Displaying publications 21 - 40 of 227 in total

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  1. Zhou JN, Lin BR, Shen HF, Pu XM, Chen ZN, Feng JJ
    Plant Dis, 2012 May;96(5):760.
    PMID: 30727539 DOI: 10.1094/PDIS-11-11-0942
    Phalaenopsis orchids, originally from tropical Asia, are mainly planted in Thailand, Singapore, Malaysia, the Philippines, and Taiwan and have gained popularity from consumers all over the world. The cultivation area of Phalaenopsis orchids has been rising and large-scale bases have been established in mainland China, especially South China because of suitable environmental conditions. In September 2011, a soft rot of Phalaenopsis aphrodita was found in a Phalaenopsis planting base in Guangzhou with an incidence of ~15%. Infected plants initially showed water-soaked, pale-to-dark brown pinpoint spots on leaves that were sometimes surrounded by a yellow halo. Spots expanded rapidly with rising humidity and temperatures, and in a few days, severely extended over the blade with a light tan color and darker brown border. Lesions decayed with odorous fumes and tissues collapsed with inclusions exuding. The bacterium advanced to the stem and pedicle. Finally, leaves became papery dry and the pedicles lodged. Six diseased samples were collected, and bacteria were isolated from the edge of symptomatic tissues after sterilization in 0.3% NaOCl for 10 min, rinsing in sterile water three times, and placing on nutrient agar for culture. Twelve representative isolates were selected for further characterization. All strains were gram negative, grew at 37°C, were positive for indole production, and utilized malonate, glucose, and sucrose but not glucopyranoside, trehalose, or palatinose. Biolog identification (version 4.20.05, Hayward, CA) was performed and Pectobacterium chrysanthemi (SIM 0.868) was confirmed for the tested isolates (transfer to genus Dickeya). PCR was used to amplify the 16S rDNAgene with primers 27f and 1492r, dnaX gene with primers dnaXf and dnaXr (3), and gyrB gene with primers gyrBf (5'-GAAGGYAAAVTKCATCGTCAGG-3') and gyrB-r1 (5'-TCARATATCRATATTCGCYGCTTTC-3') designed on the basis of the published gyrB gene sequences of genus Dickeya. BLASTn was performed online, and phylogeny trees (100% bootstrap values) were created by means of MEGA 5.05 for these gene sequences, respectively. Results commonly showed that the representative tested strain, PA1, was most homologous to Dickeya dieffenbachiae with 98% identity for 16S rDNA(JN940859), 97% for dnaX (JN989971), and 96% for gyrB (JN971031). Thus, we recommend calling this isolate D. dieffenbachiae PA1. Pathogenicity tests were conducted by injecting 10 P. aphrodita seedlings with 100 μl of the bacterial suspension (1 × 108 CFU/ml) and another 10 were injected with 100 μl of sterile water as controls. Plants were inoculated in a greenhouse at 28 to 32°C and 90% relative humidity. Soft rot symptoms were observed after 2 days on the inoculated plants, but not on the control ones. The bacterium was isolated from the lesions and demonstrated identity to the inoculated plant by the 16S rDNA sequence comparison. Previously, similar diseases of P. amabilis were reported in Tangshan, Jiangsu, Zhejiang, and Wuhan and causal agents were identified as Erwinia spp. (2), Pseudomonas grimontii (1), E. chrysanthemi, and E. carotovora subsp. carovora (4). To our knowledge, this is the first report of D. dieffenbachiae causing soft rot disease on P. aphrodita in China. References: (1) X. L. Chu and B. Yang. Acta Phytopathol. Sin. 40:90, 2010. (2) Y. M. Li et al. J. Beijing Agric. Coll. 19:41, 2004. (3) M. Sławiak et al. Eur. J. Plant Pathol. 125:245, 2009. (4) Z. Y. Wu et al. J. Zhejiang For. Coll. 27:635, 2010.
  2. Lin C, Dong J, Wei Z, Cheng KK, Li J, You S, et al.
    J Proteome Res, 2020 02 07;19(2):781-793.
    PMID: 31916767 DOI: 10.1021/acs.jproteome.9b00635
    Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Because of its high recurrence rate and heterogeneity, effective treatment for advanced stage of HCC is currently lacking. There are accumulating evidences showing the therapeutic potential of pharmacologic vitamin C (VC) on HCC. However, the metabolic basis underlying the anticancer property of VC remains to be elucidated. In this study, we used a high-resolution proton nuclear magnetic resonance-based metabolomics technique to assess the global metabolic changes in HCC cells following VC treatment. In addition, the HCC cells were also treated with oxaliplatin (OXA) to explore the potential synergistic effect induced by the combined VC and OXA treatment. The current metabolomics data suggested different mechanisms of OXA and VC in modulating cell growth and metabolism. In general, VC treatment led to inhibition of energy metabolism via NAD+ depletion and amino acid deprivation. On the other hand, OXA caused significant perturbation in phospholipid biosynthesis and phosphatidylcholine biosynthesis pathways. The current results highlighted glutathione metabolism, and pathways related to succinate and choline may play central roles in conferring the combined effect between OXA and VC. Taken together, this study provided metabolic evidence of VC and OXA in treating HCC and may contribute toward the potential application of combined VC and OXA as complementary HCC therapies.
  3. Tian F, He J, Shang S, Chen Z, Tang Y, Lu M, et al.
    Front Microbiol, 2023;14:1105786.
    PMID: 36910188 DOI: 10.3389/fmicb.2023.1105786
    Mosquitoes are capable of carrying complex pathogens, and their feeding habits on the mammalian blood can easily mediate the spread of viruses. Surveillance of mosquito-based arbovirus enables the early prevention and control of mosquito-borne arboviral diseases. The climate and geography of Yunnan Province in China are ideal for mosquitoes. Yunnan shares borders with several other countries; therefore, there exists a high risk of international transmission of mosquito-mediated infectious diseases. Previous studies have focused more on the Sino-Laos and Sino-Myanmar borders. Therefore, we focused on the neighborhoods of Malipo and Funing counties in Wenshan Prefecture, Yunnan Province, China, which are located along the Sino-Vietnam border, to investigate the species of mosquitoes and mosquito-borne viruses in the residential areas of this region. This study collected 10,800 mosquitoes from 29 species of 8 genera and grouped to isolate mosquito-borne viruses. In total, 62 isolates were isolated and classified into 11 viral categories. We demonstrated a new distribution of mosquito-borne viruses among mosquitoes in border areas, including Tembusu and Getah viruses, which can cause animal outbreaks. In addition, Dak Nong and Sarawak viruses originating from Vietnam and Malaysia, respectively, were identified for the first time in China, highlighting the complexity of mosquito-borne viruses in the Sino-Vietnam border region. The awareness of the importance of viral surveillance and prevention measures in border areas should be further encouraged to prevent future outbreaks of potentially infectious diseases.
  4. Chen Z, Wang W, Abdul Razak SR, Han T, Ahmad NH, Li X
    Cell Death Dis, 2023 Jul 24;14(7):460.
    PMID: 37488128 DOI: 10.1038/s41419-023-05930-w
    Ferroptosis is a recently discovered essential type of cell death that is mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests that ferroptosis is a double-edged sword in human cancer. However, the precise underlying molecular mechanisms and their differential roles in tumorigenesis are unclear. Therefore, in this review, we summarize and briefly present the key pathways of ferroptosis, paying special attention to the regulation of ferroptosis as well as its dual role as an oncogenic and as a tumor suppressor event in various human cancers. Moreover, multiple pharmacological ferroptosis activators are summarized, and the prospect of targeting ferroptosis in cancer therapy is further elucidated.
  5. Long V, Choi EC, Chen Z, Kamil MAA, Rajagopalan M, McMeniman E, et al.
    JMIR Dermatol, 2023 Jan 31;6:e43910.
    PMID: 37632921 DOI: 10.2196/43910
    BACKGROUND: The field of teledermatology has expanded tremendously and has been used for conditions including hidradenitis suppurativa (HS). However, due to the sensitive location of lesions, HS may be considered less suitable for teledermatology.

    OBJECTIVE: We sought to assess dermatologists' experiences and perceptions toward using teledermatology for HS relative to atopic dermatitis (AD) as a comparison.

    METHODS: A survey was disseminated electronically to practicing dermatologists in the Asia-Pacific region between February and June 2022. Differences in attitudes and perceptions between HS and AD were compared using random-effects ordered logistic regression, controlling for demographics.

    RESULTS: A total of 100 responses were obtained comprising of 76 (81.7%) dermatologists and 17 (18.3%) dermatology trainees; 62.6% (62/98) of physicians were uncomfortable with using teledermatology for HS. Multivariable regression confirmed increased perceived challenges with managing HS using teledermatology compared to AD. These challenges include the need for photography of hard-to-reach or sensitive areas (odds ratio [OR] 4.71, 95% CI 2.44-9.07; P

  6. Awad OI, Zhou B, Chen Z, Kadirgama K, Mohammed MN, Ramasamy D
    Heliyon, 2023 Nov;9(11):e22364.
    PMID: 38034680 DOI: 10.1016/j.heliyon.2023.e22364
    Polyoxymethylene dimethyl ethers (PODEn, n = 1-8) as an oxygenated fuel are a promising alternative fuel with a high oxygen concentration, a low C:H ratio, and no C-C bonds in their chemical structure. This could lead to smoke-free combustion. In this study, we chose to focus on PODE1 because of its lower cetane number, which makes it more suitable for use in spark ignition (SI) engines. However, its lower boiling point and octane number remain challenges. A low boiling point may lead to high vapour pressure and require storage and handling comparable to gaseous fuels. We investigated the effect of adding PODE1 to gasoline-ethanol blends (E10) on fuel properties, including distillation curve, octane number, phase stability, C/O/H ratio, heat of combustion, kinematic viscosity, and density. Our results showed that the blended fuels of E10 and PODE1 are stable up to 10 % PODE1, and there was no phase separation. Additionally, up to 10 % PODE1 additive had no significant side effect on the fuel properties of E10, particularly boiling point and octane number. Thus, work offers creative points by proposing a new candidate for additive fuel to gasoline-ethanol blends, which contributes to reducing the soot emission of GDI engines.
  7. Wong LP, Wu Q, Hao Y, Chen X, Chen Z, Alias H, et al.
    Int Health, 2021 May 04.
    PMID: 33945613 DOI: 10.1093/inthealth/ihab023
    BACKGROUND: We aimed to investigate the association between institution trust and public responses to the coronavirus disease 2019 (COVID-19) outbreak.

    METHODS: An Internet-based, cross-sectional survey was administered on 29 January 2020. A total of 4393 adults ≥18 y of age and residing or working in the province of Hubei, central China were included in the study.

    RESULTS: The majority of the participants expressed a great degree of trust in the information and preventive instructions provided by the central government compared with the local government. Being under quarantine (adjusted odds ratio [OR] 2.35 [95% confidence interval {CI} 1.80 to 3.08]) and having a high institutional trust score (OR 2.23 [95% CI 1.96 to 2.53]) were both strong and significant determinants of higher preventive practices scores. The majority of study participants (n=3640 [85.7%]) reported that they would seek hospital treatment if they suspected themselves to have been infected with COVID-19. Few of the participants from Wuhan (n=475 [16.6%]) and those participants who were under quarantine (n=550 [13.8%]) expressed an unwillingness to seek hospital treatment.

    CONCLUSIONS: Institutional trust is an important factor influencing adequate preventive behaviour and seeking formal medical care during an outbreak.

  8. Wang W, Zhou F, Chang Y, Cui J, He D, Du J, et al.
    Bull Environ Contam Toxicol, 2020 Mar;104(3):380-385.
    PMID: 31932904 DOI: 10.1007/s00128-020-02786-0
    In this study, three soil amendments (inorganic, liming, or organic-inorganic materials) were used in a Cd-contaminated purple field soil to investigate their impacts on soil Cd availability, enzyme (urease, catalase, sucrase, and acid phosphatase) activities, microbial biomass (carbon/nitrogen) and type (bacteria, fungi, and actinomycetes) in mustard and corn trials. Results showed that soil amendments generally decreased soil exchangeable Cd, fungi and bacterial populations while increasing the activities of all the four soil enzymes tested, microbial biomass carbon and populations of actinomycetes (p  0.05) whereas stronger effects appeared in soil organic matter and available nutrients (nitrogen, phosphorous and potassium; p 
  9. Ali N, Azzuhri SR, Johari MAM, Rashid H, Khudus MIMA, Razak MZA, et al.
    Sensors (Basel), 2021 Oct 27;21(21).
    PMID: 34770442 DOI: 10.3390/s21217132
    Tungsten disulphide (WS2) is a two-dimensional transition-metal dichalcogenide material that can be used to improve the sensitivity of a variety of sensing applications. This study investigated the effect of WS2 coating on tapered region microfiber (MF) for relative humidity (RH) sensing applications. The flame brushing technique was used to taper the standard single-mode fiber (SMF) into three different waist diameter sizes of MF 2, 5, and 10 µm, respectively. The MFs were then coated with WS2 via a facile deposition method called the drop-casting technique. Since the MF had a strong evanescent field that allowed fast near-field interaction between the guided light and the environment, depositing WS2 onto the tapered region produced high humidity sensor sensitivity. The experiments were repeated three times to measure the average transmitted power, presenting repeatability and sensing stability. Each MF sample size was tested with varying humidity levels. Furthermore, the coated and non-coated MF performances were compared in the RH range of 45-90% RH at room temperature. It was found that the WS2 coating on 2 µm MF had a high sensitivity of 0.0861 dB/% RH with linearity over 99%. Thus, MF coated with WS2 encourages enhancement in the evanescent field effect in optical fiber humidity sensor applications.
  10. Taha BA, Al Mashhadany Y, Al-Jubouri Q, Rashid ARBA, Luo Y, Chen Z, et al.
    Sci Total Environ, 2023 Jul 01;880:163333.
    PMID: 37028663 DOI: 10.1016/j.scitotenv.2023.163333
    Constantly mutating SARS-CoV-2 is a global concern resulting in COVID-19 infectious waves from time to time in different regions, challenging present-day diagnostics and therapeutics. Early-stage point-of-care diagnostic (POC) biosensors are a crucial vector for the timely management of morbidity and mortalities caused due to COVID-19. The state-of-the-art SARS-CoV-2 biosensors depend upon developing a single platform for its diverse variants/biomarkers, enabling precise detection and monitoring. Nanophotonic-enabled biosensors have emerged as 'one platform' to diagnose COVID-19, addressing the concern of constant viral mutation. This review assesses the evolution of current and future variants of the SARS-CoV-2 and critically summarizes the current state of biosensor approaches for detecting SARS-CoV-2 variants/biomarkers employing nanophotonic-enabled diagnostics. It discusses the integration of modern-age technologies, including artificial intelligence, machine learning and 5G communication with nanophotonic biosensors for intelligent COVID-19 monitoring and management. It also highlights the challenges and potential opportunities for developing intelligent biosensors for diagnosing future SARS-CoV-2 variants. This review will guide future research and development on nano-enabled intelligent photonic-biosensor strategies for early-stage diagnosing of highly infectious diseases to prevent repeated outbreaks and save associated human mortalities.
  11. Liu YZ, Zhao X, Huang YW, Chen Z, Li FC, Gao LD, et al.
    Zhonghua Yu Fang Yi Xue Za Zhi, 2012 Mar;46(3):258-63.
    PMID: 22800599
    To investigate the gene variations of influenza B virus isolated in Hunan province from 2007 to 2010.
  12. 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.
  13. 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.
  14. 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.

  15. Vermunt J, Bragg F, Halsey J, Yang L, Chen Y, Guo Y, et al.
    PMID: 34728472 DOI: 10.1136/bmjdrc-2021-002495
    INTRODUCTION: We examined the associations between long-term usual random plasma glucose (RPG) levels and cause-specific mortality risks among adults without known diabetes in China.

    RESEARCH DESIGN AND METHODS: The China Kadoorie Biobank recruited 512,891 adults (59% women) aged 30-79 from 10 regions of China during 2004-2008. At baseline survey, and subsequent resurveys of a random subset of survivors, participants were interviewed and measurements collected, including on-site RPG testing. Cause of death was ascertained via linkage to local mortality registries. Cox regression yielded adjusted HR for all-cause and cause-specific mortality associated with usual levels of RPG.

    RESULTS: During median 11 years' follow-up, 37,214 deaths occurred among 452,993 participants without prior diagnosed diabetes or other chronic diseases. There were positive log-linear relationships between RPG and all-cause, cardiovascular disease (CVD) (n=14,209) and chronic kidney disease (CKD) (n=432) mortality down to usual RPG levels of at least 5.1 mmol/L. At RPG <11.1 mmol/L, each 1.0 mmol/L higher usual RPG was associated with adjusted HRs of 1.14 (95% CI 1.12 to 1.16), 1.16 (1.12 to 1.19) and 1.44 (1.22 to 1.70) for all-cause, CVD and CKD mortality, respectively. Usual RPG was positively associated with chronic liver disease (n=547; 1.45 (1.26 to 1.66)) and cancer (n=12,680; 1.12 (1.09 to 1.16)) mortality, but with comparably lower risks at baseline RPG ≥11.1 mmol/L. These associations persisted after excluding participants who developed diabetes during follow-up.

    CONCLUSIONS: Among Chinese adults without diabetes, higher RPG levels were associated with higher mortality risks from several major diseases, with no evidence of apparent thresholds below the cut-points for diabetes diagnosis.

  16. Mullan KA, Anderson A, Shi YW, Ding JH, Ng CC, Chen Z, et al.
    Epilepsia, 2022 Feb 16.
    PMID: 35170024 DOI: 10.1111/epi.17182
    OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Antiseizure medications (ASMs) with aromatic ring structure, including carbamazepine, are among the most common culprits. Screening for human leukocyte antigen (HLA) allele HLA-B*15:02 is recommended prior to initiating treatment with carbamazepine in Asians, but this allele has low positive predictive value.

    METHODS: We performed whole genome sequencing and analyzed 6 199 696 common variants among 113 aromatic ASM-induced SJS/TEN cases and 84 tolerant controls of Han Chinese ethnicity.

    RESULTS: In the primary analysis, nine variants reached genome-wide significance (p 

  17. Chen Y, Chen Y, Shi W, Hu S, Huang Q, Liu GS, et al.
    Biosens Bioelectron, 2022 Feb 15;198:113787.
    PMID: 34864241 DOI: 10.1016/j.bios.2021.113787
    High sensitivity and capturing ratio are strongly demanded for surface plasmon resonance (SPR) sensors when applied in detection of small molecules. Herein, an SPR sensor is combined with a novel smart material, namely, MoS2 nanoflowers (MNFs), to demonstrate programmable adsorption/desorption of small bipolar molecules, i.e., amino acids. The MNFs overcoated on the plasmonic gold layer increase the sensitivity by 25% compared to an unmodified SPR sensor, because of the electric field enhancement at the gold surface. Furthermore, as the MNFs have rich edge sites and negatively charged surfaces, the MNF-SPR sensors exhibit not only much higher bipolar-molecule adsorption capability, but also efficient desorption of these molecules. It is demonstrated that the MNF-SPR sensors enable controllable detection of amino acids by adjusting solution pH according to their isoelectric points. In addition, the MNFs decorated on the plasmonic interface can be as nanostructure frameworks and modified with antibody, which allows for specific detection of proteins. This novel SPR sensor provides a new simple strategy for pre-screening of amino acid disorders in blood plasma and a universal high-sensitive platform for immunoassay.
  18. Hakeem H, Feng W, Chen Z, Choong J, Brodie MJ, Fong SL, et al.
    JAMA Neurol, 2022 Oct 01;79(10):986-996.
    PMID: 36036923 DOI: 10.1001/jamaneurol.2022.2514
    IMPORTANCE: Selection of antiseizure medications (ASMs) for epilepsy remains largely a trial-and-error approach. Under this approach, many patients have to endure sequential trials of ineffective treatments until the "right drugs" are prescribed.

    OBJECTIVE: To develop and validate a deep learning model using readily available clinical information to predict treatment success with the first ASM for individual patients.

    DESIGN, SETTING, AND PARTICIPANTS: This cohort study developed and validated a prognostic model. Patients were treated between 1982 and 2020. All patients were followed up for a minimum of 1 year or until failure of the first ASM. A total of 2404 adults with epilepsy newly treated at specialist clinics in Scotland, Malaysia, Australia, and China between 1982 and 2020 were considered for inclusion, of whom 606 (25.2%) were excluded from the final cohort because of missing information in 1 or more variables.

    EXPOSURES: One of 7 antiseizure medications.

    MAIN OUTCOMES AND MEASURES: With the use of the transformer model architecture on 16 clinical factors and ASM information, this cohort study first pooled all cohorts for model training and testing. The model was trained again using the largest cohort and externally validated on the other 4 cohorts. The area under the receiver operating characteristic curve (AUROC), weighted balanced accuracy, sensitivity, and specificity of the model were all assessed for predicting treatment success based on the optimal probability cutoff. Treatment success was defined as complete seizure freedom for the first year of treatment while taking the first ASM. Performance of the transformer model was compared with other machine learning models.

    RESULTS: The final pooled cohort included 1798 adults (54.5% female; median age, 34 years [IQR, 24-50 years]). The transformer model that was trained using the pooled cohort had an AUROC of 0.65 (95% CI, 0.63-0.67) and a weighted balanced accuracy of 0.62 (95% CI, 0.60-0.64) on the test set. The model that was trained using the largest cohort only had AUROCs ranging from 0.52 to 0.60 and a weighted balanced accuracy ranging from 0.51 to 0.62 in the external validation cohorts. Number of pretreatment seizures, presence of psychiatric disorders, electroencephalography, and brain imaging findings were the most important clinical variables for predicted outcomes in both models. The transformer model that was developed using the pooled cohort outperformed 2 of the 5 other models tested in terms of AUROC.

    CONCLUSIONS AND RELEVANCE: In this cohort study, a deep learning model showed the feasibility of personalized prediction of response to ASMs based on clinical information. With improvement of performance, such as by incorporating genetic and imaging data, this model may potentially assist clinicians in selecting the right drug at the first trial.

  19. Garg A, Keng WT, Chen Z, Sathe AA, Xing C, Kailasam PD, et al.
    J Clin Invest, 2022 Dec 01;132(23).
    PMID: 36282599 DOI: 10.1172/JCI156864
    Multiple genetic loci have been reported for progeroid syndromes. However, the molecular defects in some extremely rare forms of progeria have yet to be elucidated. Here, we report a 21-year-old man of Chinese ancestry who has an autosomal recessive form of progeria, characterized by severe dwarfism, mandibular hypoplasia, hyperopia, and partial lipodystrophy. Analyses of exome sequencing data from the entire family revealed only 1 rare homozygous missense variant (c.86C>T; p.Pro29Leu) in TOMM7 in the proband, while the parents and 2 unaffected siblings were heterozygous for the variant. TOMM7, a nuclear gene, encodes a translocase in the outer mitochondrial membrane. The TOMM complex makes up the outer membrane pore, which is responsible for importing many preproteins into the mitochondria. A proteomic comparison of mitochondria from control and proband-derived cultured fibroblasts revealed an increase in abundance of several proteins involved in oxidative phosphorylation, as well as a reduction in abundance of proteins involved in phospholipid metabolism. We also observed elevated basal and maximal oxygen consumption rates in the fibroblasts from the proband as compared with control fibroblasts. We concluded that altered mitochondrial protein import due to biallelic loss-of-function TOMM7 can cause severe growth retardation and progeroid features.
  20. 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.
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