We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Pemetrexed and immunotherapies (e.g., pembrolizumab) are approved for first-line maintenance (1LM) treatment of nonsquamous advanced/metastatic non-small-cell lung cancer (NSCLC), but real-world data on their use are limited. The objective of this study was to assess 1LM clinical outcomes, safety, and treatment patterns of immunotherapy versus immunotherapy+pemetrexed among patients with advanced/metastatic NSCLC from the EU4 (France, Germany, Italy, Spain)+UK.
Methods
Data from patients in the US, Canada, and EU4+UK with nonsquamous advanced/metastatic NSCLC without targetable mutations were collected via electronic case report form. Physician-identified patients (≥18 y) in the EU4+UK were eligible for this subgroup analysis if they achieved stable disease or complete or partial response with first-line platinum-based chemotherapy+immunotherapy (January 2019 to March 2021) and received 1LM immunotherapy or immunotherapy+pemetrexed. Patients were followed from index (1LM initiation) until last physician contact or death. Outcomes were overall survival (OS), progression-free survival (PFS), treatment patterns and duration, and adverse events.
Results
Among the selected 367 patients (male, 71.9%; mean±StDev age, 63.4±7.2 y; current/former smokers, 85.8%), 203 (55.3%) received immunotherapies, most commonly pembrolizumab (n=173; 85.2%), and 164 (44.7%) received immunotherapy+pemetrexed. Patients receiving immunotherapy had longer median adjusted OS and PFS compared to those receiving immunotherapy+pemetrexed (OS hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.36, 0.90; PFS HR: 0.58; 95% CI: 0.38, 0.79). Patients receiving immunotherapy versus patients receiving immunotherapy+pemetrexed had longer median treatment duration (14.0 vs 10.3 mo; p<0.001) and were less likely to experience anemia (19.7% vs 33.5%; p<0.01). Results were similar in the overall study population.
Conclusions
In this real-world study, among the selected patients with nonsquamous advanced/metastatic NSCLC who achieved stable disease or complete or partial response with first-line therapy, the addition of pemetrexed to immunotherapy in 1LM did not appear to confer a clinical benefit. Identifying treatments that can improve clinical outcomes for these patients remains an area of unmet need.
Modern fluvial sediments provide important information about source-to-sink process and regional tectono-magmatic events in the source area, but many factors, e.g., chemical weathering, sedimentary cycles and source-rock types, can interfere with the establishment of the source-sink system. The Lalin River (LR) and the Jilin Songhua River (JSR) are two important tributaries of the Songhua River in the Songnen Plain in NE China. They have similar flow direction, topography and identical climate backgrounds, but have notably different parent-rock types in the headwater, which provides an opportunity to explore the influencing factors of river sediment composition. To this end, the point bar sediments in the two rivers were sampled for an analysis of geochemistry (including element and Sr-Nd isotopic ratios), heavy mineral and detrital zircon U-Pb dating. The results are indicative of the fact that the two rivers have the similar geochemical composition (e.g., elements and Sr isotopes) as well as chemical weathering (CIA = 51.41–57.60, CIW = 59.68–66.11, PIA = 51.95–60.23, WIP = 56.00–65.47, Rb/Sr = 0.38–0.42) and recycling (SiO2/Al2O3 = 5.79 and 5.03, ICV = 1.0 and 1.2, CIA/WIP = 0.81–1.03) characteristics, showing a major control of climate on the low-level weathering and recycling of the river sediments. However, there are significant differences in the detrital zircon U-Pb age (a significant Mesozoic age peak for the LR but an additional Precambrian peak for the JSR), Nd isotope ratio (−6.2812–8.5830 and −8.1149–10.2411 for the LR and the JSR, respectively) and to a certain extent heavy mineral composition (e.g., for the < 63 μm fraction, a dominance of hornblende and magnetite in the LR, but haematite-limonite in the JSR) in the two river sediments, indicating that source rocks largely control the composition of the river sediments. Some of the major tectono-magmatic events (e.g., crustal growth and cratonisation of the North China Craton, closure of the Paleo-Asian Ocean, subduction and rollback of the Paleo-Pacific plate) occurring in the eastern Songnen Plain are well documented in the JSR sediments but not in the LR, the difference of which is largely regulated by the source rocks in the source area.
Cardiometabolic diseases (CMDs) including heart disease, stroke, and type 2 diabetes have been individually linked to depression. However, their combined impact on depression risk is unclear. We aimed to examine the association between cardiometabolic multimorbidity and depression and explore the role of genetic background in this association.
Methods
Within the Swedish Twin Registry, 40,080 depression-free individuals (mean age 60 years) were followed for 18 years. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. CMDs and depression were ascertained based on the National Patient Register. Cox regression was used to estimate the CMD-depression association in a classical cohort study design and a matched co-twin design involving 176 twin pairs. By comparing the associations between monozygotic and dizygotic co-twins, the contribution of genetic background was estimated.
Results
At baseline, 4809 (12.0%) participants had one CMD and 969 (2.4%) had ≥2 CMDs. Over the follow-up period, 1361 participants developed depression. In the classical cohort design, the multi-adjusted hazard ratios (95% confidence interval [CIs]) of depression were 1.52 (1.31–1.76) for those with one CMD and 1.83 (1.29–2.58) for those with ≥2 CMDs. CMDs had a greater risk effect on depression if they developed in mid-life (<60 years) as opposed to late life (≥60 years). In matched co-twin analysis, the CMD-depression association was significant among dizygotic twins (HR = 1.63, 95% CI, 1.02–2.59) but not monozygotic twins (HR = 0.90, 95% CI, 0.32–2.51).
Conclusions
Cardiometabolic multimorbidity is associated with an elevated risk of depression. Genetic factors may contribute to the association between CMDs and depression.
As a required sample preparation method for 14C graphite, the Zn-Fe reduction method has been widely used in various laboratories. However, there is still insufficient research to improve the efficiency of graphite synthesis, reduce modern carbon contamination, and test other condition methodologies at Guangxi Normal University (GXNU). In this work, the experimental parameters, such as the reduction temperature, reaction time, reagent dose, Fe powder pretreatment, and other factors, in the Zn-Fe flame sealing reduction method for 14C graphite samples were explored and determined. The background induced by the sample preparation process was (2.06 ± 0.55) × 10–15, while the 12C– beam current were better than 40μA. The results provide essential instructions for preparing 14C graphite of ∼1 mg at the GXNU lab and technical support for the development of 14C dating and tracing, contributing to biology and environmental science.
A new vacuum line to extract CO2 from carbonate and dissolved inorganic carbon (DIC) in water was established at Guangxi Normal University. The vacuum line consisted of two main components: a CO2 bubble circulation region and a CO2 purification collection region, both of which were made of quartz glass and metal pipelines. To validate its reliability, a series of carbonate samples were prepared using this system. The total recovery rate of CO2 extraction and graphitization exceeded 80%. Furthermore, the carbon content in calcium carbonate exhibited a linear relationship with the CO2 pressure within the system, demonstrating its stability and reliability. The system was also employed to prepare and analyze various samples, including calcium carbonate blanks, foraminiferal, shell, groundwater, and subsurface oil-water samples. The accelerator mass spectrometry (AMS) results indicated that the average beam current for 12C- in the samples exceeded 40 μA. Additionally, the contamination introduced during the liquid sample preparation process was approximately (1.77 ± 0.57) × 10−14. Overall, the graphitized preparation system for carbonate and DIC in water exhibited high efficiency and recovery, meeting the requirements for samples dating back to approximately 30,000 years.
This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 μg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 μg/ml and ≤ 1 μg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.
Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.
This article aims to analyze the relationship between user characteristics on social networks and influenza.
Methods:
Three specific research questions are investigated: (1) we classify Weibo updates to recognize influenza-related information based on machine learning algorithms and propose a quantitative model for influenza susceptibility in social networks; (2) we adopt in-degree indicator from complex networks theory as social media status to verify its coefficient correlation with influenza susceptibility; (3) we also apply the LDA topic model to explore users’ physical condition from Weibo to further calculate its coefficient correlation with influenza susceptibility. From the perspective of social networking status, we analyze and extract influenza-related information from social media, with many advantages including efficiency, low cost, and real time.
Results:
We find a moderate negative correlation between the susceptibility of users to influenza and social network status, while there is a significant positive correlation between physical condition and susceptibility to influenza.
Conclusions:
Our findings reveal the laws behind the phenomenon of online disease transmission, and providing important evidence for analyzing, predicting, and preventing disease transmission. Also, this study provides theoretical and methodological underpinnings for further exploration and measurement of more factors associated with infection control and public health from social networks.
This study aimed to summarise the findings of the studies assessing the effectiveness of ultraviolet C (UV-C) room disinfection in reducing the incidence rate of healthcare-associated multi-drug-resistant organism (MDRO) infections. A systematic screening was conducted using PubMed, EMBASE, and Scopus for randomised controlled trials (RCTs), quasi-experimental studies, and before–after studies, which assessed the efficacy of the UV-C disinfectant system in reducing the incidence of MDRO infections. A random-effects model was used for the analysis. Effect sizes were described as incidence rate ratio (IRR) with 95% confidence intervals (CI). Nine studies were included, all of which were conducted in the USA. No statistically significant reduction in Clostridioides difficile (CD) (IRR: 0.90, 95% CI; 0.62–1.32) and vancomycin-resistant enterococcal (VRE) infection rates (IRR 0.72, 95% CI; 0.38–1.37) was observed with the use of UV-C, but the risk of Gram-negative rod infection was reduced (IRR 0.82, 95% CI; 0.68–0.99).
Compared with nitrogen and argon, helium is lighter and can better reduce the beam loss caused by angular scattering during beam transmission. The molecular dissociation cross-section in helium is high and stable at low energies, which makes helium the prevalent stripping gas in low-energy accelerator mass spectrometry (AMS). To study the stripping behavior of 14C ions in helium at low energies, the charge state distributions of carbon ion beams with −1, +1, +2, +3, and +4 charge states were measured at energies of 70–220 keV with a compact 14C-AMS at Guangxi Normal University (GXNU). The experimental data were used to analyze the stripping characteristics of C-He in the energy range of 70–220 keV, and new charge state yields and exchange cross-sections in C-He were obtained at energies of 70–220 keV.
Bio-inspired design (BID) involves generating innovative ideas for engineering design by drawing inspiration from natural biological phenomena and systems, using a form of design-by-analogy. Despite its many successes, BID approaches encounter research challenges including unstructured data and existing models that hinder comprehension and processing, limited focus on finding biological knowledge compared to defined problems, and insufficient guidance of the ideation process with algorithms. This paper proposes a knowledge-based approach to address the challenges. The approach involves transforming unstructured data into structured knowledge, including information about natural sources, their benefits, and applications. The structured knowledge is then used to construct a semantic network, enabling designers to retrieve information for BID in two ways. Furthermore, a three-step ideation method is developed to encourage divergent thinking and explore additional potential solutions by drawing inspiration and utilizing knowledge. The knowledge-based BID approach is implemented as a tool and design cases are conducted to illustrate the process of applying this tool for BID.
A single-stage accelerator mass spectrometer (GXNU-AMS) developed for radiocarbon and tritium measurements was installed and commissioned at Guangxi Normal University in 2017. After several years of operational and methodological upgrades, its performance has been continuously improved and applied in multidisciplinary fields. Currently, the measurement sensitivity for radiocarbon and tritium is 14C/12C ∼ (3.14 ± 0.05) ×10–15 and 3H/1H ∼ (1.23 ± 0.17)×10–16, respectively, and the measurement accuracy is ∼0.6%, which can meet the measurement requirements in the nuclear, earth, environmental and life science fields. This study presents the performance characteristics of GXNU-AMS and several interesting application studies.
Polydatin is an active polyphenol displaying multifaceted benefits. Recently, growing studies have noticed its potential therapeutic effects on bone and joint disorders (BJDs). Therefore, this article reviews recent in vivo and in vitro progress on the protective role of polydatin against BJDs. An insight into the underlying mechanisms is also presented. It was found that polydatin could promote osteogenesis in vitro, and symptom improvements have been disclosed with animal models of osteoporosis, osteosarcoma, osteoarthritis and rheumatic arthritis. These beneficial effects obtained in laboratory could be mainly attributed to the bone metabolism-regulating, anti-inflammatory, antioxidative, apoptosis-regulating and autophagy-regulating functions of polydatin. However, studies on human subjects with BJDs that can lead to early identification of the clinical efficacy and adverse effects of polydatin have not been reported yet. Accordingly, this review serves as a starting point for pursuing clinical trials. Additionally, future emphasis should also be devoted to the low bioavailability and prompt metabolism nature of polydatin. In summary, well-designed clinical trials of polydatin in patients with BJD are in demand, and its pharmacokinetic nature must be taken into account.
The contemporary expansion of English is becoming remarkably rapid and exceptionally global (Ostler, 2011). In present-day China, English has gained unprecedented popularity, fueled by the nation's current political and social development (Bolton & Graddol, 2012). There is a notable trend of bilingual education using English as a medium of instruction in Chinese schools (Wei, 2013). Therefore, an increasing number of Chinese are enthusiastic about learning and using English in communication. With the active participation of youths, ‘Internet English’ has been used widely in social networking spaces. The practice of ‘English mixing’ in various Chinese homegrown social networking sites has become the most remarkable intranational use of English in today's mainland China (Zhang, 2012). Interestingly, youngsters1 often create novel meanings when using languages on the Internet as ‘teenagers are well-known for introducing innovations into language, and indeed are generally regarded as prime agents of language change’ (Palacios Martínez, 2018: 363). Many linguistic studies have dealt with the mechanisms of the evolution of word meanings in past decades (Kachru, 1983; Qin & Guo, 2020; Tan, 2009; Yang, 2005). Much evidence indicates that meanings and usages of words are variable and composite, and may turn out differently depending on how words are used in contexts.
Fat deposition and lipid metabolism are closely related to the morphology, structure and function of mitochondria. The morphology of mitochondria between fusion and fission processes is mainly regulated by protein posttranslational modification. Intermittent fasting (IF) promotes high expression of Sirtuin 3 (Sirt3) and induces mitochondrial fusion in high-fat diet (HFD)-fed mice. However, the mechanism by which Sirt3 participates in mitochondrial protein acetylation during IF to regulate mitochondrial fusion and fission dynamics remains unclear. This article demonstrates that IF promotes mitochondrial fusion and improves mitochondrial function in HFD mouse inguinal white adipose tissue. Proteomic sequencing revealed that IF increased protein deacetylation levels in HFD mice and significantly increased Sirt3 mRNA and protein expression. After transfecting with Sirt3 overexpression or interference vectors into adipocytes, we found that Sirt3 promoted adipocyte mitochondrial fusion and improved mitochondrial function. Furthermore, Sirt3 regulates the JNK-FIS1 pathway by deacetylating malate dehydrogenase 2 (MDH2) to promote mitochondrial fusion. In summary, our study indicates that IF promotes mitochondrial fusion and improves mitochondrial function by upregulating the high expression of Sirt3 in HFD mice, promoting deacetylation of MDH2 and inhibiting the JNK-FIS1 pathway. This research provides theoretical support for studies related to energy limitation and animal lipid metabolism.
We analyze a model in which an anomaly is unknown to arbitrageurs until its discovery, and test the model implications on both asset prices and arbitrageurs’ trading activities. Using data on 99 anomalies documented in the existing literature, we find that the discovery of an anomaly reduces the correlation between the returns of its decile-1 and decile-10 portfolios. This discovery effect is stronger if the aggregate wealth of hedge funds is more volatile. Finally, hedge funds increase (reverse) their positions in exploiting anomalies when their aggregate wealth increases (decreases), further suggesting that these discovery effects operate through arbitrage trading.
As optical parametric chirped pulse amplification has been widely adopted for the generation of extreme intensity laser sources, nonlinear crystals of large aperture are demanded for high-energy amplifiers. Yttrium calcium oxyborate (YCa4O(BO3)3, YCOB) is capable of being grown with apertures exceeding 100 mm, which makes it possible for application in systems of petawatt scale. In this paper, we experimentally demonstrated for the first time to our knowledge, an ultra-broadband non-collinear optical parametric amplifier with YCOB for petawatt-scale compressed pulse generation at 800 nm. Based on the SG-II 5 PW facility, amplified signal energy of approximately 40 J was achieved and pump-to-signal conversion efficiency was up to 42.3%. A gain bandwidth of 87 nm was realized and supported a compressed pulse duration of 22.3 fs. The near-field and wavefront aberration represented excellent characteristics, which were comparable with those achieved in lithium triborate-based amplifiers. These results verified the great potential for YCOB utilization in the future.
Adherence to healthy lifestyles can be beneficial for depression among adults, but the intergenerational impact of maternal healthy lifestyles on offspring depressive symptoms is unknown.
Methods
In total, 10 368 mothers in Nurses' Health Study II and 13 478 offspring in the Growing Up Today Study were paired. Maternal and offspring healthy lifestyles were defined as a composite score including a healthy diet, normal body mass index (BMI), never-smoking, light-to-moderate consumption of alcohol, and regular moderate-to-vigorous physical activity. Maternal lifestyles were assessed during their offspring's childhood. Offspring depressive symptoms were repeatedly assessed five times using the Center for Epidemiological Studies Depression Scale-10 (CESD-10); the offspring were between the ages of 14 and 30 when the first CESD-10 was assessed. Covariates included maternal variables (age at baseline, race/ethnicity, antidepressant use, pregnancy complications, etc.) and offspring age and sex.
Results
Children of mothers with the healthiest lifestyle had significantly fewer depressive symptoms (a 0.30 lower CESD-10 score, 95% confidence interval (CI) 0.09–0.50) in comparison with children of mothers with the least healthy lifestyle. The association was only found significant in female offspring but not in males. For individual maternal lifestyle factors, a normal BMI, never-smoking, and adherence to regular physical activity were independently associated with fewer depressive symptoms among the offspring. The association between maternal healthy lifestyles and offspring depressive symptoms was mediated by offspring's healthy lifestyles (mediation effect: 53.2%, 95% CI 15.8–87.3).
Conclusions
Our finding indicates the potential mechanism of intergenerational transmission of healthy lifestyles to reduce the risk of depressive symptoms in offspring.
It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid v. solid) and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15 538 participants, free of NAFLD, other liver diseases, CVD, cancer or diabetes at baseline (2013–2018 years). Added sugar intake was estimated from a validated 100-item FFQ. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazard ratios (HR) and corresponding 95 % CI for NAFLD risk with added sugar intake. During a median follow-up of 4·2 years, 3476 incident NAFLD cases were documented. After adjusting for age, sex, BMI and its change from baseline to follow-up, lifestyle factors, personal and family medical history and overall diet quality, the multivariable HR of NAFLD risk were 1·18 (95 % CI 1·06, 1·32) for total added sugars, 1·20 (95 % CI 1·08, 1·33) for liquid added sugars and 0·96 (95 % CI 0·86, 1·07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.