Publications by authors named "Jiang Li"

3,077 Publications

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Effect of acceptance and commitment therapy on rehabilitation patients with spinal cord injury.

Contemp Clin Trials Commun 2021 Dec 6;24:100778. Epub 2021 Jul 6.

Wuhu City Second People's Hospital, Affiliated to Wannan Medical College, Clinical Psychology Department, China.

This study aimed to explore the differences between the effectiveness of using a combination of rehabilitation and acceptance commitment therapy (ACT), and rehabilitation therapy alone for the treatment of spinal cord injury (SCI). The newly admitted patients with spinal cord injury whose post-traumatic stress disorder (PTSD) score was higher than 38 points were randomly categorized into the treatment group and control group, with 30 patients in each group. One group underwent ACT and rehabilitation treatment, while the other underwent rehabilitation treatment only. PTSD and functional independence measure (FIM) scores were evaluated. Changes in scores were compared between the two groups before, one month, two months, and three months after treatment. The total PTSD score in SCI patients who were treated with ACT was significantly different before and after treatment (P < 0.05). Total FIM scores were also significantly different before and after treatment (P < 0.05). The FIM score in the treatment group was significantly higher than that in the control group after 2 and 3 months of treatment (P < 0.05). The combination of rehabilitation therapy and ACT could immediately reduce stress levels and significantly improve impaired function, lifelong self-care ability, and the impact of rehabilitation therapy.
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http://dx.doi.org/10.1016/j.conctc.2021.100778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498220PMC
December 2021

Optimizing genomic control in mixed model associations with binary diseases.

Brief Bioinform 2021 Oct 13. Epub 2021 Oct 13.

Wuxi Fisheries College, Nanjing Agricultural University, People's Republic of China.

Complex computation and approximate solution hinder the application of generalized linear mixed models (GLMM) into genome-wide association studies. We extended GRAMMAR to handle binary diseases by considering genomic breeding values (GBVs) estimated in advance as a known predictor in genomic logit regression, and then reduced polygenic effects by regulating downward genomic heritability to control false negative errors produced in the association tests. Using simulations and case analyses, we showed in optimizing GRAMMAR, polygenic effects and genomic controls could be evaluated using the fewer sampling markers, which extremely simplified GLMM-based association analysis in large-scale data. Further, joint association analysis for quantitative trait nucleotide (QTN) candidates chosen by multiple testing offered significant improved statistical power to detect QTNs over existing methods.
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http://dx.doi.org/10.1093/bib/bbab426DOI Listing
October 2021

Prevalence of and Factors Associated with Club Drug Use among Secondary Vocational Students in China.

Int J Environ Res Public Health 2021 Oct 3;18(19). Epub 2021 Oct 3.

Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

To understand the prevalence of and factors associated with club drug use among Chinese secondary vocational students, a nationally representative survey was conducted. The multistage cluster sampling strategy was employed to select participants. A total of 9469 students from eleven secondary vocational schools in five cities completed self-reported questionnaires, which included information on club drug use, sociodemographic variables, individual factors, as well as peer and family related factors. The data were separately analyzed with Poisson regression models for female and male students. The overall lifetime prevalence of club drug use was 2.7% (258/9469), and male students had higher prevalence than female students (3.5% vs. 1.9%, < 0.001). Female and male students shared four risk factors (i.e., having ever smoked, perceiving social benefit expectancies, peer drug using and perceiving peer's approval of drug use) and one protective factor (i.e., having medium or high levels of refusal skills) for club drug use. Moreover, family drug using and having a part-time job were two additionally independent risk factors for club drug use among male students. These findings indicate that the problem of club drug use among Chinese secondary vocational students is worthy of attention. The prevention of club drug use should address multiple risks and protective factors on individual, peer and family levels.
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http://dx.doi.org/10.3390/ijerph181910408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507794PMC
October 2021

Cell imaging with multi-color DNA framework probes.

Chem Commun (Camb) 2021 Oct 12. Epub 2021 Oct 12.

State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.

Utilizing the programmability of the fractal DNA frameworks, multi-color probes were constructed by arranging fluorescent molecules and nucleic acid aptamers on the structure. Multiplexed cell imaging and classification was realized through pattern recognition.
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http://dx.doi.org/10.1039/d1cc04305fDOI Listing
October 2021

Imputation of missing values for electronic health record laboratory data.

NPJ Digit Med 2021 Oct 11;4(1):147. Epub 2021 Oct 11.

Geisinger Health System, Danville, PA, USA.

Laboratory data from Electronic Health Records (EHR) are often used in prediction models where estimation bias and model performance from missingness can be mitigated using imputation methods. We demonstrate the utility of imputation in two real-world EHR-derived cohorts of ischemic stroke from Geisinger and of heart failure from Sutter Health to: (1) characterize the patterns of missingness in laboratory variables; (2) simulate two missing mechanisms, arbitrary and monotone; (3) compare cross-sectional and multi-level multivariate missing imputation algorithms applied to laboratory data; (4) assess whether incorporation of latent information, derived from comorbidity data, can improve the performance of the algorithms. The latter was based on a case study of hemoglobin A1c under a univariate missing imputation framework. Overall, the pattern of missingness in EHR laboratory variables was not at random and was highly associated with patients' comorbidity data; and the multi-level imputation algorithm showed smaller imputation error than the cross-sectional method.
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http://dx.doi.org/10.1038/s41746-021-00518-0DOI Listing
October 2021

Low-frequency and rare coding variants of NUS1 contribute to susceptibility and phenotype of Parkinson's disease.

Neurobiol Aging 2021 Sep 17. Epub 2021 Sep 17.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

NUS1 has been recently identified as a candidate gene for Parkinson's disease (PD). Few studies have examined the association of NUS1 variants with PD susceptibility and phenotypes. In the first cohort, whole-exome sequencing was performed to identify variants in NUS1 exon-coding and exon-intron regions in 1542 cases and 1625 controls. 13 variants were totally detected, of which 10 rare variants and 3 low-frequency variants. Burden analysis showed that rare NUS1 variants significantly enriched in PD (p=0.016). We also performed a meta-analysis based on previous and our studies to correlate NUS1 mutations with PD susceptibility. Integrating our previous cohort (3210 cases and 2807 controls) and the first cohort identified the significant association of rs539668656 with PD risk (odds ratio (OR) = 2.82, p = 0.016). The genotype-phenotype association analysis showed that patients carrying rare variants, or rs539668656 were significantly associated with earlier onset age, depression, emotional impairment and severe disease condition. Our results support the role of NUS1 rare variants and rs539668656 towards PD susceptibility and phenotype.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.09.003DOI Listing
September 2021

At the Intersection of Gut Microbiome and Stroke: A Systematic Review of the Literature.

Front Neurol 2021 24;12:729399. Epub 2021 Sep 24.

Department of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, United States.

Ischemic and hemorrhagic stroke are associated with a high rate of long-term disability and death. Recent investigations focus efforts to better understand how alterations in gut microbiota composition influence clinical outcomes. A key metabolite, trimethylamine N-oxide (TMAO), is linked to multiple inflammatory, vascular, and oxidative pathways. The current biochemical underpinnings of microbial effects on stroke remain largely understudied. The goal of our study is to explore the current literature to explain the interactions between the human gut microbiome and stroke progression, recovery, and outcome. We also provide a descriptive review of TMAO. A systematic literature search of published articles between January 1, 1990, and March 22, 2020, was performed on the PubMed database to identify studies addressing the role of the microbiome and TMAO in the pathogenesis and recovery of acute stroke. Our initial investigation focused on human subject studies and was further expanded to include animal studies. Relevant articles were included, regardless of study design. The analysis included reviewers classifying and presenting selected articles by study design and sample size in a chart format. A total of 222 titles and abstracts were screened. A review of the 68 original human subject articles resulted in the inclusion of 24 studies in this review. To provide further insight into TMAO as a key player, an additional 40 articles were also reviewed and included. Our findings highlighted that alterations in richness and abundance of gut microbes and increased plasma TMAO play an important role in vascular events and outcomes. Our analysis revealed that restoration of a healthy gut, through targeted TMAO-reducing therapies, could provide alternative secondary prevention for at-risk patients. Biochemical interactions between the gut microbiome and inflammation, resulting in metabolic derangements, can affect stroke progression and outcomes. Clinical evidence supports the importance of TMAO in modulating underlying stroke risk factors. Lack of standardization and distinct differences in sample sizes among studies are major limitations.
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http://dx.doi.org/10.3389/fneur.2021.729399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498333PMC
September 2021

Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma.

BMC Oral Health 2021 Oct 8;21(1):506. Epub 2021 Oct 8.

Department of Stomatology, Xiangya Hospital, Central South University, Changsha, China.

Background: DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream signaling effector stimulator of interferon genes (STING) present a novel role in anti-tumor immunity. Recently, the combination of cGAS-STING agonists and immunotherapy achieved promising results in some tumor types. The correlation between cGAS-STING signaling pathway and the tumor immune microenvironment in patients with oral squamous cell carcinoma (OSCC) is unclear.

Methods: We utilized RNA sequencing and clinical data of OSCC patients from the TCGA database to investigate the correlation between cGAS-STING signaling pathway and the tumor immune microenvironment. Six cGAS-STING related genes were obtained from previous studies to establish the enrichment score of cGAS-STING pathway. The differences in survival rate, immune cell infiltration, immune-related genes expression and immune-related biological pathways were studied in the cGAS-STING clusters.

Results: We observed a better prognosis of OSCC patients in the cGAS-STING high cluster. The infiltration ratio of immune cells and the expression profiles of immune-related genes were elevated when the cGAS-STING pathway is activated. The differentially expressed genes between high and low cGAS-STING clusters were enriched in immune-related biological pathways.

Conclusions: Our findings suggest the potential benefit of combining STING agonists and immune checkpoint inhibitors in OSCC patients.
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http://dx.doi.org/10.1186/s12903-021-01813-8DOI Listing
October 2021

Hydrogen Sulfide Antagonizes Sleep Deprivation-induced Depression- and Anxiety-like Behaviors by Inhibiting Neuroinflammation in A Hippocampal Sirt1-dependent Manner.

Brain Res Bull 2021 Oct 5. Epub 2021 Oct 5.

Hengyang Key Laboratory of Neurodegeneration and Cognitive Impairment, Institute of Neuroscience, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, P. R. China; The First Affiliated Hospital, Institute of Neurology, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, P. R. China. Electronic address:

Increasing evidence confirms that sleep deprivation (SD), which induces hippocampal neuroinflammation, is a risk factor for depression. Hydrogen sulfide (HS) is a novel neuromodulator that plays antidepressant-like role. Silent mating type information regulation 2 homolog 1 (Sirt1) is well-characterized as a regulator of mood disorder. Furthermore, we have previously reported that HS upregulates Sirt1 expression in the hippocampus of SD-exposed rats. Here, we explored whether HS ameliorates depression- and anxiety-like behaviors as well as hippocampal neuroinflammatory in SD-exposed rats and whether Sirt1 mediates these protective roles of HS. In the present work, we showed that NaHS (a donor of HS) significantly alleviated depression- and anxiety-like behaviors in the SD-exposed rats tested by novelty-suppressed feeding test (NST), forced swim test (FST), tail suspension test (TST), and elevated plus maze test (EPMT) and that NaHS attenuates neuroinflammatory in the hippocampus of SD-exposed rats, as evidenced by reducing the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and chemokine CCL2, as well as increasing the levels of anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. However, Sirt1 inhibitor reversed the protective effects of HS against SD-induced depression- and anxiety-like behaviors as well as hippocampal neuroinflammatory. In conclusion, HS antagonizes SD-induced depression- and anxiety-like behaviors and neuroinflammation, which is required hippocampal Sirt1. These findings suggested that HS is a novel approach to prevent SD-induced depression and anxiety.
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http://dx.doi.org/10.1016/j.brainresbull.2021.10.002DOI Listing
October 2021

Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe.

J Exp Med 2021 Nov 7;218(11). Epub 2021 Oct 7.

Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA.

Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors.
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http://dx.doi.org/10.1084/jem.20202669DOI Listing
November 2021

Eosinophil extracellular traps drive asthma progression through neuro-immune signals.

Nat Cell Biol 2021 Oct 6;23(10):1060-1072. Epub 2021 Oct 6.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Eosinophilic inflammation is a feature of allergic asthma. Despite mounting evidence showing that chromatin filaments released from neutrophils mediate various diseases, the understanding of extracellular DNA from eosinophils is limited. Here we show that eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid are associated with the severity of asthma in patients. Functionally, we find that EETs augment goblet-cell hyperplasia, mucus production, infiltration of inflammatory cells and expressions of type 2 cytokines in experimental non-infection-related asthma using both pharmaceutical and genetic approaches. Multiple clinically relevant allergens trigger EET formation at least partially via thymic stromal lymphopoietin in vivo. Mechanically, EETs activate pulmonary neuroendocrine cells via the CCDC25-ILK-PKCα-CRTC1 pathway, which is potentiated by eosinophil peroxidase. Subsequently, the pulmonary neuroendocrine cells amplify allergic immune responses via neuropeptides and neurotransmitters. Therapeutically, inhibition of CCDC25 alleviates allergic inflammation. Together, our findings demonstrate a previously unknown role of EETs in integrating immunological and neurological cues to drive asthma progression.
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http://dx.doi.org/10.1038/s41556-021-00762-2DOI Listing
October 2021

Supercontinuum generated in an all-polarization-maintaining random fiber laser structure.

Opt Express 2021 Aug;29(18):28843-28851

We demonstrated a linearly-polarized supercontinuum (SC) directly generated in an all-polarization-maintaining random fiber laser (RFL) structure. Owing to the comparatively high Raman gain of the polarization-maintaining germanium doped fiber (GDF), the spectrum of the output SC shows an enhanced bandwidth and improved spectral flatness compared to the unpolarized counterpart. The output SC has an average output power of 4.43 W with a spectrum covering from 600 nm to 1900nm. The polarization extinction ratio (PER) is measured to be greater than 18 dB from 800 nm to 1700nm at the highest output power level. To the best of our knowledge, this is the first demonstration of a linearly-polarized SC generated directly from a RFL. This work is meaningful to help further expand the bandwidth of SC generated from a RFL and provides a simple and cost-effective method of generating linearly-polarized SC for practical applications.
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http://dx.doi.org/10.1364/OE.434691DOI Listing
August 2021

Targeting integrated epigenetic and metabolic pathways in lethal childhood PFA ependymomas.

Sci Transl Med 2021 10 6;13(614):eabc0497. Epub 2021 Oct 6.

Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.

Childhood posterior fossa group A ependymomas (PFAs) have limited treatment options and bear dismal prognoses compared to group B ependymomas (PFBs). PFAs overexpress the oncohistone-like protein EZHIP (enhancer of Zeste homologs inhibitory protein), causing global reduction of repressive histone H3 lysine 27 trimethylation (H3K27me3), similar to the oncohistone H3K27M. Integrated metabolic analyses in patient-derived cells and tumors, single-cell RNA sequencing of tumors, and noninvasive metabolic imaging in patients demonstrated enhanced glycolysis and tricarboxylic acid (TCA) cycle metabolism in PFAs. Furthermore, high glycolytic gene expression in PFAs was associated with a poor outcome. PFAs demonstrated high EZHIP expression associated with poor prognosis and elevated activating mark histone H3 lysine 27 acetylation (H3K27ac). Genomic H3K27ac was enriched in PFAs at key glycolytic and TCA cycle–related genes including hexokinase-2 and pyruvate dehydrogenase. Similarly, mouse neuronal stem cells (NSCs) expressing wild-type EZHIP (EZHIP-WT) versus catalytically attenuated EZHIP-M406K demonstrated H3K27ac enrichment at hexokinase-2 and pyruvate dehydrogenase, accompanied by enhanced glycolysis and TCA cycle metabolism. AMPKα-2, a key component of the metabolic regulator AMP-activated protein kinase (AMPK), also showed H3K27ac enrichment in PFAs and EZHIP-WT NSCs. The AMPK activator metformin lowered EZHIP protein concentrations, increased H3K27me3, suppressed TCA cycle metabolism, and showed therapeutic efficacy in vitro and in vivo in patient-derived PFA xenografts in mice. Our data indicate that PFAs and EZHIP-WT–expressing NSCs are characterized by enhanced glycolysis and TCA cycle metabolism. Repurposing the antidiabetic drug metformin lowered pathogenic EZHIP, increased H3K27me3, and suppressed tumor growth, suggesting that targeting integrated metabolic/epigenetic pathways is a potential therapeutic strategy for treating childhood ependymomas.
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http://dx.doi.org/10.1126/scitranslmed.abc0497DOI Listing
October 2021

Proton export alkalinizes intracellular pH and reprograms carbon metabolism to drive hematopoietic progenitor growth.

Blood 2021 Oct 5. Epub 2021 Oct 5.

Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States.

Proton export is often considered a detoxifying process in animal cells with monocarboxylate symporters co-exporting excessive lactate and protons during glycolysis or the Warburg effect. Here we report a novel mechanism by which lactate/H+ export is sufficient to induce cell growth. Increased lactate/proton export induces intracellular alkalization that selectively activates catalysis by key metabolic gatekeeper enzymes, HK1/PKM2/G6PDH, thereby enhancing glycolytic and pentose phosphate pathway carbon flux. The result is increased nucleotide levels, NADPH/NADP+ ratio and cell proliferation. Simply increasing the lactate/proton symporter, MCT4, or sodium-proton antiporter, NHE1 was sufficient to increase intracellular-pH (pHi) and give normal hematopoietic cells a significant competitive growth advantage in vivo. This process does not require additional cytokine triggers and is exploited in malignancy where leukemogenic mutations epigenetically increase MCT4. Inhibiting MCT4 decreased intracellular pH, carbon flux and eliminated acute myeloid leukemia-initiating-cells without cytotoxic chemotherapy. Intracellular alkalization is a primitive mechanism by which proton partitioning can directly reprogram carbon metabolism for cell growth.
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http://dx.doi.org/10.1182/blood.2021011563DOI Listing
October 2021

Thermal shrinkage reveals the feasibility of pulse-delay photocuring technique.

Dent Mater 2021 Oct 1. Epub 2021 Oct 1.

Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA. Electronic address:

Objectives: To resolve the feasibility of the pulse-delay photocuring technique as a clinical strategy for reducing the detrimental polymerization stress induced in dental composites during the photocuring process.

Methods: Model dental composites with high and low-filler contents were cured with the pulse-delay photocuring technique using different combinations of photocuring variables (irradiance, exposure time, and delay time). Irradiance used ranged from 0.1W/cm to 4W/cm. The exposure time of the first pulse varied from 0.2s to 27.2s and the delay times ranged from 10s to 120s. The radiant exposure was varied from 4J/cm to 20J/cm. A cantilever-beam based instrument (NIST Standards Reference Instrument 6005) was used to implement the photocuring technique for the measurement of the polymerization properties (the degree of monomer conversion, polymerization stress induced due to shrinkage, and temperature change due to the reaction exotherm and curing light absorbance) simultaneously in real-time. These properties were compared with those obtained using the conventional photocuring technique (i.e., using a constant irradiance for a fixed exposure time, a uniform exposure).

Results: There exists a minimum radiant exposure, such that a reduction in the polymerization stress can be achieved without sacrificing the degree of monomer conversion by using the pulse-delay over the conventional photocuring technique. More specifically, stress reductions of up to 19% and 32% was observed with the pulse-delay when compared with the conventional photocuring technique at an irradiance of 0.5W/cm and 4W/cm, respectively. The reduction occurred when the exposure time of the first pulse was greater than, but closer to, the gelation time (i.e., lower than the vitrification time) of the composite, regardless of the delay time used. Lower thermal shrinkage (contraction) during the post-curing time, rather than the stress relaxation during the delay time or lower degree of monomer conversion as claimed in the literature, is the cause of the reduction in the polymerization stress.

Significance: The study clarifies a long-standing confusion and controversy on the applicability of the pulse-delay photocuring technique for reducing the polymerization stress and promotes its potential clinical success for dental restorative composites.
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http://dx.doi.org/10.1016/j.dental.2021.09.007DOI Listing
October 2021

Characterization of Vaccine Tweets During the Early Stage of the COVID-19 Outbreak in the United States: Topic Modeling Analysis.

JMIR Infodemiology 2021 Jan-Dec;1(1):e25636. Epub 2021 Sep 14.

College of Media and International Culture Zhejiang University Hangzhou China.

Background: During the early stages of the COVID-19 pandemic, developing safe and effective coronavirus vaccines was considered critical to arresting the spread of the disease. News and social media discussions have extensively covered the issue of coronavirus vaccines, with a mixture of vaccine advocacies, concerns, and oppositions.

Objective: This study aimed to uncover the emerging themes in Twitter users' perceptions and attitudes toward vaccines during the early stages of the COVID-19 outbreak.

Methods: This study employed topic modeling to analyze tweets related to coronavirus vaccines at the start of the COVID-19 outbreak in the United States (February 21 to March 20, 2020). We created a predefined query (eg, "COVID" AND "vaccine") to extract the tweet text and metadata (number of followers of the Twitter account and engagement metrics based on likes, comments, and retweeting) from the Meltwater database. After preprocessing the data, we tested Latent Dirichlet Allocation models to identify topics associated with these tweets. The model specifying 20 topics provided the best overall coherence, and each topic was interpreted based on its top associated terms.

Results: In total, we analyzed 100,209 tweets containing keywords related to coronavirus and vaccines. The 20 topics were further collapsed based on shared similarities, thereby generating 7 major themes. Our analysis characterized 26.3% (26,234/100,209) of the tweets as , 25.4% (25,425/100,209) as , 12.9% (12,882/100,209) as , 12.7% (12,696/100,209) as , 9.9% (9908/100,209) as , 8.1% (8155/100,209) as , and 4.9% (4909/100,209) as . Different themes demonstrated some changes over time, mostly in close association with news or events related to vaccine developments. Twitter users who discussed conspiracy theories, the efficacy of vaccines and treatments, and financial concerns had more followers than those focused on other vaccine themes. The engagement level-the extent to which a tweet being retweeted, quoted, liked, or replied by other users-was similar among different themes, but tweets venting negative emotions yielded the lowest engagement.

Conclusions: This study enriches our understanding of public concerns over new vaccines or vaccine development at early stages of the outbreak, bearing implications for influencing vaccine attitudes and guiding public health efforts to cope with infectious disease outbreaks in the future. This study concluded that public concerns centered on general policy issues related to coronavirus vaccines and that the discussions were considerably mixed with political views when vaccines were not made available. Only a small proportion of tweets focused on conspiracy theories, but these tweets demonstrated high engagement levels and were often contributed by Twitter users with more influence.
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http://dx.doi.org/10.2196/25636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448459PMC
September 2021

Novel Rotational Combination Regimen of Skin Topicals Improves Facial Photoaging: Efficacy Demonstrated in Double-Blinded Clinical Trials and Laboratory Validation.

Front Med (Lausanne) 2021 17;8:724344. Epub 2021 Sep 17.

Centre for Dermatology Research, National Institute for Health Research Manchester Biomedical Research Centre, Stopford Building, University of Manchester, Manchester, United Kingdom.

Topical antiaging products are often a first-line intervention to counter visible signs of facial photoaging, aiming for sustained cosmetic improvement. However, prolonged application of a single active topical compound was observed clinically to lead to a plateau effect in improving facial photoaging. In view of this, we set out to reduce this effect systematically using a multi-tiered approach with laboratory evidence and clinical trials. The objective of the study was to evaluate the effects of active topical ingredients applied either alone, in combination, or in a rotational manner on modulation of facial photoaging. The study methodology included , organotypic, and skin explants; biopsy study; as well as clinical trials. We demonstrate for the first time that a pair of known antiaging ingredients applied rotationally, on human dermal fibroblasts, maximized pro-collagen I production. Indeed, rotational treatment with retinol and phytol/glycolic acid (PGA) resulted in better efficacy than application of each active ingredient alone as shown by explants and biopsy study, with penetration of active ingredients confirmed by Raman spectroscopy. Furthermore, two split-face, randomized, double-blinded clinical trials were conducted, one for 12 months to compare treated vs. untreated and the other for 6 months followed by a 2-month regression to compare treated vs. commercially marketed products. In both studies, rotational regimen showed superior results to its matching comparison as assessed by clinical grading and image analysis of crow's feet wrinkles. In conclusion, rotational regimen using retinol and PGA is effective in treating facial photoaging signs with long-lasting benefits.
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http://dx.doi.org/10.3389/fmed.2021.724344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484331PMC
September 2021

Delayed Initiation of ECMO Is Associated With Poor Outcomes in Patients With Severe COVID-19: A Multicenter Retrospective Cohort Study.

Front Med (Lausanne) 2021 16;8:716086. Epub 2021 Sep 16.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China.

Extracorporeal membrane oxygenation (ECMO) is a rapidly evolving therapy for acute lung and/or heart failure. However, the information on the application of ECMO in severe coronavirus disease 2019 (COVID-19) is limited, such as the initiation time. Especially in the period and regions of ECMO instrument shortage, not all the listed patients could be treated with ECMO in time. This study aimed to investigate and clarify the timing of ECMO initiation related to the outcomes of severe patients with COVID-19. The results show that ECMO should be initiated within 24 h after the criteria are met. In this retrospective, multicenter cohort study, we enrolled all ECMO patients with confirmed COVID-19 at the three hospitals between December 29, 2019 and April 5, 2020. Data on the demographics, clinical presentation, laboratory profile, clinical course, treatments, complications, and outcomes were collected. The primary outcomes were successful ECMO weaning rate and 60-day mortality after ECMO. Successful weaning from ECMO means that the condition of patients improved with adequate oxygenation and gas exchange, as shown by the vital signs, blood gases, and chest X-ray, and the patient was weaned from ECMO for at least 48 h. A total of 31 patients were included in the analysis. The 60-day mortality rate after ECMO was 71%, and the ECMO weaning rate was 26%. Patients were divided into a delayed ECMO group [3 (interquartile range (IQR), 2-5) days] and an early ECMO group [0.5 (IQR, 0-1) days] based on the time between meeting the ECMO criteria and ECMO initiation. In this study, 14 and 17 patients were included in the early and delayed treatment groups, respectively. Early initiation of ECMO was associated with decreased 60-day mortality after ECMO (50 vs. 88%, = 0.044) and an increased ECMO weaning rate (50 vs. 6%, = 0.011). In ECMO-supported patients with COVID-19, delayed initiation of ECMO is a risk factor associated with a poorer outcome. Clinical trial submission: March 19, 2020. Registry name: A medical records-based study for the clinical application of extracorporeal membrane oxygenation in the treatment of severe respiratory failure patients with novel coronavirus pneumonia (COVID-19). Chinese Clinical Trial Registry: https://www.chictr.org.cn/showproj.aspx?proj=51267,identifier:~ChiCTR2000030947.
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http://dx.doi.org/10.3389/fmed.2021.716086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481658PMC
September 2021

Learning Grasp Configuration Through Object-Specific Hand Primitives for Posture Planning of Anthropomorphic Hands.

Front Neurorobot 2021 15;15:740262. Epub 2021 Sep 15.

State Key Laboratory of Robotics and Systems, Harbin Institute of Technology, Harbin, China.

The proposal of postural synergy theory has provided a new approach to solve the problem of controlling anthropomorphic hands with multiple degrees of freedom. However, generating the grasp configuration for new tasks in this context remains challenging. This study proposes a method to learn grasp configuration according to the shape of the object by using postural synergy theory. By referring to past research, an experimental paradigm is first designed that enables the grasping of 50 typical objects in grasping and operational tasks. The angles of the finger joints of 10 subjects were then recorded when performing these tasks. Following this, four hand primitives were extracted by using principal component analysis, and a low-dimensional synergy subspace was established. The problem of planning the trajectories of the joints was thus transformed into that of determining the synergy input for trajectory planning in low-dimensional space. The average synergy inputs for the trajectories of each task were obtained through the Gaussian mixture regression, and several Gaussian processes were trained to infer the inputs trajectories of a given shape descriptor for similar tasks. Finally, the feasibility of the proposed method was verified by simulations involving the generation of grasp configurations for a prosthetic hand control. The error in the reconstructed posture was compared with those obtained by using postural synergies in past work. The results show that the proposed method can realize movements similar to those of the human hand during grasping actions, and its range of use can be extended from simple grasping tasks to complex operational tasks.
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http://dx.doi.org/10.3389/fnbot.2021.740262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480411PMC
September 2021

Course of papilloedema following surgical decompression in CHIARI I malformation with raised intracranial pressure.

BMJ Case Rep 2021 Oct 1;14(10). Epub 2021 Oct 1.

University Hospital of North Staffordshire NHS Trust, Stoke-on-Trent, UK.

Arnold-Chiari malformations (ACM) is a rare congenital hindbrain maldevelopment, leading to downward herniation of the cerebellar tonsils. Clinical features relates to cerebrospinal fluid disturbances, manifesting as symptoms of headaches, pseudotumour-like episodes, cranial nerve palsies and cerebellar dysfunction. Ocular manifestations includes varying ophthalmoloplegia and accommodation abnormalities. Papilloedema has been rarely implicated and remains an uncommon feature of ACM. We report a case of ACM who developed papilloedema and visual disturbance, that was successfully treated with suboccipital decompression. The presentation of patients with ACM-I and papilloedema unaccompanied by localising signs may resemble that of IIH. Neuroimaging with special attention to the craniocervical junction in saggital and transverse planes is crucial. Surgical decompression of the posterior fossa seems to improve headache symptoms and clinical signs of papilloedema.
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http://dx.doi.org/10.1136/bcr-2016-218228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488732PMC
October 2021

Hepatic inflammatory pseudotumor-like follicular dendritic cell tumor with hepatic lymphoma history: A case report and literature review.

Medicine (Baltimore) 2021 Oct;100(39):e27392

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.

Rationale: Hepatic inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a very rare disease. Till now, only 19 cases were reported in the English literature. However, the coexistence of IPT-like sarcoma and non-Hodgkin lymphoma (NHL) in the same patient has never been reported. In this report, we presented a case of hepatic IPT-like FDC with hepatic NHL history of which both were successfully resected.

Patient Concerns: We reported a case of a 47-year-old male patient who presented with right upper abdominal discomfort. Nineteen years ago, he underwent liver resection of segment VII for hepatic NHL (B-cell lymphoma). He had a history of chronic hepatitis B virus infection. Serum alpha fetoprotein level was normal. However, imaging studies revealed a well-circumscribed, solid mass in the right hepatic lobe, he came back to the clinic because he was worried about a recurrence of the B-cell lymphoma.

Diagnoses: Based on the patient's past medical history and magnetic resonance imaging results, and he was diagnosed as hepatocellular carcinoma or hepatic NHL preoperatively.

Interventions: Right hemi-hepatectomy was performed on this patient.

Outcomes: Histological report showed features of a mixture of chronic inflammatory cells and variable amounts of spindle cells. Also, immuno-histo-chemical studies demonstrated that all the tumor cells showed strong nuclear in situ labeling for EBV-encoded small RNAs and strongly positive stainings with CD21 and CD35. The patient tolerated the surgery well, recovered smoothly and he was discharged on postoperative day 7 (day 7). The patient is still disease free after a follow-up of over 50 months.

Conclusions: To our knowledge, this is the first report demonstrating hepatic IPT-like FDC sarcoma in a patient with primary hepatic NHL history. In regards to treatment, complete surgical resection should be performed and would acquire excellent long-term outcomes.
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http://dx.doi.org/10.1097/MD.0000000000027392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483863PMC
October 2021

gen. nov., sp. nov., an anaerobic, pyruvate-degrading bacterium from Shengli oilfield, and proposal of fam. nov. in the phylum .

Int J Syst Evol Microbiol 2021 Sep;71(9)

Key Laboratory of Development and Application of Rural Renewable Energy, Biogas Institute of Ministry of Agriculture, Chengdu 610041, PR China.

A strictly anaerobic, thermophilic, Gram-stain-negative bacterium, named as strain S15, was isolated from oily sludge of Shengli oilfield in PR China. Cells of strain S15 were straight or slightly curved rods with 0.4-0.8 µm width × 1.4-3 µm length and occurred mostly in pairs or short chains. Endospore-formation was not observed. The strain grew optimally at 55 °C (range from 30-65 °C), pH 6.5 (pH 6.0-8.5) and 0-30 g l NaCl (optimum with 10 g l NaCl). Yeast extract was an essential growth factor for strain S15. The major cellular fatty acid was iso-C (58.2 %), and the main polar lipids were amino phospholipid (APL), glycolipids (GLs) and phosphatidylethanolamine (PE). The G+C content of DNA of strain S15 was 52.2 mol%. Strain S15 shared 89.8 % 16S rRNA gene similarity with the most related organism DSM 22491 in the phylum . The paired genomic average amino acid identity (AAI) and percentage of conserved proteins (POCP) values showed relatedness of less than 58.0 and 39.7 % with type strains of the species in the phylum . On the basis of phenotypic, phylogenetic and phylogenomic evidences, strain S15 constitutes a novel species in a novel genus, for the name gen. nov., sp. nov. is proposed. The type strain is S15 (=CCAM 583=JCM 33159). fam. nov. is also proposed.
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http://dx.doi.org/10.1099/ijsem.0.005031DOI Listing
September 2021

Lung function, airway and peripheral basophils and eosinophils are associated with molecular pharmacogenomic endotypes of steroid response in severe asthma.

Thorax 2021 Sep 27. Epub 2021 Sep 27.

Department of Pediatrics, Division of Respiratory Medicine, University of California San Diego, La Jolla, California, USA

Introduction: Asthma is a complex disease with heterogeneous expression/severity. There is growing interest in defining asthma endotypes consistently associated with different responses to therapy, focusing on type 2 inflammation (Th2) as a key pathological mechanism. Current asthma endotypes are defined primarily by clinical/laboratory criteria. Each endotype is likely characterised by distinct molecular mechanisms that identify optimal therapies.

Methods: We applied unsupervised (without clinical criteria) principal component analysis on sputum airway cells RNA-sequencing transcriptomic data from 19 asthmatics from the Severe Asthma Research Program at baseline and 6-8 weeks follow-up after a 40 mg dose of intramuscular corticosteroids. We investigated principal components PC1, PC3 for association with 55 clinical variables.

Results: PC3 was associated with baseline Th2 clinical features including blood (rank-sum p=0.0082) and airway (rank-sum p=0.0024) eosinophilia, FEV change (Kendall tau-b R=-0.333 (-0.592 to -0.012)) and follow-up FEV albuterol response (Kendall tau-b R=0.392 (0.079 to 0.634)). PC1 with blood basophlia (rank-sum p=0.0191). The top 5% genes contributing to PC1, PC3 were enriched for distinct immune system/inflammation ontologies suggesting distinct subject-specific clusters of transcriptomic response to corticosteroids. PC3 association with FEV change was reproduced in silico in a comparable independent 14-subject (baseline, 8 weeks after daily inhaled corticosteroids (ICS)) airway epithelial cells microRNAome dataset.

Conclusions: Transcriptomic PCs from this unsupervised methodology define molecular pharmacogenomic endotypes that may yield novel biology underlying different subject-specific responses to corticosteroid therapy in asthma, and optimal personalised asthma care. Top contributing genes to these PCs may suggest new therapeutic targets.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215523DOI Listing
September 2021

Metabolism of Phenolics of Roots under In Vitro Digestion and Colonic Fermentation as Well as Their In Vivo Antioxidant Activity in Rats.

Foods 2021 Sep 8;10(9). Epub 2021 Sep 8.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.

Diels et Gilg is a herbaceous perennial species distributed mainly in southern China. The root (THR) has been prevalently consumed as a functional tea or dietary supplement. In vitro digestion models, including colonic fermentation, were built to evaluate the release and stability of THR phenolics with the method of HPLC-QqQ-MS/MS and UPLC-Qtof-MS/MS. From the oral cavity, the contents of total phenolic and flavonoid began to degrade. Quercetin-3-rutinoside, quercetin-3-glucoside, kaempferol-3-rutinoside, and kaempferol-3-glucoside were metabolized as major components and they were absorbed in the form of glycosides for hepatic metabolism. On the other hand, the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, and glutathione (GSH) content were significantly increased, while malondialdehyde (MDA) content was decreased in plasma and tissues of rats treated with THR extract in the oxidative stress model. These results indicated that the THR extract is a good antioxidant substance and has good bioavailability, which can effectively prevent some chronic diseases caused by oxidative stress. It also provides a basis for the effectiveness of THR as a traditional functional food.
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http://dx.doi.org/10.3390/foods10092123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470164PMC
September 2021

Multiple C-H⋯anion and N-H⋯anion hydrogen bond directed two-dimensional crystalline nanosheets with precise distance control of surface charges for enhanced DNA capture.

Soft Matter 2021 Sep 27. Epub 2021 Sep 27.

PCFM Lab, and GDHPRC Lab, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China.

Utilizing combined non-covalent interactions and introducing anions as structure-directing factors to build oriented self-assembly and 2D crystalline nanosheet superstructures with precise distance control of surface charges in competitive aqueous solvents still represents a formidable challenge for supramolecular chemists. Here we report a simple, efficient, and general strategy for multiple C-H/N-H⋯anion hydrogen bond enhanced π-π interaction directed 2D oriented self-assembly in water, which is based on the head-to-tail association of perylene monoimide dimers (PMIs) by directing N-H⋯anion interactions to position the anions to the C-H of π systems (PMIs). Interesting, this behavior only occurs for size-matched anions (Cl to NO; <45 Å), while larger anions could not form 2D crystalline nanosheet superstructures. The results show that crystalline nanosheet superstructures with precise distance control of surface charges can effectively capture DNA, possibly due to their high surface charge density and the distance match between the distance of surface charges and the distance between adjacent base pairs.
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http://dx.doi.org/10.1039/d1sm01152aDOI Listing
September 2021

Preliminary quantitative analysis of vertebral microenvironment changes in type 2 diabetes mellitus using FOCUS IVIM-DWI and IDEAL-IQ sequences.

Magn Reson Imaging 2021 Sep 21;84:84-91. Epub 2021 Sep 21.

Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an 271000, Shandong, China. Electronic address:

Purpose: To explore the application of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI) on account of field-of-view optimized and constrained undistorted single shot (FOCUS) and iteraterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation(IDEAL-IQ) sequences in evaluating the vertebral microenvironment changes of type 2 diabetes mellitus(T2DM) patients and the correlation with bone mineral density(BMD).

Method: 128 T2DM patients (mean age 63.4 ± 5.28 years) underwent both dual-energy X-ray absorptiometry (DEXA) and spine MRI. The FOCUS IVIM-DWI and IDEAL-IQ derived parameters of the vertebral body(L1, L2, L3, L4)were measured on corresponding maps of the lumbar spine. The subjects were divided into 3 groups according to T-scores as follows: normal (n = 37), osteopenia (n = 43), and osteoporosis(n = 48) group.One-way analysis of variance (ANOVA) were used to compare the vertebral parameters(ADC, ADC, f, FF, R2*) among three BMD cohorts.Receiver operating characteristic (ROC) analyses and Spearman's rank correlation were performed to test the diagnostic performance and the correlation between them respectively.

Results: There were significant differences in vertebral ADC, ADC, FF and R2* between the three groups (P < 0.05).Statistically, BMD was moderately negatively correlated with FF (r = -0.584, P < 0.001) and weakly positively with ADC (r = 0.334, P < 0.001), meanwhile moderately positively correlated with R2*(r = 0.509, P < 0.001) and ADC(0.545, P < 0.001).ADC was moderately negatively correlated with FF (r = -0.417, P < 0.001), weakly positively correlated with R2*(0.359, P < 0.001).Compared with the area under the curve (AUC) of ADC, ADC, FF and R2*, the AUC of ADC was higher in identifying between normal and abnormal(osteopenia and osteoporosis), normal from osteopenia, while the AUC of FF was higher in identifying osteopenia from osteoporosis.

Conclusions: FOCUS IVIM-DWI and IDEAL-IQ of lumbar spine might be useful to evaluate the vertebral microenvironment changes of T2DM patients.
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http://dx.doi.org/10.1016/j.mri.2021.09.008DOI Listing
September 2021

Dynamic changes in human single-cell transcriptional signatures during fatal sepsis.

J Leukoc Biol 2021 Sep 24. Epub 2021 Sep 24.

Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California, USA.

Systemic infections, especially in patients with chronic diseases, may result in sepsis: an explosive, uncoordinated immune response that can lead to multisystem organ failure with a high mortality rate. Patients with similar clinical phenotypes or sepsis biomarker expression upon diagnosis may have different outcomes, suggesting that the dynamics of sepsis is critical in disease progression. A within-subject study of patients with Gram-negative bacterial sepsis with surviving and fatal outcomes was designed and single-cell transcriptomic analyses of peripheral blood mononuclear cells (PBMC) collected during the critical period between sepsis diagnosis and 6 h were performed. The single-cell observations in the study are consistent with trends from public datasets but also identify dynamic effects in individual cell subsets that change within hours. It is shown that platelet and erythroid precursor responses are drivers of fatal sepsis, with transcriptional signatures that are shared with severe COVID-19 disease. It is also shown that hypoxic stress is a driving factor in immune and metabolic dysfunction of monocytes and erythroid precursors. Last, the data support CD52 as a prognostic biomarker and therapeutic target for sepsis as its expression dynamically increases in lymphocytes and correlates with improved sepsis outcomes. In conclusion, this study describes the first single-cell study that analyzed short-term temporal changes in the immune cell populations and their characteristics in surviving or fatal sepsis. Tracking temporal expression changes in specific cell types could lead to more accurate predictions of sepsis outcomes and identify molecular biomarkers and pathways that could be therapeutically controlled to improve the sepsis trajectory toward better outcomes.
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http://dx.doi.org/10.1002/JLB.5MA0721-825RDOI Listing
September 2021

Qingre Yiqi Method along with Oral Hypoglycemic Drugs in Treating Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Evid Based Complement Alternat Med 2021 11;2021:4395228. Epub 2021 Sep 11.

Graduate School, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China.

Objective: To evaluate the efficacy of the Qingre Yiqi method in the treatment of type 2 diabetes mellitus (T2DM) with meta-analysis.

Method: The randomized controlled trials (RCTs) of the Qingre Yiqi method in the treatment of T2DM in the PubMed, Medline, EMBase, Cochrane Library, Web of Science, Weipu Journal, China Knowledge Network (CNKI), and Wanfang database were conducted. Three reviewers independently conducted the screening, extracted the data, and assessed methodological quality. Data analysis was performed using Rev Man 5.3 software for statistical analysis.

Results: A total of 15 RCTs, including 1440 patients, were included. The results showed that compared with oral hypoglycemic drugs alone, the add-on treatment of the Qingre Yiqi method could significantly improve Chinese medicine syndrome (OR (95%CI) = 3.66 [2.47,5.42], < 0.00001) and lower the level of HbA1c (MD (95%CI) = -0.68 [0.91, -0.45], < 0.00001), triglyceride (TG) (MD (95%CI) = -0.38 [-0.58,-0.17], =0.0004), low-density lipoprotein cholesterol (LDL-C) (MD (95%CI) = -0.25 [-0.37, -0.13], < 0.0001), and total cholesterol(TC) (MD(95%CI) = -0.40[-0.67, -0.13], =0.003). In terms of fasting blood glucose (FBG) and postprandial blood sugar (PBG), subgroup analysis showed that the baseline of FBG and the number of combined oral hypoglycemic drugs of PBG were the major sources of heterogeneity.

Conclusion: Compared with the standard treatment, the Qingre Yiqi method along with oral hypoglycemic drugs showed the more beneficial effects for T2DM on improving TCM syndromes and reducing the blood glucose and partial lipid parameter.
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http://dx.doi.org/10.1155/2021/4395228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452389PMC
September 2021

The Immune Landscape of Chinese Head and Neck Adenoid Cystic Carcinoma and Clinical Implication.

Front Immunol 2021 6;12:618367. Epub 2021 Sep 6.

Radiotherapy Division, Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Novel systemic agents and effective treatment strategies for recurrence adenoid cystic carcinoma (ACC) of the head and neck are still worthy of further exploration. Here, we analyzed the mutations and expression profiles of 75 Chinese ACC patients, characterized the prognostic value of the immune signature for recurrence or distant metastasis, and explored the potential of immunotherapeutic biomarkers in ACC. In general, MYB fusion and somatic mutations accounted for a high proportion, which was 46.7% (35/75). ACCs displayed an overall low mutation burden and lack of programmed cell death ligand-1 (PD-L1) expression. The antigen-presenting machinery (APM) expression score and immune infiltration score (IIS) were the lowest among ACC patients, compared with other cancer types. For 61 primary cases, the locoregional recurrence-free survival (LRRFS) was statistically significantly correlated with the IIS [univariate analysis; hazard ratio (HR) = 0.32; 95% CI, 0.11-0.92; p = 0.035] and T-cell infiltration score (TIS) (univariate analysis; HR = 0.33; 95% CI, 0.12-0.94; p = 0.037]. Patients with lower IIS (log-rank p = 0.0079) or TIS (log-rank p = 0.0079) had shorter LRRFS. Additionally, solid pattern was also a prognostic factor related to locoregional recurrence, whereas postoperative radiotherapy (PORT) exerted its beneficial effects. We further evaluated the pretreatment immune profile of five ACC patients treated with PD-1 inhibitors. Patients who responded to camrelizumab or pembrolizumab observed elevated APM and TIS, compared with patients with progressive disease. Our study highlights the immune infiltration pattern and messenger RNA (mRNA) signatures of Chinese ACC patients, which has the potential value for prognosis and immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.618367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450584PMC
September 2021

Machine learning and atherosclerotic cardiovascular disease risk prediction in a multi-ethnic population.

NPJ Digit Med 2020 Sep 23;3(1):125. Epub 2020 Sep 23.

Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.

The pooled cohort equations (PCE) predict atherosclerotic cardiovascular disease (ASCVD) risk in patients with characteristics within prespecified ranges and has uncertain performance among Asians or Hispanics. It is unknown if machine learning (ML) models can improve ASCVD risk prediction across broader diverse, real-world populations. We developed ML models for ASCVD risk prediction for multi-ethnic patients using an electronic health record (EHR) database from Northern California. Our cohort included patients aged 18 years or older with no prior CVD and not on statins at baseline (n = 262,923), stratified by PCE-eligible (n = 131,721) or PCE-ineligible patients based on missing or out-of-range variables. We trained ML models [logistic regression with L penalty and L lasso penalty, random forest, gradient boosting machine (GBM), extreme gradient boosting] and determined 5-year ASCVD risk prediction, including with and without incorporation of additional EHR variables, and in Asian and Hispanic subgroups. A total of 4309 patients had ASCVD events, with 2077 in PCE-ineligible patients. GBM performance in the full cohort, including PCE-ineligible patients (area under receiver-operating characteristic curve (AUC) 0.835, 95% confidence interval (CI): 0.825-0.846), was significantly better than that of the PCE in the PCE-eligible cohort (AUC 0.775, 95% CI: 0.755-0.794). Among patients aged 40-79, GBM performed similarly before (AUC 0.784, 95% CI: 0.759-0.808) and after (AUC 0.790, 95% CI: 0.765-0.814) incorporating additional EHR data. Overall, ML models achieved comparable or improved performance compared to the PCE while allowing risk discrimination in a larger group of patients including PCE-ineligible patients. EHR-trained ML models may help bridge important gaps in ASCVD risk prediction.
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http://dx.doi.org/10.1038/s41746-020-00331-1DOI Listing
September 2020
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