Displaying publications 41 - 60 of 231 in total

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  1. Jelen MM, Chen Z, Kocjan BJ, Burt FJ, Chan PK, Chouhy D, et al.
    J Virol, 2014 Jul;88(13):7307-16.
    PMID: 24741079 DOI: 10.1128/JVI.00621-14
    Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution.

    IMPORTANCE: This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new, complete HPV6 genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease, and/or gender. We additionally identified several HPV6 lineage- and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within the L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination, and molecular assay development studies.

  2. Hu J, Pradit S, Loh PS, Chen Z, Guo C, Le TPQ, et al.
    Mar Pollut Bull, 2024 Jan 29;200:116064.
    PMID: 38290368 DOI: 10.1016/j.marpolbul.2024.116064
    Mangrove forests can help to mitigate climate change by storing a significant amount of carbon (C) in soils. Planted mangrove forests have been established to combat anthropogenic threats posed by climate change. However, the efficiency of planted forests in terms of soil organic carbon (SOC) storage and dynamics relative to that of natural forests is unclear. We assessed SOC and nutrient storage, SOC sources and drivers in a natural and a planted forest in southern Thailand. Although the planted forest stored more C and nutrients than the natural forest, the early-stage planted forest was not a strong sink relative to mudflat. Both forests were predominated by allochthonous organic C and nitrogen limited, with total nitrogen being a major driver of SOC in both cases. SOC showed a significant decline along land-to-sea and depth gradients as a result of soil texture, nutrient availability, and pH in the natural forest.
  3. Lim WX, Chen Z, Ahmed A
    Med Biol Eng Comput, 2022 Mar;60(3):633-642.
    PMID: 35083634 DOI: 10.1007/s11517-021-02487-8
    Diabetic retinopathy (DR) is a chronic eye condition that is rapidly growing due to the prevalence of diabetes. There are challenges such as the dearth of ophthalmologists, healthcare resources, and facilities that are unable to provide patients with appropriate eye screening services. As a result, deep learning (DL) has the potential to play a critical role as a powerful automated diagnostic tool in the field of ophthalmology, particularly in the early detection of DR when compared to traditional detection techniques. The DL models are known as black boxes, despite the fact that they are widely adopted. They make no attempt to explain how the model learns representations or why it makes a particular prediction. Due to the black box design architecture, DL methods make it difficult for intended end-users like ophthalmologists to grasp how the models function, preventing model acceptance for clinical usage. Recently, several studies on the interpretability of DL methods used in DR-related tasks such as DR classification and segmentation have been published. The goal of this paper is to provide a detailed overview of interpretability strategies used in DR-related tasks. This paper also includes the authors' insights and future directions in the field of DR to help the research community overcome research problems.
  4. Lim WX, Chen Z
    Med Biol Eng Comput, 2024 Apr 23.
    PMID: 38649629 DOI: 10.1007/s11517-024-03093-0
    Diabetic retinopathy disease contains lesions (e.g., exudates, hemorrhages, and microaneurysms) that are minute to the naked eye. Determining the lesions at pixel level poses a challenge as each pixel does not reflect any semantic entities. Furthermore, the computational cost of inspecting each pixel is expensive because the number of pixels is high even at low resolution. In this work, we propose a hybrid image processing method. Simple Linear Iterative Clustering with Gaussian Filter (SLIC-G) for the purpose of overcoming pixel constraints. The SLIC-G image processing method is divided into two stages: (1) simple linear iterative clustering superpixel segmentation and (2) Gaussian smoothing operation. In such a way, a large number of new transformed datasets are generated and then used for model training. Finally, two performance evaluation metrics that are suitable for imbalanced diabetic retinopathy datasets were used to validate the effectiveness of the proposed SLIC-G. The results indicate that, in comparison to prior published works' results, the proposed SLIC-G shows better performance on image classification of class imbalanced diabetic retinopathy datasets. This research reveals the importance of image processing and how it influences the performance of deep learning networks. The proposed SLIC-G enhances pre-trained network performance by eliminating the local redundancy of an image, which preserves local structures, but avoids over-segmented, noisy clips. It closes the research gap by introducing the use of superpixel segmentation and Gaussian smoothing operation as image processing methods in diabetic retinopathy-related tasks.
  5. Tee MZ, Er YX, Easton AV, Yap NJ, Lee IL, Devlin J, et al.
    Microbiome, 2022 Dec 07;10(1):214.
    PMID: 36476263 DOI: 10.1186/s40168-022-01385-x
    BACKGROUND: While microbiomes in industrialized societies are well characterized, indigenous populations with traditional lifestyles have microbiomes that are more akin to those of ancient humans. However, metagenomic data in these populations remains scarce, and the association with soil-transmitted helminth infection status is unclear. Here, we sequenced 650 metagenomes of indigenous Malaysians from five villages with different prevalence of helminth infections.

    RESULTS: Individuals from villages with higher prevalences of helminth infections have more unmapped reads and greater microbial diversity. Microbial community diversity and composition were most strongly associated with different villages and the effects of helminth infection status on the microbiome varies by village. Longitudinal changes in the microbiome in response to albendazole anthelmintic treatment were observed in both helminth infected and uninfected individuals. Inference of bacterial population replication rates from origin of replication analysis identified specific replicating taxa associated with helminth infection.

    CONCLUSIONS: Our results indicate that helminth effects on the microbiota were highly dependent on context, and effects of albendazole on the microbiota can be confounding for the interpretation of deworming studies. Furthermore, a substantial quantity of the microbiome remains unannotated, and this large dataset from an indigenous population associated with helminth infections is a valuable resource for future studies. Video Abstract.

  6. Xu G, Zhang C, Lee SY, Chen Z, Zeng X
    Mitochondrial DNA B Resour, 2023;8(1):181-185.
    PMID: 36713297 DOI: 10.1080/23802359.2023.2168114
    Christella dentata (Forssk.) Brownsey & Jermy (Thelypteridaceae) is endemic to the tropical and subtropical regions of Africa, Asia, and Asia Pacific. In this study, the complete chloroplast genome sequence of C. dentata was assembled using next-generation sequencing data. The complete chloroplast genome was 151,662 bp in length and had a typical quadripartite structure, which consisted of a small single-copy region (21,776 bp) and a large single-copy region (82,624 bp) that were separated by a pair of inverted repeats (23,631 bp each). A total of 131 genes were predicted, including 89 protein coding (CDS), 34 tRNA, and eight rRNA genes. The overall GC content of the chloroplast genome was 42.48%. Based on the concatenated shared unique CDS sequence dataset, phylogenetic analysis using both the maximum-likelihood and the Bayesian inference methods revealed that C. dentata is placed within Thelypteridaceae and is closely related to Christella appendiculata. Such genetic information would be useful for studies on the evolution pattern in ferns. The availability of chloroplast genome sequence for the species also paves the way to resolving the complicated relationship among members of Christella.
  7. Xu G, Li Z, Chen Z, Lee SY, Kong X
    Mitochondrial DNA B Resour, 2023;8(10):1137-1140.
    PMID: 37928400 DOI: 10.1080/23802359.2023.2270207
    Oreocharis argyreia var. angustifolia of Gesneriaceae is widely distributed in South China, including Guangdong, Guangxi, Hunan, and Jiangxi provinces. However, genetic information of this species is limited, further contributing to the taxonomic complications surrounding this species. Thus, in this study, we assembled and characterized the complete chloroplast genome of O. argyreia var. angustifolia as a genomic resource for future studies. The complete plastid genome was 154,675 bp in size, with a pair of inverted repeat regions of 25,329 bp each, separating the 85,977-bp large and 18,040-bp small single copy regions. A total of 131 genes were predicted, consisting of 86 protein-coding, 37 tRNA, and eight rRNA genes. The overall GC content was 37.6%. Phylogenetic analysis based on 79 shared unique CDS resulted in a fully resolved phylogenetic tree using both the maximum likelihood and Bayesian inference methods. Based on current circumscription, both methods indicated that Oreocharis is monophyletic; O. argyreia var. angustifolia diverged after O. chienii, which then followed by the divergence of the other three species included namely, O. continifolia, O. esquirolii, and O. mileensis. The genomic data obtained will be useful for future studies on the phylogenetics and evolution of Gesneriaceae.
  8. Zeng N, Gao W, Chen Z, Chong JY, Lee SY, Xu G
    Mitochondrial DNA B Resour, 2024;9(4):465-469.
    PMID: 38591052 DOI: 10.1080/23802359.2024.2316069
    Strobilanthes dalzielii of Acanthaceae is an herb species with potentially extensive applications for its pharmaceutical and ornamental values. Due to taxonomic complications and limited genetic information, the structural characteristics, and phylogenetic relationships of the S. dalzielii chloroplast genome were assembled and characterized here for the first time. The complete chloroplast genome of S. dalzielii was 144,580 bp in length. The genome is quadripartite in structure and consists of a large single-copy region (92,137 bp) and a small single-copy region (17,669 bp), which are separated by a pair of inverted repeats (each 17,387 bp). A total of 125 genes were annotated, including 80 protein-coding, 37 transfer RNA, and eight ribosomal RNA genes. The overall GC content was 36.4%. Phylogenetic analysis based on the complete chloroplast genome sequence of 21 taxa within the tribe Ruellieae of Acanthaceae using the maximum likelihood and Bayesian inference methods revealed that Strobilanthes diverged after Ruellia; S. dalzielii is closely related to S. tonkinensis. The genomic data obtained from this study will serve as valuable information to the species delimitation and genetic classification of Strobilanthes.
  9. Jenkins TM, Jones SC, Lee CY, Forschler BT, Chen Z, Lopez-Martinez G, et al.
    Mol Phylogenet Evol, 2007 Mar;42(3):612-21.
    PMID: 17254806
    Coptotermes gestroi, the Asian subterranean termite (AST), is an economically important structural and agricultural pest that has become established in many areas of the world. For the first time, phylogeography was used to illuminate the origins of new found C. gestroi in the US Commonwealth of Puerto Rico; Ohio, USA; Florida, USA; and Brisbane, Australia. Phylogenetic relationships of C. gestroi collected in indigenous locations within Malaysia, Thailand, and Singapore as well as from the four areas of introduction were investigated using three genes (16S rRNA, COII, and ITS) under three optimality criteria encompassing phenetic and cladistic assumptions (maximum parsimony, maximum likelihood, and neighbor-joining). All three genes showed consistent support for a close genetic relationship between C. gestroi samples from Singapore and Ohio, whereas termite samples from Australia, Puerto Rico, and Key West, FL were more closely related to those from Malaysia. Shipping records further substantiated that Singapore and Malaysia were the likely origin of the Ohio and Australia C. gestroi, respectively. These data provide support for using phylogeography to understand the dispersal history of exotic termites. Serendipitously, we also gained insights into concerted evolution in an ITS cluster from rhinotermitid species in two genera.
  10. Ali H, Muhammad A, Bala NS, Wang G, Chen Z, Peng Z, et al.
    Mol Phylogenet Evol, 2018 10;127:1000-1009.
    PMID: 29981933 DOI: 10.1016/j.ympev.2018.07.003
    Wolbachia pipientis is a diverse, ubiquitous and most prevalent intracellular bacterial group of alpha-Proteobacteria that is concerned with many biological processes in arthropods. The coconut hispine beetle (CHB), Brontispa longissima (Gestro) is an economically important pest of palm cultivation worldwide. In the present study, we comprehensively surveyed the Wolbachia-infection prevalence and mitochondrial DNA (mtDNA) polymorphism in CHB from five different geographical locations, including China's Mainland and Taiwan, Vietnam, Thailand, Malaysia and Indonesia. A total of 540 sequences were screened in this study through three different genes, i.e., cytochrome oxidase subunit I (COI), Wolbachia outer surface protein (wsp) and multilocus sequencing type (MLST) genes. The COI genetic divergence ranges from 0.08% to 0.67%, and likewise, a significant genetic diversity (π = 0.00082; P = 0.049) was noted within and between all analyzed samples. In the meantime, ten different haplotypes (H) were characterized (haplotype diversity = 0.4379) from 21 different locations, and among them, H6 (46 individuals) have shown a maximum number of population clusters than others. Subsequently, Wolbachia-prevalence results indicated that all tested specimens of CHB were found positive (100%), which suggested that CHB was naturally infected with Wolbachia. Wolbachia sequence results (wsp gene) revealed a high level of nucleotide diversity (π = 0.00047) under Tajima's D test (P = 0.049). Meanwhile, the same trend of nucleotide diversity (π = 0.00041) was observed in Wolbachia concatenated MLST locus. Furthermore, phylogenetic analysis (wsp and concatenated MLST genes) revealed that all collected samples of CHB attributed to same Wolbachia B-supergroup. Our results strongly suggest that Wolbachia bacteria and mtDNA were highly concordant with each other and Wolbachia can affect the genetic structure and diversity within the CHB populations.
  11. Cui Y, Hada K, Kawashima T, Kino M, Lin W, Mizuno Y, et al.
    Nature, 2023 Sep;621(7980):711-715.
    PMID: 37758892 DOI: 10.1038/s41586-023-06479-6
    The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.
  12. Lawrenson K, Li Q, Kar S, Seo JH, Tyrer J, Spindler TJ, et al.
    Nat Commun, 2015 Sep 22;6:8234.
    PMID: 26391404 DOI: 10.1038/ncomms9234
    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
  13. Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, et al.
    Nat Genet, 2015 Feb;47(2):164-71.
    PMID: 25581431 DOI: 10.1038/ng.3185
    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
  14. Wang K, Goldenberg A, Dorison CA, Miller JK, Uusberg A, Lerner JS, et al.
    Nat Hum Behav, 2021 Aug;5(8):1089-1110.
    PMID: 34341554 DOI: 10.1038/s41562-021-01173-x
    The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 12 May 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.c.4878591.v1.
  15. Zhou X, Yan Z, Hou J, Zhang L, Chen Z, Gao C, et al.
    Oncogene, 2024 Feb;43(7):495-510.
    PMID: 38168654 DOI: 10.1038/s41388-023-02923-z
    Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in the world with poor prognosis. Despite the promising applications of immunotherapy, the objective response rate is still unsatisfactory. We have previously shown that Hippo/YAP signaling acts as a powerful tumor promoter in ESCC. However, whether Hippo/YAP signaling is involved in tumor immune escape in ESCC remains largely unknown. Here, we show that YAP directly activates transcription of the "don't eat me" signal CD24, and plays a crucial role in driving tumor cells to avoid phagocytosis by macrophages. Mechanistically, YAP regulates CD24 expression by interacting with TEAD and binding the CD24 promoter to initiate transcription, which facilitates tumor cell escape from macrophage-mediated immune attack. Our animal model data and clinical data show that YAP combined with CD24 in tumor microenvironment redefines the impact of TAMs on the prognosis of ESCC patients which will provide a valuable basis for precision medicine. Moreover, treatment with YAP inhibitor altered the distribution of macrophages and suppressed tumorigenesis and progression of ESCC in vivo. Together, our study provides a novel link between Hippo/YAP signaling and macrophage-mediated immune escape, which suggests that the Hippo-YAP-CD24 axis may act as a promising target to improve the prognosis of ESCC patients. A proposed model for the regulatory mechanism of Hippo-YAP-CD24-signaling axis in the tumor-associated macrophages mediated immune escape.
  16. Akhtar Z, Gallagher MM, Yap YG, Leung LWM, Elbatran AI, Madden B, et al.
    Pacing Clin Electrophysiol, 2021 05;44(5):875-882.
    PMID: 33792080 DOI: 10.1111/pace.14232
    BACKGROUND: Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc).

    METHOD: For 293 consecutive patients admitted to our hospital via the emergency department for COVID-19 between 01/03/20 -18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID-19.

    RESULTS: Patients who died were older than survivors (82 vs 69.8 years, p 455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04-2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2-2.6]).

    CONCLUSION: QTc prolongation occurs in COVID-19 illness and is associated with poor outcome.

  17. Lin C, Chen Z, Zhang L, Wei Z, Cheng KK, Liu Y, et al.
    Parasit Vectors, 2019 Jun 13;12(1):300.
    PMID: 31196218 DOI: 10.1186/s13071-019-3554-0
    BACKGROUND: Hepatic alveolar echinococcosis (HAE) is caused by the growth of Echinococcus multilocularis larvae in the liver. It is a chronic and potentially lethal parasitic disease. Early stage diagnosis for this disease is currently not available due to its long asymptomatic incubation period. In this study, a proton nuclear magnetic resonance (1H NMR)-based metabolomics approach was applied in conjunction with multivariate statistical analysis to investigate the altered metabolic profiles in blood serum and urine samples obtained from HAE patients. The aim of the study was to identify the metabolic signatures associated with HAE.

    RESULTS: A total of 21 distinct metabolic differences between HAE patients and healthy individuals were identified, and they are associated with perturbations in amino acid metabolism, energy metabolism, glyoxylate and dicarboxylate metabolism. Furthermore, the present results showed that the Fischer ratio, which is the molar ratio of branched-chain amino acids to aromatic amino acids, was significantly lower (P 

  18. Wu M, Li M, Yuan J, Liang S, Chen Z, Ye M, et al.
    Pharmacol Res, 2020 05;155:104693.
    PMID: 32057896 DOI: 10.1016/j.phrs.2020.104693
    Hormone therapy continues to be a favourable option in the management of menopausal symptomatology, but the associated risk-benefit ratios with respect to neurodegenerative diseases remain controversial. The study aim was to determine the relation between menopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in human subjects. A literature search was performed in PubMed/Medline, Cochrane collaboration, and Scopus databases from onset of the database to September 2019. Random-effects model was used to estimate pooled odd ratio (OR) and 95 % confidence intervals (CI). Subgroup analysis was performed based on the type and formulation of hormone. In addition, the time-response effect of this relationship was also assessed based on duration of hormone therapy. Associations between hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in menopausal women were reported in 28 studies. Pooled results with random effect model showed a significant association between hormone therapy and Alzheimer's disease (OR 1.08, 95 % CI 1.03-1.14, I2: 69 %). This relationship was more pronounced in patients receiving the combined estrogen-progestogen formulation. Moreover, a significant non-linear time-response association between hormone therapy and Alzheimer's disease was also identified (Coef1 = 0.0477, p1<0.001; Coef2 = -0.0932, p2<0.001). Similarly, pooled analysis revealed a significant association between hormone therapy and all-cause dementia (OR 1.16, 95 % CI 1.02-1.31, I2: 19 %). Interestingly, no comparable relationship was uncovered between hormone therapy as a whole and Parkinson's disease (OR 1.14, 95 % CI 0.95-1.38, I2: 65 %); however, sub-group analysis revealed a significant relationship between the disease and progestogen (OR 3.41, 95 % CI 1.23-9.46) or combined estrogen-progestogen formulation use (OR 1.49, 95 % CI 1.34-1.65). Indeed, this association was also found to be driven by duration of exposure (Coef1 = 0.0626, p1 = 0.04). This study reveals a significant direct relationship between the use of certain hormonal therapies and Alzheimer's disease, all-cause dementia, and Parkinson's disease in menopausal women. However, the association appears to shift in direct after five years in the context of Alzheimer's disease, adding further weight to the critical window or timing hypothesis of neurodegeneration and neuroprotection.
  19. Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Feb 19;116(7):071801.
    PMID: 26943527 DOI: 10.1103/PhysRevLett.116.071801
    A search for narrow resonances in proton-proton collisions at sqrt[s]=13  TeV is presented. The invariant mass distribution of the two leading jets is measured with the CMS detector using a data set corresponding to an integrated luminosity of 2.4  fb^{-1}. The highest observed dijet mass is 6.1 TeV. The distribution is smooth and no evidence for resonant particles is observed. Upper limits at 95% confidence level are set on the production cross section for narrow resonances with masses above 1.5 TeV. When interpreted in the context of specific models, the limits exclude string resonances with masses below 7.0 TeV, scalar diquarks below 6.0 TeV, axigluons and colorons below 5.1 TeV, excited quarks below 5.0 TeV, color-octet scalars below 3.1 TeV, and W^{'} bosons below 2.6 TeV. These results significantly extend previously published limits.
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