Publications by authors named "Ting Shi"

253 Publications

Uncovering the role of impurity sugars on the crystallization of d-tagatose crystal: Experiments and molecular dynamics simulations.

Food Chem 2022 Jul 22;397:133762. Epub 2022 Jul 22.

School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, 300072 Tianjin, PR China; The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, 300072 Tianjin, PR China.

Impurity sugars produced in upstream process of functional sugars are significantly impacting the product quality. In this work, the effect of congeners (d-maltose (d-MAL), d-fructose (d-FRU), d-glucose (d-GLU)) on primary and secondary nucleation of d-tagatose (d-TAG) crystals was investigated. The impurity sugars showed an inhibition on primary nucleation of d-TAG crystals, while a promotion on the secondary nucleation of d-TAG. Interestingly, the impact of impurity sugars on d-TAG crystal growth was similar to that on primary nucleation. The diffusion ability, hydrogen bonding forming ability, interaction energy of d-TAG crystal surfaces and impurity sugars were evaluated by molecular dynamics (MD) simulations to reveal the nucleation and growth behavior. Based on the above findings, we designed the d-TAG crystallization experiments, and obtained d-TAG crystals with uniform particle size distribution and regular morphology. This study helps to understand the influence of impurity sugars on crystallization, guiding the industrial manufacturing of functional sugars.
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http://dx.doi.org/10.1016/j.foodchem.2022.133762DOI Listing
July 2022

Bioinformatics Study of Family Genes and Their Expression in Response to Different Hormones Treatments during Japanese Apricot Fruit Development and Ripening.

Plants (Basel) 2022 Jul 22;11(15). Epub 2022 Jul 22.

College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China.

Auxin/indole-3-acetic acid () is a transcriptional repressor in the auxin signaling pathway that plays a role in several plant growth and development as well as fruit and embryo development. However, it is unclear what role they play in Japanese apricot () fruit development and maturity. To investigate the role of genes in fruit texture, development, and maturity, we comprehensively identified and expressed 19 genes, and demonstrated their conserved domains and homology across species. The majority of genes are highly responsive and expressed in different hormone treatments. , and showed a substantial increase in expression, suggesting that these genes are involved in fruit growth and maturity. During fruit maturation, alteration in the expression of genes in response to 1-Methylcyclopropene (1-MCP) treatment revealed an interaction between auxin and ethylene. The current study investigated the response of development regulators to auxin during fruit ripening, with the goal of better understanding their potential application in functional genomics.
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http://dx.doi.org/10.3390/plants11151898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332017PMC
July 2022

The analysis of genetic structure and characteristics of the chloroplast genome in different Japanese apricot germplasm populations.

BMC Plant Biol 2022 Jul 21;22(1):354. Epub 2022 Jul 21.

College of Horticulture, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China.

Background: Chloroplast (cp) genomes are generally considered to be conservative and play an important role in population diversity analysis in plants, but the characteristics and diversity of the different germplasm populations in Japanese apricot are still not clear.

Results: A total of 146 cp genomes from three groups of wild, domesticated, and bred accessions of Japanese apricot were sequenced in this study. The comparative genome analysis revealed that the 146 cp genomes were divided into 41 types, and ranged in size from 157,886 to 158,167 bp with a similar structure and composition to those of the genus Prunus. However, there were still minor differences in the cp genome that were mainly caused by the contraction and expansion of the IR region, and six types of SSR in which mono-nucleotide repeats were the most dominant type of repeats in the cp genome. The genes rpl33 and psbI, and intergenic regions of start-psbA, rps3-rpl22, and ccsA-ndhD, showed the highest nucleotide polymorphism in the whole cp genome. A total of 325 SNPs were detected in the 146 cp genomes, and more than 70% of the SNPs were in region of large single-copy (LSC). The SNPs and haplotypes in the cp genome indicated that the wild group had higher genetic diversity than the domesticated and bred groups. In addition, among wild populations, Southwest China, including Yunnan, Tibet, and Bijie of Guizhou, had the highest genetic diversity. The genetic relationship of Japanese apricot germplasm resources in different regions showed a degree of correlation with their geographical distribution.

Conclusion: Comparative analysis of chloroplast genomes of 146 Japanese apricot resources was performed to analyze the used to explore the genetic relationship and genetic diversity among Japanese apricot resources with different geographical distributions, providing some reference for the origin and evolution of Japanese apricot.
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http://dx.doi.org/10.1186/s12870-022-03731-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306182PMC
July 2022

Insight into substrate-assisted catalytic mechanism and stereoselectivity of bifunctional nocardicin thioesterase.

Proteins 2022 Jul 6. Epub 2022 Jul 6.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

The inversion from L- to D-stereochemistry endows peptides improved bioactivity and enhanced resistance to many proteases and peptidases. To strengthen the biostability and bioavailability of peptide drugs, enzymatic epimerization becomes an important way to incorporate D-amino acid into peptide backbones. Recently, a bifunctional thioesterase NocTE, which is responsible for the epimerization and hydrolysis of the C-terminal (p-hydroxyphenyl)glycine residue of β-lactam antibiotic nocardicin A, exclusively directs to the generation of D-diastereomers. Different from other epimerases, NocTE exhibits unique stereochemical selectivity. Herein, we investigated the catalytic mechanism of NocTE via molecular dynamic (MD) simulations and quantum mechanical/molecular mechanics (QM/MM) calculations. Through structural analyses, two key water molecules around the reaction site were found to serve as proton mediators in epimerization. The structural characteristics inspired us to propose a substrate-assisted mechanism for the epimerization, where multi-step proton transfers were mediated by water molecules and β-lactam ring, and the free energy barrier was calculated to be 20.3 kcal/mol. After that, the hydrolysis of D-configured substrate was energetically feasible with the energy barrier of 14.3 kcal/mol. As a comparison, the energy barrier for the direct hydrolysis of L-configured substrate was obtained to be 24.0 kcal/mol. Our study provides mechanistic insights into catalytic activities of bifunctional thioesterase NocTE, uncovers more clues to the molecular basis for stereochemical selectivity and paves the way for the directed biosynthesis of novel peptide drugs with various stereostructural characteristics by enzyme rational design.
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http://dx.doi.org/10.1002/prot.26395DOI Listing
July 2022

Deriving and validating a risk prediction model for long COVID-19: protocol for an observational cohort study using linked Scottish data.

BMJ Open 2022 07 6;12(7):e059385. Epub 2022 Jul 6.

Usher Institute, The University of Edinburgh, Edinburgh, UK.

Introduction: COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID.

Methods And Analysis: We will use the national Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, a population-level linked dataset of routine electronic healthcare data from 5.4 million individuals in Scotland. We will identify potential indicators for long-COVID by identifying patterns in primary care data linked to information from out-of-hours general practitioner encounters, accident and emergency visits, hospital admissions, outpatient visits, medication prescribing/dispensing and mortality. We will investigate the potential indicators of long-COVID by performing a matched analysis between those with a positive reverse transcriptase PCR (RT-PCR) test for SARS-CoV-2 infection and two control groups: (1) individuals with at least one negative RT-PCR test and never tested positive; (2) the general population (everyone who did not test positive) of Scotland. Cluster analysis will then be used to determine the final definition of the outcome measure for long-COVID. We will then derive, internally and externally validate a prediction model to identify the epidemiological risk factors associated with long-COVID.

Ethics And Dissemination: The EAVE II study has obtained approvals from the Research Ethics Committee (reference: 12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279). Study findings will be published in peer-reviewed journals and presented at conferences. Understanding the predictors for long-COVID and identifying the patient groups at greatest risk of persisting symptoms will inform future treatments and preventative strategies for long-COVID.
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http://dx.doi.org/10.1136/bmjopen-2021-059385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260199PMC
July 2022

Role of GBP1 in innate immunity and potential as a tuberculosis biomarker.

Sci Rep 2022 Jun 30;12(1):11097. Epub 2022 Jun 30.

Department of Infectious Diseases, Children's Hospital of Soochow University, 303 Jingde Road, Suzhou, Jiangsu, China.

Tuberculosis (TB) is a global health problem of major concern. Identification of immune biomarkers may facilitate the early diagnosis and targeted treatment of TB. We used public RNA-sequencing datasets of patients with TB and healthy controls to identify differentially expressed genes and their associated functional networks. GBP1 expression was consistently significantly upregulated in TB, and 4492 differentially expressed genes were simultaneously associated with TB and high GBP1 expression. Weighted gene correlation analysis identified 12 functional modules. Modules positively correlated with TB and high GBP1 expression were associated with the innate immune response, neutrophil activation, neutrophil-mediated immunity, and NOD receptor signaling pathway. Eleven hub genes (GBP1, HLA-B, ELF4, HLA-E, IFITM2, TNFRSF14, CD274, AIM2, CFB, RHOG, and HORMAD1) were identified. The least absolute shrinkage and selection operator model based on hub genes accurately predicted the occurrence of TB (area under the receiver operating characteristic curve = 0.97). The GBP1-module-pathway network based on the STRING database showed that GBP1 expression correlated with the expression of interferon-stimulated genes (GBP5, BATF2, EPSTI1, RSAD2, IFI44L, IFIT3, and OAS3). Our study suggests GBP1 as an optimal diagnostic biomarker for TB, further indicating an association of the AIM2 inflammasome signaling pathway in TB pathology.
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http://dx.doi.org/10.1038/s41598-022-15482-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247026PMC
June 2022

Genus : A Prolific Producer of Natural Products.

Mar Drugs 2022 May 31;20(6). Epub 2022 May 31.

College of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao 266590, China.

Actinomycetes are currently one of the major sources of bioactive secondary metabolites used for medicine development. Accumulating evidence has shown that , a key class of actinomycetes, has the ability to produce novel bioactive natural products. This review covers the sources, distribution, bioactivities, biosynthesis, and structural characteristics of compounds isolated from in the period between March 2018 and 2021. Our results reveal that 67% of -derived natural products are reported for the first time, and 73% of them are isolated from marine . The chemical structures of the -derived compounds have diverse skeletons, concentrating on the categories of polyketides, peptides, terphenyls, and alkaloids. Almost 50% of the natural products isolated from have been discovered to display various bioactivities. These results fully demonstrate the great potential of the genus to produce novel bioactive secondary metabolites that may serve as a structural foundation for the development of novel drugs.
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http://dx.doi.org/10.3390/md20060374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231205PMC
May 2022

Bioactivity-Guided Screening of Antimicrobial Secondary Metabolites from Antarctic Cultivable Fungus CH-6 Combined with Molecular Networking.

Mar Drugs 2022 May 19;20(5). Epub 2022 May 19.

State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266200, China.

With the increasingly serious antimicrobial resistance, discovering novel antibiotics has grown impendency. The Antarctic abundant microbial resources, especially fungi, can produce unique bioactive compounds for adapting to the hostile environment. In this study, three Antarctic fungi, sp. HSXSD-11-1, sp. HSXSD-12 and CH-6, were found to have the potential to produce antimicrobial compounds. Furthermore, the crude extracts of CH-6 displayed the strongest antimicrobial activities with 72.3-84.8% growth inhibition against and . The secondary metabolites of CH-6 were researched by bioactivity tracking combined with molecular networking and led to the isolation of two new -pyrones, acrostalapyrones A () and B (), along with one known analog (), and three known indole diketopiperazines (-). The absolute configurations of and were identified through modified Mosher's method. Compounds and showed strong antimicrobial activities. Remarkably, the antibacterial activity of against displayed two times higher than that of the positive drug Ciprofloxacin. This is the first report to discover -pyrones from the genus , and the significant antimicrobial activities of and against and . This study further demonstrates the great potential of Antarctic fungi in the development of new compounds and antibiotics.
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http://dx.doi.org/10.3390/md20050334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146861PMC
May 2022

Clinical features of COVID-19 for integration of COVID-19 into influenza surveillance: A systematic review.

J Glob Health 2022 04 14;12:05012. Epub 2022 Apr 14.

Centre for Population Health Sciences, Usher Institute, University of Edinburgh, Edinburgh, Scotland, UK.

Background: In November 2020, the World Health Organization (WHO) created interim guidance on how to integrate testing for SARS-CoV-2 into existing influenza surveillance systems. Influenza-like illness (ILI) and severe acute respiratory illness (SARI) case definitions have been used to specify the case definition of COVID-19 for surveillance purposes. This review aims to assess whether the common clinical features of COVID-19 have changed to the point that the criteria used to identify both COVID-19 and influenza in surveillance programs needs to be altered.

Methods: A systematic review of reviews following PRISMA-P guidelines was conducted using the "COVID-19 evidence review" database from August 19, 2020, to August 19, 2021. Reviews providing pooled estimates of the prevalence of clinical features of COVID-19 within the general population, diagnosed by polymerase chain reaction or rapid diagnostic test, were included. These were critically appraised and sensitivity analysis was undertaken to examine potential causes of bias.

Results: Fourteen reviews were identified, including three on adults only and three on children only. For all reviews, combined fever (median prevalence = 73.0%, IQR = 58.3-78.7) and cough (45.1%, IQR = 28.9-54.0) were the most common features. These were followed by loss of taste or smell (45.1%, IQR = 28.9-54.0), hypoxemia (33%, one review), fatigue (26.4%, IQR = 9.0-39.4) and expectoration (23.9%, IQR = 23.3-25.5). Fever and cough continued to be the most prevalent features for adults and children, with subsequent symptoms being similar for adults only. However, the pattern differed for children, with headache (34.3%, IQR = 18-50.7) and nasal congestion (20%, one review) being the third and fourth commonest symptoms.

Conclusions: The prevalent features found in this recent review were the same as the ones identified at the beginning of the pandemic. Therefore, the current approach of using the ILI and SARI criteria which incorporate fever and cough will identify COVID-19 cases in addition to influenza. Interestingly, children may present with different features, as headaches and nasal congestion were more common in this group. Future research could examine this further and investigate whether symptomology changes with new variants of COVID-19.
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http://dx.doi.org/10.7189/jogh.12.05012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107308PMC
April 2022

Impact on emergency and elective hospital-based care in Scotland over the first 12 months of the pandemic: interrupted time-series analysis of national lockdowns.

J R Soc Med 2022 May 3:1410768221095239. Epub 2022 May 3.

Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, EH16 4UX UK.

Objectives: COVID-19 has resulted in the greatest disruption to National Health Service (NHS) care in its over 70-year history. Building on our previous work, we assessed the ongoing impact of pandemic-related disruption on provision of emergency and elective hospital-based care across Scotland over the first year of the pandemic.

Design: We undertook interrupted time-series analyses to evaluate the impact of ongoing pandemic-related disruption on hospital NHS care provision at national level and across demographics and clinical specialties spanning the period 29 March 2020-28 March 2021.

Setting: Scotland, UK.

Participants: Patients receiving hospital care from NHS Scotland.

Main Outcome Measures: We used the percentage change of accident and emergency attendances, and emergency and planned hospital admissions during the pandemic compared to the average admission rate for equivalent weeks in 2018-2019.

Results: As restrictions were gradually lifted in Scotland after the first lockdown, hospital-based admissions increased approaching pre-pandemic levels. Subsequent tightening of restrictions in September 2020 were associated with a change in slope of relative weekly admissions rate: -1.98% (-2.38, -1.58) in accident and emergency attendance, -1.36% (-1.68, -1.04) in emergency admissions and -2.31% (-2.95, -1.66) in planned admissions. A similar pattern was seen across sex, socioeconomic status and most age groups, except children (0-14 years) where accident and emergency attendance, and emergency admissions were persistently low over the study period.

Conclusions: We found substantial disruption to urgent and planned inpatient healthcare provision in hospitals across NHS Scotland. There is the need for urgent policy responses to address continuing unmet health needs and to ensure resilience in the context of future pandemics.
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http://dx.doi.org/10.1177/01410768221095239DOI Listing
May 2022

Global Disease Burden of Respiratory Syncytial Virus in Preterm Children in 2019: A Systematic Review and Individual Participant Data Meta-Analysis Protocol.

J Infect Dis 2022 Aug;226(Supplement_1):S135-S141

Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.

Existing guidelines on respiratory syncytial virus (RSV) prophylaxis differ greatly by gestational age (GA) and other underlying risk factors, highlighting the data gaps in RSV disease burden among preterm infants. We will conduct a systematic review and individual participant data (IPD) meta-analysis of RSV global disease burden among preterm-born children. Three databases, Medline, Embase, and Global Health, will be searched for relevant studies on RSV disease burden for 2019 or before in preterm-born children published between 1 January 1995 and 31 December 2021. IPD will be sought by contacting the investigators identified from published literature and from existing collaboration networks. One-stage and 2-stage random-effects meta-analyses will be used to combine information from IPD and non-IPD studies to produce summary RSV burden estimates of incidence rate, hospital admission rate, and in-hospital case fatality ratio. The framework will be extended to examine subgroup(s) with the most substantial RSV disease burden.
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http://dx.doi.org/10.1093/infdis/jiac078DOI Listing
August 2022

Increased COVID-19 mortality rate in rare disease patients: a retrospective cohort study in participants of the Genomics England 100,000 Genomes project.

Orphanet J Rare Dis 2022 04 12;17(1):166. Epub 2022 Apr 12.

Institute of Health Informatics, University College London, London, UK.

Background: Several common conditions have been widely recognised as risk factors for COVID-19 related death, but risks borne by people with rare diseases are largely unknown. Therefore, we aim to estimate the difference of risk for people with rare diseases comparing to the unaffected.

Method: To estimate the correlation between rare diseases and COVID-19 related death, we performed a retrospective cohort study in Genomics England 100k Genomes participants, who tested positive for Sars-Cov-2 during the first wave (16-03-2020 until 31-July-2020) of COVID-19 pandemic in the UK (n = 283). COVID-19 related mortality rates were calculated in two groups: rare disease patients (n = 158) and unaffected relatives (n = 125). Fisher's exact test and logistic regression was used for univariable and multivariable analysis, respectively.

Results: People with rare diseases had increased risk of COVID19-related deaths compared to the unaffected relatives (OR [95% CI] = 3.47 [1.21- 12.2]). Although, the effect was insignificant after adjusting for age and number of comorbidities (OR [95% CI] = 1.94 [0.65-5.80]). Neurology and neurodevelopmental diseases was significantly associated with COVID19-related death in both univariable (OR [95% CI] = 4.07 [1.61-10.38]) and multivariable analysis (OR [95% CI] = 4.22 [1.60-11.08]).

Conclusions: Our results showed that rare disease patients, especially ones affected by neurology and neurodevelopmental disorders, in the Genomics England cohort had increased risk of COVID-19 related death during the first wave of the pandemic in UK. The high risk is likely associated with rare diseases themselves, while we cannot rule out possible mediators due to the small sample size. We would like to raise the awareness that rare disease patients may face increased risk for COVID-19 related death. Proper considerations for rare disease patients should be taken when relevant policies (e.g., returning to workplace) are made.
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http://dx.doi.org/10.1186/s13023-022-02312-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9003178PMC
April 2022

Toward a Treatment of Cancer: Design and In Vitro/In Vivo Evaluation of Uncharged Pyrazoline Derivatives as a Series of Novel SHP2 Inhibitors.

Int J Mol Sci 2022 Mar 23;23(7). Epub 2022 Mar 23.

State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266200, China.

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) is a non-receptor protein tyrosine phosphatase (PTP) encoded by the gene, which is involved in the RAS/MAPK cell signaling transduction process. SHP2 has been shown to contribute to the progression of various cancers and is emerging as an important target for anti-tumor drug research. However, past efforts to develop SHP2 inhibitors into drugs have been unsuccessful owing to the positively charged nature of the active site pocket tending to bind negatively charged groups that are usually non-drug-like. Here, a series of uncharged pyrazoline derivatives were designed and developed as new SHP2 inhibitors using a structure-based strategy. Compound , which exhibited the strongest SHP2 inhibitory activity, bound directly to the catalytic domain of SHP2 in a competitive manner through multiple hydrogen bonds. Compound affected the RAS/MAPK signaling pathway by inhibiting SHP2, and subsequently induced apoptosis and growth inhibition of HCT116 cells in vitro and in vivo. Notably, the oral administration of compound in large doses showed no obvious toxicity. In summary, our findings provide a basis for the further development of compound as a safe, effective and anti-tumor SHP2 inhibitor.
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http://dx.doi.org/10.3390/ijms23073497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998978PMC
March 2022

Axes of Prognosis: Identifying Subtypes of COVID-19 Outcomes.

AMIA Annu Symp Proc 2021 21;2021:1198-1207. Epub 2022 Feb 21.

Health Data Research UK, London, United Kingdom.

COVID-19 is a disease with vast impact, yet much remains unclear about patient outcomes. Most approaches to risk prediction of COVID-19 focus on binary or tertiary severity outcomes, despite the heterogeneity of the disease. In this work, we identify heterogeneous subtypes of COVID-19 outcomes by considering 'axes' of prognosis. We propose two innovative clustering approaches - 'Layered Axes' and 'Prognosis Space' - to apply on patients' outcome data. We then show how these clusters can help predict a patient's deterioration pathway on their hospital admission, using random forest classification. We illustrate this methodology on a cohort from Wuhan in early 2020. We discover interesting subgroups of poor prognosis, particularly within respiratory patients, and predict respiratory subgroup membership with high accuracy. This work could assist clinicians in identifying appropriate treatments at patients' hospital admission. Moreover, our method could be used to explore subtypes of 'long COVID' and other diseases with heterogeneous outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861682PMC
March 2022

Novel insights into the dissemination route of Japanese apricot (Prunus mume Sieb. et Zucc.) based on genomics.

Plant J 2022 05 5;110(4):1182-1197. Epub 2022 Apr 5.

College of Horticulture, Nanjing Agricultural University, Nanjing, Jiangsu, China.

Japanese apricot (Prunus mume) is an attractive fruit tree originating from China, and its cultivation history dates back 7000 years. In this study, we investigated the genetic diversity, population structure, and genetic relationship of Japanese apricots in different regions of China and Japan. The analyses of the genetic variation between wild and cultivated populations improved our understanding of the general mechanisms of domestication and improvement. A total of 146 accessions of Japanese apricot from different geographic locations were sequenced. The genetic diversity of wild and domesticated accessions (3.60 × 10 and 3.51 × 10 , respectively) from China was high, and the effect of artificial selection pressure on domesticated accessions was small; however, the genetic diversity of artificially bred accessions decreased significantly (2.68 × 10 ) compared to domesticated accessions, which had an obvious improvement bottleneck effect. The chloroplast genome results showed that 41 haplotypes were detected, and Japanese apricots from the Yunnan region had the most haplotypes and the highest genetic diversity. The results revealed the dissemination route of Japanese apricot, not only along the Yangtze River basin system (from southwest China to Hunan, Jiangxi, and Anhui, and finally to the Jiangsu, Zhejiang, and Shanghai areas). Additionally, we discovered a second route for Japanese apricot dispersion, which was mostly in the Pearl River basin system, from southwest China to Libo of Guizhou and then to the Guangdong, Fujian, and Taiwan areas. This also showed that Japanese-bred accessions originated from Zhejiang, China. In addition, selective sweep analysis showed that most of the high-impact single nucleotide polymorphisms were identified in genes related to glucose metabolism, aromatic compound metabolism, flowering time, dormancy, and resistance to abiotic stress during the domestication and improvement of Japanese apricot.
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http://dx.doi.org/10.1111/tpj.15731DOI Listing
May 2022

Distinct outcomes, ABL1 mutation profile, and transcriptome features between p190 and p210 transcripts in adult Philadelphia-positive acute lymphoblastic leukemia in the TKI era.

Exp Hematol Oncol 2022 Mar 11;11(1):13. Epub 2022 Mar 11.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China.

Background: The differential signaling and outcome of patients with p190 or p210 transcripts of BCR-ABL1 have been systematically investigated in chronic myeloid leukemia rather than in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL).

Methods: We analyzed the outcomes and ABL1 mutation profiles in 305 consecutive adult patients with Ph ALL treated with chemotherapy plus tyrosine kinase inhibitors. We also studied transcriptome features in two newly diagnosed patients with p190 and p210 using single-cell RNA sequencing (scRNA-seq).

Results: P190 and p210 were found in 199 (65%) and 106 (35%) patients, respectively. Compared to patients with p190, a higher white blood cell count (p = 0.05), platelet count (p = 0.047), BCR-ABL1 transcript level (p < 0.001), and lower bone marrow blasts (p = 0.003) were found in patients with p210. Patients with p210 had fewer types of ABL1 mutations (4 vs. 16) and a higher prevalence of T315I and E225K/V mutations (91.3% vs. 68.6%; p = 0.031). Patients with p210 had a similar complete remission rate (91.0% vs. 90.1%; p = 0.805) but a lower complete molecular remission rate at 1 month (9.9% vs. 22.0%; p = 0.031) compared with p190. Patients with p210 had lower 3-year overall survival (OS) and disease-free survival (DFS) rates than those with p190 (3-year DFS: 10.4% vs. 9.2%, p = 0.069, 3-year OS: 44.3% vs. 38.2%, p = 0.018, respectively). Multivariate analysis revealed that p210 was independently associated with worse OS [HR 1.692 (95% CI 1.009-2.838), p = 0.046]. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was associated with a better prognosis in patients with p210 (p < 0.0001). In addition, scRNA-seq data showed distinct molecular and cellular heterogeneity between bone marrow cells of the two transcripts.

Conclusions: Ph ALL patients with p190 and p210 had different clinical characteristics, outcomes, ABL1 mutation profiles, and transcriptome features. Allo-HSCT could improve the outcomes of patients with p210.
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http://dx.doi.org/10.1186/s40164-022-00265-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915539PMC
March 2022

Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.

PLoS Med 2022 02 22;19(2):e1003916. Epub 2022 Feb 22.

Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.

Background: In 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates.

Methods And Findings: We conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK "lockdown". Data were obtained for Scotland from the Public Health Scotland "COVID19 wider impacts on the health care system" dashboard and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; 3 doses of "6-in-1" diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age. We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels. In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86- to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83). The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake.

Conclusions: In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.
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http://dx.doi.org/10.1371/journal.pmed.1003916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863286PMC
February 2022

First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales.

PLoS Med 2022 02 22;19(2):e1003927. Epub 2022 Feb 22.

Usher Institute, The University of Edinburgh, Edinburgh, United Kingdom.

Background: Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales.

Methods And Findings: We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates.

Conclusions: In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.
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http://dx.doi.org/10.1371/journal.pmed.1003927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8863261PMC
February 2022

Adenosine deaminase as a marker for the severity of infectious mononucleosis secondary to EBV in children.

BMC Infect Dis 2022 Feb 21;22(1):164. Epub 2022 Feb 21.

Pediatric intensive care unit, Children's Hospital of Soochow University, 303 Jingde Road, Suzhou, 215000, Jiangsu, China.

Background: Infectious mononucleosis, a common disease in children and young adults, is often accompanied by elevated transaminase levels and rarely, liver failure. This study aimed to determine whether adenosine deaminase is a marker of severity in children with infectious mononucleosis, especially those with elevated alanine transaminase levels.

Methods: This case-control study was conducted at the Children's Hospital of Soochow University. A total of 104 children with infectious mononucleosis and 50 controls with other acute infections and fever, tonsillitis, or lymphadenitis, were enrolled in the study. Among the 104 children with infectious mononucleosis, 54 had normal alanine transaminase levels and 50 had elevated alanine transaminase levels. The children's clinical and laboratory data were analyzed to assess the diagnostic value of adenosine deaminase in the three groups.

Results: The adenosine deaminase level in the infectious mononucleosis group was significantly higher than that in the control group (P < 0.001). The adenosine deaminase levels were highly correlated with lymphocyte count, CD3CD8 T cells (%), CD4/CD8 ratio, and CD3CD19 (%) (r > 0.7, P < 0.01). The sensitivity and specificity of adenosine deaminase in predicting children with infectious mononucleosis were 97.1% and 94.0%, respectively. Furthermore, multivariate regression analysis revealed that adenosine deaminase level was a risk factor for elevated alanine transaminase in children with infectious mononucleosis.

Conclusions: Adenosine deaminase may be a marker of the severity of infectious mononucleosis in children, and a predictor of elevated alanine transaminase in children with infectious mononucleosis.
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http://dx.doi.org/10.1186/s12879-022-07150-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862226PMC
February 2022

Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.

BMJ Open 2022 02 14;12(2):e050062. Epub 2022 Feb 14.

Public Health Scotland, Glasgow, UK.

Introduction: The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK.

Methods And Analysis: We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations.

Ethics And Dissemination: We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.
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http://dx.doi.org/10.1136/bmjopen-2021-050062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844955PMC
February 2022

Venetoclax-ponatinib for T315I/compound-mutated Ph+ acute lymphoblastic leukemia.

Blood Cancer J 2022 01 28;12(1):20. Epub 2022 Jan 28.

Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.

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http://dx.doi.org/10.1038/s41408-022-00621-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799711PMC
January 2022

Identify potential prognostic indicators and tumor-infiltrating immune cells in pancreatic adenocarcinoma.

Authors:
Ting Shi Ge Gao

Biosci Rep 2022 02;42(2)

Department of Clinical Laboratory, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha 410005, Hunan, China.

Background: Pancreatic adenocarcinoma (PAAD) is a kind of highly malignant tumor and lacks early diagnosis method and effective treatment. Tumor microenvironment (TME) is of great importance for the occurrence and development of PAAD. Thus, a comprehensive overview of genes and tumor-infiltrating immune cells (TICs) related to TME dynamic changes conduce to develop novel therapeutic targets and prognostic indicators.

Methods: We used MAlignant Tumors using Expression data (ESTIMATE) algorithm to analyze the transcriptome RNA-seq data of 182 PAAD cases on The Cancer Genome Atlas (TCGA) platform. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) network, COX regression analysis and gene set enrichment analysis (GSEA) were carried out to get the hub genes related to the prognosis of PAAD patients. These core genes were validated in GEPIA. CXCL10 expression as a poor prognostic indicator was validated in GEO database. Finally, CIBERSORT algorithm was applied to understand the status of TICs.

Results: A total of 715 up-regulated differential expression genes (DEGs) and 57 down-regulated DEGs were found simultaneously in stromal and immune groups. These DEGs were mainly enriched in immune recognition, activation and response processes. CD4, CXCL12, CXCL10, CCL5 and CXCL9 were the top five core genes. Then, the validation of these genes showed that CD4, CXCL10, CXCL5, CXCL9 were up-regulated in PAAD. Among the core genes, CXCL10 had a negative correlation with the survival time of PAAD patients. CD8+ T cells, CD4+ T cells memory activated, macrophages M1 had positive correlation of CXCL10 expression, whereas regulatory T cells (Tregs), macrophages M0 and B cells memory had negative correlation.

Conclusion: We generated a series of genes related to TME with prognostic implications and TICs in PAAD, which have the potential to be novel immunotherapy targets and prognostic markers. The data showed that CXCL10 was favorable as a poor prognostic indicator in PAAD patients.
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http://dx.doi.org/10.1042/BSR20212523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859426PMC
February 2022

Income distribution and health: What do we know from Chinese data?

PLoS One 2022 24;17(1):e0263008. Epub 2022 Jan 24.

Department of Economics, Lehigh University, Bethlehem, PA, United States of America.

In the last four decades, the problem of income inequality has gradually become one of the most serious social problems in China at both the regional and individual levels. Recently, the central government announced that the main social contradiction is that between people's growing need for a better life and unbalanced and insufficient economic development. In this study, we analyse the effects of income distribution on individuals' health using a series of indicators of income distribution and different measures of individuals' health status. By utilizing data from the China Health and Nutrition Survey (CHNS) from 1989 to 2015, our empirical findings show that self-reported health (SRH), activities of daily living (ADLs), and diabetes mellitus appear to be negatively related to the income share of rich people when average income is equalized among counties, which indicates that individuals' health will deteriorate as the income share of rich people increases. In addition, our results show that there is an inverted U-shaped relationship between income inequality, as measured by the county-level Gini coefficient, and individuals' health status. We also find that income inequality affects health through the accessibility of healthcare facilities and public infrastructures and through hazardous health behaviours such as smoking and alcohol use. These findings suggest that reducing income inequality could be an important means of improving the overall health of China's population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263008PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786202PMC
February 2022

COVID-19 vaccine uptake, effectiveness, and waning in 82,959 health care workers: A national prospective cohort study in Wales.

Vaccine 2022 02 15;40(8):1180-1189. Epub 2022 Jan 15.

Population Data Science, Swansea University Medical School, Swansea University, UK.

Background: While population estimates suggest high vaccine effectiveness against SARS-CoV-2 infection, the protection for health care workers, who are at higher risk of SARS-CoV-2 exposure, is less understood.

Methods: We conducted a national cohort study of health care workers in Wales (UK) from 7 December 2020 to 30 September 2021. We examined uptake of any COVID-19 vaccine, and the effectiveness of BNT162b2 mRNA (Pfizer-BioNTech) against polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection. We used linked and routinely collected national-scale data within the SAIL Databank. Data were available on 82,959 health care workers in Wales, with exposure extending to 26 weeks after second doses.

Results: Overall vaccine uptake was high (90%), with most health care workers receiving theBNT162b2 vaccine (79%). Vaccine uptake differed by age, staff role, socioeconomic status; those aged 50-59 and 60+ years old were 1.6 times more likely to get vaccinated than those aged 16-29. Medical and dental staff, and Allied Health Practitioners were 1.5 and 1.1 times more likely to get vaccinated, compared to nursing and midwifery staff. The effectiveness of the BNT162b2 vaccine was found to be strong and consistent across the characteristics considered; 52% three to six weeks after first dose, 86% from two weeks after second dose, though this declined to 53% from 22 weeks after the second dose.

Conclusions: With some variation in rate of uptake, those who were vaccinated had a reduced risk of PCR-confirmed SARS-CoV-2 infection, compared to those unvaccinated. Second dose has provided stronger protection for longer than first dose but our study is consistent with waning from seven weeks onwards.
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http://dx.doi.org/10.1016/j.vaccine.2021.11.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760602PMC
February 2022

Risk of serious COVID-19 outcomes among adults with asthma in Scotland: a national incident cohort study.

Lancet Respir Med 2022 04 13;10(4):347-354. Epub 2022 Jan 13.

Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK; Asthma UK Centre for Applied Research, Usher Institute, University of Edinburgh, Edinburgh, Scotland, UK. Electronic address:

Background: There is considerable uncertainty over whether adults with asthma should be offered booster vaccines against SARS-CoV-2 and, if so, who should be prioritised for booster vaccination. We were asked by the UK's Joint Commission on Vaccination and Immunisation to undertake an urgent analysis to identify which adults with asthma were at an increased risk of serious COVID-19 outcomes to inform deliberations on booster COVID-19 vaccines.

Methods: This national incident cohort study was done in all adults in Scotland aged 18 years and older who were included in the linked dataset of Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II). We used data from EAVE II to investigate the risk of COVID-19 hospitalisation and the composite outcome of intensive care unit (ICU) admission or death from COVID-19 among adults with asthma. A Cox proportional hazard model was used to derive adjusted hazard ratios (HRs) and 95% CIs for the association between asthma and COVID-19 hospital admission and ICU admission or death, stratified by markers of history of an asthma attack defined by either oral corticosteroid prescription (prednisolone, prednisone, and dexamethasone) in the 2 years before March 1, 2020, or hospitalisation for asthma before March 1, 2020. Analyses were adjusted for age, sex, socioeconomic status, comorbidity, previous hospitalisation, and vaccine status.

Findings: Between March 1, 2020, and July 27, 2021, 561 279 (12·7%) of 4 421 663 adults in Scotland had clinician-diagnosed-and-recorded-asthma. Among adults with asthma, 39 253 (7·0%) had confirmed SARS-CoV-2 infections, of whom 4828 (12·3%) were admitted to hospital for COVID-19 (among them, an estimated 600 [12·4%] might have been due to nosocomial infections). Adults with asthma were found to be at an increased risk of COVID-19 hospital admission (adjusted HR 1·27, 95% CI 1·23-1·32) compared with those without asthma. When using oral corticosteroid prescribing in the preceding 2 years as a marker for history of an asthma attack, the adjusted HR was 1·54 (95% CI 1·46-1·61) for those with three or more prescribed courses of oral corticosteroids, 1·37 (1·26-1·48) for those with two prescribed courses, 1·30 (1·23-1·37) for those with one prescribed course, and 1·15 (1·11-1·21) for those without any courses, compared with those aged 18 years or older without asthma. Adults with asthma were found to be at an increased risk of COVID-19 ICU admission or death compared with those without asthma (adjusted HR 1·13, 95 % CI 1·05-1·22). The adjusted HR was 1·44 (95% CI 1·31-1·58) for those with three or more prescribed courses of oral corticosteroids, 1·27 (1·09-1·48) for those with two prescribed courses, 1·04 (0·93-1·16) for those with one prescribed course, and 1·06 (0·97-1·17) for those without any course, compared with adults without asthma.

Interpretation: Adults with asthma who have required two or more courses of oral corticosteroids in the previous 2 years or a hospital admission for asthma before March 1, 2020, are at increased risk of both COVID-19 hospitalisation and ICU admission or death. Patients with a recent asthma attack should be considered a priority group for booster COVID-19 vaccines.

Funding: UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, and Scottish Government.
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http://dx.doi.org/10.1016/S2213-2600(21)00543-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758152PMC
April 2022

SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland.

Nat Med 2022 03 13;28(3):504-512. Epub 2022 Jan 13.

University of Edinburgh Usher Institute, Edinburgh, UK.

Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18-44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9-38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1-6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2-78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7-92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5-99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.
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http://dx.doi.org/10.1038/s41591-021-01666-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938271PMC
March 2022

Hospitalization rate of respiratory syncytial virus-associated acute lower respiratory infection among young children in Suzhou, China, 2010-2014.

Influenza Other Respir Viruses 2022 Jul 5;16(4):789-799. Epub 2022 Jan 5.

Department of Epidemiology, School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Background: There is a limited amount of data in China on the disease burden of respiratory syncytial virus- (RSV) associated acute lower respiratory infection (ALRI) among young children. This study aimed to estimate the hospitalization rate of RSV-associated ALRI (RSV-ALRI) among children aged 0-59 months in Suzhou, China.

Methods: All cases from children hospitalized with ALRI who were aged 0-59 months in Suzhou University Affiliated Children's Hospital during January 2010 to December 2014 were retrospectively identified. Detailed diagnosis and treatment data were collected by reviewing each individual's medical chart. In accordance with the World Health Organization (WHO) influenza disease burden estimation, the hospitalization rate of RSV-ALRI among children aged 0-59 months in Suzhou, China, was then estimated.

Results: Out of the 28,209 ALRI cases, 19,317 (68.5%) were tested for RSV, of which the RSV positive proportion was 21.3% (4107/19,317). The average hospitalization rate of RSV-ALRI for children aged 0-59 months was 14 (95% confidence interval [CI]:14-14)/1000 children years, and that for children aged 0-5, 6-11, 12-23, and 24-59 months were 70 (95% CI: 67-73), 31 (95% CI: 29-33), 11 (95% CI: 10-12), and 3 (95% CI: 3-3)/1000 children years, respectively.

Conclusion: A considerable degree of RSV-ALRI hospitalization exists among children aged 0-59 months, particularly in those under 1 year of age. Therefore, an effective monoclonal antibody or vaccine is urgently needed to address the substantial hospitalization burden of RSV infection.
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http://dx.doi.org/10.1111/irv.12958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178065PMC
July 2022

Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.

Lancet 2022 01 20;399(10319):25-35. Epub 2021 Dec 20.

Usher Institute, University of Edinburgh, Edinburgh, UK. Electronic address:

Background: Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants-especially delta (B.1.617.2)-is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon).

Methods: In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2-3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs.

Findings: 1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54-2·62) at 10-11 weeks, 3·01 (2·26-3·99) at 14-15 weeks, and 5·43 (4·00-7·38) at 18-19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01-2·61) at 10-11 weeks, 3·10 (2·63-3·64) at 14-15 weeks, and 4·71 (3·83-5·78) at 18-19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7-87·0) at 2-3 weeks, to 75·9% (72·9-78·6) at 14-15 weeks, and 63·7% (59·6-67·4) at 18-19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4-87·3) at 2-3 weeks, to 59·7% (54·6-64·2) at 14-15 weeks, and 42·2% (32·4-50·6) at 18-19 weeks.

Interpretation: We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19.

Funding: UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.

Translation: For the Portuguese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S0140-6736(21)02754-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8687670PMC
January 2022
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