Displaying publications 1 - 20 of 64 in total

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  1. Lee VWY, Li A, Li JTS
    Tob Induc Dis, 2021;19:28.
    PMID: 33867905 DOI: 10.18332/tid/133633
    INTRODUCTION: Smoking is a modifiable risk factor for many diseases. The public should recognize the impact of smoking on their health and their wealth. The current study aimed to evaluate the cost burden of smoking to target Asia-Pacific countries.

    METHODS: The current study estimated the annual spending and lifetime spending of smokers in the target Asia-Pacific countries (Hong Kong, Malaysia, Thailand, South Korea, Singapore, and Australia) on purchasing cigarettes, as well as predicted the revenue that could be generated if smokers spent the money on investment instead of buying cigarettes. Smokers' spending on cigarettes and the potential revenue generated from investment were estimated based on the selling prices of cigarettes, Standards & Poor's 500 Index, and life expectancies of smokers. Data were extracted from reports released by the World Health Organization or government authorities.

    RESULTS: The annual expenses (in US$) on purchasing one pack of cigarettes, in decreasing order, were: Australia ($5628.30), Singapore ($3777.75), Hong Kong ($2799.55), Malaysia ($1529.35), South Korea ($1467.30), and Thailand ($657.00). The lifetime spending on purchasing one pack of cigarettes each day were: Australia ($308993.67), Singapore ($207398.48), Hong Kong ($151735.61 for male and $166853.18 for female), South Korea ($80261.31), Malaysia ($72338.26), and Thailand ($31207.50).

    CONCLUSIONS: The cost burden of smoking is high from a smoker's perspective. Smokers should recognize the high economic burden and quit smoking to enjoy better health and wealth.

  2. Li A, Zain NM, Yusuf A, Deng H, He Q
    Nurse Educ Pract, 2024 Jul;78:103988.
    PMID: 38843688 DOI: 10.1016/j.nepr.2024.103988
    OBJECTIVE: The purpose of this meta-analysis was to assess the effects of online education for practical skills among nursing students.

    METHODS: This research was done by searching PubMed, Embase, CINAHL, and Web of Science electronic databases from inception to August 18, 2023, to identify English-language articles. Data extraction, quality assessment, and literature screening were carried out independently by two researchers. The Cochrane risk of bias tool and the Methodological Items for Nonrandomized Studies (MINORS) tool were used to assess the risk of bias of the included studies. Meta-analysis was carried out using Review Manager (RevMan) version 5.3 software.

    RESULTS: Eighteen studies involving 2274 nursing students met the inclusion criteria. Nursing students' skills (SMD = 0.43, 95 % CI [0.33, 0.54], P<0.00001), knowledge (SMD = 0.16, 95 % CI (0.02, 0.30], P = 0.02), satisfaction (SMD = 0.29, 95 % CI (0.10, 0.47], P < 0.01), and confidence (SMD = 0.56, 95 % CI [0.29, 0.83], P < 0.0001) were all significantly improved by the online teaching intervention compared with traditional face-to-face instruction. Self-efficacy (SMD = 0.1, 95 % CI [-0.13, 0.33], P = 0.41) was also improved, but the difference was not statistically significant.

    CONCLUSION: Online learning is a novel and efficient approach to teaching practical skills to nursing students. Online education can enhance students' knowledge, skills, confidence, and learning satisfaction, and it is superior to traditional classroom instruction. The findings of this study can serve as a basis for the development of standardized online teaching techniques and assessment metrics.

  3. Han C, Zhai C, Li A, Ma Y, Hallajzadeh J
    Front Cardiovasc Med, 2024;11:1432468.
    PMID: 39553846 DOI: 10.3389/fcvm.2024.1432468
    Myocardial infarction (MI), a widespread cardiovascular issue, mainly occurs due to blood clot formation in the coronary arteries, which reduces blood flow to the heart muscle and leads to cell death. Incorporating exercise into a lifestyle can significantly benefit recovery and reduce the risk of future cardiac events for MI patients. Non-coding RNAs (ncRNAs) play various roles in the effects of exercise on myocardial infarction (MI). ncRNAs regulate gene expression, influence cardiac remodeling, angiogenesis, inflammation, oxidative stress, apoptosis, cardioprotection, and cardiac electrophysiology. The expression of specific ncRNAs is altered by exercise, leading to beneficial changes in heart structure, function, and recovery after MI. These ncRNAs modulate molecular pathways that contribute to improved cardiac health, including reducing inflammation, enhancing angiogenesis, promoting cell survival, and mitigating oxidative stress. Furthermore, they are involved in regulating changes in cardiac remodeling, such as hypertrophy and fibrosis, and can influence the electrical properties of the heart, thereby decreasing the risk of arrhythmias. Knowledge on MI has entered a new phase, with investigations of ncRNAs in physical exercise yielding invaluable insights into the impact of this therapeutic modality. This review compiled research on ncRNAs in MI, with an emphasis on their applicability to physical activity.
  4. Dong HC, Lundholm N, Teng ST, Li A, Wang C, Hu Y, et al.
    Harmful Algae, 2020 09;98:101899.
    PMID: 33129456 DOI: 10.1016/j.hal.2020.101899
    The diatom genus Pseudo-nitzschia, which has been associated with amnesic shellfish poisoning events globally, is also one of the key harmful microalga groups in Guangdong coastal waters, off the north coast of the South China Sea. In order to explore the diversity and toxigenic characteristics, Pseudo-nitzschia isolates were established. Based on a combination of morphological and molecular features, in total 26 different Pseudo-nitzschia taxa were identified, including two new species, P. uniseriata H.C. Dong & Yang Li and P. yuensis H.C. Dong & Yang Li. Morphologically, P. uniseriata is unique by having striae mainly comprising one row of poroids, which are simple without divided hymen internally, and each poroid containing one, seldom two sectors. Pseudo-nitzschia yuensis is characterized by having striae comprising one to two rows of poroids. In biseriate striae, the poroids are polygonal and irregularly distributed, and a discontinuous row of poroids may be present in the middle. In uniseriate striae, the poroids usually contain 1-5 sectors. Both taxa are well differentiated from other Pseudo-nitzschia species in phylogenetic analyses inferred from ITS2 sequence-structure information. Pseudo-nitzschia uniseriata is sister to P. lineola, whereas P. yuensis forms a group together with P. micropora and P. delicatissima. When comparing ITS2 secondary structure, two hemi-compensatory base change (HCBCs) are found between P. uniseriata and P. lineola. One compensatory base change (CBC) and four HCBCs are found between P. yuensis and P. delicatissima, and there is one CBC and five HCBCs between P. yuensis and P. micropora. The ability of cultured strains to produce particulate DA (pDA) revealed production of pDA in twenty-nine strains belonging to seven species: P. bipertita, P. caciantha, P. cuspidata, P. fraudulenta, P. fukuyoi, P. lundholmiae and P. multiseries. This is the first report of P. bipertita being toxic, with pDA content of 15.6 ± 2.1 fg cell-1. The presence of brine shrimps significantly increased pDA content in P. cuspidata, P. fukuyoi, P. lundholmiae and P. multiseries 1.4 to 7 times, and induced pDA production in P. fraudulenta from below detection limit to 17.5 ± 1.6 fg cell-1. The highest pDA concentration, 4830.5 ± 120.3 fg cell-1, was detected in P. multiseries, a level much lower than previous reports on P. multiseries from North America and Europe. Overall, the cellular toxin levels in Pseudo-nitzschia spp. were low in Guangdong coastal isolates.
  5. Chen XM, Pang JX, Huang CX, Lundholm N, Teng ST, Li A, et al.
    J Phycol, 2021 Feb;57(1):335-344.
    PMID: 33174223 DOI: 10.1111/jpy.13101
    To explore the species diversity and toxin profile of Pseudo-nitzschia, monoclonal strains were established from Chinese southeast coastal waters. The morphology was examined under light and transmission electron microscopy. The internal transcribed spacer region of ribosomal DNA was sequenced for phylogenetic analyses, and the secondary structure of ITS2 was predicted and compared among allied taxa. A combination of morphological and molecular data showed the presence of two new species, Pseudo-nitzschia hainanensis sp. nov. and Pseudo-nitzschia taiwanensis sp. nov. Pseudo-nitzschia hainanensis was characterized by a dumpy-lanceolate valve with slightly blunt apices and a central nodule, as well as striae comprising two rows of poroids. Pseudo-nitzschia taiwanensis was characterized by a slender-lanceolate valve, and striae comprising one row of split poroids. The poroid structure mainly comprised two sectors. Both taxa constituted their own monophyletic lineage in the phylogenetic analyses inferred from ITS2 rDNA and were well differentiated from other Pseudo-nitzschia species. Morphologically, P. hainanensis and P. taiwanensis could be assigned to the Pseudo-nitzschia delicatissima and the Pseudo-nitzschia pseudodelicatissima complex, respectively. Particulate domoic acid was measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), but no detectable pDA was found. With the description of the two new species, the species diversity of genus Pseudo-nitzschia reaches 58 worldwide, among which 31 have been recorded from Chinese coastal waters.
  6. Qin Y, Huang X, Chen H, Liu X, Li Y, Hou J, et al.
    BMC Infect Dis, 2020 Jul 29;20(1):551.
    PMID: 32727383 DOI: 10.1186/s12879-020-05260-8
    BACKGROUND: Talaromyces marneffei (TM) is a dimorphic fungus mainly prevalent in Southeast Asian countries, which often causes disseminated life-threatening infection. TM infection often occurs in HIV/AIDS patients even in the antiretroviral therapy (ART) era. However, there has as yet, not been a systematic analysis of the prevalence of TM infection in HIV-infected populations in Asia.

    METHODS: In this study, we searched Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang from inception to 21 November 2018 for studies reporting TM infection in people living with HIV/AIDS (PLWHA). Our meta-analysis included studies investigating the prevalence of TM infection in PLWHA. Reviews, duplicate studies, and animal studies were excluded. A random effects model was used to estimate pooled prevalence, and meta-regression analysis was conducted to explore potential factors for heterogeneity.

    RESULTS: 159,064 patients with HIV infection in 33 eligible studies were included in our meta-analysis. The pooled prevalence of TM infection in PLWHA was 3.6%. Vietnam had the highest prevalence (6.4%), followed by Thailand (3.9%), China (3.3%), India (3.2%) and Malaysia (2.1%). In China, TM infection was most prevalent in South China (15.0%), while the burden in Southwest China was not very heavy (0.3%). CD4+ T-cell counts below 200 cells/mm3 contributed to the increased risk of TM infection in PLWHA (OR 12.68, 95%CI: 9.58-16.77). However, access to ART did not significantly decrease the risk of TM infection in PLWHA.

    CONCLUSIONS: The burden of TM infection in Asia is heavy, and varies from region to region. PLWHA in lower latitude areas are more likely to suffer from TM infection. Optimization of diagnostic tools and universal screening for TM in vulnerable people to ensure early case detection and prompt antifungal treatment should be considered.

  7. Ai H, Lee YY, Xie X, Tan CP, Ming Lai O, Li A, et al.
    Food Chem, 2023 Jun 30;412:135558.
    PMID: 36716631 DOI: 10.1016/j.foodchem.2023.135558
    Palm olein (POL) was modified by enzymatic interesterification with different degrees of acyl migration in a solvent-free packed bed reactor. The fatty acid and acylglycerol composition, isomer content, thermodynamic behavior, and relationship between crystal polymorphism, solid fat content (SFC), crystal microstructure, and texture before and after modification were studied. We found that the increase in sn-2 saturation interesterification was not only due to the generated tripalmitin (PPP) but also caused by acyl migration, and the SFC profiles were changed accordingly. The emergence of high melting point acylglycerols was an important factor accelerating the crystallization rate, further shortening the crystallization induction time, leading to the formation of large crystal spherulites, thereby reducing the hardness. The transformation from the β' to the β form occurred during post-hardening during storage. The isomer content also affected the physicochemical properties of the modified POL.
  8. Ke W, Lee YY, Cheng J, Tan CP, Lai OM, Li A, et al.
    Food Chem, 2024 Feb 01;433:137374.
    PMID: 37683471 DOI: 10.1016/j.foodchem.2023.137374
    Enzymatic glycerolysis produced ground nut oil-based diacylglycerols (GNO-DAG) with a purity of 43.28 ± 0.89% (GNO-DAG40). GNO-DAG80 (with a DAG purity of 87.33 ± 0.61%) was obtained after purification using molecular distillation. Traditional palm oil was mixed with the "liquid" DAG as margarine base oils. Subsequent evaluations of palm oil-DAG-based fats (PO-GNO DAG) as a margarine replacement in a W/O model system showed that the material was an ideal functional base oil with improved aeration properties and plasticity during application. The binary system physical, textural and crystallization property were determined, and the compatibility of the binary mixed system was analyzed by constructing a phase diagrams. The PO-GNO DAG showed decent compatibility between the two phases and had better texture and rheological properties. In addition, PO-GNO DAG40 showed better apparent viscosity and aeration characteristics than PO-GNO DAG80, with potential application in the food specialty fats industry.
  9. Li A, Abrahim A, Islam M, Mejías E, Hafizati Abdul Halim N, Frew R, et al.
    Food Chem, 2024 Feb 15;434:137451.
    PMID: 37748289 DOI: 10.1016/j.foodchem.2023.137451
    One of the most common types of adulteration of honey involves the addition of invert sugar syrups. A new method was developed to measure the stable isotope ratios of carbon and carbon-bound non-exchangeable (CBNE) hydrogen from specific molecular positions in fructose and glucose in honey. This was achieved through periodate oxidation of the sugars to produce formaldehyde, followed by reaction with ammonia to form hexamethylenetetramine (HMT). The preparation was simplified, optimized, and validated by isotopic analysis of replicate syntheses of HMT from fructose, glucose, sugar syrup and a representative authentic honey sample. The optimized method had a repeatability standard deviation from 1.5‰ to 3.0‰ and from 0.1‰ to 0.4‰ for δ2H and δ13C, respectively. This methodology has advantages over alternative isotopic methods, for measuring CBNE hydrogen isotope ratios in sugars, in terms of time, sensitivity and operability and offers a complementary method to differentiate authentic honey from invert sugar syrups.
  10. Ke W, Lee YY, Tan CP, Li A, Zhang Y, Wang Y, et al.
    Food Chem, 2025 Feb 01;464(Pt 2):141722.
    PMID: 39442221 DOI: 10.1016/j.foodchem.2024.141722
    Diacylglycerol (DAG) is a novel functional structural lipid, but its application in base oils remains underexplored. This research investigated the effect of three liquid oils (groundnut oil, corn oil, and flaxseed oil), with varying polyunsaturated fatty acid (PUFA) (39.60, 69.50, and 77.65 %) and DAG content (0.00, 40.00, 80.00 %), on the crystallization behaviors of palm-based oil. DAG (40.00 %), obtained through enzymatic glycerolysis and molecular distillation, was found to stabilize the binary system with good compatibility and fine crystal structure. "Liquid" DAG played a dual role: diluting solid lipids, and promoting crystallization. Increasing DAG content led to larger crystalline domain size, while higher PUFA content accelerated crystallization and increased crystal orderliness, though decreasing crystal density. These results demonstrated the clear influence of PUFA and DAG content on palm-based oil crystallization. This knowledge can guide the utilization of different unsaturated DAGs for tailored fat crystallization in food application.
  11. Choi JR, Yong KW, Tang R, Gong Y, Wen T, Yang H, et al.
    Adv Healthc Mater, 2017 Jan;6(1).
    PMID: 27860384 DOI: 10.1002/adhm.201600920
    Paper-based devices have been broadly used for the point-of-care detection of dengue viral nucleic acids due to their simplicity, cost-effectiveness, and readily observable colorimetric readout. However, their moderate sensitivity and functionality have limited their applications. Despite the above-mentioned advantages, paper substrates are lacking in their ability to control fluid flow, in contrast to the flow control enabled by polymer substrates (e.g., agarose) with readily tunable pore size and porosity. Herein, taking the benefits from both materials, the authors propose a strategy to create a hybrid substrate by incorporating agarose into the test strip to achieve flow control for optimal biomolecule interactions. As compared to the unmodified test strip, this strategy allows sensitive detection of targets with an approximately tenfold signal improvement. Additionally, the authors showcase the potential of functionality improvement by creating multiple test zones for semi-quantification of targets, suggesting that the number of visible test zones is directly proportional to the target concentration. The authors further demonstrate the potential of their proposed strategy for clinical assessment by applying it to their prototype sample-to-result test strip to sensitively and semi-quantitatively detect dengue viral RNA from the clinical blood samples. This proposed strategy holds significant promise for detecting various targets for diverse future applications.
  12. Li A, Wang Q, Huang Y, Hu L, Li S, Wang Q, et al.
    Virus Res, 2023 Apr 15;328:199080.
    PMID: 36882131 DOI: 10.1016/j.virusres.2023.199080
    Chinese sacbrood virus (CSBV) is the most severe pathogen of Apis cerana, which leads to serious fatal diseases in bee colonies and eventual catastrophe for the Chinese beekeeping industry. Additionally, CSBV can potentially infect Apis mellifera by bridging the species barrier and significantly affect the productivity of the honey industry. Although several approaches, such as feeding royal jelly, traditional Chinese medicine, and double-stranded RNA treatments, have been employed to suppress CSBV infection, their practical applicabilities are constrained due to their poor effectiveness. In recent years, specific egg yolk antibodies (EYA) have been increasingly utilized in passive immunotherapy for infectious diseases without any side effects. According to both laboratory research and practical use, EYA have demonstrated superior protection for bees against CSBV infection. This review provided an in-depth analysis of the issues and drawbacks in this field in addition to provide a thorough summary of current advancements in CSBV studies. Some promising strategies for the synergistic study of EYA against CSBV, including the exploitation of novel antibody drugs, novel TCM monomer/formula determination, and development of nucleotide drugs, are also proposed in this review. Furthermore, the prospects for the future perspectives of EYA research and applications are presented. Collectively, EYA would terminate CSBV infection soon, as well as will provide scientific guidance and references to control and manage other viral infections in apiculture.
  13. Ai H, Lee YY, Lu Y, Tan CP, Lai OM, Li A, et al.
    Poult Sci, 2024 Nov 22;104(1):104579.
    PMID: 39657466 DOI: 10.1016/j.psj.2024.104579
    An experiment was conducted to evalute the effects of adding palm olein (POL), modified palm olein (high degree of acyl migration palm olein, H-AMD), and lard (total fatty acid saturation degree is similar to palm olein) to the diet of broilers. The study assessed production performance, fatty acid absorption, and abdominal fat deposition. A total of 100 one-week-old female broiler chicks were randomly assigned to three-tiered pens and fed five experimental diets. Enzymatic interesterification of POL causes acyl migration, transforming 1-palmitoyl-2,3-dioleoyl-sn-glycerol (sn-POO) and 1,3-dipalmitoyl-2-oleoyl-sn-glycerol (sn-POP) into 1,3-dioleoyl-2-palmitoyl-sn-glycerol (sn-OPO) and 1,2-dipalmitoyl-3-oleoyl-sn-glycerol (sn-PPO), which increases the saturated fatty acid content at the sn-2 position. Feeding broilers with this modified oil has improved the absorption effect of saturated fatty acids and increased the content of palmitic acid in abdominal tissue by 1.55%-1.69%. The impact on the content and positional distribution of fatty acids deposited in the body is limited. Low-density lipoprotein cholesterol (LDL-C) levels decreased by 34%, while high-density lipoprotein cholesterol (HDL-C) levels increased by 23%, resulting in a lower risk of atherosclerosis. No significant differences have been observed in carcass yield results of the POL and H-AMD groups. Compared with animal-derived oils such as lard which are also rich in saturated fatty acids at the sn-2 position, plant-derived oils such as POL and its modified products have a smaller effect on abdominal fat deposition.
  14. 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.
  15. Ye Q, Gao Y, Patel RJ, Cao B, Li A, Powell J, et al.
    Science, 2024 Apr 05;384(6691):26-28.
    PMID: 38574143 DOI: 10.1126/science.adp2180
  16. Li A, Ling L, Qin H, Arabi YM, Myatra SN, Egi M, et al.
    Am J Respir Crit Care Med, 2022 Nov 01;206(9):1107-1116.
    PMID: 35763381 DOI: 10.1164/rccm.202112-2743OC
    Rationale: Directly comparative data on sepsis epidemiology and sepsis bundle implementation in countries of differing national wealth remain sparse. Objectives: To evaluate across countries/regions of differing income status in Asia 1) the prevalence, causes, and outcomes of sepsis as a reason for ICU admission and 2) sepsis bundle (antibiotic administration, blood culture, and lactate measurement) compliance and its association with hospital mortality. Methods: A prospective point prevalence study was conducted among 386 adult ICUs from 22 Asian countries/regions. Adult ICU participants admitted for sepsis on four separate days (representing the seasons of 2019) were recruited. Measurements and Main Results: The overall prevalence of sepsis in ICUs was 22.4% (20.9%, 24.5%, and 21.3% in low-income countries/regions [LICs]/lower middle-income countries/regions [LMICs], upper middle-income countries/regions, and high-income countries/regions [HICs], respectively; P 
  17. Li A, Ling L, Qin H, Arabi YM, Myatra SN, Egi M, et al.
    Crit Care, 2024 Jan 23;28(1):30.
    PMID: 38263076 DOI: 10.1186/s13054-024-04804-7
    BACKGROUND: There is conflicting evidence on association between quick sequential organ failure assessment (qSOFA) and sepsis mortality in ICU patients. The primary aim of this study was to determine the association between qSOFA and 28-day mortality in ICU patients admitted for sepsis. Association of qSOFA with early (3-day), medium (28-day), late (90-day) mortality was assessed in low and lower middle income (LLMIC), upper middle income (UMIC) and high income (HIC) countries/regions.

    METHODS: This was a secondary analysis of the MOSAICS II study, an international prospective observational study on sepsis epidemiology in Asian ICUs. Associations between qSOFA at ICU admission and mortality were separately assessed in LLMIC, UMIC and HIC countries/regions. Modified Poisson regression was used to determine the adjusted relative risk (RR) of qSOFA score on mortality at 28 days with adjustments for confounders identified in the MOSAICS II study.

    RESULTS: Among the MOSAICS II study cohort of 4980 patients, 4826 patients from 343 ICUs and 22 countries were included in this secondary analysis. Higher qSOFA was associated with increasing 28-day mortality, but this was only observed in LLMIC (p 

  18. Li A, Geyer FC, Blecua P, Lee JY, Selenica P, Brown DN, et al.
    NPJ Breast Cancer, 2019 11 19;5:44.
    PMID: 31754629 DOI: 10.1038/s41523-019-0140-8
    [This corrects the article DOI: 10.1038/s41523-019-0115-9.].
  19. Li A, Geyer FC, Blecua P, Lee JY, Selenica P, Brown DN, et al.
    NPJ Breast Cancer, 2019;5:23.
    PMID: 31428676 DOI: 10.1038/s41523-019-0115-9
    Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD.
  20. Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.
    Phys Rev Lett, 2024 Mar 22;132(12):121901.
    PMID: 38579207 DOI: 10.1103/PhysRevLett.132.121901
    The observation of WWγ production in proton-proton collisions at a center-of-mass energy of 13 TeV with an integrated luminosity of 138  fb^{-1} is presented. The observed (expected) significance is 5.6 (5.1) standard deviations. Events are selected by requiring exactly two leptons (one electron and one muon) of opposite charge, moderate missing transverse momentum, and a photon. The measured fiducial cross section for WWγ is 5.9±0.8(stat)±0.8(syst)±0.7(modeling)  fb, in agreement with the next-to-leading order quantum chromodynamics prediction. The analysis is extended with a search for the associated production of the Higgs boson and a photon, which is generated by a coupling of the Higgs boson to light quarks. The result is used to constrain the Higgs boson couplings to light quarks.
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