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Background: In meningiomas, CDKN2A/B deletions are associated with poor outcomes but are rare in most cohorts (1-5%). Large molecular datasets are therefore required to explore these deletions and their relationship to other prognostic CDKN2A alterations. Methods: We utilized multidimensional molecular data of 560 meningiomas from 5 independent cohorts to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Results: Meningiomas with either CDKN2A/B deletions (partial or homozygous loss) or an intact CDKN2A gene locus but elevated mRNA expression (CDKN2Ahigh) both had poor clinical outcomes. Increased CDKN2A mRNA expression was a poor prognostic factor independent of CDKN2A deletion. CDKN2A expression and p16 protein increased with tumor grade and more aggressive molecular and methylation groups. CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycling pathways dysregulated at different checkpoints. p16 immunohistochemistry was unreliable in differentiating between meningiomas with and without CDKN2A deletions, but increased positivity was associated with increased mRNA expression. CDKN2Ahigh meningiomas were associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. Conclusions: These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.
This study aimed to analyse the temporal and spatial trends in the burden of anxiety disorders and major depressive disorder related to bullying victimisation on global, regional and country scales.
Data were from the 2019 Global Burden of Disease (GBD) Study. We assessed the global disability-adjusted life years (DALYs, per 100 000 population) of anxiety disorders and major depressive disorder attributable to bullying victimisation by age, sex and geographical location. The percentage changes in age-standardised rates of DALYs were used to quantify temporal trends, and the annual rate changes across 204 countries and territories were used to present spatial trends. Furthermore, we examined the relationship between the sociodemographic index (SDI) and the burden of anxiety disorders as well as major depressive disorder attributable to bullying victimisation and its spatial and temporal characteristics globally.
From 1990 to 2019, the global DALY rates of anxiety disorders and major depressive disorder attributable to bullying victimisation increased by 23.31 and 26.60%, respectively, with 27.27 and 29.07% for females and 18.88 and 23.84% for males. Across the 21 GBD regions, the highest age-standardised rates of bullying victimisation-related DALYs for anxiety disorders were in North Africa and the Middle East and for major depressive disorder in High-income North America. From 1990 to 2019, the region with the largest percentage increase in the rates of DALYs was High-income North America (54.66% for anxiety disorders and 105.88% for major depressive disorder), whereas the region with the slowest growth rate or largest percentage decline was East Asia (1.71% for anxiety disorders and −25.37% for major depressive disorder). In terms of SDI, this study found overall upward trends of bullying-related mental disorders in areas regardless of the SDI levels, although there were temporary downward trends in some stages of certain areas.
The number and rates of DALYs of anxiety disorders and major depressive disorder attributable to bullying victimisation increased from 1990 to 2019. Effective strategies to eliminate bullying victimisation in children and adolescents are needed to reduce the burden of anxiety disorders and major depressive disorder. Considering the large variations in the burden by SDI and geographic location, future protective actions should be developed based on the specific cultural contexts, development status and regional characteristics of each country.
Manure is a primary source of methane (CH4) emissions into the atmosphere. A large proportion of CH4 from manure is emitted during storage, but this varies with storage methods. In this research, we tested whether covering a manure heap with plastic reduces CH4 emission during a short-term composting process. A static chamber method was used to detect the CH4 emission rate and the change of the physicochemical properties of cattle manure which was stored either uncovered (treatment UNCOVERED) or covered with plastic (treatment COVERED) for 30-day periods during the four seasons? The dry matter content of the COVERED treatment was significantly less than the UNCOVERED treatment (P < 0.01), and the C/N ratio of the COVERED treatment significantly greater than the UNCOVERED treatment (P > 0.05) under high temperature. In the UNCOVERED treatment, average daily methane (CH4) emissions were in the order summer > spring > autumn > winter. CH4 emissions were positively correlated with the temperature (R2 = 0.52, P < 0.01). Compared to the UNCOVERED treatment, the daily average CH4 emission rates from COVERED treatment manure were less in the first 19 days of spring, 13 days of summer, 10 days of autumn and 30 days of winter. In summary, covering the manure pile with plastic reduces the evaporation of water during storage; and in winter, long-term covering with plastic film reduces the CH4 emissions during the storage of manure.
Previous research on respiratory infection transmission among university students has primarily focused on influenza. In this study, we explore potential transmission events for multiple respiratory pathogens in a social contact network of university students. University students residing in on-campus housing (n = 590) were followed for the development of influenza-like illness for 10-weeks during the 2012–13 influenza season. A contact network was built using weekly self-reported contacts, class schedules, and housing information. We considered a transmission event to have occurred if students were positive for the same pathogen and had a network connection within a 14-day period. Transmitters were individuals who had onset date prior to their infected social contact. Throat and nasal samples were analysed for multiple viruses by RT-PCR. Five viruses were involved in 18 transmission events (influenza A, parainfluenza virus 3, rhinovirus, coronavirus NL63, respiratory syncytial virus). Transmitters had higher numbers of co-infections (67%). Identified transmission events had contacts reported in small classes (33%), dormitory common areas (22%) and dormitory rooms (17%). These results suggest that targeting person-to-person interactions, through measures such as isolation and quarantine, could reduce transmission of respiratory infections on campus.
Development of high energy density solid-state batteries with Li metal anodes has been limited by uncontrollable growth of Li dendrites in liquid and solid electrolytes (SEs). This, in part, may be caused by a dearth of information about mechanical properties of Li, especially at the nano- and microlength scales and microstructures relevant to Li batteries. We investigate Li electrodeposited in a commercial LiCoO2/LiPON/Cu solid-state thin-film cell, grown in situ in a scanning electron microscope equipped with nanomechanical capabilities. Experiments demonstrate that Li was preferentially deposited at the LiPON/Cu interface along the valleys that mimic the domain boundaries of underlying LiCoO2 (cathode). Cryogenic electron microscopy analysis of electrodeposited Li revealed a single-crystalline microstructure, and in situ nanocompression experiments on nano-pillars with 360–759 nm diameters revealed their average Young's modulus to be 6.76 ± 2.88 GPa with an average yield stress of 16.0 ± 6.82 MPa, ~24x higher than what has been reported for bulk polycrystalline Li. We discuss mechanical deformation mechanisms, stiffness, and strength of nano-sized electrodeposited Li in the framework of its microstructure and dislocation-governed nanoscale plasticity of crystals, and place it in the parameter space of existing knowledge on small-scale Li mechanics. The enhanced strength of Li at small scales may explain why it can penetrate and fracture through much stiffer and harder SEs than theoretically predicted.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
To evaluate the upper airway morphology changes associated with ageing in adult Chinese patients with obstructive sleep apnoea.
A total of 124 male patients diagnosed with obstructive sleep apnoea by overnight polysomnography, who underwent upper airway computed tomography, were enrolled. The linear dimensions, cross-sectional area and volume of the upper airway region and the surrounding bony frame were measured. The association between ageing and upper airway morphology was analysed.
Soft palate length, minimum cross-sectional area of the retroglossal region, lateral dimensions at the minimum cross-sectional area of the retropalatal and retroglossal regions, nasopharyngeal volume, and average cross-sectional area of the nasopharyngeal region were found to significantly increase with ageing in all patients, while the upper airway shape flattened with ageing. The volume of the retropalatal region increased with ageing among the patients with a body mass index of less than 24 kg/m2. The volume of parapharyngeal fat pad increased with ageing among patients with a body mass index greater than 28 kg/m2.
A number of dimensional, cross-sectional and volumetric parameters of the pharynx increased with age, indicating that non-anatomical factors may play a more important role in the pathogenesis of obstructive sleep apnoea in aged patients.
Grape seed procyanidins (GSPs), widely known for their beneficial health properties, fail to bring about the expected improvement in piglets’ growth performance. The effects of dietary supplementation with GSPs on nutrient utilisation may be a critical influencing factor. Hence, the purpose of this study was to investigate the effects of dietary supplementation with GSPs on nutrient utilisation and gut function in weaned piglets. One hundred and twenty crossbred piglets were allocated randomly to four treatment groups, with three replicate pens per treatment and 10 piglets per pen. Each group was given one of the four dietary treatments: the basal diet (control group) or the basal diet with the addition of 50-, 100- or 150-mg/kg GSPs. The trial lasted 28 days. Faeces were collected from d 12 to 14 and from d 26 to 28 for measuring the coefficient of total tract apparent digestibility (CTTAD) of the nutrients. Blood samples were collected on d 14 and 28 for detecting the blood biochemical parameters. Two piglets per pen were slaughtered to collect the pancreas and intestinal digesta for evaluating the digestive enzyme activity and the coefficient of ileal apparent digestibility (CIAD) of the nutrients. On d 14 and 28, supplementation with 150-mg/kg GSPs significantly decreased the CTTAD of DM and CP in piglets. On d 14, GSPs supplementation at a concentration of 150 mg/kg led to a remarkable decrease in the CIAD of CP and gross energy (GE). On d 28, GSPs supplementation at a dose of 150 mg/kg generated a marked decline in the CIAD of DM, GE, CP and ether extract. Grape seed procyanidins supplementation at concentrations of 100 or 150 mg/kg inhibited the activities of lipase and amylase. In contrast, the jejunum mucosa maltase and sucrase activities increased due to the inclusion of GSPs at a concentration of 100 mg/kg in the piglet diet. Compared with the levels of the control group, the serum glucose and total protein levels were enhanced significantly by supplementation with GSPs at 100 mg/kg and reduced dramatically at 150 mg/kg. The serum diamine oxidase activity and endotoxin levels were decreased by GSPs supplementation in piglet diets. In conclusion, higher concentrations of GSPs in weaned piglet diets attenuated nutrient digestion and inhibited digestive enzyme activity; however, suitable concentrations of GSPs could promote brush-border enzyme activity, enhance serum glucose and total protein concentrations and decrease epithelial permeability.
In 2014/2015, International Medical Corps (IMC) operated two Ebola Treatment Units (ETUs) in Liberia and three in Sierra Leone when the Ebola virus disease epidemic killed over 11,000 people across Liberia, Sierra Leone and Guinea. As Ebola cases declined in Liberia, IMC Psychosocial teams transitioned to working in communities highly affected by the epidemic. This article describes IMC's experience with developing and implementing a community-based mental health and psychosocial group intervention in a rural, severely affected Liberian town – Mawah – where 46 out of approximately 800 community members were infected, 39 of whom died. In this paper, we present how the group intervention, named ‘Social Reconnection Groups’, was developed and implemented. We then discuss intervention strengths, challenges, key lessons learnt and recommendations for how Social Reconnection Groups can be adapted for use in similar settings.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
To investigate the morphology and dimensions of the vestibular aqueduct on axial, single-oblique and double-oblique computed tomography images.
The computed tomography temporal bone scans of 112 patients were retrospectively evaluated. Midpoint and opercular measurements were performed using axial, single-oblique and double-oblique images. Morphometric analyses were also conducted. The vestibular aqueduct sizes on axial, single-oblique and double-oblique images were compared.
At the midpoint, the mean (± standard deviation) vestibular aqueduct measured 0.61 ± 0.23 mm, 0.74 ± 0.27 mm and 0.82 ± 0.38 mm on axial, single-oblique and double-oblique images, respectively; at the operculum, the vestibular aqueduct measured 0.91 ± 0.30 mm, 1.11 ± 0.45 mm and 1.66 ± 1.07 mm on the respective images. The co-efficients of variation of the vestibular aqueduct measured at the midpoint were 37.4 per cent, 36.5 per cent and 47.5 per cent on axial, single-oblique and double-oblique images, respectively; at the operculum, the measurements were 33.0 per cent, 40.5 per cent and 64.5 per cent. Regarding morphology, the vestibular aqueduct was fissured (33.5 per cent), tubular (64.3 per cent) or invisible (2.2 per cent).
The morphology and dimensions of the vestibular aqueduct were highly variable among axial, single-oblique and double-oblique images.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
The oxidative study has always been particularly topical in poultry science. However, little information about the occurrence of cellular apoptosis and autophagy through the reactive oxygen species (ROS) generation in nuclear factor-κB (NF-κB) signal pathway was reported in the liver of broilers exposed to hydrogen peroxide (H2O2). So we investigated the change of growth performance of broilers exposed to H2O2 and further explored the occurrence of apoptosis and autophagy, as well as the expression of NF-κB in these signaling pathways in the liver. A total of 320 1-day-old Arbor Acres male broiler chickens were raised on a basal diet and randomly divided into five treatments which were arranged as non-injected treatment (Control), physiological saline (0.75%) injected treatment (Saline) and H2O2 treatments (H2O2(0.74), H2O2(1.48) and H2O2(2.96)) received an intraperitoneal injection of H2O2 with 0.74, 1.48 and 2.96 mM/kg BW. The results showed that compared to those in the control and saline treatments, 2.96 mM/kg BW H2O2-treated broilers exhibited significantly higher feed/gain ratio at 22 to 42 days and 1 to 42 days, ROS formation, the contents of oxidation products, the mRNA expressions of caspases (3, 6, 8), microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I, autophagy-related gene 6, Bcl-2 associated X and protein expressions of total caspase-3 and total LC3-II, and significantly lower BW gain at 22 to 42 days and 1 to 42 days, the activities of total superoxide dismutase and glutathione peroxidase, the expression of NF-κB in the liver. Meanwhile, significantly higher feed/gain ratio at 1 to 42 days, ROS formation, the contents of protein carbonyl and malondialdehyde, the mRNA expression of caspase-3 and the protein expressions of total caspase-3 and total LC3-II, as well as significantly lower BW gain at 22 to 42 days and 1 to 42 days were observed in broilers received 1.48 mM/kg BW H2O2 treatment than those in control and saline treatments. These results indicated that oxidative stress induced by H2O2 had a negative effect on histomorphology and redox status in the liver of broilers, which was associated with a decline in growth performance of broilers. This may attribute to apoptosis and autophagy processes triggered by excessive ROS that suppress the NF-κB signaling pathway.
Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal’s response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed. Interestingly, acute cold exposure induced browning of porcine sWAT, smaller adipocytes and the upregulated expression of UCP1, PGC1α, PGC1β, C/EBPβ, Cidea, UCP3, CKMT1 and PM20D1. Conversely, chronic cold exposure impaired the browning process, reduced mitochondrial numbers and the expression of browning markers, including UCP1, PGC1α and PRDM16. The present study demonstrated that acute cold exposure (but not chronic cold exposure) induces porcine sWAT browning. Thus, browning of porcine sWAT could be a novel strategy to balance the body temperature of piglets, and thus could be protective against cold exposure.
We utilized de-identified data to evaluate increases in four outcomes during influenza outbreak periods (IOPs) including: hospitalization, intensive care unit admission, mechanical ventilation or death for adults aged 18 years or older with medically attended acute respiratory illnesses (MAARI) admitted to any of Maryland's 50 acute-care hospitals over 12 years. Weekly numbers of positive influenza tests in the Maryland area were obtained from the US Center for Disease Control and Prevention interactive website. The fewest consecutive weeks around the peak week containing at least 85% of the positive tests defined the IOP. Weekly counts of individual study outcomes were positively correlated with regional weekly counts of positive influenza tests during all the IOPs over 12 years. Also, rate ratios comparing daily occurrences of each study outcome between the IOP and non-IOP were significantly elevated. These results confirm conclusions of previous studies that influenza outbreaks are clearly associated with deaths and increased use of advanced medical resources by patients with MAARI. These data analyses suggest that increased efforts to develop more effective influenza vaccines and therapeutics should be a priority.
Large numbers of high quality graphene transistors were fabricated by chemical vapor deposition and packaged into a standard electronics assembly, enabling the readout of graphene properties on the benchtop. After chemical functionalization, these sensors demonstrate sensitivity into the pM range to inflammation (IL6) and Zika virus (ZIKV NS1) biomarkers. Signal-to-noise ratio (SNR) of graphene biosensors is over an order of magnitude greater than established diagnostic and biophysical assays, namely ELISA and BLI respectively. High precision measurements of protein kinetics captured using this technology, commercially available as the AGILE R100, are comparable to both clinical diagnostic and state-of-the-art biomolecule characterization tools. These results demonstrate that graphene-based platforms are highly attractive biological sensors for next generation diagnostics.
In individuals with latent tuberculosis (TB) infection, those living with human immunodeficiency virus (HIV) had a 20–37 times higher risk of developing active TB compared to those without HIV infection. Systematic testing and treatment of latent TB infection are priorities in HIV-infected persons. In China, the prevalence of HIV infection in men who have sex with men (MSM) has gradually increased in the past decade. However, the prevalence of TB infection has been studied sparsely in HIV-infected MSM. Hence, we conducted a pilot study in MSM living with HIV infection in Xi'an city to evaluate TB infection status by means of interferon-γ release assay (IGRA). A total of 182 HIV-infected MSM were included in this study, the prevalence of IGRA positivity was observed to be 8·79% (16/182). IGRA quantitative results were not statistically influenced by the CD4 cell counts of the study participants. However, IGRA positivity was found to be lower than our previously reported data from the general population. This suggests that immunological deficiency might decrease the sensitivity of IGRA and thus increase the number of false negatives. Our primary results, suggesting systematic testing and treatment of latent TB infection together with active case-finding, were equally important for TB control in persons living with HIV infection.
Foxtail millet (Setaria italica (L.) P. Beauv.) is a naturally stress-tolerant plant, a major reserve crop and a model for panicoid grasses. The recent completion of the S. italica genome facilitates identification and characterization of WRKY transcription factor family proteins that are important regulators of major plant processes, including growth, development and stress response. The present study identified 103 WRKY transcription factor-encoding genes in the S. italica genome. The genes were named SiWRKY1–SiWRKY103 according to their order on the chromosomes. A comprehensive expression analysis of SiWRKY genes among four different tissues was performed using publicly available RNA sequencing data. Eighty-four SiWRKY genes were more highly expressed in root tissue than in other tissues and nine genes were only expressed in roots. Additionally, real-time quantitative polymerase chain reaction was performed to comprehensively analyse the expression of all SiWRKY genes in response to dehydration. Results indicated that most SiWRKY genes (over 0.8) were up-regulated by drought stress. In conclusion, genome-wide identification and expression profiling of SiWRKY genes provided a set of candidates for cloning and functional analyses in plants’ response to drought stress.
This study aimed to comprehensively evaluate factors that influence the likelihood of syphilis infection from risk-taking behaviours and medical conditions. A retrospective case-control study was conducted by enrolling 664 syphilis inpatients (excluding 11 congenital syphilis patients) and 800 sex- and age-matched controls. Medical histories, clinical data and patient interview data were collected and subjected to logistic regression analyses. The prevalence of syphilis in the study population was 3·9% (675/17 304). By univariate analysis, syphilis infection was associated with migration between cities, marital status, smoking, reproductive history, hypertension, elevated blood urea nitrogen (BUN) and infection with hepatitis B virus (HBV) (P < 0·05). A high rate of syphilis-HBV co-infection was observed in HIV-negative patients and further research revealed an association between syphilis and specific HBV serological reactivity. Syphilis was also associated with the frequency, duration and status of tobacco use. Multivariate analysis indicated that syphilis infection was independently associated with migration between cities [adjusted odds ratio (aOR) 1·368, 95% confidence interval (CI) 1·048–1·785], current smoking (aOR 1·607, 95% CI 1·177–2·195), elevated BUN (aOR 1·782, 95% CI 1·188–2·673) and some serological patterns of HBV infection. To prevent the spread of infectious diseases, inpatients and blood donors should be tested for HIV, syphilis, HBV and HCV simultaneously.