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The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Atherosclerosis is a major contributor to cardiovascular diseases and mortality globally. The progression of atherosclerotic disease results in the expansion of plaques and the development of necrotic cores. Subsequent plaque rupture can lead to thrombosis, occluding blood vessels, and end-organ ischemia with consequential ischemic injury. Atherosclerotic plaques are formed by the accumulation of lipid particles overloaded in the subendothelial layer of blood vessels. Abnormally elevated blood lipid levels and impaired endothelial function are the initial factors leading to atherosclerosis. The atherosclerosis research has never been interrupted, and the previous view was that the pathogenesis of atherosclerosis is an irreversible and chronic process. However, recent studies have found that the progression of atherosclerosis can be halted when patients’ blood lipid levels are reversed to normal or lower. A large number of studies indicates that it can inhibit the progression of atherosclerosis lesions and promote the regression of atherosclerotic plaques and necrotic cores by lowering blood lipid levels, improving the repair ability of vascular endothelial cells, promoting the reverse cholesterol transport in plaque foam cells and enhancing the ability of macrophages to phagocytize and clear the necrotic core of plaque. This article reviews the progress of research on the mechanism of atherosclerotic plaque regression. Our goal is to provide guidance for developing better therapeutic approaches to atherosclerosis by reviewing and analyzing the latest scientific findings.

Abstract Objectives The excessive adduction of ventricular folds has been observed in patients with dysphonia and professional singers. Whether these changes in the ventricular folds are the cause or just a result of disease progression remains unclear, and their potential pathological and physiological implications are yet to be determined. This study aimed to examine the impact of different degrees of ventricular adduction on acoustics, aerodynamics, and vocal fold vibration. Methods The excised models of mild and severe ventricular adduction were established. We recorded the vibration pattern of vocal folds and ventricular folds and measured acoustic metrics, including fundamental frequency (F0), Jitter, Shimmer, harmonic‐to‐noise ratio (HNR), and sound pressure level (SPL). Furthermore, we evaluated the aerodynamics index through phonation threshold pressure (PTP), phonation instability pressure (PIP), mean flow rate (MFR), phonation threshold flow (PTF), and phonation instability flow (PIF). Results Irregular vibrations of the ventricular fold were observed during ventricular adduction. Notably, mild and severe ventricular adduction conditions showed a significant increase in PTP, Shimmer, and Jitter, whereas MFR, PIF, and HNR decreased compared with the control condition. Conclusions Ventricular adduction leads to the deterioration of acoustic and aerodynamic parameters. The aperiodic and irregular vibration of the ventricular folds may be responsible for this phenomenon, although further experiments are warranted. Understanding the functioning of ventricular folds can be beneficial in directing the treatment of muscle tension dysphonia and improving voice training techniques. Level of evidence: level 4.

ObjectiveTo investigate the correlation between chronic rhinosinusitis (CRS) and bronchial asthma, focusing on the CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP), as well as their impact on lung function.MethodsA total of 141 patients diagnosed with chronic nasal-sinus inflammation were included in this study. Clinical data, including medical histories, nasal endoscopy scores, CT scores, symptom scores, and quality of life assessments, were collected.ResultsAmong the patients with CRSsNP, 23.8% had concomitant bronchial asthma. The incidence of asthma was significantly associated with the severity of sinus involvement in CRSsNP patients (p = 0.049). Pulmonary function impairment was correlated with the severity of sinus inflammation in CRSsNP patients (p = 0.019). Quality of life was significantly affected in patients with concomitant asthma and CRSsNP or CRSwNP.ConclusionChronic rhinosinusitis, both with and without nasal polyps, is closely correlated with bronchial asthma. Pulmonary function impairment is associated with the extent of inflammatory lesions in CRSsNP. Although CRSwNP does not significantly affect pulmonary function, the treatment of sinus diseases can contribute to the control of asthma.

BackgroundFatigue is one of the most common and burdensome symptoms for patients with multiple sclerosis (PwMS), considerably impacting their quality of life and employment. Numerous reports have described the prevalence of MS-related fatigue, but there is no global consensus on this matter.ObjectiveTo examine the global prevalence of MS-related fatigue and identify sources of heterogeneity in the published literature.MethodsA systematic review and meta-analysis were conducted. A comprehensive search of the PubMed, EMBASE, Cochrane Library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), and Wanfang database for potential literature from 2000 to January 31, 2024. A random effects model was used to calculate the prevalence of MS-related fatigue. Subgroup analyses and a meta-regression were used to explore the sources of heterogeneity.ResultsSixty-nine studies from 27 countries were included. The global prevalence of MS-related fatigue was 59.1%, and it has decreased every decade since 2000. Fatigue was prevalent among females, those with lower education levels, those who were older, those with greater disability, and those with longer MS durations. The meta-regression revealed that fatigue measurement instruments were the largest source of heterogeneity.ConclusionThe prevalence of MS-related fatigue is quite high. Healthcare professionals should screen for and manage fatigue for PwMS as early as possible and pay attention to populations with a high prevalence of fatigue. The high heterogeneity among the prevalence rates due to differences in the fatigue scales suggests the importance of reaching a consensus on the best screening tools for MS-related fatigue.

The miRNA plays a key role in the regulation of hormone signaling in insects. The pathways by which miRNAs affect hormone levels are unclear in the honeybee (Apis mellifera), an indispensable pollinator in nature. In this study, ame-miR-5119 was overexpressed and knocked down in larvae by feeding mimics and inhibitors, respectively, and we determined that ame-miR-5119 regulates hormone signaling through the target gene ecdysis triggering hormone (Eth), which affects the larval-pupal transition of workers. The results showed that ame-miR-5119 with a length of 19 nt targets six genes related to the hormone pathway. We focused on Eth and found that ame-miR-5119 and Eth exhibited reverse expression patterns during the transition from larval to pupal stages in workers. Dual luciferase assay confirmed the negative regulatory between ame-miR-5119 and Eth. Overexpression of ame-miR-5119 decreased the mRNA level of Eth, and the Eth receptor (Ethr) expression was not significantly affected, but the expression levels of juvenile hormone (JH) pathway related genes juvenile hormone acid methyltransferase (Jhamt) and Krüppel homolog 1 (Kr-h1) were significantly reduced. In contrast, knockdown of ame-miR-5119 increased the mRNA level of Eth, and the expression of Ethr, Jhamt and Kr-h1 was significantly upregulated. ame-miR-5119 did not affect larval body weight. The number of larvae overexpressing ame-miR-5119 survived in the prepupal stage was lower than that in the control group, and the number of pupations reduced at 11-day-old. The number of larvae that knocked down ame-miR-5119 survived in the prepupal stage was significantly higher than that in the control group, and the number of pupations increased at 11-day-old. These results indicated that ame-miR-5119 negatively regulates the expression of Eth, indirectly inhibits the expression of Ethr, Jhamt, and Kr-h1, and affects the JH biosynthesis, thereby preventing the metamorphic transition from larva to pupa in worker bees. These findings provide evidence that the miRNA regulation of hormone levels in honey bees.

Reducing CO2 emissions represents a global challenge, and the mobility sectors account for a considerable portion of total emissions, with marked disparities across diverse economies. Viewed from a macroscopic perspective, countries and regions around the world can be categorized in various ways. However, relying on a single or a few indicators often proves inadequate to meet the classification requirements for carbon reduction and sustainable development. In this study, employing machine learning and guided by 10 economic indicators, we classified 188 countries/regions into 6 identifiable clusters. Subsequently, by applying ratio analysis and random forest methodologies, we conducted a matrix-based analysis that elucidates the distinct emission characteristics of each mobility sector. Feature importance analysis revealed that for highly developed economies, the total population's contribution was significant, especially in domestic and international aviation, accounting for 50% and 25% of emissions, respectively. In contrast, for lower-middle-income countries and regions, while the total population still played a pivotal role, its influence was most pronounced in railway transportation, reaching 67%. For rapidly developing economies, domestic aviation emissions reached a peak influence of 61%. These insights emphasize the necessity for strategies tailored to the unique attributes of economic entities.

Abstract Aim To systematically review longitudinal studies investigating the impact of dental visiting patterns on oral health across the life course. Methods Five databases (MEDLINE, Embase, Scopus, Web of Science, CINAHL) were searched up to March 2023. Results were screened based on eligibility criteria in a two-stage process: title and abstract, and full-text review. A backward search of reference lists and a forward search of citations of the included papers was also conducted. The quality of the included papers was assessed using the Newcastle-Ottawa Scale. Key study information was extracted and a narrative synthesis of the findings was performed. Results Eleven papers from five longitudinal studies in five countries (Australia, Brazil, China, New Zealand, Sweden) met the inclusion criteria. Studies of moderate to high quality consistently reported that regular dental attendance was associated with having less dental caries experience, fewer missing teeth and better oral health-related quality of life. Inconsistent findings were observed for decayed teeth, and no association was found for periodontal condition. Conclusions This review highlights an association between regular dental visiting pattern and improved oral health, notably less dental caries experience and better oral health-related quality of life. Dental attendance emerges as an important predictor of oral health across the life course, underscoring the importance of routine dental care. Registration information The PROSPERO registration number is CRD42023396380.

To address the challenges posed by propagation channel impairments and to meet the high data rate requirements of laser communications, this study introduces a pioneering low-density parity-check (LDPC) decoder characterized by its high throughput and low complexity. The unique design of this decoder, based on an inter-frame pipeline and intra-frame parallel (IFPP-IFP) scheme, is specifically tailored to maximize the efficiency of processing units, leading to a substantial increase in decoding throughput. The implementation of IFPP is realized through a novel full-overlap message passing (FOMP) scheme and a dynamic address access (DAA) algorithm, distinguishing it from current solutions. Additionally, the decoder employs a message packing strategy and low-complexity data alignment units to effectively achieve IFP. Compared to existing solutions, our hardware implementation on the Xilinx XCKU060 FPGA demonstrates significant progress. The decoder achieves a decoding throughput of 2.67 Gb/s at 10 iterations and 350MHz. Remarkably, when five decoders are used on a single FPGA device, the throughput soars to 13.3 Gb/s, outperforming state-of-the-art designs by 1.3 times and concurrently reducing resource consumption by half. This combination of resource efficiency and enhanced throughput highlights the innovative and superior nature of our proposed approach.

Abstract Background In the era of antiretroviral therapy (ART), central nervous system (CNS) complications in patients with human immunodeficiency virus (HIV) infection are sometimes associated with cerebrospinal fluid (CSF) viral escape. Here, we reported a case of persistent CNS viral escape with recurrent symptomatic encephalitis, which had ultimate stabilization achieved by a combination of ART adjustment and corticosteroids. Case presentation A 27-year-old man with HIV infection complained of recurrent headaches during the last year. His magnetic resonance imaging (MRI) presented diffused bilateral white matter lesions, and laboratory tests confirmed elevated CSF protein level, lymphocytic pleocytosis, and detectable CSF HIV RNA (774 copies/mL). Plasma HIV RNA was well suppressed with tenofovir, lamivudine, and lopinavir/ritonavir. Prednisone 60 mg once daily was initiated to reduce intracranial inflammation, followed by a good clinical response, with CSF HIV RNA still detectable (31.1 copies/mL). During the gradual tapering of prednisone, his headache relapsed, and booming viral loads were detected in both CSF (4580 copies/mL) and plasma (340 copies/mL) with consistent drug-resistant mutations. Thereupon, prednisone was resumed and the ART regimen was switched to zidovudine, lamivudine, and dolutegravir according to drug resistance tests. Persistent clinical recovery of symptoms, neuroimaging, and laboratory abnormalities were observed in the follow-up visits. Conclusion CSF and plasma HIV RNA and further drug resistance tests should be monitored in HIV-infected patients with neurologic symptoms, as opportunistic infections or tumors can be ruled out. ART optimization using a sensitive regimen may be crucial for addressing CSF viral escape and the related encephalitis.

Recently reported van der Waals layered honeycomb rare-earth chalcohalides REChX (RE = rare earth, Ch = chalcogen, and X = halogen) are considered to be promising Kitaev spin liquid (KSL) candidates. The high-quality single crystals of YbOCl, a representative member of the family with an effective spin of 1/2, are available now. The crystalline electric field (CEF) excitations in a rare-earth spin system are fundamentally important for understanding both finite-temperature and ground-state magnetism but remain unexplored in YbOCl so far. In this paper, we conduct a comprehensive Raman scattering study to unambiguously identify the CEF excitations in YbOCl and determine the CEF parameters and wave functions. Our Raman experiments further reveal the anomalous nonlinear CEF splitting under magnetic fields. We have grown single crystals of YbOCl, the nonmagnetic LuOCl, and the diluted magnetic Lu_{0.86}Yb_{0.14}OCl to make a completely comparative investigation. Polarized Raman spectra on the samples at 1.8 K allow us to clearly assign all the Raman-active phonon modes and explicitly identify the CEF excitations in YbOCl. The CEF excitations are further examined using temperature-dependent Raman measurements and careful symmetry analysis based on Raman tensors related to CEF excitations. By applying the CEF Hamiltonian to the experimentally determined CEF excitations, we extract the CEF parameters and eventually determine the CEF wave functions. The study experimentally pins down the CEF excitations in the Kitaev compound YbOCl and sets a foundation for understanding its finite-temperature magnetism and exploring the possible nontrivial spin ground state.

Urban historical heritage areas serve as vital repositories of urban culture and history, playing a crucial role in cultural inheritance and the promotion of urban development. The protection and development of these heritage areas are essential for preserving the cultural characteristics and architectural styles of cities. Despite the growing body of research, a comprehensive review of the dynamic evolution, research frontiers, and future trajectories in this field remains absent. To bridge this gap, this study draws on the Web of Science Core Collection database, selecting 828 papers published between 2000 and 2024 that focus on urban historical heritage conservation and development. By employing Python programming and network analysis tools, this study conducted a systematic analysis of research structures and trends over the past 25 years. The results indicate that countries such as China and Italy, along with their respective research institutions, are at the forefront of global research in this area. Furthermore, this study identified research hotspots, including historic districts, sustainable urban development, urban regeneration, risk assessment, 3D modeling, digital documentation, and cultural tourism. This research not only discusses the challenges faced in the field but also explores future development trends, providing new theoretical perspectives and practical guidance for subsequent studies.

YbOCl is a representative member of the van der Waals layered honeycomb rare-earth chalcohalide RChX (R = rare earth; Ch = O, S, Se, and Te; and X = F, Cl, Br, and I) family reported recently. Its spin ground state remains to be explored experimentally. We grew high-quality single crystals of YbOCl and conducted comprehensive thermodynamic, elastic, and inelastic neutron scattering experiments down to 50 mK. The experiments reveal an antiferromagnetic phase below 1.3 K which is identified as a spin ground state with an intralayer ferromagnetic and interlayer antiferromagnetic ordering. By applying sophisticated numerical techniques to a honeycomb (nearest-neighbor)–triangle (next-nearest-neighbor) model Hamiltonian which accurately describes the highly anisotropic spin system, we are able to simulate the experiments well and determine the diagonal and off-diagonal spin-exchange interactions. The simulations give an antiferromagnetic Kitaev term comparable to the Heisenberg one. The experiments under magnetic fields allow us to establish a magnetic field–temperature phase diagram around the spin ground state. Most interestingly, a relatively small magnetic field (∼0.3 to 3 T) can significantly suppress the antiferromagnetic order, suggesting an intriguing interplay of the Kitaev interaction and magnetic fields in the spin system. The present study provides fundamental insights into the highly anisotropic spin systems and opens a window to look into Kitaev spin physics in a rare-earth-based system.

Land Use and Land Cover Change (LULCC) introduces considerable uncertainties in its relationship with carbon emissions, posing challenges to nature-based climate mitigation. The effective establishment and protection of carbon sinks through land use management lack clarity. To address this challenge, this study utilized top-down interannual grided CO2 data from satellite observations, revealing a 7 % decline in carbon sinks in mainland China from 2016 to 2019. Faced with this anomaly, we proposed a novel approach that combined machine learning with traditional regression analysis, to investigate the nonlinear relationship between annual spatiotemporal variations in net carbon exchange and LULCC. Sentinel-2 imagery was employed for high-resolution (10 m) LULC classification based on uniform rules. Particularly, time-series LULC class probabilities were considered and estimated using a deep learning framework via the Google Earth Engine (GEE) cloud platform, which allows us to access the effects of dynamic LULCC. GIS methods were applied to enhance machine learning interpretability, integrating multi-source remote sensing datasets, particularly for capturing nonlinear features in spatiotemporal aspects of LULCC and carbon emissions. Threshold effects revealed how LULCC transformed areas were associated with carbon sinks or sources. The results mapped carbon sink shrinkage locations, highlighting correlations with significant reductions in snow cover (−6.25 %), changing water patterns (−1.3 %), urban expansion (1 %), and mixed forest changes (regrowth of 4 % and deforestation of −1%). This research aims to advance understanding of carbon emissions through remote sensing, bridging different Earth observation data within a geostatistical context, and expects to provide a new validation method for the bottom-up approach.

Background: Hematopoietic cell signal transducer (HCST) and tyrosine kinase-binding protein (TYROBP) are triggering receptors expressed on myeloid cells 2 (TREM2), which are pivotal in the immune response to disease. Despite growing evidence underscoring the significance of TREM2, HCST, and TYROBP in certain forms of tumorigenesis, a comprehensive pan-cancer analysis of these proteins is lacking. Methods: Multiple databases were synthesized to investigate the relationship between TREM2, HCST, TYROBP, and various cancer types. These include prognosis, methylation, regulation by long non-coding RNAs and transcription factors, immune signatures, pathway activity, microsatellite instability (MSI), tumor mutational burden (TMB), single-cell transcriptome profiling, and drug sensitivity. Results: TREM2, HCST, and TYROBP displayed extensive somatic changes across numerous tumors, and their mRNA expression and methylation levels influenced patient outcomes across multiple cancer types. long non-coding RNA (lncRNA) -messenger RNA (mRNA) and TF-mRNA regulatory networks involving TREM2, HCST, and TYROBP were identified, with lncRNA MEG3 and the transcription factor SIP1 emerging as potential key regulators. Further immune analyses indicated that TREM2, HCST, and TYROBP play critical roles in immune-related pathways and macrophage differentiation, and may be significantly associated with TGF-β and SMAD9. Furthermore, the expression of TREM2, HCST, and TYROBP correlated with the immunotherapy markers TMB and MSI, and influenced sensitivity to immune-targeted drugs, thereby indicating their potential as predictors of immunotherapy outcomes. Conclusion: This study offers valuable insights into the roles of TREM2, HCST, and TYROBP in tumor immunotherapy, suggesting their potential as prognostic markers and therapeutic targets for various cancers.

Abstract The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell‐surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non‐small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second‐generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first‐generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET‐targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next‐generation sequencing (NGS), reverse transcription‐polymerase chain reaction (RT‐PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.

Hydrothermal carbonation carbon (HTCC) is emerging as a promising material for the adsorption and photodegradation of environmental contaminants. However, the chemical and structural properties of HTCC derived from different lignocellulose biomass have obvious impacts on adsorption and photodegradation. This work employed three different lignocellulose components, including cellulose, hemicellulose, and lignin to synthesize HTCC within a hydrothermal temperature range of 210~290 °C. In comparison to HTCC derived from cellulose and hemicellulose, HTCC derived from lignin (HTCC-L) demonstrated the optimal synergistic adsorption and photodegradation ability for TC degradation, achieving a 63.5% removal efficiency within 120 min. Characterization highlighted the crucial involvement of oxygenated functional groups, especially carboxyl groups, presented on the surface of HTCC-L in TC adsorption. Moreover, the photodegradation of HTCC-L was found to follow a non-radical mechanism, characterized by the charge transformation occurring between the excited unpaired electrons of HTCC-L and TC adsorbed on its surface. This work clarified the differences in HTCC derived from different lignocellulose components on the adsorption and photodegradation of organic pollutants, and provided a novel perspective on the application of HTCC in water treatment.

Objectives: To explore whether: (i) people with severe mental illness (SMI) experience worse oral health than the general population, and (ii) the risk factors for poor oral health in people with SMI. Methods: Cross-sectional data were extracted from the National Health and Nutrition Examination Survey (1999–2016), including on self-rated oral health, oral pain, tooth loss, periodontitis stage, and number of decayed, missing, and filled teeth. Candidate risk factors for poor oral health included demographic characteristics, lifestyle factors, physical health comorbidities, and dental hygiene behaviours. Ordinal logistic regression and zero-inflated negative binomial models were used to explore predictors of oral health outcomes. Results: There were 53,348 cases included in the analysis, including 718 people with SMI. In the fully adjusted model, people with SMI were more likely to suffer from tooth loss (OR 1.60, 95% CI: 1.34–1.92). In people with SMI, risk factors identified for poor oral health outcomes were older age, white ethnicity, lower income, smoking history, and diabetes. Engaging in physical activity and daily use of dental floss were associated with better oral health outcomes. Conclusions: People with SMI experience higher rates of tooth loss than the general population, and certain subgroups are particularly at risk. Performing regular physical exercise and flossing may lower the risk of poor oral health, while smoking and diabetes may increase the risk. These findings suggest opportunities for targeted prevention and early intervention strategies to mitigate adverse oral health outcomes in people with SMI.

With the emergence of Level 4 automated vehicles, it is necessary to investigate the impact of these vehicles on mode choice. Previous studies have looked at the potential benefits and drawbacks of automated vehicles, but there has been little research done on how these vehicles will impact individuals’ travel behaviors. This paper proposes a needs-based approach to study the impact of Level 4 automated vehicles on mode choice. The approach takes into consideration the travel needs of different individuals and their willingness to adopt new technologies. Through a stated preference survey in China, the data on travel preferences and the perceived safety levels of automated vehicles can be collected. Then, a model is built to simulate the adoption of Level 4 automated vehicles and estimate the mode split for different scenarios. The results indicated that private AV modes are preferred, and business and nonwork trips may be the targeted market for all AV modes. Overall, value of automation increases with income for private modes, with large variance. Furthermore, Pro-AV attitude has a positive effect on value of automation, especially for self-owned AV and AV subscription. Accordingly, the needs-based approach demonstrates a promising method to study the impact of new technologies on travel behaviors and provides insights for policy makers to promote more sustainable transportation systems.

ObjectivesThis study aims to systematically review the existing literature and critically appraise the evidence of genome-wide association studies (GWAS) on periodontitis. This study also aims to synthesise the findings of genetic risk variants of periodontitis from included GWAS.MethodsA systematic search was conducted on PubMed, GWAS Catalog, MEDLINE, GLOBAL HEALTH and EMBASE via Ovid for GWAS on periodontitis. Only studies exploring single-nucleotide polymorphisms(SNPs) associated with periodontitis were eligible for inclusion. The quality of the GWAS was assessed using the Q-genie tool. Information such as study population, ethnicity, genomic data source, phenotypic characteristics(definition of periodontitis), and GWAS methods(quality control, analysis stages) were extracted. SNPs that reached conventional or suggestive GWAS significance level(5e-8 or 5e-06) were extracted and synthesized.ResultsA total of 15 good-quality GWAS on periodontitis were included (Q-genie scores ranged from 38-50). There were huge heterogeneities among studies. There were 11 identified risk SNPs (rs242016, rs242014, rs10491972, rs242002, rs2978951, rs2738058, rs4284742, rs729876, rs149133391, rs1537415, rs12461706) at conventional GWAS significant level (pConclusionGWAS of periodontitis showed high heterogeneity of methodology used and provided limited SNPs statistics, making identifying reliable risk SNPs challenging. A clear guidance in dental research with requirement of expectation to make GWAS statistics available to other investigators are needed.

BackgroundImmune-checkpoint inhibitors(ICIs) combined with chemotherapy are emerging as an effective first-line treatment in advanced non-small cell lung cancer (NSCLC); however, reports on the magnitude of effectiveness and safety are conflicting.MethodsRelevant articles published before February 2022 were searched in PubMed, Embase, and the Cochrane Library. The study included all randomized controlled trials that evaluated ICIs with chemotherapy versus chemotherapy for the treatment of NSCLC. Among the outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs).ResultsOur meta-analysis included a total of 12 studies. Overall analysis indicated that ICIs plus chemotherapy could significantly improve OS (HR = 0.79; 95% CI: 0.74-0.84; I2 = 44.4%, P = 0.055), PFS (HR = 0.62; 95% CI: 0.59-0.67; I2 = 75.3%, P = 0.000), and ORR (RR = 1.48; 95% CI: 1.27-1.73; I2 = 79.0%, P = 0.000) when compared to chemotherapy treatments. Subgroup analysis showed that PD-1/PD-L1 inhibitors combined with chemotherapy significantly improved OS, PFS, and ORR when compared with chemotherapy with decreased grade 1-2 TRAEs. In addition, female patients with nonsquamous histology might receive more OS benefit from ICIs plus chemotherapy when compared to chemotherapy alone. Despite the fact that CTLA-4 inhibitors combined with chemotherapy increased PFS, there were no benefits gained in OS nor ORR. When PD-L1/CTLA-4 inhibitors were added to chemotherapy, the risk of grade 3-5 adverse events increased whereas PD-1 inhibitors did not.ConclusionsICIs plus chemotherapy, compared with chemotherapy, were associated with significantly improved PFS, ORR, and OS in NSCLC therapy. However, PD-L1/CTLA-4 inhibitors plus chemotherapy could increase the risk of grade 3-5 adverse events, but not PD-1 inhibitors plus chemotherapy.

Background: This study aimed to assess the overall reporting quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) formulas for patients with diabetes, and to identify factors associated with better reporting quality.Methods: Four databases including PubMed, Embase, Cochrane Library and Web of Science were systematically searched from their inception to December 2022. The reporting quality was assessed based on the Consolidated Standards of Reporting Trials (CONSORT) statement and its CHM formula extension. The overall CONSORT and its CHM formula extension scores were calculated and expressed as proportions separately. We also analyzed the pre-specified study characteristics and performed exploratory regressions to determine their associations with the reporting quality.Results: Seventy-two RCTs were included. Overall reporting quality (mean adherence) were 53.56% and 45.71% on the CONSORT statement and its CHM formula extension, respectively. The strongest associations with reporting quality based on the CONSORT statement were multiple centers and larger author numbers. Compliance with the CHM formula extension, particularly regarding the disclosure of the targeted traditional Chinese medicine (TCM) pattern (s), was generally insufficient.Conclusion: The reporting quality of RCTs in CHM formulas for diabetes remains unsatisfactory, and the adherence to the CHM formula extension is even poorer. In order to ensure transparent and standardized reporting of RCTs, it is essential to advocate for or even mandate adherence of the CONSORT statement and its CHM formula extension when reporting trials in CHM formulas for diabetes by both authors and editors.

IntroductionLimited water and soil phosphorus (P) availability often hampers lucerne productivity in semiarid regions. Plastic film mulch and P application typically enhance young lucerne (2–3 years) productivity by increasing soil water use and P availability. However, the prolonged impact of film mulch and P application on lucerne productivity as the stand ages remains unclear.MethodsThis study conducted a 9-year field experiment on the semiarid Loess Plateau to investigate how film mulch and P application affect lucerne forage yield, soil water content, and soil fertility. The field experiment used a split-plot design with randomized blocks, in which the whole plots were with (M1) and without plastic film mulch (M0), and the split plots were four P rates (0 (P0), 9.7 (P1), 19.2 (P2), and 28.8 (P3) kg P ha−1).Results and discussionThe M1 treatment produced significantly higher lucerne forage yields than the M0 treatment during the first five years, but the yield-increasing effect of film mulch gradually diminished over time, with no effect in Years 6–8, and lower yields than the M0 treatment in Year 9. Phosphorus fertilization significantly increased forage yield after Year 3 in the M0 treatment, but only in Years 3–5 in the M1 treatment. In Years 2–5, film mulch significantly increased soil organic carbon, total nitrogen (N), inorganic N, and microbial biomass carbon in P0, P1, and P2 but not in P3. However, in Years 7–9, film mulch significantly decreased soil available potassium (K), organic carbon mineralization, lucerne density, and shoot K concentration, but did not reduce soil N and P availability at any level P of application. Moreover, plastic film mulch significantly increased the soil water content at 0–300 cm deep from Year 7 onwards. In conclusion, film mulch ceased to enhance lucerne production beyond year 6, which could not be attributed to soil water content, N or P availability but was partially associated with reduced soil K availability. Consequently, future research should focus on soil K availability, and K addition should be considered after five years in lucerne pastures mulched with plastic film in semiarid areas.

Objective To evaluate the health systems efficiency in China and Association of Southeast Asian Nations (ASEAN) countries from 2015 to 2020.Design Health efficiency analysis using data envelopment analysis (DEA) and stochastic frontier approach analysis.Setting Health systems in China and ASEAN countries.Methods DEA-Malmquist model and SFA model were used to analyse the health system efficiency among China and ASEAN countries, and the Tobit regression model was employed to analyse the factors affecting the efficiency of health system among these countries.Results In 2020, the average technical efficiency, pure technical efficiency and scale efficiency of China and 10 ASEAN countries’ health systems were 0.700, 1 and 0.701, respectively. The average total factor productivity (TFP) index of the health systems in 11 countries from 2015 to 2020 was 0.962, with a decrease of 1.4%, among which the average technical efficiency index was 1.016, and the average technical progress efficiency index was 0.947. In the past 6 years, the TFP index of the health system in Malaysia was higher than 1, while the TFP index of other countries was lower than 1. The cost efficiency among China and ASEAN countries was relatively high and stable. The per capita gross domestic product (current US$) and the urban population have significant effects on the efficiency of health systems.Conclusions Health systems inefficiency is existing in China and the majority ASEAN countries. However, the lower/middle-income countries outperformed high-income countries. Technical efficiency is the key to improve the TFP of health systems. It is suggested that China and ASEAN countries should enhance scale efficiency, accelerate technological progress and strengthen regional health cooperation according to their respective situations.

Abstract Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non–small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2‐altered NSCLC, including conventional chemotherapy, programmed death 1 (PD‐1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody‐drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T‐DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2‐mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2‐targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2‐altered NSCLC, focusing on the diagnosis and treatment strategies.

Abstract Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in‐depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

Abstract Background Care practices for very preterm infants and the mortality and morbidity of the infants vary widely among countries and regions with different levels of economic development, including the different areas in China. We aimed to compare the obstetric and delivery room practices of two representative tertiary newborn centers in the northwestern and southern regions of China and the mortality and morbidity of their very preterm infants. Methods A retrospective cohort study was conducted. Very preterm infants born between 220/7 and 316/7 weeks of gestation, and admitted to Qinghai Red Cross Hospital (QHH) and Shenzhen Baoan Women’s and Children’s Hospital (SZH) from January 1, 2018 to December 31, 2020, were included. The infants’ characteristics and short-term outcomes, and the hospitals’ care practices were compared between the two cohorts. Results Three hundred and two infants in QHH and 505 infants in SZH were enrolled, and the QHH cohort was more mature than the SZH cohort was (gestational age 30.14 (29.14–31.14) vs. 29.86 (27.86–31.00 weeks, respectively), p

Adipose tissue is a major component for the regulation of energy homeostasis by storage and release of lipids. As a core element of RNA‐induced silencing complex, argonaute2 (Ago2) plays critical role in maintenance of systemic metabolic demand. Here, we show that high‐fat‐diet‐fed mice exhibit an increase in body mass alongside systematic insulin resistance and altered rate of energy expenditure. Interestingly, Ago2 expression is associated with obesity and an increased amount of adipose tissue. Moreover, increased levels of Ago2 inhibited the expression of AMPKα by promoting its targeting by miR‐148a, the most abundant microRNA in adipose tissues. Those results suggested that Ago2–miR‐148a–AMPKα signaling pathway play an important function in the developing obesity and adiposity, and will further provide basic research data for the potential clinical treatment of obesity.

ABSTRACT Many studies have suggested that gut microbiota dysbiosis may be one of the pathogenesis factors of diabetes mellitus (DM), while it is not clear whether it is involved in the development of diabetic kidney diseases (DKD). The objective of this study was to determine bacterial taxa biomarkers during the progression of DKD by investigating bacterial compositional changes in early and late DKD. 16S rRNA gene sequencing was performed on fecal samples, including the diabetes mellitus (DM), DNa (early DKD), and DNb (late DKD) groups. Taxonomic annotation of microbial composition was performed. Samples were sequenced on the Illumina NovaSeq platform. At the genus level, we found counts of Fusobacterium, Parabacteroides, and Ruminococcus_gnavus were significantly elevated both in the DNa group (P = 0.0001, 0.0007, and 0.0174, respectively) and the DNb group (P

To observe meteorite ablation, simulation experiments were conducted on the L5 ordinary chondrite and IAB-MG iron meteorites in an arc-heated facility and three flight conditions were reproduced. To mimic the high heating rates and the significant shear stress that meteorites experience during Earth entry, the samples were machined into 9° spherical cones with a 20 mm nose radius. High-quality video, the surface temperature, a time-resolved spectrum, and infrared video were recorded. The atom species were determined via spectroscopy to analyze the ablation products. Due to the electrode erosion and dissociation of air, the atomic lines of copper, nitrogen, and oxygen were detected in all the tests. Although the copper atom is a pollutant to the flow field, the five copper lines were used to determine the flow-field temperature. The ablation rates and effective heat of ablation of both the samples were measured under different conditions. The results indicate that shear stress is the dominant factor influencing meteorite ablation. Furthermore, the diversity between stony and iron meteorites suggests that the mass loss of stony meteorites depends on the fragmentation of the main body and that of iron meteorites depends on the shearing loss of the molten layer. Then, the fusion crusts were analyzed, the microstructures of the samples were obtained, the crust thicknesses were measured, and the elemental distribution of the stony meteorites was determined via energy dispersion spectroscopy. The study results explain the differences in the ablation and recrystallization process between stony and iron meteorites.

Abstract Objective In recent years, the lung cancer incidence has grown and the population is younger. We intend to find out the true detection rate of pulmonary nodules and the incidence of lung cancer in the population and search for the risk factors. Method Hospital employees ≥40 years old who underwent low‐dose computed tomography (CT) lung cancer screening from January 2019 to March 2022 were selected to record CT‐imaging characteristics, pathology, staging, and questionnaires to investigate past history, smoking history, diet, mental health, etc. PM2.5 and radiation intake in radiation‐related occupation received monitoring in hospital. Result The detection rate of suspicious pulmonary nodules was 9.1% (233/2552), and the incidence rate of lung cancer (including adenocarcinoma in situ) was 4.0% (103/2552). Morbidity among doctors, nurses, technicians, administers, and logistics was no difference (p = 0.184), but higher in women than in men (4.7% vs 2.4% p = 0.002). The invasiveness increased with age and CT density of nodules (p = 0.018). The relationship between lung cancer morbidity and PM2.5 was not clear (p = 0.543); and no lung cancer has been found in employees related ionizing radiation. Conclusion The high screening rate has brought about a high incidence of lung cancer. At present, the risk factor analysis of lung cancer based on small samples cannot find the direct cause. Most of the ground glass opacity (GGO)s detected by LDCT screening are indolent, but there are also rapidly progressive lung cancer. A predictive model to identify active and indolent GGO is necessary.

Abstract This paper proposes a small‐area and low‐power all‐digital duty cycle corrector with de‐skew circuit. By adopting the proposed delay unit containing a pre‐charge transistor, half cycle delay line can accurately generate half‐cycle delay, thus ensuring that the circuit can achieve duty cycle correction with small area and low power. To achieve high‐precision clock synchronization, the proposed de‐skew circuit utilizes a high‐resolution two‐stage digital control delay line to eliminate the additional clock skew between the input clock and output clock of the circuit. The test chip is fabricated in 130 nm CMOS process and the area only occupies 0.009 mm2. The chip testing results show that duty cycle correction error is within 3.2% and phase error is less than 16 ps when input duty cycle from 20% to 80% at the frequency range from 380 MHz to 1.25 GHz. And the proposed circuit only consumes 3 mW when supply voltage is 1.2 V and clock frequency is 1 GHz.

ObjectiveThe purpose of this study was to develop and validate a predictive model based on a machine learning (ML) approach to identify patients with DKA at increased risk of AKI within 1 week of hospitalization in the intensive care unit (ICU).MethodsPatients diagnosed with DKA from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database according to the International Classification of Diseases (ICD)-9/10 code were included. The patient’s medical history is extracted, along with data on their demographics, vital signs, clinical characteristics, laboratory results, and therapeutic measures. The best-performing model is chosen by contrasting the 8 Ml models. The area under the receiver operating characteristic curve (AUC), sensitivity, accuracy, and specificity were calculated to select the best-performing ML model.ResultsThe final study enrolled 1,322 patients with DKA in total, randomly split into training (1,124, 85%) and validation sets (198, 15%). 497 (37.5%) of them experienced AKI within a week of being admitted to the ICU. The eXtreme Gradient Boosting (XGBoost) model performed best of the 8 Ml models, and the AUC of the training and validation sets were 0.835 and 0.800, respectively. According to the result of feature importance, the top 5 main features contributing to the XGBoost model were blood urea nitrogen (BUN), urine output, weight, age, and platelet count (PLT).ConclusionAn ML-based individual prediction model for DKA-associated AKI (DKA-AKI) was developed and validated. The model performs robustly, identifies high-risk patients early, can assist in clinical decision-making, and can improve the prognosis of DKA patients to some extent.

Summary: The preparation of water-based adhesives with high bonding strength for various substrates is challenging. Moreover, to construct a sustainable society, it is highly desirable to develop a cost-effective way to achieve the reuse of plastic wastes. Herein, using polymethylmethacrylate (PMMA) chemicals or wastes as raw materials, water-based adhesives with high bonding strength for various substrates are prepared through a simple one-step hydrolysis strategy. The adhesives possess the maximum bonding strength of 7.1 MPa to iron, 4.2 MPa to wood, and ∼1.5 MPa to plastics. The adhesives have a world-record bonding strength to metal when compared with that of current reported water-based adhesives. Our method is low cost, simple, environmentally friendly, and suitable for large-scale industrial production. More importantly, using plastic wastes as raw materials opens up a new and low-cost way to turn wastes into valuables, which will greatly contribute to construct a sustainable society.

BackgroundSince the current commonly used birth growth curves are unsuitable for neonates in high-altitude areas; this study aimed to establish birth growth curves for full-term neonates residing at 2,000–3,000 m.MethodsThis cross-sectional study retrospectively analyzed the physical measurement data of 1,546 full-term neonates delivered at the Red Cross Hospital of Qinghai province, China, from July 2021 to April 2022. The percentile curves of birth weight, length, and head circumference of neonates of different gestational ages and genders were developed using curve fitting. The newly developed birth-weight percentile reference was compared with the INTERGROWTH-21st Neonatal Growth Curve (International Standard) and the Chinese Neonate Growth Curve (Chinese Standard).ResultsThe median birth weight, length, and head circumference of the study population were 3,200 g, 52.0 cm, and 32.8 cm, respectively, except for the group with a gestational age of 37 weeks. The growth indicators of male infants in all groups were higher than those of the female infants (P

IntroductionThe effect of Yiqi Fumai lyophilized injection (YQFM) on acute heart failure (AHF) patients has been evaluated in a large sample, randomized, controlled trial (AUGUST-AHF RCT study). However, restrictive eligibility criteria from a randomized clinical trial may raise concerns about the generalizability of the results to under-represented groups or complex patients with multimorbidity. Therefore, we intend to conduct the AUGUST-AHF cohort study which aims to assess the effectiveness of YQFM in patients with AHF in a real-world setting and compare the results with AUGUST-AHF RCT study.Methods and analysisThis prospective, multicenter cohort study will be conducted at 50 secondary and tertiary hospitals in China and comprise 1,200 patients with AHF. The participants will be followed for up to at least 180 days. The primary outcome is a composite of 90-day all-cause mortality or readmission for heart failure. The secondary outcomes include length of hospital stay, cardiac-specific death, MACE, NYHA cardiac function classification. Cox proportional-hazards regression models will be used to estimate the association between YQFM use and the primary outcome. The primary analysis will use propensity-score matching methods to balance the differences in baseline variables between treatment cohorts.Ethics and disseminationApproval for the study has been obtained from the Ethical Committee of Dongzhimen Hospital (approval No. 2022DZMEC-327-02) and registered at ClinicalTrials.gov (NCT05586048). The study results will be published in peer-reviewed journals and presented at scientific conferences.

Abstract. In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

The output of renewable energy is strongly uncertain and random, and the distribution of voltage and reactive power in regional power grids is changed with the access to large-scale renewable energy. In order to quantitatively evaluate the influence of renewable energy access on voltage and reactive power operation, a novel combinational evaluation method of voltage and reactive power in regional power grids containing renewable energy is proposed. Firstly, the actual operation data of renewable energy and load demand are clustered based on the K-means algorithm, and several typical scenarios are divided. Then, the entropy weight method (EWM) and the analytic hierarchy process (AHP) are combined to evaluate the voltage qualified rate, voltage fluctuation, power factor qualified rate and reactive power reserve in typical scenarios. Besides, the evaluation results are used as the training samples for back-propagation (BP) neural networks. The proposed combinational evaluation method can calculate the weight coefficient of the indexes adaptively with the change of samples, which simplifies the calculation process of the indexes’ weight. At last, the case simulation of an actual regional power grid is provided, and the historical data of one year is taken as the sample for training, evaluating and analyzing. And finally, the effectiveness of the proposed method is verified based on the comparison with the existing method. The evaluated results could provide reference and guidance to the operation analysis and planning of renewable energy.

Abstract The COVID-19 pandemic has caused various impacts on people’s lives, while changes in people’s lives have shown mixed effects on mitigating the spread of the SARS-CoV-2 virus. Understanding how to capture such two-way interactions is crucial, not only to control the pandemic but also to support post-pandemic urban recovery policies. As suggested by the life-oriented approach, the above interactions exist with respect to a variety of life domains, which form a complex behavior system. Through a review of the literature, this paper first points out inconsistent evidence about behavioral factors affecting the spread of COVID-19, and then argues that existing studies on the impacts of COVID-19 on people’s lives have ignored behavioral co-changes in multiple life domains. Furthermore, selected uncertain trends of people’s lives for the post-pandemic recovery are described. Finally, this paper concludes with a summary about “what should be computed?” in Computational Urban Science with respect to how to catch up with delays in the SDGs caused by the COVID-19 pandemic, how to address digital divides and dilemmas of e-society, how to capture behavioral co-changes during the post-pandemic recovery process, and how to better manage post-pandemic recovery policymaking processes.

A flawless, extremely loose, membrane, efficient for multivalent ions separation, has been successfully synthesized by the in-situ formation approach. The as-synthesized nanofiltration (NF) membrane, NF_PES-Zr, proceeded from a thin film layer of nanoparticles (NPs) zirconium that coated the platform of the polyethersulfone (PES) ultrafiltration (UF) membrane through a bio-glue made from dopamine hydrochloric and sodium bicarbonate buffer. The estimation of the average pore size of the novel organic-inorganic NF membrane NF_PES-Zr using the filtration velocity approach of Guerout-Elford-Ferry was close to 0.9 nm. NF_PES-Zr membrane holds a record in permeate water flux release of about 62.5 and was revealed to be effective for multivalent ions separation. A 5 days-test performed on NF_PES-Zr demonstrated its long-term stability and showed a rejection rate of 93.4% and 37.8% respectively for and . HIGHLIGHTS Organic-inorganic membrane preparation.; Nanoparticle zirconium deposition by in-situ formation method.; Modification of an ultrafiltration membrane to a nanofiltration membrane.; Energy dispersive spectrometry (EDS) associated with field emission scanning electron microscopy (FESEM) for membrane surface structures characterization.; High flux membrane for ions separation.;

Abstract Background Interleukin-10 (IL-10) is an independent factor for predicting adverse outcomes in pediatric patients with hemophagocytic lymphohistiocytosis (HLH). However, little is known about its prognostic value in adult patients. Methods This single center retrospective study was conducted to explore the prognostic value of IL-10 in 101 adults newly diagnosed with HLH. The serum interleukin levels were quantitatively determined by chemiluminescence using cytokine profiling kits. Results Serum IL-10 levels were significantly increased in adult HLH patients. Elevated IL-10 levels was correlated with lower concentrations of hemoglobin (r = − 0.279, P = 0.005). IL-10 levels were significantly lower in patients with macrophage activation syndrome (MAS) than in those with infection-associated HLH (IAHS) and malignancy-associated HLH (MAHS) (P = 0.033, P = 0.012). Patients with MAS had relatively longer survival than those with IAHS and MAHS (P 1050 µg/L and IL-10 ≥ 129 pg/mL were poor prognostic factors for survival. However, multivariate analysis revealed that only high serum IL-10 levels (≥ 129 pg/mL) at diagnosis and high post-treatment ferritin levels (> 1050 µg/L) were independent risk factors for poor overall survival in adult HLH patients (HR: 4.087, 95% CI 2.064–8.090, P

BackgroundGenomic profiling of cerebrospinal fluid (CSF) can be used to detect actionable mutations and guide clinical treatment of non-small cell lung cancer (NSCLC) patients with central nervous system (CNS) metastases. Examining the performance of CSF samples in real-world settings can confirm the potential of CSF genotyping for guiding therapy in clinical practice.Patients and MethodsWe included 1,396 samples from 970 NSCLC patients with CNS metastases in real-world settings. All samples underwent targeted next-generation sequencing of 1,021 cancer-relevant genes. In total, 100 CSF samples from 77 patients who had previously received targeted treatment were retrospectively analyzed to explore the mechanisms of TKI-resistance.ResultsFor NSCLC patients with CNS metastases, CSF samples were slightly more often used for genomic sequencing in treated patients with only distant CNS metastases compared to other patients (10.96% vs. 0.81–9.61%). Alteration rates in CSF samples were significantly higher than those in plasma, especially for copy number variants (CNV). The MSAFs of CSF samples were significantly higher than those of plasma and tumor tissues (all p

Abstract Objectives Cardiovascular disease (CVD) is a major cause of mortality; periodontal disease (PD) affects up to 50% of the world's population. Observational evidence has demonstrated association between CVD and PD. Absent from the literature is a systematic review and meta‐analysis of longitudinal cohort studies quantifying CVD risk in PD populations compared to non‐PD populations. To examine the risk of incident CVD in people with PD in randomised controlled trials and longitudinal cohort studies. Material and Methods We searched Medline, EMBASE and Cochrane databases up to 9th Oct 2019 using keywords and MeSH headings using the following concepts: PD, CVD, longitudinal and RCT study design. CVD outcomes included but were not restricted to any CVD, myocardial infarction, coronary heart disease (CHD) and stroke. Diagnosis method and severity of PD were measured either clinically or by self‐report. Studies comparing incident CVD in PD and non‐PD populations were included. Meta‐analysis and meta‐regression was performed to determine risk of CVD in PD populations and examine the effects of PD diagnosis method, PD severity, gender and study region. Results Thirty‐two longitudinal cohort studies were included after full text screening; 30 were eligible for meta‐analysis. The risk of CVD was significantly higher in PD compared to non‐PD (relative risk [RR]: 1.20, 95% CI: 1.14–1.26). CVD risk did not differ between clinical or self‐reported PD diagnosis (RR = 0.97, 95% CI: 0.87–1.07,). CVD risk was higher in men (RR: 1.16, 95% CI: 1.08–1.25) and severe PD (RR: 1.25, 95% CI: 1.15–1.35). Among all types of CVD, the risk of stroke was highest (RR = 1.24; 95% CI:1.12–1.38), the risk of CHD was also increased (RR = 1.14; 95% CI:1.08–1.21). Conclusion This study demonstrated modest but consistently increased risk of CVD in PD populations. Higher CVD risk in men and people with severe PD suggests population‐targeted interventions could be beneficial.

Faults are inevitable in building energy systems, such as heating, ventilation, air conditioning and refrigeration systems. With the increasing utilization of these systems, their fault detection and diagnosis has become more significant for maintaining their operation and performance. The rapid development of data analytics has led to fault detection and diagnosis using data-based algorithms considering building intelligence. Feature engineering, which focuses on generating near minimum and optimal model inputs from the original dataset, is a fundamental technique to balance efficiency and accuracy of fault detection and diagnosis models. The generated inputs are fault features which ensures a better description of fault operations owing to their stronger fault indicative capability than original data. However, since most feature engineering research has been implemented alongside the development of data-based algorithms, most studies fail to effectively distinguish and understand their roles in fault detection and diagnosis models. To fill this research gap, this study presented the problems and mechanisms associated with feature engineering, comprehensively reviewed about 200 papers on the topic of feature engineering for heating, ventilation, air conditioning and refrigeration system fault detection and diagnosis tasks over the past 15 years. Firstly, feature engineering studies are divided according to their feature-generation technique, into manual and automated techniques. Next, feature engineering studies are analysed in terms of data type, system type, fault type, operation statue, methods and fault features. The desirable characteristics of feature engineering works are then discussed in terms of their capability of rapidly generating indicative, decoupled, interpretable and new fault features to enhance fault detection and diagnosis accuracy; the efficiency, reliability and robustness of feature engineering process; the mutual adaptability between feature engineering and fault detection and diagnosis; and their widespread applicability for more fault types and system operations. The challenges affecting feature engineering studies are discussed in terms of data volume, data diversity and quality, along with the performance evaluation of feature engineering with respect to feature engineering algorithms, fault detection and diagnosis models, fault features and online application constraints. Future work should aim to design a hybrid, heuristic, robust and automated feature engineering strategy under the guidance of expert knowledge and practical application constraints that consider the relationships between fault-related features and real-time fault impacts with energy consumption, occupants' thermal comfort, etc.

Abstract Acinetobacter baumannii is a highly antibiotic resistant Gram-negative bacterium that causes life-threatening infections in humans with a very high mortality rate. A. baumannii is an extracellular pathogen with poorly understood virulence mechanisms. Here we report that A. baumannii employs the release of outer membrane vesicles (OMVs) containing the outer membrane protein A (OmpAAb) to promote bacterial pathogenesis and dissemination. OMVs containing OmpAAb are taken up by mammalian cells where they activate the host GTPase dynamin-related protein 1 (DRP1). OmpAAb mediated activation of DRP1 enhances its accumulation on mitochondria that causes mitochondrial fragmentation, elevation in reactive oxygen species (ROS) production and cell death. Loss of DRP1 rescues these phenotypes. Our data show that OmpAAb is sufficient to induce mitochondrial fragmentation and cytotoxicity since its expression in E. coli transfers its pathogenic properties to E. coli. A. baumannii infection in mice also induces mitochondrial damage in alveolar macrophages in an OmpAAb dependent manner. We finally show that OmpAAb is also required for systemic dissemination in the mouse lung infection model. In this study we uncover the mechanism of OmpAAb as a virulence factor in A. baumannii infections and further establish the host cell factor required for its pathogenic effects.

One stable marker of face perception appears to be left-side bias, the tendency to rely more on information conveyed by the left side of the face than the right. Previous studies have shown that left-side bias is influenced by familiarity and prior experience with face stimuli. Since other-race facial recognition is characterized by reduced familiarity, in contrast to own-race facial recognition, the phenomenon of left-side bias is expected to be weaker for other-race faces. Among Chinese participants, face inversion has been found to eliminate the left-side bias associated with own-race faces. Therefore, it is of interest to know whether face inversion influences left-side bias for non-Chinese research participants and can be generalized across own- and other-race faces. This study assessed 65 Caucasian participants using upright and inverted chimeric Caucasian and Asian faces in an identity similarity-judgment task. Although a significant left-side bias was observed for upright own-race faces, this bias was eliminated by facial inversion, indicating that such a bias depends on the applicability of configural processing strategies. For other-race faces, there was no left-side bias in the upright condition. Interestingly, the inverted presentation yielded a right-side bias. These results show that while left-side bias is affected by familiarity differences between own- and other-race faces, it is a universal phenomenon for upright faces. Inverted presentation strongly reduces left-side bias and may even cause it to revert to right-side bias, suggesting that left-side bias depends on configural face processing.

Abstract Background Several obesity susceptibility loci in genes, including GNPDA2, SH2B1, TMEM18, MTCH2, CDKAL1, FAIM2, and MC4R, have been identified by genome-wide association studies. The purpose of this study was to investigate whether these loci are associated with the concurrence of obesity and type 2 diabetes in Chinese Han patients. Methods Using the SNaPshot technique, we genotyped seven single nucleotide polymorphisms (SNPs) in 439 Chinese patients living in Northeast China who presented at The Second Hospital of Jilin University. We analyzed the associations between these seven alleles and clinical characteristics. Results Risk alleles near TMEM18 (rs6548238) were associated with increased waist circumference, waist/hip ratio, body mass index (BMI), fasting plasma glucose, hemoglobin A1c, diastolic blood pressure, triglycerides, total cholesterol, and low-density lipoprotein-cholesterol; risk alleles of CDKAL1 (rs7754840) were associated with increased waist circumference and waist/hip ratio; and FAIM2 (rs7138803) risk alleles were linked to increased BMI, diastolic blood pressure, and triglycerides (all P

A powerful forward error correction (FEC) scheme based on the serial concatenation of Bose-Chaudhuri-Hocquenghen (BCH) and low-density parity-check (LDPC) codes has been adopted by the second generation digital video broadcast (DVB-S2) standard due to their near Shannon limit performance. This paper proposes an efficient FEC encoder core to support different DVB-S2 codes for variable coding modulation (VCM) schemes of low earth orbit (LEO) satellite-ground communications. By exploring the properties of different concatenated BCH-LDPC codes and reusing the computation units and memories, the compatibility is achieved and the utilization of hardware resources is improved. Besides, parallel computing is performed to speed up the acquisition of check bits, which allows the encoding throughput to be increased. Hardware architecture implementation on Xilinx XC7K325t field programmable gate array (FPGA) shows that the encoding throughput rate of the proposed FEC encoder core can reach 1.19 Gb/s. And the overall data throughput is improved by 30.9% compared with the constant coding modulation (CCM) schemes.

Cities exposed their vulnerabilities during the COVID-19 pandemic. Unprecedented policies restricted human activities but left a unique opportunity to quantify anthropogenic effects on urban air pollution. This study aimed to explore the underlying urban development issues behind these restrictions and support a sustainable transition. The data from ground stations and Sentinel-5P satellite were used to assess the temporal and spatial anomalies of NO2. Beijing China was selected for a case study because this mega city maintained a “dynamic zero-COVID” policy with adjusted restrictions, which allowed for better tracking of the effects. The time-series decomposition and prediction regression model were employed to estimate the normal NO2 levels in 2020. The deviation between the observations and predictions was identified and attributed to the policy interventions, and spatial stratified heterogeneity statistics were used to quantify the effects of different policies. Workplace closures (54.8%), restricted public transport usage (52.3%), and school closures (46.4%) were the top three restrictions that had the most significant impacts on NO2 anomalies. These restrictions were directly linked to mismatched employment and housing, educational inequality, and long-term road congestion issues. Promoting the transformation of urban spatial structures can effectively alleviate air pollution.

In this paper, magnetic molecularly imprinted polymers (MMIPs) were fabricated on the surface of Fe3O4 by surface molecular imprinting technology, which can selectively adsorb 17β-estradiol (E2). The optimized experiments demonstrated that MMIPs possessed the best adsorption capacity when methanol was used as the solvent and MAA was used as the crosslinking agent, with a molar ratio of E2: MMA: EGDMA as 1:4:50. SEM, FTIR, and XRD were employed to investigate the morphologies of MMIPs and the results demonstrated that the MMIPs that can selectively adsorb E2 were successfully prepared on Fe3O4 particles. The adsorption experiments showed that 92.1% of E2 was adsorbed by the MMIPs, which is higher than the magnetic non-molecularly imprinted polymers (MNIPs). The Freundlich isotherm model was more suitable to describe the adsorption process of E2 by MMIPs. Meanwhile, MMIPs had a better recognition ability for E2 and its structural analogs such as estrone and estriol. The MMIPs still had good adsorption performance after methanol regeneration five times. The prepared MMIPs had the advantages of efficient adsorption ability and high reusability, so they can be applied for selective recognition and removal of E2.