et al. demonstrate a more robust scheme that achieves single-shot readout even when using inefficient detection optics.

High fidelity single-shot readout of qubits is a crucial component for fault-tolerant quantum computing and scalable quantum networks. In recent years, the nitrogen-vacancy (NV) center in diamond has risen as a leading platform for the above applications. The current single-shot readout of the NV electron spin relies on resonance fluorescence method at cryogenic temperature. However, the spin-flip process interrupts the optical cycling transition, therefore, limits the readout fidelity. Here, we introduce a spin-to-charge conversion method assisted by near-infrared (NIR) light to suppress the spin-flip error. This method leverages high spin-selectivity of cryogenic resonance excitation and flexibility of photoionization. We achieve an overall fidelity > 95% for the single-shot readout of an NV center electron spin in the presence of high strain and fast spin-flip process. With further improvements, this technique has the potential to achieve spin readout fidelity exceeding the fault-tolerant threshold, and may also find applications on integrated optoelectronic devices. The NV centre in diamond has been used extensively in quantum information processing; however fault-tolerant readout of its spin remains challenging. Here, Zhang et al demonstrate a robust scheme that achieves high-fidelity readout via spin to charge conversion.

Background: Slow transit constipation (STC) is becoming a common and frequently occurring disease in today’s society, and it is necessary to explore the safe and effective treatment of STC. Method: Our study aimed to investigate whether the laxative effect of Maren pills (MRW) is associated with the regulation of intestinal microflora and intestinal metabolism in the colon. Loperamide hydrochloride-induced STC rats received MRW intragastrically for two consecutive weeks to evaluate the laxative effect of MRW involving the regulation of intestinal microflora, intestinal metabolism, and 5-HT signaling pathway. Intestinal microflora was detected by 16s rDNA sequencing, intestinal metabolism of short-chain fatty acids (SCFAs) was detected by HPLC, and the 5-HT signaling pathway was detected by WB, ELISA, immunofluorescence, and immunohistochemical analysis. Results: Our results revealed that the treatments with MRW increased not only the body weight, 24-h fecal number, 24-h wet fecal weight, 24-h dry fecal weight, fecal water content, and the intestinal propulsion rate but also the colonic goblet cell number, colonic Muc-2 protein expression, and colonic mucus layer thickness in the STC model rats. Moreover, MRW activated the 5-HT pathway by increasing the levels of 5-HT, 5-HIAA, 5-HT4R, CFTR, cAMP, and PKA in the colon tissue of STC rats. The 16S rDNA sequencing results showed that MRW improved the colonic microflora structure in colonic contents of STC rats, mainly by increasing Lactobacillus and decreasing Prevotella . Finally, we found that MRW regulated the SCFA metabolism in the colonic contents of the STC rats, mainly by increasing the contents of acetic acid, propionic acid, and butyric acid; the relative abundance of Lactobacillus was positively correlated with either contents of acetic acid, propionic acid, and butyric acid, and the relative abundance of Clostridium was negatively correlated. Conclusion: Our study further showed that MRW could improve constipation in STC rats, and the mechanism may be by regulating the intestinal microflora structure and improving the metabolism of SCFAs.

Myocardial ischemia/reperfusion (MI/R) injury is a common clinical problem after myocardial infarction without effective therapy. Loureirin B (LrB) is a kind of flavonoid with anti-inflammatory and antifibrotic activities. However, the effect of LrB on MI/R and its underlying mechanism remains elusive. In the present study, a mouse model of MI/R was established by coronary artery occlusion. Administration of LrB (0.5 mg/kg or 1 mg/kg) for 4 weeks effectively improved left ventricular (LV) function and reduced myocardial infarction in MI/R mice. MI/R-induced expression of IL-6, TNF-α, and IL-1β in the hearts was reduced by LrB treatment. Histological analysis showed that LrB attenuated myocardial collagen deposition. LrB downregulated fibronectin, collagen I, collagen III, and α-SMA expression. Notably, LrB inhibited the expression of profibrotic plasminogen activator inhibitor-1 (PAI-1), transforming growth factor (TGF)-β1, TGF-β1R, and p-Smad2/3. Consistently, LrB inhibited the activation of TGF-β1/Smad signaling pathway and the expression of fibrosis-related proteins in angiotensin (Ang) II-treated cardiac fibroblasts (CFs). Overexpression of PAI-1 abolished the effects of LrB on Ang II-treated CFs, suggesting that LrB may function through regulating PAI-1. These results indicated that LrB may alleviate MI/R-induced myocardial fibrosis by inhibiting PAI-1/TGF-β1/Smad signaling pathway. Thus, LrB may be a potential drug in the treatment of MI/R injury.