| 1. |
- Wang, Yangong, et al.
(författare)
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Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy
- 2024
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Ingår i: NATURE MEDICINE. - 1078-8956 .- 1546-170X. ; 30, s. 1395-1405
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making. Using exome sequencing data from one of the largest cohorts of children with cerebral palsy, the genetic diagnostic rates of single-nucleotide and copy number variants were assessed and a sizeable fraction found to be clinically actionable.
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| 2. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 3. |
- Jin, Ying-Hui, et al.
(författare)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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| 4. |
- Jin, Yingzhi, et al.
(författare)
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Investigation on voltage loss in organic triplet photovoltaic devices based on Ir complexes
- 2019
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Ingår i: Journal of Materials Chemistry C. - : ROYAL SOC CHEMISTRY. - 2050-7526 .- 2050-7534. ; 7:47, s. 15049-15056
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Tidskriftsartikel (refereegranskat)abstract
- Voltage losses in singlet material-based organic photovoltaic devices (OPVs) have been intensively studied, whereas, only a few investigations on triplet material-based OPVs (T-OPVs) are reported. To investigate the voltage loss in T-OPVs, two homoleptic iridium(iii) complexes based on extended pi-conjugated benzo[g]phthalazine ligands, Ir(Ftbpa)(3) and Ir(FOtbpa)(3), are synthesized as sole electron donors. T-OPVs are fabricated by mixing two donors with phenyl-C-71-butyric acid methyl ester (PC71BM) as an electron acceptor. Insertion of oxygen-bridges as flexible inert delta-spacers in Ir(FOtbpa)(3) has slightly elevated both the lowest unoccupied molecular orbital and the highest occupied molecular orbital levels compared to those of Ir(Ftbpa)(3), which results in a lower charge transfer (CT) state energy (E-CT) for Ir(FOtbpa)(3)-based devices. However, a higher V-oc (0.88 V) is observed for Ir(FOtbpa)(3)-based devices than those of Ir(Ftbpa)(3) (0.80 V). To understand the above result, the morphologies of the two blend films are studied, which excludes the influence of morphology. Furthermore, radiative and non-radiative recombination in two devices is quantitatively investigated, which suggests that a higher V-oc can be attributed to reduced radiative and non-radiative recombination loss for the Ir(FOtbpa)(3)-based devices.
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| 5. |
- Jin, Yingzhi, et al.
(författare)
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Limitations and Perspectives on Triplet-Material-Based Organic Photovoltaic Devices
- 2019
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Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 31:22
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Tidskriftsartikel (refereegranskat)abstract
- Organic photovoltaic cells (OPVs) have attracted broad attention and become a very energetic field after the emergence of nonfullerene acceptors. Long-lifetime triplet excitons are expected to be good candidates for efficiently harvesting a photocurrent. Parallel with the development of OPVs based on singlet materials (S-OPVs), the potential of triplet materials as photoactive layers has been explored. However, so far, OPVs employing triplet materials in a bulk heterojunction have not exhibited better performance than S-OPVs. Here, the recent progress of representative OPVs based on triplet materials (T-OPVs) is briefly summarized. Based on that, the performance limitations of T-OPVs are analyzed. The shortage of desired triplet materials with favorable optoelectronic properties for OPVs, the tradeoff between long lifetime and high binding energy of triplet excitons, as well as the low charge mobility in most triplet materials are crucial issues restraining the efficiencies of T-OPVs. To overcome these limitations, first, novel materials with desired optoelectronic properties are urgently demanded; second, systematic investigation on the contribution and dynamics of triplet excitons in T-OPVs is necessary; third, close multidisciplinary collaboration is required, as proved by the development of S-OPVs.
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| 6. |
- Montoliu-Gaya, Laia, et al.
(författare)
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Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.
- 2024
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Ingår i: Acta neuropathologica. - 1432-0533. ; 147:1
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Tidskriftsartikel (refereegranskat)abstract
- Plasma-to-autopsy studies are essential for validation of blood biomarkers and understanding their relation to Alzheimer's disease (AD) pathology. Few such studies have been done on phosphorylated tau (p-tau) and those that exist have made limited or no comparison of the different p-tau variants. This study is the first to use immunoprecipitation mass spectrometry (IP-MS) to compare the accuracy of eight different plasma tau species in predicting autopsy-confirmed AD. The sample included 123 participants (AD=69, non-AD=54) from the Boston University Alzheimer's disease Research Center who had an available ante-mortem plasma sample and donated their brain. Plasma samples proximate to death were analyzed by targeted IP-MS for six different tryptic phosphorylated (p-tau-181, 199, 202, 205, 217, 231), and two non-phosphorylated tau (195-205, 212-221) peptides. NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Binary logistic regressions tested the association between each plasma peptide and autopsy-confirmed AD status. Area under the receiver operating curve (AUC) statistics were generated using predicted probabilities from the logistic regression models. Odds Ratio (OR) was used to study associations between the different plasma tau species and CERAD and Braak classifications. All tau species were increased in AD compared to non-AD, but p-tau217, p-tau205 and p-tau231 showed the highest fold-changes. Plasma p-tau217 (AUC=89.8), p-tau231 (AUC=83.4), and p-tau205 (AUC=81.3) all had excellent accuracy in discriminating AD from non-AD brain donors, even among those with CDR<1). Furthermore, p-tau217, p-tau205 and p-tau231 showed the highest ORs with both CERAD (ORp-tau217=15.29, ORp-tau205=5.05 and ORp-tau231=3.86) and Braak staging (ORp-tau217=14.29, ORp-tau205=5.27 and ORp-tau231=4.02) but presented increased levels at different amyloid and tau stages determined by neuropathological examination. Our findings support plasma p-tau217 as the most promising p-tau species for detecting AD brain pathology. Plasma p-tau231 and p-tau205 may additionally function as markers for different stages of the disease.
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| 7. |
- Pompermaier, Laura, et al.
(författare)
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Impact of COVID-19 on global burn care
- 2022
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Ingår i: Burns. - : Elsevier Science Ltd. - 0305-4179 .- 1879-1409. ; 48:6, s. 1301-1310
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Tidskriftsartikel (refereegranskat)abstract
- Background: Worldwide, different strategies have been chosen to face the COVID-19-patient surge, often affecting access to health care for other patients. This observational study aimed to investigate whether the standard of burn care changed globally during the pan-demic, and whether country acute accent s income, geographical location, COVID-19-transmission pat-tern, and levels of specialization of the burn units affected reallocation of resources and access to burn care.Methods: The Burn Care Survey is a questionnaire developed to collect information on the capacity to provide burn care by burn units around the world, before and during the pandemic. The survey was distributed between September and October 2020. McNemar`s test analyzed differences between services provided before and during the pandemic, chi 2 or Fishers exact test differences between groups. Multivariable logistic regression analyzed the independent effect of different factors on keeping the burn units open during the pandemic.Results: The survey was completed by 234 burn units in 43 countries. During the pandemic, presence of burn surgeons did not change (p = 0.06), while that of anesthetists and dedi-cated nursing staff was reduced (< 0.01), and so did the capacity to manage patients in all age groups (p = 0.04). Use of telemedicine was implemented (p < 0.01), collaboration be-tween burn centers was not. Burn units in LMICs and LICs were more likely to be closed, after adjustment for other factors.Conclusions: During the pandemic, most burn units were open, although availability of standard resources diminished worldwide. The use of telemedicine increased, suggesting the implementation of new strategies to manage burns. Low income was independently associated with reduced access to burn care.(c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 8. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 9. |
- Wang, Yangong, et al.
(författare)
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TEP1 is a risk gene for sporadic cerebral palsy
- 2021
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Ingår i: Journal of genetics and genomics. - : Elsevier BV. - 1673-8527. ; 48:12, s. 1134-1138
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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