Machine learning of spectra-property relationship for imperfect and small chemistry data.

Machine learning (ML) is causing profound changes to chemical research through its powerful statistical and mathematical methodological capabilities. However, the nature of chemistry experiments often sets very high hurdles to collect high-quality data that are deficiency free, contradicting the need of ML to learn from big data. Even worse, the black-box nature of most ML methods requires more abundant data to ensure good transferability. Herein, we combine physics-based spectral descriptors with a symbolic regression method to establish interpretable spectra-property relationship. Using the machine-learned mathematical formulas, we have predicted the adsorption energy and charge transfer of the CO-adsorbed Cu-based MOF systems from their infrared and Raman spectra. The explicit prediction models are robust, allowing them to be transferrable to small and low-quality dataset containing partial errors. Surprisingly, they can be used to identify and clean error data, which are common data scenarios in real experiments. Such robust learning protocol will significantly enhance the applicability of machine-learned spectroscopy for chemical science.

The first pineoblastoma case report of a patient with Sotos syndrome harboring NSD1 germline mutation.

Germline mutations of NSD1 are associated with Sotos syndrome, characterized by distinctive facial features, overgrowth, and developmental delay. Approximately 3% of individuals with Sotos syndrome develop tumors. In this study, we describe an infant in pineoblastoma with facial anomalies, learning disability and mild autism at 1 years diagnosed as Sotos syndrome owing to carrying a novel mutation de novo germline NSD1 likely pathogenic variant. This patient expands both the mutation and phenotype spectrum of the Sotos Syndrome and provides new clinical insights into the potential mechanism of underlying pinealoblastoma pathology.

Inflammatory burden of adolescents with childhood maltreatment: results from baseline data of a school cohort.

Increasing studies have investigated inflammatory burden of adults with childhood adversity, but less is known about how childhood maltreatment affects the inflammation level of adolescents. Baseline data of a school cohort of physical and mental health status and life experience survey on primary and secondary school students in Anhui Province, China was used. Childhood maltreatment of children and adolescents was assessed by Chinese version of Childhood Trauma Questionnaire-Short Form (CTQ-SF). Urine samples were collected to assess levels of soluble urokinase Plasminogen Activator Receptor (suPAR), C-reactive protein (CRP) and cytokines interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA). Logistic regression was conducted to examine the association between childhood maltreatment exposure and risk of high inflammation burden. A total of 844 students were included with mean age 11.41 ± 1.57 years old. Adolescents with emotional abuse were significantly more likely to have high level of IL-6 (OR = 3.59, 95% CI 1.16-11.14). In addition, adolescents with emotional abuse were more likely to show high IL-6 and high suPAR combination (OR = 33.41, 95% CI 1.69-659.22), and high IL-6 and low CRP combination (OR = 4.34, 95% CI 1.29-14.55). Subgroup analyses showed that emotional abuse was associated with high IL-6 burden among boys or adolescents with depression. Childhood emotional abuse was positively associated with higher burden of IL-6. Early detection and prevention of emotional abuse for children and adolescents, especially for boys or adolescents with depression status, may be helpful for preventing elevated inflammatory burden and related health problems.

Association between adverse childhood experiences and sleep quality, emotional and behavioral problems and academic achievement of children and adolescents.

The impact of adverse childhood experiences (ACEs) on adult health has been extensively examined, but the association between ACEs and sleep, emotion, behavior and academic outcomes of children and adolescents is not well known. A total of 6363 primary and middle school students were included to examine the effect of ACEs on sleep quality, emotional and behavioral problems and academic achievement and further explore the mediation role of sleep quality and emotional and behavioral problems. Children and adolescents with ACE exposure had 1.37 times risk of poor sleep quality (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI]: 1.21-1.55), 1.91 times risk of emotional and behavioral problems (adjusted OR = 1.91, 95%CI: 1.69-2.15) and 1.21 times risk of self-reported lower academic achievement (adjusted OR = 1.21, 95%CI: 1.08-1.36). Most types of ACEs were significantly associated with poor sleep quality, emotional and behavioral problems and lower academic achievement. There were dose-response relationships between cumulative ACE exposure and risk of poor sleep quality, emotional and behavioral problems, and lower academic achievement. Sleep quality and emotional and behavioral performance mediated 45.9% of the effect of ACEs exposure on math scores and 15.2% of the effect of ACEs exposure on English scores. Early detection and prevention of ACEs among children and adolescents are urgent and essential, and targeted interventions for sleep and emotional and behavioral performance as well as early educational interventions are recommended for children with ACEs exposure.

Potential Regulatory Networks and Heterosis for Flavonoid and Terpenoid Contents in Pak Choi: Metabolomic and Transcriptome Analyses.

Pak choi exhibits a diverse color range and serves as a rich source of flavonoids and terpenoids. However, the mechanisms underlying the heterosis and coordinated regulation of these compounds-particularly isorhamnetin-remain unclear. This study involved three hybrid combinations and the detection of 528 metabolites from all combinations, including 26 flavonoids and 88 terpenoids, through untargeted metabolomics. Analysis of differential metabolites indicated that the heterosis for the flavonoid and terpenoid contents was parent-dependent, and positive heterosis was observed for isorhamnetin in the two hybrid combinations (SZQ, 002 and HMG, ZMG). Moreover, there was a high transcription level of flavone 3'-O-methyltransferase, which is involved in isorhamnetin biosynthesis. The third group was considered the ideal hybrid combination for investigating the heterosis of flavonoid and terpenoid contents. Transcriptome analysis identified a total of 12,652 DEGs (TPM > 1) in various groups that were used for comparison, and DEGs encoding enzymes involved in various categories, including "carotenoid bio-synthesis" and "anthocyanin biosynthesis", were enriched in the hybrid combination (SZQ, 002). Moreover, the category of anthocyanin biosynthesis also was enriched in the hybrid combination (HMG, ZMG). The flavonoid pathway demonstrated more differential metabolites than the terpenoid pathway did. The WGCNA demonstrated notable positive correlations between the dark-green modules and many flavonoids and terpenoids. Moreover, there were 23 ERF genes in the co-expression network (r ≥ 0.90 and p < 0.05). Thus, ERF genes may play a significant role in regulating flavonoid and terpenoid biosynthesis. These findings enhance our understanding of the heterosis and coordinated regulation of flavonoid and terpenoid biosynthesis in pak choi, offering insights for genomics-based breeding improvements.

Is early time to positivity of blood culture associated with clinical prognosis in patients with Klebsiella pneumoniae bloodstream infection?

The association between time to positivity (TTP) of blood culture and the clinical prognosis of patients with Klebsiella pneumoniae bloodstream infection (BSI) remains unclear. A retrospective study of 148 inpatients with BSI caused by K. pneumoniae was performed at Shanghai Tongji Hospital, China, from October 2016-2020. The total in-hospital fatality rate was 32%. The median TTP was 11.0 (7.7-16.1) h and the optimal cutoff for prediction of in-hospital mortality was 9.4 h according to the ROC curve. Early TTP (<9.4 h) was a risk factor for in-hospital mortality by univariate analysis (OR = 2.5, 95% CI 1.2-5.0, P = 0.01), but not by multivariate analysis (OR = 2.7, 95% CI 1.0-7.4, P = 0.06). Old age, serum creatinine, white blood cells, and C-reactive protein values were risk factors for in-hospital mortality by multivariate analysis. Early TTP was not a risk factor for septic shock (OR = 1.8, 95% CI 0.6-5.1, P = 0.27) or ICU admission (OR = 1.0, 95% CI 1.0-1.0, P = 0.32). In conclusion, the in-hospital fatality rate of patients with K. pneumoniae BSI was relatively high and associated with an early TTP of blood cultures. However, no increased risk of mortality, septic shock or ICU admission was evident in early TTP patients.

CDC50A might be a novel biomarker of epithelial ovarian cancer-initiating cells.

BACKGROUND: The aim of this work was to screen and validate biomarkers of ovarian cancer-initiating cells to detect the mechanisms of recurrence of epithelial ovarian cancer (EOC). METHODS: Stably labelled the amino acid in side population (SP) cells of epithelial ovarian cancer which were rich in cancer-initiating cells and non-SP cells with isotope in culture and differentially expressed cellular membrane proteins in SP cells were identified through proteomics technology. The new candidate biomarker was screened and validated through RT-PCR and western blot. Both in cell lines and primary EOC, cancer-initiating biofunctions of CDC50A positive cells were validated. Moreover, the characteristics of mesenchymal transition (EMT) was also detected and the correlation between the biomarker and clinical prognosis was observed. RESULTS: Through proteomics technology, candidate protein CDC50A was screened, and its significantly differential expression in SP cells was validated. CDC50A-positive cells from cell lines and primary ovarian cancer tissues were validated to show characteristics of cancer-initiating cells both in vitro and in vivo, including sphere-forming, self-renewal, differentiation, tumor metastasis and tumorigenicity in mice. The relationship between CDC50A-positive cells from primary tissues and tumour metastasis was confirmed based on their mesenchymal transition characteristics. Among 16 high-grade ovarian serous cancer patients, a high ratio of CDC50A-positive cells in primary tumours was correlated with a shorter platinum-free interval (p = 0.031, HR 0.260, 95% CI 0.77 ~ 0.885). CONCLUSION: CDC50A could be used to screen ovarian cancer-initiating cells and might be a new target to resolve tumour development in EOC patients.

A case of bacteremia caused by Slackia exigua in a patient with liver abscess, which caused by fish puncture through the stomach wall.

We present a case of hepatic abscess caused by a fish puncture through the gastric wall and the development of Slackia exigua infection.

The essential roles of OsFtsH2 in developing the chloroplast of rice.

BACKGROUND: Filamentation temperature-sensitive H (FtsH) is an ATP-dependent zinc metalloprotease with ATPase activity, proteolysis activity and molecular chaperone-like activity. For now, a total of nine FtsH proteins have been encoded in rice, but their functions have not revealed in detail. In order to investigate the molecular mechanism of OsFtsH2 here, several osftsh2 knockout mutants were successfully generated by the CRISPR/Cas9 gene editing technology. RESULTS: All the mutants exhibited a phenotype of striking albino leaf and could not survive through the stage of three leaves. OsFtsH2 was located in the chloroplast and preferentially expressed in green tissues. In addition, osftsh2 mutants could not form normal chloroplasts and had lost photosynthetic autotrophic capacity. RNA sequencing analysis indicated that many biological processes such as photosynthesis-related pathways and plant hormone signal transduction were significantly affected in osftsh2 mutants. CONCLUSIONS: Overall, the results suggested OsFtsH2 to be essential for chloroplast development in rice.

Does aspirin reduce the incidence, recurrence, and mortality of colorectal cancer? A meta-analysis of randomized clinical trials.

BACKGROUND: Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of all cancer deaths in the USA. Some evidences are shown that aspirin can reduce the morbidity and mortality of different cancers, including CRC. Aspirin has become a new focus of cancer prevention and treatment research so far; clinical studies, however, found conflicting conclusions of its anti-cancer characteristics. This study is to summarize the latest evidence of correlation between aspirin use and CRC and/or colorectal adenomas. METHODS: Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. The pooled relative risk (RR) with 95% confidence interval (CI) was used to estimate the effect of aspirin on colorectal cancer and/or colorectal adenomas. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: The result showed that aspirin use was not associated with incidence of CRC (RR 0.97; 95% CI 0.84-1.12; P = 0.66; I2 = 34%), aspirin use was found to be associated with reduced recurrence of colorectal adenomas (RR 0.83; 95% CI 0.72-0.95; P = 0.006; I2 = 63%) and reduced mortality of CRC (RR 0.79; 95% CI 0.64-0.97; P = 0.02; I2 = 14%). Subgroup analysis found a statistically significant association in low dose with a pooled RR of 0.85 (95% CI 0.74-0.99; P = 0.03; I2 = 31%). CONCLUSIONS: This meta-analysis of randomized controlled trial data indicates that aspirin reduces the overall risk of recurrence and mortality of CRC and/or colorectal adenomas. Incidence of CRC was also reduced with low-dose aspirin. The emerging evidence on aspirin's cancer protection role highlights an exciting time for cancer prevention through low-cost interventions. TRIAL REGISTRATION: Clinicaltrials.gov no: CRD42020208852; August 18, 2020; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020208852 ).

Radiofrequency ablation versus stereotactic body radiotherapy for hepatocellular carcinoma: a meta-analysis.

The present meta-analysis was performed to evaluate the efficacy of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) patients. A systematic literature search was conducted of online databases prior to February 21, 2021. Eleven articles involving 8429 patients were included. The pooled hazard ratio for overall survival (OS) of RFA versus SBRT was 0.79 (p < 0.001). Statistically significant differences were found in the 1-, 2-, 3-, 4- and 5-year pooled OS and freedom from local progression (FFLP) rates between the two groups, favoring the RFA arms. However, the pooled local control (LC) rates were higher in the SBRT arm. RFA provided better OS and FFLP for treating HCC, while SBRT achieved superior LC. PROSPERO registration number: CRD42020207877.

Lay abstract Radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) are two common nonsurgical methods for the treatment of hepatocellular carcinoma patients. The purpose of this meta-analysis was to compare the efficacy of the two methods. The analysis included 11 original studies after online databases search prior to 21 February 2021. The results showed that RFA provided better survival benefits and less local disease progression for the treatment of HCC patients, while SBRT obtained superior local control of tumor tissues.

Human intracellular ISG15 prevents interferon-α/ß over-amplification and auto-inflammation.

Intracellular ISG15 is an interferon (IFN)-α/ß-inducible ubiquitin-like modifier which can covalently bind other proteins in a process called ISGylation; it is an effector of IFN-α/ß-dependent antiviral immunity in mice. We previously published a study describing humans with inherited ISG15 deficiency but without unusually severe viral diseases. We showed that these patients were prone to mycobacterial disease and that human ISG15 was non-redundant as an extracellular IFN-γ-inducing molecule. We show here that ISG15-deficient patients also display unanticipated cellular, immunological and clinical signs of enhanced IFN-α/ß immunity, reminiscent of the Mendelian autoinflammatory interferonopathies Aicardi-Goutières syndrome and spondyloenchondrodysplasia. We further show that an absence of intracellular ISG15 in the patients' cells prevents the accumulation of USP18, a potent negative regulator of IFN-α/ß signalling, resulting in the enhancement and amplification of IFN-α/ß responses. Human ISG15, therefore, is not only redundant for antiviral immunity, but is a key negative regulator of IFN-α/ß immunity. In humans, intracellular ISG15 is IFN-α/ß-inducible not to serve as a substrate for ISGylation-dependent antiviral immunity, but to ensure USP18-dependent regulation of IFN-α/ß and prevention of IFN-α/ß-dependent autoinflammation.

Coronavirus infections and immune responses.

Coronaviruses (CoVs) are by far the largest group of known positive-sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV-induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.

Rh(III)-Catalyzed Oxidative Coupling of Benzoic Acids with Geminal-Substituted Vinyl Acetates: Synthesis of 3-Substituted Isocoumarins.

The Rh(III)-catalyzed C-H activation initiated cyclization of benzoic acids with electron-rich geminal-substituted vinyl acetates was described. The reaction was employed to prepare a range of 3-aryl and 3-alkyl substituted isocoumarins selectively.

Association Between Adverse Childhood Experiences and Academic Performance Among Children and Adolescents: A Global Meta-Analysis.

This study was conducted to quantify the association of adverse childhood experiences (ACEs) and the academic performance of children and adolescents. The literature was systematically searched in six electronic databases, and a meta-analysis was conducted. Twenty studies with a total of 1,196,631 children and adolescents from five countries were included. Meta-analysis showed that ACE score was positively associated with poor academic achievement, grade repetition, and special education support. Compared with children and adolescents without any ACE, those with one or more ACE had a significantly higher risk of poor academic achievement (pooled odds ratio [OR]: 1.45, 95% confidence interval [CI] [1.13, 1.85], I2 = 82.6%) and grade repetition (pooled OR: 1.36, 95% CI [1.29, 1.43], I2 = 71.0%). Moreover, all types of ACEs were positively associated with poor academic achievement and grade repetition. In addition, there was a significant dose-response relationship between the ACE score and the risk of poor academic achievement. This study supported that ACE had a significant impact on the academic performance of children and adolescents. Based on these findings, we recommend that early screening of ACEs for children and adolescent is critical and appropriate support and prevention in education should be developed for those with ACEs. Further studies are needed to further explore the long-term effect of ACEs on education and its gender differences.

Label-Free Data Mining of Scientific Literature by Unsupervised Syntactic Distance Analysis.

Label-free data mining can efficiently feed large amounts of data from the vast scientific literature into artificial intelligence (AI) processing systems. Here, we demonstrate an unsupervised syntactic distance analysis (SDA) approach that is capable of mining chemical substances, functions, properties, and operations without annotation. This SDA approach was evaluated in several areas of research from the physical sciences and achieved performance in information mining comparable to that of supervised learning, as shown by its satisfactory scores of 0.62-0.72, 0.60-0.82, and 0.86-0.95 in precision, recall, and accuracy, respectively. We also showcase how our approach can assist robotic chemists programmed to perform research focused on double-perovskite colloidal nanocrystals, gold colloidal nanocrystals, oxygen evolution reaction catalysts, and enzyme-like catalysts by designing materials, formulations, and synthesis parameters based on data mined from 1.1 million literature references.

Lipidomics Analysis Explores the Mechanism of Renal Injury in Rat Induced by 3-MCPD.

3-monochloropropane-1,2-diol (3-MCPD) is a food-process toxic substance, and its main target organ is the kidney. The present study examined and characterized the nephrotoxicity and the lipidomic mechanisms in a model of kidney injury in Sprague Dawley (SD) rats treated with high (45 mg/kg) and low (30 mg/kg) doses of 3-MCPD. The results showed that the ingestion of 3-MCPD led to a dose-dependent increase in serum creatinine and urea nitrogen levels and histological renal impairment. The oxidative stress indicators (MDA, GSH, T-AOC) in the rat kidney altered in a dose-dependent manner in 3-MCPD groups. The lipidomics analysis revealed that 3-MCPD caused kidney injury by interfering with glycerophospholipid metabolism and sphingolipid metabolism. In addition, 38 lipids were screened as potential biomarkers. This study not only revealed the mechanism of 3-MCPD renal toxicity from the perspective of lipidomics but also provided a new approach to the study of 3-MCPD nephrotoxicity.

Machine Learning Descriptors for Data-Driven Catalysis Study.

Traditional trial-and-error experiments and theoretical simulations have difficulty optimizing catalytic processes and developing new, better-performing catalysts. Machine learning (ML) provides a promising approach for accelerating catalysis research due to its powerful learning and predictive abilities. The selection of appropriate input features (descriptors) plays a decisive role in improving the predictive accuracy of ML models and uncovering the key factors that influence catalytic activity and selectivity. This review introduces tactics for the utilization and extraction of catalytic descriptors in ML-assisted experimental and theoretical research. In addition to the effectiveness and advantages of various descriptors, their limitations are also discussed. Highlighted are both 1) newly developed spectral descriptors for catalytic performance prediction and 2) a novel research paradigm combining computational and experimental ML models through suitable intermediate descriptors. Current challenges and future perspectives on the application of descriptors and ML techniques to catalysis are also presented.

Molecular genomic landscape of pediatric solid tumors in Chinese patients: implications for clinical significance.

PURPOSE: Pediatric solid tumors are significantly different from adult tumors. Studies have revealed genomic aberrations in pediatric solid tumors, but these analyses were based on Western populations. Currently, it is not known to what extent the existing genomic findings represent differences in ethnic backgrounds. EXPERIMENTAL: DESIGN: We retrospectively analyzed the basic clinical characteristics of the patients, including age, cancer type, and sex distribution, and further analyzed the somatic and germline mutations of cancer-related genes in a Chinese pediatric cohort. In addition, we investigated the clinical significance of genomic mutations on therapeutic, prognostic, diagnostic, and preventive actions. RESULTS: Our study enrolled 318 pediatric patients, including 234 patients with CNS tumors and 84 patients with non-CNS tumors. Somatic mutation analysis showed that there were significant differences in mutation types between CNS tumors and non-CNS tumors. P/LP germline variants were identified in 8.49% of patients. In total, 42.8% patients prompted diagnostic, 37.7% patients prompted prognostic, 58.2% patients prompted therapeutic, and 8.5% patients prompted tumor-predisposing and preventive, and we found that genomic findings might improve clinical management. CONCLUSIONS: Our study is the first large-scale study to analyze the landscape of genetic mutations in pediatric patients with solid tumors in China. Genomic findings in CNS and non-CNS solid pediatric tumors provide evidence for the clinical classification and individualized treatment of pediatric tumors, and they will facilitate improvement of clinical management. Data presented in this study should serve as a reference to guide the future design of clinical trials.

A Novel Germline SDHA Gene Mutation and Co-Occurring Somatic KIT Activating Mutation in a Patient With Pediatric Central Nervous System Germ Cell Tumor: Case Report.

Central nervous system germ cell tumors (CNS GCTs) are a heterogeneous group of primary CNS tumors. GCTs are more common and mostly observed in pediatric and young adult patients. CNS GCTs are divided into germinomas and non-germinomatous germ cell tumors (NGGCTs), with different therapeutic strategies depending on diagnosis. Herein, we report a patient with pediatric central nervous system germinoma harboring a somatic KIT p.Y823D and a heterozygous germline SDHA p. T396Nfs*14 mutation detected by next generation sequencing. After surgery, the patient received chemotherapy (temozolomide + nedaplatin + etoposide). This is the first report of a Chinese pediatric patient with CNS GCT harboring concurrent germline SDHA and somatic KIT mutation, which enriches molecular profiles of CNS GCTs and provides more molecular evidence of clinical diagnosis and potential targeted therapy in CNS GCTs.