ZnS Nanoseeds Sealed in N, P, S Co-Doped Carbon Hollow Rhombic Dodecahedra as a Superlithiophilic Host for Dendrite-Free Lithium Metal Anodes.

Lithium (Li) metal is considered a hopeful anode for next-generation Li-ion batteries thanks to its ultra-high theoretical specific capacity, extra-low theoretical density, and low negative potential. However, the uncontrolled growth of Li dendrites and volume fluctuation during plating/stripping processes severely hamper its commercial application. Herein, ZnS seeds sealed in N, P, S co-doped carbon hollow rhombic dodecahedra (ZnS@NPS-C HRD) is fabricated as a superlithiophilic host for Li metal anodes (LMAs) to solve the above problems. In addition, the Li nucleation and deposition mechanism on ZnS@NPS-C HRD is investigated by in situ optical microscopy, ex-situ X-ray diffraction, scanning electron microscopy, and theoretical calculations. Owing to the synergistic strategy of ZnS seeds-inducing nucleation and Li-limited growth, the as-prepared composite exhibits stability for 300 cycles in asymmetric cells and a long lifespan over 1100 h in symmetric cells. Moreover, the ZnS@NPS-C HRD@Li|LiFePO4 full cell demonstrates a reversible capacity of 100.91 mAh g-1 after 400 cycles at 1 C.

Integration of proteomics and transcriptomics to construct a prognostic signature of renal clear cell carcinoma.

Background: Protein information is often replaced by RNA data in studies to understand cancer-related biological processes or molecular functions, and proteins of prognostic significance in Kidney clear cell carcinoma (KIRC) remain to be mined. Methods: The cancer genome atlas program (TCGA) data was utilized to screen for proteins that are prognostically significant in KIRC. Machine learning algorithms were employed to develop protein prognostic models. Additionally, immune infiltration abundance, somatic mutation differences, and immunotherapeutic responses were analyzed in various protein risk subgroups. Ultimately, the validation of protein-coding genes was confirmed by utilizing an online database and implementing quantitative real-time PCR (qRT-PCR). Results: The patients were divided into two risk categories based on prognostic proteins, and notable disparities in both overall survival (OS) and progression free interval (PFI) were observed between the two groups. The OS was more unfavorable in the high-risk group, and there was a noteworthy disparity in the level of immune infiltration observed between the two groups. In addition, the nomogram showed high accuracy in predicting survival in KIRC patients. Conclusion: In this research, we elucidated the core proteins associated with prognosis in terms of survival prediction, immunotherapeutic response, somatic mutation, and immune microenvironment. Additionally, we have developed a reliable prognostic model with excellent predictive capabilities.

Constraints on crustal compositional architecture across the North China-Altaids transition and implications for craton margin reworking.

The phase of secular evolution of continents is manifested as the degree of compositional differentiation, modification and maturation of continental crusts, which is vital in understanding the mechanism of continental evolution but is difficult to quantify. Here we use integrated passive- and active-source seismic profiling to conduct joint analysis and inversion and derive Vs and Vp/Vs section models across the North China Craton (NCC) to southeastern Altaids boundary zone that bears a tectonic transition from a reworked ancient craton margin to a Phanerozoic accretionary orogen. We systematically exploited the imaged multiple physical properties as precise and delicate proxies to constrain the compositional architecture in the crust across this important tectonic transition subject to various crustal evolutional phases. Our Vs and Vp/Vs imaging, together with the existing isotopic data, characterizes the Yin Shan-Yan Shan belt as the northern NCC margin with layered homogeneous compositions that point to an evolved crust. However, the lower-crustal low-Vs/high-Vp/Vs signature that overlaps the shallowly dipping to horizontal reflective fabrics suggests that the crust of the northern NCC margin has undergone considerable reworking through lower-crustal-stretching-assisted melt migration and mixing since the late Paleozoic to Mesozoic eras. The process probably involved crust-mantle interaction and thus resulted in a compositionally modified ancient crustal basement. On the contrary, the southeastern Altaids domain manifests crustal complexity in compositions and structures inferred to be indicative of a juvenile crust of the Phanerozoic accretionary orogen. Our results provide deep physical-property constraints that shed new light on the crustal evolution of a complex craton margin.

Predicting bladder cancer survival with high accuracy: insights from MAPK pathway-related genes.

The mitogen-activated protein kinase (MAPK) pathway plays a critical role in tumor development and immunotherapy. Nevertheless, additional research is necessary to comprehend the relationship between the MAPK pathway and the prognosis of bladder cancer (BLCA), as well as its influence on the tumor immune microenvironment. To create prognostic models, we screened ten genes associated with the MAPK pathway using COX and least absolute shrinkage and selection operator (LASSO) regression analysis. These models were validated in the Genomic Data Commons (GEO) cohort and further examined for immune infiltration, somatic mutation, and drug sensitivity characteristics. Finally, the findings were validated using The Human Protein Atlas (HPA) database and through Quantitative Real-time PCR (qRT-PCR). Patients were classified into high-risk and low-risk groups based on the prognosis-related genes of the MAPK pathway. The high-risk group had poorer overall survival than the low-risk group and showed increased immune infiltration compared to the low-risk group. Additionally, the nomograms built using the risk scores and clinical factors exhibited high accuracy in predicting the survival of BLCA patients. The prognostic profiling of MAPK pathway-associated genes represents a potent clinical prediction tool, serving as the foundation for precise clinical treatment of BLCA.

COVID-19 pandemic amplified mortality rates among adolescents with bipolar disorder through family-related factors.

BACKGROUND: Recently, a growing number of adolescents have been afflicted with mental disorders, with annual morbidity rates on the rise. This trend has been exacerbated by the global coronavirus disease 2019 (COVID-19) pandemic, leading to a surge in suicide and self-harm rates among this demographic. AIM: To investigate the impact of the COVID-19 pandemic on adolescent bipolar disorder (BD), along with the underlying factors contributing to heightened rates of suicide and self-harm among adolescents. METHODS: A comprehensive statistical analysis was conducted utilizing clinical interviews and self-reports obtained from patients or their guardians. Diagnostic criteria for BDs were based on the Diagnostic and statistical manual of mental disorders, international classification of diseases-11, and the National institute of mental health research domain criteria. Statistical analyses were performed using SPSS 26.0 software, with significance set at P < 0.05. RESULTS: A cohort of 171 adolescents diagnosed with BD between January 1, 2018, and December 31, 2022, was included in the analysis. The gender distribution was 2.8:1 (female to male), with ages ranging from 11 to 18 years old. Major factors contributing to adolescent BDs included familial influences, academic stress, genetic predisposition and exposure to school-related violence. Notably, a significant increase in suicide attempts and self-harm incidents was observed among adolescents with BD during the COVID-19 pandemic. Statistical analysis indicated that the pandemic exacerbated familial discord and heightened academic stress, thereby amplifying the prevalence of suicidal behavior and self-harm among adolescents. CONCLUSION: The COVID-19 pandemic has exacerbated familial tensions and intensified the incidence of suicide and self-harm among adolescents diagnosed with BD. This study underscores the urgent need for societal, familial and educational support systems to prioritize the well-being of adolescents and offers valuable insights and guidelines for the prevention, diagnosis and treatment of adolescent BDs.

Effects of Exercise Habits and Gender on Sports e-Learning Behavior: Evidence from an Eye-Tracking Study.

Background/Objective: In the post-epidemic era, an increasing number of individuals were accustomed to learning sports and physical activity knowledge online for fitness and health demands. However, most previous studies have examined the influence of e-learning materials and resources on learners and have neglected intrinsic factors such as experience and physiological characteristics. Therefore, we conducted a study to investigate the effect of exercise habits and gender on sports e-learning behavior via eye-tracking technology. Methods: We recruited a sample of 60 undergraduate students (mean age = 19.6) from a university in Nanjing, China. They were randomly assigned into 4 groups based on 2 genders × 2 exercise habits. Their gaze behavior was collected by an eye-tracking device during the experiment. The cognitive Load Test and Learning Effect Test were conducted at the end of the individual experiment. Results: (1) Compared to the non-exercise habit group, the exercise habit group had a higher fixation count (P<0.05), a shorter average fixation duration (P<0.05), a smaller average pupil diameter (P<0.05), and a lower subjective cognitive load (P<0.05) and better learning outcome (P<0.05). (2) Male participants showed a greater tendency to process information from the video area of interest (AOIs), and had lower subjective cognitive load (P < 0.05) and better learning outcomes (P < 0.05). (3) There was no interaction effect between exercise habits and gender for any of the indicators (P > 0.05). Conclusion: Our results indicate that exercise habits effectively enhance sports e-learning outcomes and reduce cognitive load. The exercise habits group showed significant improvements in fixation counts, average fixation duration, and average pupil diameter. Furthermore, male subjects exhibited superior learning outcomes, experienced lower cognitive load, and demonstrated greater attentiveness to dynamic visual information. These conclusions are expected to improve sports e-learning success and address educational inequality.

In Vivo Fluorescent Labeling of Foam Cell-Derived Extracellular Vesicles as Circulating Biomarkers for In Vitro Detection of Atherosclerosis.

Real-time monitoring of the development of atherosclerosis (AS) is key to the management of cardiovascular disease (CVD). However, existing laboratory approaches lack sensitivity and specificity, mostly due to the dearth of reliable AS biomarkers. Herein, we developed an in vivo fluorescent labeling strategy that allows specific staining of the foam cell-derived extracellular vesicles (EVs) in atherosclerotic plaques, which are released into the blood as circulating biomarkers for in vitro detection of AS. This strategy relies on a self-assembled nanoprobe that could recognize foam cells specifically, where the probe is degraded by the intracellular HClO to produce a trifluoromethyl-bearing boron-dipyrromethene fluorophore (termed B-CF3), a lipophilic dye that can be transferred to the exosomal membranes. These circulating B-CF3-stained EVs can be detected directly on a fluorescence spectrometer or microplate reader without resorting to any sophisticated analytical method. This liquid-biopsy format enables early detection and real-time differentiation of lesion vulnerability during AS progression, facilitating effective CVD management.

Cost-effectiveness analysis of tislelizumab in combination with chemotherapy for the first-line treatment of patients with metastatic or recurrent nasopharyngeal carcinoma in China.

BACKGROUND: The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first-line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost-effective in China. The purpose of this study is to evaluate the cost-effectiveness of tislelizumab plus GP for the first-line treatment of R/M NPC from the perspective of the Chinese healthcare system. METHODS: A partitioned survival model with three discrete health states was constructed to evaluate the cost-effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE-309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality-adjusted life years (QALYs), total cost, and incremental cost-benefit ratio (ICER). RESULTS: The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost-effective at the willingness-to-pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD-L1 expression had little impact on the ICER of this regimen. CONCLUSION: In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first-line treatment, is more cost-effective than the GP regimen in China.

Cost-effectiveness analysis of sintilimab plus IBI305 versus sorafenib for unresectable hepatic cell carcinoma in China.

BACKGROUND: Sintilimab combined with IBI305 treatment regimen had potential clinical benefits than sorafenib in the first-line treatment of patients with unresectable hepatic cell carcinoma (HCC). However, whether sintilimab plus IBI305 has economic benefits in China remains unclear. METHODS: From the perspective of Chinese payers, we used the Markov model to simulate patients with HCC receiving treatment with sintilimab plus IBI305 and sorafenib. The transition probability between health states was estimated using the parametric survival model, and the cumulative medical costs and utility of the two treatment methods were estimated. Considering the incremental cost-effectiveness ratios (ICERs) as the evaluation index, sensitivity analyses were performed to explore the impact of uncertainty on the results. RESULTS: Compared to sorafenib, sintilimab plus IBI305 generated an additional $17552.17 and 0.33 quality-adjusted life years, resulting in an ICER of $52817.89. The analysis outcomes were most sensitive to the total cost of sintilimab plus IBI305. With a willingness-to-pay threshold of $38,334, sintilimab plus IBI305 showed a 1.28% probability of being cost-effective. The total cost of sintilimab plus IBI305 should be reduced by at least 31.9% to be accepted by Chinese payers. CONCLUSIONS: Regardless of whether the price of sintilimab plus IBI305 and sorafenib is covered by Medicare, sintilimab plus IBI305 is unlikely to be cost-effective for first-line treatment of patients with unresectable HCC.

Effectiveness of exercise intervention on improving fundamental motor skills in children with autism spectrum disorder: a systematic review and meta-analysis.

Background: Autism spectrum disorder (ASD) is a severe public health concern, and most of the children with ASD experience a substantial delay in FMS. This study aimed to investigate the effectiveness of exercise interventions in improving FMS in children with ASD, and provide evidence to support the scientific use of exercise interventions in practice. Methods: We searched seven online databases (PubMed, Scopus, Web of Science, Embase, EBSCO, Clinical Trials, and The Cochrane Library) from inception to May 20, 2022. We included randomized control trials of exercise interventions for FMS in children with ASD. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database Scale. Stata 14.0 software was used for meta-analysis, forest plotting, subgroup analysis, heterogeneity analysis, and meta-regression. Results: Thirteen studies underwent systematic review (541 participants), of which 10 underwent meta-analysis (297 participants). Overall, exercise interventions significantly improved overall FMS in children with ASD. Regarding the three categories of FMS, exercise interventions significantly improved LMS (SMD = 1.07; 95% CI 0.73 to 1.41, p < 0.001), OCS (SMD = 0.79; 95% CI 0.32 to 1.26, p = 0.001), and SS (SMD = 0.72; 95% CI 0.45 to 0.98, p < 0.0001). Conclusion: exercise interventions can effectively improve the FMS of children with ASD. The effects on LMS are considered as large effect sizes, while the effects on OCS and SS are considered as moderate effect sizes. These findings can inform clinical practice. Systematic review registration: https://inplasy.com/inplasy-2022-12-0013/.

Insights of Life Molecules' Dynamic Distribution in Live Cells via Sequence-Structure Bispecific Fluorescent RNA.

Life molecules' distributions in live systems construct the complex dynamic reaction networks, whereas it is still challenging to demonstrate the dynamic distributions of biomolecules in live systems. Herein, we proposed a dynamic analysis strategy via sequence-structure bispecific RNA with state-adjustable molecules to monitor the dynamic concentration and spatiotemporal localization of these biomolecules in live cells based on the new insight of fluorescent RNA (FLRNA) interactions and their mechanism of fluorescence enhancement. Typically, computer-based nucleic acid-molecular docking simulation and molecular theoretical calculation have been proposed to provide a simple and straightforward method for guiding the custom-design of FLRNA. Impressively, a novel FLRNA with sequence and structure bispecific RNA named as a structure-switching aptamer (SSA) was introduced to monitor the real-time concentration and spatiotemporal localization of biomolecules, contributing to a deeper insight of the dynamic monitoring and visualization of biomolecules in live systems.

Ground and excited states of even-numbered Hubbard ring at half-filling: comparison of the extended Gutzwiller approach with exact diagonalization.

It remains a great challenge in condensed matter physics to develop a method to treat strongly correlated many-body systems with balanced accuracy and efficiency. We introduce an extended Gutzwiller (EG) method incorporating a manifold technique, which builds an effective manifold of the many-body Hilbert space, to describe the ground-state (GS) and excited-state (ES) properties of strongly correlated electrons. We systematically apply an EG projector onto the GS and ES of a non-interacting system. Diagonalization of the true Hamiltonian within the manifold formed by the resulting EG wavefunctions gives the approximate GS and ES of the correlated system. To validate this technique, we implement it on even-numbered fermionic Hubbard rings at half-filling with periodic boundary conditions, and compare the results with the exact diagonalization (ED) method. The EG method is capable of generating high-quality GS and low-lying ES wavefunctions, as evidenced by the high overlaps of wavefunctions between the EG and ED methods. Favorable comparisons are also achieved for other quantities including the total energy, the double occupancy, the total spin and the staggered magnetization. With the capability of accessing the ESs, the EG method can capture the essential features of the one-electron removal spectral function that contains contributions from states deep in the excited spectrum. Finally, we provide an outlook on the application of this method on large extended systems.

Cost-effectiveness analysis of durvalumab plus chemotherapy as first-line treatment for biliary tract cancer.

Objective: The TOPAZ-1 trial reported a significant survival benefit of durvalumab in combination with chemotherapy for the first-line treatment of biliary tract cancer (BTC). However, no studies have evaluated the economics of this treatment option. The aim of this study was to assess the cost effectiveness of durvalumab plus chemotherapy compared to placebo plus chemotherapy from the perspective of US and Chinese payers. Methods: Based on clinical data from the TOPAZ-1 trial, a Markov model was developed to simulate 10-year life expectancy and total healthcare costs for patients with BTC. The treatment group received durvalumab in combination with chemotherapy and the control group received placebo plus chemotherapy. The primary outcomes analyzed included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). Uncertainty in the analysis results was assessed by sensitivity analysis. Results: For US payers, the placebo plus chemotherapy group had a total cost of $56,157.05 and a utility of 1.10 QALYs, while the durvalumab plus chemotherapy group had a total cost of $217,069.25, a utility of 1.52 QALYs, resulting in an ICER of $381,864.39/QALY. For Chinese payers, the ICER of durvalumab plus chemotherapy group was $367,608.51/QALY. Sensitivity analysis showed that the analysis was most sensitive to the price of durvalumab. For US and Chinese payers, under the respective willing to pay thresholds, the likelihood of the durvalumab plus chemotherapy arm being cost-effective was 0%. Conclusions: Both in China and in the US, durvalumab in combination with chemotherapy is not a cost-effective option for the first-line treatment of BTC compared with chemotherapy.

m6A-related lncRNA-based immune infiltration characteristic analysis and prognostic model for colonic adenocarcinoma.

BACKGROUND: Colonic adenocarcinoma (COAD) is a common gastrointestinal tract tumor, and its occurrence and progression are typically associated with genomic instability, tumor-suppressor gene and oncogene mutations, and tumor mutational load. N6-methyladenosine (m6A) modification of RNAs and long non-coding RNA (lncRNA) expression are important in tumorigenesis and progression. However, the regulatory roles of m6A-associated lncRNAs in the tumor microenvironment, stratification of prognosis, and immunotherapy are unclear. METHODS: We screened 43 prognostic lncRNAs linked to m6A and performed consistent molecular typing of COAD using consensus clustering. The single-sample Gene Set Enrichment Analysis and ESTIMATE algorithms were used to assess the immune characteristics of different subgroups. Covariation between methylation-related prognostic lncRNAs was eliminated by least absolute shrinkage and selection operator Cox regression. A nomogram was created and evaluated by combining the methylation-related prognostic lncRNA model with other clinical factors. The relationship between the prognostic model grouping and microsatellite instability, immunophenotype score, and tumor mutation burden was validated using R scripts. Finally, we used a linkage map to filter sensitive medicines to suppress the expression of high-risk genes. Three m6A-associated lncRNA modes were identified in 446 COAD specimens with different clinical endpoints and biological statuses. Risk scores were constructed based on the m6A-associated lncRNA signature genes. Patients with lower risk scores showed superior immunotherapy responses and clinical benefits compared to those with higher risk scores. Lower risk scores were also correlated with higher immunophenotype scores, tumor mutation burden, and mutation rates in significantly mutated genes (e.g., FAT4 and MUC16). Piperidolate, quinostatin, and mecamylamin were screened for their abilities to suppress the expression of high-risk genes in the model. CONCLUSIONS: Quantitative assessment of m6A-associated lncRNAs in single tumors can enhance the understanding of tumor microenvironment profiles. The prognostic model constructed using m6A-associated lncRNAs may facilitate prognosis and immunotherapy stratification of patients with COAD; finally, three drugs with potential therapeutic value were screened based on the model.

A double-switch pHLIP system enables selective enrichment of circulating tumor microenvironment-derived extracellular vesicles.

Circulating tumor microenvironment-derived extracellular vesicles (cTME-EVs) are gaining considerable traction in cancer research and liquid biopsy. However, the study of cTME-EVs is largely limited by the dearth of a general isolation technique to selectively enrich cTME-EVs from biological fluids for downstream analysis. In this work, we broke through this dilemma by presenting a double-switch pH-low insertion peptide (D-S pHLIP) system to exclusively harvest cTME-EVs from the blood serum of tumor mouse models. This D-S pHLIP system consists of a highly sensitive pH-driven conformational switch (pKa ≈ 6.8) that allows specific installation of D-S pHLIP on the EV membranes in TME (pH 6.5 to 6.8) and a unique hook-like switch to "lock" the peptide securely on the cTME-EVs during the systemic circulation. The D-S pHLIP-anchored cTME-EVs were magnetically enriched and then analyzed with high-resolution messenger RNA sequencing, by which more than 18 times the number of TME-related differentially expressed genes and 10 times the number of hub genes were identified, compared with those achieved by the gold-standard ultracentrifugation. This work could revolutionize basic TME research as well as clinical liquid biopsy for cancer.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy versus chemotherapy as the first-line treatment for advanced esophageal cancer.

OBJECTIVE: The KEYNOTE-590 trial showed that individuals with advanced esophageal cancer who received Pembrolizumab in combination with chemotherapy as a first-line regimen achieved a significant extension of survival. However, this treatment option increases the financial burden on patients and the economic benefits remain to be further evaluated. METHODS: A Markov model was used to simulate 10-year survival of patients with esophageal cancer from the perspective of United States (US) Medicare payers. We evaluated the economics of Pembrolizumab plus chemotherapy in the PD-L1 positive score (CPS ≥10) and any PD-L1 expression groups, respectively. We estimated total costs, quality-adjusted life years (QALYs), and calculated incremental cost effectiveness ratios (ICERs). Sensitivity analyses were conducted to explore the impact of uncertainties on the results. Subgroup analysis was also performed. RESULTS: The analysis results showed that the ICER for pembrolizumab plus chemotherapy versus chemotherapy alone was $293,513.17/QALYs in the any PD-L1 expression group. This exceeded the threshold of willingness to pay ($150,000/QALYs). ICERs were most sensitive to the cost of pembrolizumab and the ICERs exceeded $150,000/QALYs in all subgroups. CONCLUSIONS: Evidence suggests that first-line pembrolizumab in combination with chemotherapy is not a cost-effective option for advanced esophageal cancer in the US, regardless of PD-L1 expression status.

Cost-Effectiveness Analysis of Sintilimab Combined with Chemotherapy Versus Chemotherapy Alone as the First-Line Treatment for Advanced Esophageal Cancer.

Background: Esophageal cancer has a poor prognosis and currently ranks sixth in global cancer mortality rates. The ORIENT-15 trial showed sintilimab plus chemotherapy significantly improved survival when compared to chemotherapy alone. This study aimed to evaluate the cost-effectiveness of sintilimab, a programmed death-ligand 1 (PD-L1) inhibitor, plus chemotherapy in treating patients with esophageal cancer compared with chemotherapy alone. Methods: A Markov model with a 10-year horizon was developed based on the perspective of the Chinese healthcare payers. We conducted a cost-effectiveness analysis for sintilimab combined with chemotherapy based on a questionnaire. Patients were grouped into the sintilimab group based on a positive score of 10 or more (combined positive score (CPS) ≥ 10 groups), and those with any other PD-L1 expression were randomized into patient groups. We estimated the cost and the effectiveness of sintilimab on the quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) was computed. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness results. Results: In the base-case analysis, compared with chemotherapy alone, the ICER of sintilimab plus chemotherapy for all patients was $21024.05 per QALY, and in the CPS≥10 group, it was $20974.23 per QALY. This was lower than $37653 per QALY. One-way sensitivity analysis demonstrated that ICERs were most sensitive to the price of sintilimab. Conclusion: The study demonstrated that sintilimab plus chemotherapy for advanced esophageal cancer as its first-line treatment would be more cost-effective than chemotherapy alone in Chinese patients.

A rotationally invariant approach based on Gutzwiller wave function for correlated electron systems.

We introduce a rotationally invariant approach combined with the Gutzwiller conjugate gradient minimization method to study correlated electron systems. In the approach, the Gutzwiller projector is parametrized based on the number of electrons occupying the onsite orbitals instead of the onsite configurations. The approach efficiently groups the onsite orbitals according to their symmetry and greatly reduces the computational complexity, which yields a speedup of20∼50×in the minimal basis energy calculation of dimers. The computationally efficient approach promotes more accurate calculations beyond the minimal basis that is inapplicable in the original approach. A large-basis energy calculation of F2demonstrates favorable agreements with standard quantum-chemical calculations Bytautaset al(2007J. Chem. Phys.127164317).

Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma.

Background: The treatment paradigm of unresectable malignant pleural mesothelioma (MPM) has changed in recent years. Checkmate 743 demonstrate that nivolumab plus ipilimumab showed good clinical benefits compared with chemotherapy in the treatment of MPM. The study is aim to evaluate the cost-effectiveness of Nivolumab plus ipilimumab vs. platinum plus chemotherapy for the first-line treatment of unresectable MPM. Methods: A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of nivolumab plus ipilimumab and chemotherapy over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CheckMate 743 trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness's results. Results: In the base case analysis, the incremental healthcare costs and QALYs for Nivolumab plus Ipilimumab vs. chemotherapy are $196,604.22 and 0.53, respectively, resulting an incremental cost-effectiveness ratio (ICER) of $372,414.28/QALYs for the model cohort of patients with locally advanced or metastatic MPM. However, Probabilistic sensitivity analysis showed that there was no probability that Nivolumab plus ipilimumab was cost-effective within the fluctuation range of other model parameters in first-line in unresectable MPM. The results of one-way sensitivity analysis showed that the cost of Nivolumab was the most sensitive parameter. Conclusions: The ICER of Nivolumab plus ipilimumab is above the theoretical willingness-to-pay threshold in the U.S, which suggests that first-line nivolumab plus ipilimumab for unresectable MPM may be not a cost-effective choice.

In-Sequence High-Specificity Dual-Reporter Unlocking of Fluorescent Probe Enables the Precise Identification of Atherosclerotic Plaques.

The formation of atherosclerotic plaques is the root cause of various cardiovascular diseases (CVDs). Effective CVD interventions thus call for precise identification of the plaques to aid clinical assessment, diagnosis, and treatment of such diseases. In this study, we introduce a dual-target sequentially activated fluorescence reporting system, termed in-sequence high-specificity dual-reporter unlocking (iSHERLOCK), to precisely identify the atherosclerotic plaques in vivo and ex vivo. ISHERLOCK was achieved by creating a three-in-one fluorescent probe that permits highly specific and sensitive detection of lipid droplets and hypochlorous acid via "off-on" and ratiometric readouts, respectively. Based on this format, the upregulated lipid accumulation and oxidative stress-the two hallmarks of atherosclerosis (AS)-were specifically measured in the atherosclerotic plaques, breaking through the barrier of precise tissue biopsy of AS and thus aiding effective CVD stewardship.