Displaying publications 1 - 20 of 158 in total

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  1. Twining JP, Sutherland C, Zalewski A, Cove MV, Birks J, Wearn OR, et al.
    Proc Natl Acad Sci U S A, 2024 Mar 19;121(12):e2312252121.
    PMID: 38466845 DOI: 10.1073/pnas.2312252121
    The social system of animals involves a complex interplay between physiology, natural history, and the environment. Long relied upon discrete categorizations of "social" and "solitary" inhibit our capacity to understand species and their interactions with the world around them. Here, we use a globally distributed camera trapping dataset to test the drivers of aggregating into groups in a species complex (martens and relatives, family Mustelidae, Order Carnivora) assumed to be obligately solitary. We use a simple quantification, the probability of being detected in a group, that was applied across our globally derived camera trap dataset. Using a series of binomial generalized mixed-effects models applied to a dataset of 16,483 independent detections across 17 countries on four continents we test explicit hypotheses about potential drivers of group formation. We observe a wide range of probabilities of being detected in groups within the solitary model system, with the probability of aggregating in groups varying by more than an order of magnitude. We demonstrate that a species' context-dependent proclivity toward aggregating in groups is underpinned by a range of resource-related factors, primarily the distribution of resources, with increasing patchiness of resources facilitating group formation, as well as interactions between environmental conditions (resource constancy/winter severity) and physiology (energy storage capabilities). The wide variation in propensities to aggregate with conspecifics observed here highlights how continued failure to recognize complexities in the social behaviors of apparently solitary species limits our understanding not only of the individual species but also the causes and consequences of group formation.
  2. Peffault de Latour R, Röth A, Kulasekararaj AG, Han B, Scheinberg P, Maciejewski JP, et al.
    N Engl J Med, 2024 Mar 14;390(11):994-1008.
    PMID: 38477987 DOI: 10.1056/NEJMoa2308695
    BACKGROUND: Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. Iptacopan, a first-in-class oral factor B inhibitor, has been shown to improve hemoglobin levels in these patients.

    METHODS: In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5-treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion.

    RESULTS: In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without transfusion; none of the 35 anti-C5-treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5-treated patients did not require or receive transfusion; in the second trial, no patients required or received transfusion. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan.

    CONCLUSIONS: Iptacopan treatment improved hematologic and clinical outcomes in anti-C5-treated patients with persistent anemia - in whom iptacopan showed superiority to anti-C5 therapy - and in patients who had not received complement inhibitors. (Funded by Novartis; APPLY-PNH ClinicalTrials.gov number, NCT04558918; APPOINT-PNH ClinicalTrials.gov number, NCT04820530.).

  3. Guo L, Li S, Xie S, Bian L, Shaharudin S
    Sci Rep, 2024 Feb 09;14(1):3310.
    PMID: 38331984 DOI: 10.1038/s41598-024-53853-z
    The digital healthcare (DH) system has recently emerged as an advanced rehabilitation approach that promotes rehabilitation training based on virtual reality (VR) and augmented reality (AR). The purpose of this meta-analysis study is to review and assess the impact of DH systems on pain and physical function among patients diagnosed with knee joint pain. Between January 2003 and September 2023, studies that met the listed inclusion criteria were gathered from Scopus, PubMed, Web of Science, and EBSCO databases. The analysis of standardized mean difference (SMD) was carried out with 95% confidence interval (95% CI) (PROSPERO registration number: CRD42023462538). Eight research papers were selected, which collectively involved 194 males and 279 females. The meta-analysis outcomes revealed that DH intervention significantly improved balance (SMD, 0.41 [0.12, 0.69], p 
  4. Li W, Wang F, Wang X, Xu W, Liu F, Hu R, et al.
    J Biochem Mol Toxicol, 2024 Feb;38(2):e23645.
    PMID: 38348716 DOI: 10.1002/jbt.23645
    Prostate cancer (PCa) is an extremely common genitourinary malignancy among elderly men. Many evidence have shown the efficacy of curcumin (CUR) in inhibiting the progression of PCa. However, the pharmacological function of CUR in PCa is still not quite clear. In this research, CUR was found to suppress the proliferation and enhance the apoptotic rate in in vitro PCa cell models in a dose- and time-dependent manner. In a xenograft animal model, the administration of CUR contributed to a significant decrease in the growth of the xenograft tumor induced by the transplanted PC-3 cells. Ubiquitin-conjugating enzyme E2 C is implicated in the modulation of multiple types of cancers. In humans, the expression levels of UBE2C are significantly higher in PCa versus benign prostatic hyperplasia. Treatment with CUR decreased the expression of UBE2C, whereas it increased miR-483-3p expression. In contrast with the control mice, the CUR-treated mice showed a significant reduction in UBE2C and Ki-67 in PCa cells. The capability of proliferation, migration, and invasion of PCa cells was inhibited by the knockdown of UBE2C mediated by siRNA. Furthermore, dual luciferase reporter gene assay indicated the binding of miR-483-3p to UBE2C. In summary, CUR exerts its antitumor effects through regulation of the miR-483-3p/UBE2C axis by decreasing UBE2C and increasing miR-483-3p. The findings may also provide new molecular markers for PCa diagnosis and treatment.
  5. Li S, Mohamed Nor N, Kaliappan SR
    Heliyon, 2024 Jan 30;10(2):e24630.
    PMID: 38304776 DOI: 10.1016/j.heliyon.2024.e24630
    The prevalence of overweight among Chinese children under 5 years of age has been increasing steadily. Using data from China Health and Nutrition Survey (CHNS) spanning from 1991 to 2015, this study investigates the relationship between maternal employment status, maternal education level, and the prevalence of child overweight among Chinese children under 5 years old. The findings indicate that having mothers with low middle school education significantly reduces their children's body mass index z-scores (BMIZ) (p 
  6. Li Y, Dong W, Zhang L, Yang Y, Song Y, Shi N, et al.
    Aesthet Surg J, 2024 Jan 25.
    PMID: 38271268 DOI: 10.1093/asj/sjae010
    BACKGROUND: Large and long ears are regarded as symbols of wealth and health in eastern Asian culture, patients with lying ears wish their ears to be more exposed and prominent. Surgeries correcting lying ears have been documented.

    OBJECTIVES: We report correction of lying ears and aesthetic modification of helix and ear lobule with HA injections.

    METHODS: We performed HA injections at auriculocephalic sulcus (AS) to increase cranioauricular angle (CA) and correct lying ears. The injections at helix and lobule were case-specific. The CA was measured and photographs were taken at baseline and 1-, 3-, 6-, and 10-month follow-ups. Efficacy was assessed using a 5-point global aesthetic improvement scale (GAIS). Adverse events (AEs) were recorded.

    RESULTS: Forty-six patients (92 ears) received HA injections and completed follow-ups. Instant correction outcomes were observed. Sixteen (34.8%) patients received one touch-up injection, whose clinical efficacy persisted for 1 to 1.5 years. The GAIS for over 90% of cases with touch-up treatment was "very much improved" or "much improved" at all follow-ups. The GAIS for over 70% of cases without touch-up treatment was "very much improved" or "much improved" at 1, 3, and 6-month follow-ups. CA increased significantly compared with the baseline. Patients also reported "more V-shaped face shape" and "lifted jawline" effects. No serious AEs occurred.

    CONCLUSIONS: As an alternative technique to surgeries, HA filler injections at AS effectively corrected lying ears. This technique produced immediate, long-lasting, and aesthetically pleasing results. The side effects and downtime were minimal.

  7. Li S, Mohamed Nor N, Kaliappan SR
    Heliyon, 2024 Jan 15;10(1):e23887.
    PMID: 38187311 DOI: 10.1016/j.heliyon.2023.e23887
    China is committed to reduce child malnutrition outcomes (CMO) rates to less than 5 % by 2030 in order to meet the Sustainable Development Goal (SDG). Yet, this is still an enormous challenge for China, particularly in disadvantaged areas, due to regional and urban-rural disparities. Using China Health and Nutrition Survey (CHNS) data from 1991 to 2015 and fixed-effect models, this study investigates the social determinants of stunting (n = 4012) measured by height-for-age z score (HAZ) and wasting (n = 4229) measured by weight-for-height z score (WHZ) in children under the age of five. According to the empirical findings, the significant social determinants of child stunting encompassed whether the child is insured (p 
  8. Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
  9. Tang W, Bai X, Zhou Y, Sonne C, Wu M, Lam SS, et al.
    Nat Food, 2024 Jan;5(1):72-82.
    PMID: 38177223 DOI: 10.1038/s43016-023-00910-x
    Dietary exposure to methylmercury (MeHg) causes irreversible damage to human cognition and is mitigated by photolysis and microbial demethylation of MeHg. Rice (Oryza sativa L.) has been identified as a major dietary source of MeHg. However, it remains unknown what drives the process within plants for MeHg to make its way from soils to rice and the subsequent human dietary exposure to Hg. Here we report a hidden pathway of MeHg demethylation independent of light and microorganisms in rice plants. This natural pathway is driven by reactive oxygen species generated in vivo, rapidly transforming MeHg to inorganic Hg and then eliminating Hg from plants as gaseous Hg°. MeHg concentrations in rice grains would increase by 2.4- to 4.7-fold without this pathway, which equates to intelligence quotient losses of 0.01-0.51 points per newborn in major rice-consuming countries, corresponding to annual economic losses of US$30.7-84.2 billion globally. This discovered pathway effectively removes Hg from human food webs, playing an important role in exposure mitigation and global Hg cycling.
  10. Shi Y, Li S, Li Y, Jiang L, Khan FU, Waiho K, et al.
    Mar Environ Res, 2024 Jan;193:106282.
    PMID: 38042633 DOI: 10.1016/j.marenvres.2023.106282
    Despite being widely distributed in Asia, Carcinoscorpius rotundicauda is often overlooked and, its population status remains unclear. Moreover, it is threatened by illegal harvesting and degradation of mangrove ecosystems. Protecting its habitat is essential for population and biodiversity conservation, as mangroves provide nursery grounds and food supply for C. rotundicauda. This review discusses the biological characteristics of C. rotundicauda, including ecology, nutrition, life history, toxicology, and immunology. It also presents information about its distribution and population status. The review emphasizes the challenges faced by C. rotundicauda and proposes a conservation framework that involves the participation of local residents to facilitate conservation efforts. Collaboration between local residents and communities is proposed to protect and monitor the mangrove ecosystem. Additionally, this framework can support field research, protect C. rotundicauda juveniles and other species, and ensure the livelihood of local residents through participation in carbon trading markets and eco-industries such as eco-farming and eco-tourism.
  11. Li S, Li W, Cheng Y, Liu J, Wei G, Wang B
    Biodivers Data J, 2024;12:e113427.
    PMID: 38235166 DOI: 10.3897/BDJ.12.e113427
    BACKGROUND: The Asian leaf litter toads of the genus Leptobrachella Smith, 1925 (Anura, Megophryidae) inhabit the forest floor and rocky streams in hilly evergreen forests and are widely distributed from southern China, west to north-eastern India and Myanmar, through mainland Indochina to Peninsular Malaysia and the Island of Borneo.

    NEW INFORMATION: A new species of the Asian leaf litter toad genus Leptobrachella from Guizhou Province, China is described. Molecular phylogenetic analyses, based on mitochondrial 16S rRNA and COI genes and nuclear RAG1 gene sequences indicated that the new species is genetically divergent from its congeners. The new species could be distinguished from its congeners by a combination of the following characters: (1) body of medium size in males (SVL 31.9 - 32.9 mm); (2) distinct black spots present on flanks; (3) toes rudimentarily webbed, with wide lateral fringes; (4) skin on dorsum shagreened with fine tiny granules and short ridges; (5) heels overlapped when thighs are positioned at right angles to the body; (6) tibia-tarsal articulation reaching interior corner of the eye.A new species of the Asian leaf litter toad genus Leptobrachella from Guizhou Province, China is described. Molecular phylogenetic analyses, based on mitochondrial 16S rRNA and COI genes and nuclear RAG1 gene sequences indicated that the new species is genetically divergent from its congeners. The new species could be distinguished from its congeners by a combination of the following characters: (1) body of medium size in males (SVL 31.9 - 32.9 mm); (2) distinct black spots present on flanks; (3) toes rudimentarily webbed, with wide lateral fringes; (4) skin on dorsum shagreened with fine tiny granules and short ridges; (5) heels overlapped when thighs are positioned at right angles to the body; (6) tibia-tarsal articulation reaching interior corner of the eye.

  12. Wong WM, Tham YC, Simunovic MP, Chen FK, Luu CD, Chen H, et al.
    Asia Pac J Ophthalmol (Phila), 2024;13(1):100030.
    PMID: 38233300 DOI: 10.1016/j.apjo.2023.100030
    PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region.

    DESIGN: Multi-national, multi-center collaborative network.

    METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries.

    RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists.

    CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

  13. Li S, Nor NM, Kaliappan SR
    SSM Popul Health, 2023 Dec;24:101533.
    PMID: 37916186 DOI: 10.1016/j.ssmph.2023.101533
    Research on the impact of childhood nutrition on adult health and human capital has been extensively studied in developed countries, but research in China on this topic is limited. Nowadays, for children's nutritional status, while significant progress has been made in addressing childhood undernutrition in China, regional disparities persist, conversely, the prevalence of childhood overweight continues to rise. For adults' health human capital, the burden of chronic non-communicable diseases among Chinese residents is gradually increasing, over 50% of Chinese residents are overweight or obese, with obesity being one of the risk factors for other chronic diseases. Therefore, this study uses national representative data from 1991 to 2015 China Health and Nutrition Survey (CHNS), matched with individual information from their childhood, to examine the relationship between childhood nutrition and adult health human capital. Based on the two-way fixed effects models and logit models, the study finds that childhood nutrition status measured by height-for-age z score (HAZ) significantly and continuously has been influencing adult health human capital measured by height, BMI, self-rated health (SRH), whether have been sick in last four weeks (SH). BMI-for-age z score (BMIZ) significantly and continuously influence adult health human capital measured by BMI, blood pressure, and perceived stress (PS). Among that, this study places special emphasis on the long-lasting effects of late childhood and adolescence (ages exceeding 6) on the progressive height accumulation and sustained presence of elevated blood pressure. In conclusion, reducing childhood overweight and promoting linear growth and development throughout the whole childhood can reduce the future burden of disease on the nation.
  14. Sun Q, Yang J, Zhang M, Zhang Y, Ma H, Tran NT, et al.
    J Biol Chem, 2023 Dec;299(12):105463.
    PMID: 37977221 DOI: 10.1016/j.jbc.2023.105463
    Ferroptosis, characterized by iron-dependent cell death, has recently emerged as a critical defense mechanism against microbial infections. The present study aims to investigate the involvement of exosomes in the induction of ferroptosis and the inhibition of bacterial infection in crustaceans. Our findings provide compelling evidence for the pivotal role of exosomes in the immune response of crustaceans, wherein they facilitate intracellular iron accumulation and activate the ferroptotic pathways. Using RNA-seq and bioinformatic analysis, we demonstrate that cytochrome P450 (CYP) can effectively trigger ferroptosis. Moreover, by conducting an analysis of exosome cargo proteins, we have identified the participation of six-transmembrane epithelial antigen of prostate 4 in the regulation of hemocyte ferroptotic sensitivity. Subsequent functional investigations unveil that six-transmembrane epithelial antigen of prostate 4 enhances cellular Fe2+ levels, thereby triggering Fenton reactions and accelerating CYP-mediated lipid peroxidation, ultimately culminating in ferroptotic cell death. Additionally, the Fe2+-dependent CYP catalyzes the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid, which activates the peroxisome proliferator-activated receptor. Consequently, the downstream target of peroxisome proliferator-activated receptor, cluster of differentiation 36, promotes intracellular fatty acid accumulation, lipid peroxidation, and ferroptosis. These significant findings shed light on the immune defense mechanisms employed by crustaceans and provide potential strategies for combating bacterial infections in this species.
  15. Ye Z, Nguyen TL, Dite GS, MacInnis RJ, Schmidt DF, Makalic E, et al.
    Breast Cancer Res, 2023 Oct 25;25(1):127.
    PMID: 37880807 DOI: 10.1186/s13058-023-01733-1
    BACKGROUND: Mammogram risk scores based on texture and density defined by different brightness thresholds are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. We aimed to investigate causal relationships between these intercorrelated mammogram risk scores to determine their relevance to breast cancer aetiology.

    METHODS: We used digitised mammograms for 371 monozygotic twin pairs, aged 40-70 years without a prior diagnosis of breast cancer at the time of mammography, from the Australian Mammographic Density Twins and Sisters Study. We generated normalised, age-adjusted, and standardised risk scores based on textures using the Cirrus algorithm and on three spatially independent dense areas defined by increasing brightness threshold: light areas, bright areas, and brightest areas. Causal inference was made using the Inference about Causation from Examination of FAmilial CONfounding (ICE FALCON) method.

    RESULTS: The mammogram risk scores were correlated within twin pairs and with each other (r = 0.22-0.81; all P 

  16. Feng S, Xie X, Liu J, Li A, Wang Q, Guo D, et al.
    J Nanobiotechnology, 2023 Oct 10;21(1):370.
    PMID: 37817254 DOI: 10.1186/s12951-023-02139-z
    Microalgae as the photosynthetic organisms offer enormous promise in a variety of industries, such as the generation of high-value byproducts, biofuels, pharmaceuticals, environmental remediation, and others. With the rapid advancement of gene editing technology, CRISPR/Cas system has evolved into an effective tool that revolutionised the genetic engineering of microalgae due to its robustness, high target specificity, and programmability. However, due to the lack of robust delivery system, the efficacy of gene editing is significantly impaired, limiting its application in microalgae. Nanomaterials have become a potential delivery platform for CRISPR/Cas systems due to their advantages of precise targeting, high stability, safety, and improved immune system. Notably, algal-mediated nanoparticles (AMNPs), especially the microalgae-derived nanoparticles, are appealing as a sustainable delivery platform because of their biocompatibility and low toxicity in a homologous relationship. In addition, living microalgae demonstrated effective and regulated distribution into specified areas as the biohybrid microrobots. This review extensively summarised the uses of CRISPR/Cas systems in microalgae and the recent developments of nanoparticle-based CRISPR/Cas delivery systems. A systematic description of the properties and uses of AMNPs, microalgae-derived nanoparticles, and microalgae microrobots has also been discussed. Finally, this review highlights the challenges and future research directions for the development of gene-edited microalgae.
  17. Sharuddin SS, Ramli N, Yusoff MZM, Muhammad NAN, Ho LS, Maeda T
    J Appl Microbiol, 2023 Oct 04;134(10).
    PMID: 37757470 DOI: 10.1093/jambio/lxad219
    AIMS: This study aimed to investigate the effect of palm oil mill effluent (POME) final discharge on the active bacterial composition, gene expression, and metabolite profiles in the receiving rivers to establish a foundation for identifying potential biomarkers for monitoring POME pollution in rivers.

    METHODS AND RESULTS: The POME final discharge, upstream (unpolluted by POME), and downstream (effluent receiving point) parts of the rivers from two sites were physicochemically characterized. The taxonomic and gene profiles were then evaluated using de novo metatranscriptomics, while the metabolites were detected using qualitative metabolomics. A similar bacterial community structure in the POME final discharge samples from both sites was recorded, but their composition varied. Redundancy analysis showed that several families, particularly Comamonadaceae and Burkholderiaceae [Pr(>F) = 0.028], were positively correlated with biochemical oxygen demand (BOD5) and chemical oxygen demand (COD). The results also showed significant enrichment of genes regulating various metabolisms in the POME-receiving rivers, with methane, carbon fixation pathway, and amino acids among the predominant metabolisms identified (FDR  4, and PPDE > 0.95). This was further validated through qualitative metabolomics, whereby amino acids were detected as the predominant metabolites.

    CONCLUSIONS: The results suggest that genes regulating amino acid metabolism have significant potential for developing effective biomonitoring and bioremediation strategies in river water influenced by POME final discharge, fostering a sustainable palm oil industry.

  18. Feng M, Tan K, Zhang H, Duan X, Li S, Ma H, et al.
    Fish Shellfish Immunol, 2023 Oct;141:109059.
    PMID: 37678479 DOI: 10.1016/j.fsi.2023.109059
    High stocking density has been regarded as an adverse factor in bivalve aquaculture. However, its subsequent molecular response to pathogenic bacteria has been little studied. In order to study the question, a novel MyD88 was first cloned using adult noble scallops Chlamys nobilis (CnMyD88), and its tissue distribution was investigated. Then, 1860 juvenile scallops were divided into two groups with two initial densities of high density (200 individuals/layer, HD) and normal density (110 individuals/layer, ND) and in-situ cultured for three months, in which their growth, survival, and the differential expression of CnMyD88 were examined, respectively. Finally, scallops were injected with the Vibrio parahaemolyticus to assess the temporal expression of CnMyD88. As the results show, CnMyD88 cDNA has a full length of 2241 bp and contains an 1107 bp ORF that encodes a 368-derived protein. It was widely expressed in examined tissues with a significantly higher level in hemolymph, intestine, mantle, and gonad than others. Besides, the HD group showed lower growth (0.39 ± 0.05 mm/day) and survival (37.00 ± 8.49%) than the ND group (0.55 ± 0.02 mm/day and 76.82 ± 5.78%). More importantly, the HD group exhibited significantly lower expression levels of CnMyD88 in their examined tissues than the ND group. After V. parahaemolyticus challenging, CnMyD88 had significantly lower expression levels in the scallops from the HD group than that of the scallops from the ND group at 6th, 24th, and 36th. The present results indicated that high stocking density not only made adverse impacts on growth and survival but also may induce immunosuppression in the noble scallop. Therefore, appropriate low stocking density may be worth considering to adopt in scallop aquaculture.
  19. Özgüroğlu M, Kilickap S, Sezer A, Gümüş M, Bondarenko I, Gogishvili M, et al.
    Lancet Oncol, 2023 Sep;24(9):989-1001.
    PMID: 37591293 DOI: 10.1016/S1470-2045(23)00329-7
    BACKGROUND: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.

    METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.

    FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.

    FUNDING: Regeneron Pharmaceuticals and Sanofi.

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