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To describe the real-world clinical impact of a commercially available plasma cell-free DNA metagenomic next-generation sequencing assay, the Karius test (KT).
Methods:
We retrospectively evaluated the clinical impact of KT by clinical panel adjudication. Descriptive statistics were used to study associations of diagnostic indications, host characteristics, and KT-generated microbiologic patterns with the clinical impact of KT. Multivariable logistic regression modeling was used to further characterize predictors of higher positive clinical impact.
Results:
We evaluated 1000 unique clinical cases of KT from 941 patients between January 1, 2017–August 31, 2023. The cohort included adult (70%) and pediatric (30%) patients. The overall clinical impact of KT was positive in 16%, negative in 2%, and no clinical impact in 82% of the cases. Among adult patients, multivariable logistic regression modeling showed that culture-negative endocarditis (OR 2.3; 95% CI, 1.11–4.53; P .022) and concern for fastidious/zoonotic/vector-borne pathogens (OR 2.1; 95% CI, 1.11–3.76; P .019) were associated with positive clinical impact of KT. Host immunocompromised status was not reliably associated with a positive clinical impact of KT (OR 1.03; 95% CI, 0.83–1.29; P .7806). No significant predictors of KT clinical impact were found in pediatric patients. Microbiologic result pattern was also a significant predictor of impact.
Conclusions:
Our study highlights that despite the positive clinical impact of KT in select situations, most testing results had no clinical impact. We also confirm diagnostic indications where KT may have the highest yield, thereby generating tools for diagnostic stewardship.
Despite growing awareness of the mental health damage caused by air pollution, the epidemiologic evidence on impact of air pollutants on major mental disorders (MDs) remains limited. We aim to explore the impact of various air pollutants on the risk of major MD.
Methods
This prospective study analyzed data from 170 369 participants without depression, anxiety, bipolar disorder, and schizophrenia at baseline. The concentrations of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), particulate matter with aerodynamic diameter > 2.5 μm, and ≤ 10 μm (PM2.5–10), nitrogen dioxide (NO2), and nitric oxide (NO) were estimated using land-use regression models. The association between air pollutants and incident MD was investigated by Cox proportional hazard model.
Results
During a median follow-up of 10.6 years, 9 004 participants developed MD. Exposure to air pollution in the highest quartile significantly increased the risk of MD compared with the lowest quartile: PM2.5 (hazard ratio [HR]: 1.16, 95% CI: 1.09–1.23), NO2 (HR: 1.12, 95% CI: 1.05–1.19), and NO (HR: 1.10, 95% CI: 1.03–1.17). Subgroup analysis showed that participants with lower income were more likely to experience MD when exposed to air pollution. We also observed joint effects of socioeconomic status or genetic risk with air pollution on the MD risk. For instance, the HR of individuals with the highest genetic risk and highest quartiles of PM2.5 was 1.63 (95% CI: 1.46–1.81) compared to those with the lowest genetic risk and lowest quartiles of PM2.5.
Conclusions
Our findings highlight the importance of air pollution control in alleviating the burden of MD.
The high-power narrow-linewidth fiber laser has become the most widely used high-power laser source nowadays. Further breakthroughs of the output power depend on comprehensive optimization of stimulated Brillouin scattering (SBS), stimulated Raman scattering (SRS) and transverse mode instability (TMI). In this work, we aim to further surpass the power record of all-fiberized and narrow-linewidth fiber amplifiers with near-diffraction-limited (NDL) beam quality. SBS is suppressed by white-noise-signal modulation of a single-frequency seed. In particular, the refractive index of the large-mode-area active fiber in the main amplifier is controlled and fabricated, which could simultaneously increase the effective mode field area of the fundamental mode and the loss coefficient of higher-order modes for balancing SRS and TMI. Subsequent experimental measurements demonstrate a 7.03 kW narrow-linewidth fiber laser with a signal-to-noise ratio of 31.4 dB and beam quality factors of Mx2 = 1.26, My2 = 1.25. To the best of our knowledge, this is the highest reported power with NDL beam quality based on a directly laser-diode-pumped and all-fiberized format, especially with narrow-linewidth spectral emission.
The liver has multiple functions such as detoxification, metabolism, synthesis and storage. Folate is a water-soluble vitamin B9, which participates in one-carbon transfer reactions, maintains methylation capacity and improves oxidative stress. Folic acid is a synthetic form commonly used as a dietary supplement. The liver is the main organ for storing and metabolising folate/folic acid, and the role of folate/folic acid in liver diseases has been widely studied. Deficiency of folate results in methylation capacity dysfunction and can induce liver disorders. However, adverse effects of excessive use of folic acid on the liver have also been reported. This review aims to explore the mechanism of folate/folic acid in different liver diseases, promote further research on folate/folic acid and contribute to its rational clinical application.
In the current study, cryoconite samples were collected from six glaciers on the Tibetan Plateau to analyze n-alkanes and n-alkenes. The findings revealed that the concentrations of n-alkanes and n-alkenes varied from 40.1 to 496.1 μg g−1 and from 4.6 to 13.8 μg g−1, respectively. The carbon preference index of the long-chain n-alkanes ranged from 3.3 to 8.4, and the average chain length ranged from 28.7 to 29.3. Moreover, the δ13C of the n-alkanes in cryoconites were within the range of C3 plants, demonstrating that the n-alkanes in cryoconites were only derived from vascular plants. However, the δDmean were more negative than that of C3 plants, which could be caused by dry and humid conditions of glaciers. Unlike n-alkanes, n-alkenes ranged from C17:1 to C30:1 and showed a weak even-over-odd carbon number preference in the Dongkemadi, Yuzhufeng, Laohugou and Tianshan glacier, but a weak odd carbon preference in the Qiyi glacier. The n-alkenes in the YL Snow Mountains showed an obvious odd-over-even carbon number predominance from C17:1 to C22:1 with Cmax at C19:1, and the even-over-odd carbon number preference from C23:1 to C30:1 with Cmax at C28:1. This demonstrated that the n-alkenes of cryoconites may be mainly derived from in situ production in glaciers.
The COVID-19 pandemic led to an initial increase in the incidence of carbapenem-resistant Enterobacterales (CRE) from clinical cultures in South-East Asia hospitals, which was unsustained as the pandemic progressed. Conversely, there was a decrease in CRE incidence from surveillance cultures and overall combined incidence. Further studies are needed for future pandemic preparedness.
In this work, a confined-doped fiber with the core/inner-cladding diameter of 40/250 μm and a relative doping ratio of 0.75 is fabricated through a modified chemical vapor deposition method combined with the chelate gas deposition technique, and subsequently applied in a tandem-pumped fiber amplifier for high-power operation and transverse mode instability (TMI) mitigation. Notably, the impacts of the seed laser power and mode purity are preliminarily investigated through comparative experiments. It is found that the TMI threshold could be significantly affected by the seed laser mode purity. The possible mechanism behind this phenomenon is proposed and revealed through comprehensive comparative experiments and theoretical analysis. Finally, a maximum output power of 7.49 kW is obtained with the beam quality factor of approximately 1.83, which is the highest output power ever reported in a forward tandem-pumped confined-doped fiber amplifier. This work could provide a good reference and practical solution to improve the TMI threshold and realize high-power high-brightness fiber lasers.
Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
Aims
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
Method
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
Results
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
Conclusions
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal–striatal–thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative to controls. However, as adult OCD patients often have high rates of co-morbid anxiety and long durations of illness, little is known about the functional connectivity of these networks in relation to OCD specifically, or in young patients near illness onset.
Methods
In this study, unmedicated female patients with OCD (ages 8–21 years, n = 23) were compared to age-matched female patients with anxiety disorders (n = 26), and healthy female youth (n = 44). Resting-state functional connectivity was used to determine the strength of functional connectivity within and between OST, CON, and DMN.
Results
Functional connectivity within the CON was significantly greater in the OCD group as compared to the anxiety and healthy control groups. Additionally, the OCD group displayed greater functional connectivity between OST and CON compared to the other two groups, which did not differ significantly from each other.
Conclusions
Our findings indicate that previously noted network connectivity differences in pediatric patients with OCD were likely not attributable to co-morbid anxiety disorders. Moreover, these results suggest that specific patterns of hyperconnectivity within CON and between CON and OST circuitry may characterize OCD relative to non-OCD anxiety disorders in youth. This study improves understanding of network dysfunction underlying pediatric OCD as compared to pediatric anxiety.
Salicylic acid (SA), a phytohormone, has been considered to be a key regulator mediating plant defence against pathogens. It is still vague how SA activates plant defence against herbivores such as chewing and sucking pests. Here, we used an aphid-susceptible wheat variety to investigate Sitobion avenae response to SA-induced wheat plants, and the effects of exogenous SA on some defence enzymes and phenolics in the plant immune system. In SA-treated wheat seedlings, intrinsic rate of natural increase (rm), fecundity and apterous rate of S. avenae were 0.25, 31.4 nymphs/female and 64.4%, respectively, and significantly lower than that in the controls (P < 0.05). Moreover, the increased activities of phenylalanine-ammonia-lyase, polyphenol oxidase (PPO) and peroxidase in the SA-induced seedlings obviously depended on the sampling time, whereas activities of catalase and 4-coumarate:CoA ligase were suppressed significantly at 24, 48 and 72 h in comparison with the control. Dynamic levels of p-coumaric acid at 96 h, caffeic acid at 24 and 72 h and chlorogenic acid at 24, 48 and 96 h in wheat plants were significantly upregulated by exogenous SA application. Nevertheless, only caffeic acid content was positively correlated with PPO activity in SA-treated wheat seedlings (P = 0.031). These findings indicate that exogenous SA significantly enhanced the defence of aphid-susceptible wheat variety against aphids by regulating the plant immune system, and may prove a potential application of SA in aphid control.
In present study, we explored the effects and the underlying mechanisms of phospholipase C (PLC) mediating glucose-induced changes in intestinal glucose transport and lipid metabolism by using U-73122 (a PLC inhibitor). We found that glucose incubation activated the PLC signal and U-73122 pre-incubation alleviated the glucose-induced increase in plcb2, plce1 and plcg1 mRNA expression. Meanwhile, U-73122 pre-treatment blunted the glucose-induced increase in sodium/glucose co-transporters 1/2 mRNA and protein expressions. U-73122 pre-treatment alleviated the glucose-induced increase in TAG content, BODIPY 493/503 fluorescence intensity, lipogenic enzymes (glucose 6-phospate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme and fatty acid synthase (FAS)) activity and the mRNA expressions of lipogenic genes and related transcription factors (6pgd, g6pd, fas, acca, srebp1 and carbohydrate response element-binding protein (chrebp)) in intestinal epithelial cells of yellow catfish. Further research found that U-73122 pre-incubation mitigated the glucose-induced increase in the ChREBP protein expression and the acetylation level of ChREBP in HEK293T cells. Taken together, these data demonstrated that the PLC played a major role in the glucose-induced changes of glucose transport and lipid metabolism and provide a new perspective for revealing the molecular mechanism of glucose-induced changes of intestinal glucose absorption, lipid deposition and metabolism.
The outbreak of COVID-19 generated severe emotional reactions, and restricted mobility was a crucial measure to reduce the spread of the virus. This study describes the changes in public emotional reactions and mobility patterns in the Chinese population during the COVID-19 outbreak.
Methods
We collected data on public emotional reactions in response to the outbreak through Weibo, the Chinese Twitter, between 1st January and 31st March 2020. Using anonymized location-tracking information, we analyzed the daily mobility patterns of approximately 90% of Sichuan residents.
Results
There were three distinct phases of the emotional and behavioral reactions to the COVID-19 outbreak. The alarm phase (19th–26th January) was a restriction-free period, characterized by few new daily cases, but a large amount public negative emotions [the number of negative comments per Weibo post increased by 246.9 per day, 95% confidence interval (CI) 122.5–371.3], and a substantial increase in self-limiting mobility (from 45.6% to 54.5%, changing by 1.5% per day, 95% CI 0.7%–2.3%). The epidemic phase (27th January–15th February) exhibited rapidly increasing numbers of new daily cases, decreasing expression of negative emotions (a decrease of 27.3 negative comments per post per day, 95% CI −40.4 to −14.2), and a stabilized level of self-limiting mobility. The relief phase (16th February–31st March) had a steady decline in new daily cases and decreasing levels of negative emotion and self-limiting mobility.
Conclusions
During the COVID-19 outbreak in China, the public's emotional reaction was strongest before the actual peak of the outbreak and declined thereafter. The change in human mobility patterns occurred before the implementation of restriction orders, suggesting a possible link between emotion and behavior.
The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) to identify malnutrition risk in patients with liver disease. However, little is known about the application of the RFH-NPT to screen for the risk of malnutrition in China, where patients primarily suffer from hepatitis virus-related cirrhosis. A total of 155 cirrhosis patients without liver cancer or uncontrolled co-morbid illness were enrolled in this prospective study. We administered the Nutritional Risk Screening 2002 (NRS-2002), RFH-NPT, Malnutrition Universal Screening Tool (MUST) and Liver Disease Undernutrition Screening Tool (LDUST) to the patients within 24 h after admission and performed follow-up observations for 1·5 years. The RFH-NPT and NRS-2002 had higher sensitivities (64·8 and 52·4 %) and specificities (60 and 70 %) than the other tools with regard to screening for malnutrition risk in cirrhotic patients. The prevalence of nutritional risk was higher under the use of the RFH-NPT against the NRS-2002 (63 v. 51 %). The RFH-NPT tended more easily to detect malnutrition risk in patients with advanced Child–Pugh classes (B and C) and lower Model for End-stage Liver Disease scores (<15) compared with NRS-2002. RFH-NPT score was an independent predictive factor for mortality. Patients identified as being at high malnutrition risk with the RFH-NPT had a higher mortality rate than those at low risk; the same result was not obtained with the NRS-2002. Therefore, we suggest that using the RFH-NPT improves the ability of clinicians to predict malnutrition risk in patients with cirrhosis primarily caused by hepatitis virus infection at an earlier stage.
For the guarantee of the long-distance transport of the bunches of China Initiative Accelerator Driven System (CIADS), a new scheme is proposed that extra magnetic field is used in the accelerator-target coupling section before the windowless target to minimize the self-modulation (SM) mechanism. Particle-in-cell simulations are carried out to study the influence of the solenoidal magnetic field on the self-modulation mechanism when long proton bunches move in the background plasmas. The long proton bunches used in the simulations are similar to these in the linear accelerator of CIADS. It is found that the presence of the solenoidal magnetic field will significantly inhibit the self-modulation process. For the strong magnetic field, the longitudinal separation and transverse focusing of the long bunches disappear. We attribute these phenomena to the reason that the strong solenoidal magnetic field restricts the transverse movement of plasma electrons. Thus, there are not enough electrons around the bunch to compensate the space charge effect. Moreover, without transverse current, the longitudinal pinched effect disappears, and the long bunch can not be separated into small pulses anymore.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
Aims
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Method
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
Results
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
Conclusions
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
Health system reform is considered a tough issue worldwide. Great efforts have been made toward health system building and strengthening. However, it is still unclear which health system is appropriate for different countries. This study aimed to systematically compare the characteristics of the establishment periods between eighty-eight counties of National Health Service (NHS) and Social Health Insurance (SHI).
Methods:
Forty-eight NHS countries and forty SHI countries with data availability were selected. The establishment years of current health systems and other eighteen indicators in economics, society, population and health during establishment periods were collected. Comparison between NHS and SHI was conducted by descriptive analysis of every indicator.
Results:
Most NHS countries were established during the cold war, while SHI had been set up since the cold war ended. The median of gross domestic product (GDP) per capita, urbanization rate and aging rate of SHI were USD 1535 in current dollars, 58.2 percent and 9.8 percent, respectively; compared with USD 1387, 41.2 percent and 4.7 percent, respectively of NHS. NHS countries had a smaller total population, lower mortality rate and elderly dependency ratio, while the birth rate and children's dependency ratio were higher. SHI countries showed a higher life expectancy and lower mortality rate in infants and children. NHS countries spent less in total health expenditure and a lower proportion of GDP. The median health expenditure per capita of SHI and NHS were USD 188 and USD 131 in current dollars, respectively. There was little difference among maternal mortality rates, and public and private health expenditure proportions.
Conclusions:
NHS and SHI countries had different characteristics during the health system establishment periods. NHS was established earlier than SHI overall, so that SHI revealed higher levels in economic and social development. Health outcomes of NHS countries were slightly lower than SHI ones, while health expenditure was more in SHI countries. Specific social, economic, demographic and health conditions should be considered when countries are building their own health systems.
To identify the prevalence of posttraumatic stress disorder (PTSD) and its determinants among adolescents more than 4 years after the 2008 Wenchuan earthquake.
Method
Adolescents (1,125 total) from 2 junior high schools in areas affected by the catastrophic earthquake were followed up for 3 years. The self-rating PTSD scale based on the Manual of Mental Disorders, 4th Edition (DSM-IV) and the Chinese Classification and Diagnostic Criteria of Mental Disorders, 2nd Edition, Revised (CCMD-2-R) was collected at 53 months, and determinant data were collected repeatedly. Logistic regression was used for a determinants analysis.
Results
The prevalence of overall PTSD was 23.4% among the sample. The risk factors for PTSD were older age (OR=1.52, 95% CI: 1.20~1.92), and death or injury of a family member in the earthquake (OR=1.61, 95% CI: 1.09~2.37). Adolescents who had moderate-to-severe common mental health problems were more likely to have PTSD symptoms, with ORs from 3.98 to 17.67 (All P<0.05). Self-esteem remained a protective factor for PTSD regardless of age, whereas positive coping was a protective factor for PTSD when adolescents were older.
Conclusion
PTSD symptoms among adolescent survivors of a catastrophic earthquake seemed to persist over time. Long-term interventions are needed to alleviate PTSD symptoms among adolescent survivors. (Disaster Med Public Health Preparedness. 2019;13:414-418)
Northeastern China is a region of high tick abundance, multiple tick-borne pathogens and likely human infections. The spectrum of diseases caused by tick-borne pathogens has not been objectively evaluated in this region for clinical management and for comparison with other regions globally where tick-transmitted diseases are common. Based on clinical symptoms, PCR, indirect immunofluorescent assay and (or) blood smear, we identified and described tick-borne diseases from patients with recent tick bite seen at Mudanjiang Forestry Central Hospital. From May 2010 to September 2011, 42% (75/180) of patients were diagnosed with a specific tick-borne disease, including Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis, human babesiosis and spotted fever group rickettsiosis. When we compared clinical and laboratory features to identify factors that might discriminate tick-transmitted infections from those lacking that evidence, we revealed that erythema migrans and neurological manifestations were statistically significantly differently presented between those with and without documented aetiologies (P < 0.001, P = 0.003). Twelve patients (6.7%, 12/180) were co-infected with two tick-borne pathogens. We demonstrated the poor ability of clinicians to identify the specific tick-borne disease. In addition, it is necessary to develop specific laboratory assays for optimal diagnosis of tick-borne diseases.