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Patients with early-stage COPD were assigned to usual care plus tiotropium or placebo. Tiotropium resulted in better FEV 1 values. The annual decline in the prebronchodilator FEV 1 was similar in the two groups, but a benefit from tiotropium was seen in postbronchodilator FEV 1 .

In recent years, functional genomics approaches combining genetic information with bulk RNA-sequencing data have identified the downstream expression effects of disease-associated genetic risk factors through so-called expression quantitative trait locus (eQTL) analysis. Single-cell RNA-sequencing creates enormous opportunities for mapping eQTLs across different cell types and in dynamic processes, many of which are obscured when using bulk methods. Rapid increase in throughput and reduction in cost per cell now allow this technology to be applied to large-scale population genetics studies. To fully leverage these emerging data resources, we have founded the single-cell eQTLGen consortium (sc-eQTLGen), aimed at pinpointing the cellular contexts in which disease-causing genetic variants affect gene expression. Here, we outline the goals, approach and potential utility of the sc-eQTLGen consortium. We also provide a set of study design considerations for future single-cell eQTL studies.

The amorphous nature of metallic glasses makes them interesting for structural applications. However, the interplay between the nature of atomic structures and mechanical properties remains poorly understood. Dynamic micropillar tests now show the important contribution of the inelastic deformation of atomistic free-volume zones to the deformation behaviour of metallic glasses. The amorphous nature of metallic glasses and their mechanical properties make them interesting for structural applications. However, the interplay between the nature of atomic structures in metallic glasses and mechanical properties remains poorly understood. In this study, high-frequency dynamic micropillar tests have been used to probe both atomic clusters and flow defects in metallic glasses. We show that loosely bonded atomistic free-volume zones that are enveloped elastically by tightly bonded atomic clusters show a deformation character similar to supercooled liquids. At room temperature, the effective viscosity of these free-volume zones is of the order of 1×10 8  Pa s before the occurrence of shear banding. The confined liquid-like deformation of free-volume zones leads to significant mechanical hysteresis in micropillars under dynamic loading, providing important insight into how atomistic structural features affect the deformation behaviours in metallic glasses in the apparent elastic regime. The inelastic behaviour also serves as the basis for the superior damping resistance of metallic glasses.

Studies reporting the historical trends of SO2, NOx, CO, and nonmethane volatile organic compounds emissions in China using unified approaches and sources are limited. Here we established 66‐year emission trends of these four species in China. Six primary anthropogenic sources were included, and we made a series of improvements to the few existing inventories based on detailed statistical data, recently published emission factors, and technology renewal to reduce the uncertainties. National SO2, NOx, CO, and nonmethane volatile organic compounds emissions in 2015 were 27.1, 20.6, 188, and 28.4 Mt, with annual growth rates of 5.8%, 5.9%, 3.8%, and 4.6% since 1949, respectively. In recent years, fossil fuel combustion was the major contributor to SO2, NOx, and CO emissions, whereas industrial process contributed most to VOCs emissions. Our results revealed a 10% decrease in the SO2 emissions from 2005 to 2010 as a result of improvements in the flue gas desulfurization installation rate. NOx emissions stopped rising and started falling in 2011, with technology renewal and the penetration of end‐of‐pipe control measures in industrial boilers and cement production. Furthermore, we calculated future speciated VOCs emissions and ozone formation potential under alternative policy scenarios and projected to reduce emissions by 10% (compared with 2013 levels) with stringent control measures in 2020. A reactivity‐based control strategy was proposed to achieve greater ozone formation potential reductions while requiring less VOCs emissions reduction. Plain Language Summary Over past half century, the emissions of air pollutants generated through human activities in China have increased rapidly. The study of long‐term emissions trends will improve our understanding of human influence on climate change and air quality. Here we established 66‐year emission trends of four major species for the first time and evaluated the impact of government policy on emission. The central government initialed the most stringent ever action plan in China to cut emissions, for example, from 1 January 2018, China began to levy environmental protection tax, aimed at SO2, NOx, CO, VOCs, and other pollutants. Our result reveals a decrease in the SO2 and NOx emissions, consistent with satellite observation, while VOCs emissions continued to rise. The emission‐based reduction plan for VOCs have been implemented nationwide. In this study, we further proposed a reactivity‐based control strategy to improve the air quality more effectively. Key Points Historical emission trends were evaluated for SO2, NOx, CO, and volatile organic compounds (VOCs) in China since 1949 National SO2 and NOx emissions started to decline in 2007 and 2012, respectively, while VOCs emissions kept on rising A reactivity‐based control strategy was proposed to achieve greater OFP reduction with less VOCs emissions reduction

Multiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease’s molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45–65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management. The genetic factors involved in disease progression and drug resistance in multiple myeloma (MM) are varied and complex. Here, genomic and transcriptomic profiling of 511 relapsed and refractory MM patients reveals genetic alterations in several oncogenic pathways contributing to progression and resistance to MM therapies.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein–coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies. The International Myeloma Working Group conveyed panel of experts to review patient and disease-related factors affecting efficacy and safety of immunotherapy, summarize existing information on sequencing therapy and provide a series of core recommendations.

Electrocaloric effect (ECE) has the potential applications in solid-state refrigeration with the features of high efficiency and environmentally friendly. Large adiabatic temperature change in a wide temperature range is needed for electrocaloric effect to meet the requirement of commercially application. In this work, giant electrocaloric effect is found in PbTiO 3 nanoparticle with double-vortex domain structure in a wide temperature range by using phase field method, which the lowest and highest adiabatic temperature change (Δ T ) is 7.2 K and 16.5 K, respectively. The influence of misfit strain on the ECE of PbTiO 3 nanoparticle with the double-vortex domain structure is investigated, and results show that the compress misfit strain can enhance the ECE, but the tensile misfit strain reduces the ECE. This work reveals a way to obtain giant ECE of ferroelectric materials by domain engineering and strain engineering in a wide temperature range.

Background:The association between radiomic features derived from sacroiliac joint (SIJ) magnetic resonance imaging (MRI) and genomic characteristics in axial Spondyloarthritis (axSpA) remains poorly understood. The hypothesis driving this study is that radiomic characteristics of the SIJ-MRI in axSpA might reflect underlying genetic alterations.Objectives:The primary objective of this study was to explore the correlation between radiomic labels (Radscore) related to axSpA and mRNA expression profiles.Methods:A retrospective cohort of 1256 patients with low back pain (axSpA=922, non-axSpA=334) was enrolled. Additionally, a prospective cohort of 116 patients (axSpA=60, non-axSpA=56) was included. Radiomics features were derived from SIJ-MRI data of all patients, divided into training (854), testing (370), and internal validation (116 prospective patients) groups and reduced using mRMR and LASSO algorithms. Patients were categorized into Radscore-H(higher than cutoff) and Radscore-L (lower than cutoff) groups based on the cutoff value of radiomics features. Blood sample of these 116 patients were collected and high-throughput sequencing was further performed. Differentially expressed genes (DEGs) were identified through comparisons between Radscore-H and Radscore-L, as well as between axSpA and non-axSpA. Overlapping genes were determined and Spearman correlate analysis was performed to explore the correlation between overlapping genes and retained radiomics features.Results:A total of 1037 radiomics features were extracted and reduced to 13 features to construct the Radscore. 227 and 145 DEGs were further identified between axSpA and non-axSpA groups, and between Radscore+ and Radscore- groups, respectively. Among them, 27 overlapping genes were detected. Subsequent correlation analysis determined AC018645.2, AP005329.1, DTL, ESCO2, LINC02085, PZP, with certain genes showed a strong correlation with Radscore and specific radiomic features.Conclusion:This study suggests that genes such as AC018645. [2], AP005329. [1], DTL, ESCO2, LINC02085, PZP may play a role in the radiographic phenotypes of axial spondyloarthritis. The correlation between these genes and specific radiomic features provides insights into potential genetic mechanisms underlying axSpA radiographic characteristics.REFERENCES:[1] Chen, M.T., H.A. Lu, S.J. Copley, et al, A Novel Radiogenomics Biomarker for Predicting Treatment Response and Pneumotoxicity From Programmed Cell Death Protein or Ligand-1 Inhibition Immunotherapy in NSCLC[J]. Journal of Thoracic Oncology, 2023. 18(6): p. 718-730. doi: 10.1523/JNEUROSCI.1448-22.2022.[2] Spielvogel, C.P., S. Stoiber, L. Papp, et al, Radiogenomic markers enable risk stratification and inference of mutational pathway states in head and neck cancer[J]. European Journal of Nuclear Medicine and Molecular Imaging, 2023. 50(2): p. 546-558. doi: 10.1007/s00259-022-05973-9.Figure 1.A comprehensive visualization of gene expression data. (A) Volcano plot in identification DEGs between axSpA and non-axSpA. (B) Volcano plot in identification DEGs between Radscore-H and Radscore-L. (C) Venn plot in identification overlap DEGs of axSpA and non-axSpA, Radscore-H and Radscore-L.Figure 2.A heatmap showcasing the correlation between included radiomic features and transcriptomics in axial spondyloarthritis.***: P<0.001; **: P<0.01; *: <0.01≤P<0.05Acknowledgements:This work was supported by National Natural Science Foundation of China (Grant No. 82201997).Disclosure of Interests:None declared.

Cognitive impairment commonly occurs among older people worldwide. Although the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet was associated with better cognitive function and lower risk of cognitive impairment, it could not be applied to older Chinese due to the traditional dietary characteristics in China. We aimed to develop the Chinese version of the MIND (cMIND) diet and verify its association with cognitive impairment among older Chinese individuals. A cross-sectional study. We included a total of 11,245 participants from the Chinese Longitudinal Healthy Longevity Study (CLHLS) follow-up survey in 2018. The mean age of the participants at study baseline was 84.06 (±11.46) years. We established the cMIND diet based on current evidence in the diet-cognition field, combined with Chinese dietary characteristics. The verification of its association with cognitive impairment was conducted using the data from the CLHLS follow-up survey. Adherence to the cMIND diet was assessed by the cMIND diet score, which was calculated from a food frequency questionnaire. Cognitive impairment was identified by the Mini-Mental State Examination. Instrumental activities of daily living (IADL) disability was defined according to the self-reported performance of eight activities. The cMIND diet comprised 11 brain-healthy food groups and 1 unhealthy food group. The median cMIND diet score of all participants was 4.5 (from a total of 12 points) and the prevalence of cognitive impairment was 15.2%. Compared with the lowest tertile, the highest tertile score was associated with lower odds of cognitive impairment (odds ratio (OR)=0.60, 95% confidence interval (CI): 0.51–0.72) and IADL disability (OR=0.86, 95% CI: 0.75–0.98) in the full-adjusted model. We developed the cMIND diet that was suitable for older Chinese individuals, and our results suggested that higher adherence to the cMIND diet was associated with reduced odds of cognitive impairment and IADL disability. In view of the limitations of cross-sectional design in the study, further research is clearly warranted.

SummaryDespite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor.IntroductionTo compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture.MethodsCommunity-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients.ResultsBy 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not.ConclusionWhile both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income.Trial registrationClinicalTrials.gov: NCT01401556