Early detection of nasopharyngeal carcinoma: performance of a short contrast-free screening magnetic resonance imaging.

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.

Eagle jugular syndrome presenting with intracranial hypertension - Diagnosis and illustration of pathophysiology by multi-modality imaging.

Eagle jugular syndrome is an uncommon condition caused by compression of an elongated styloid process onto the internal jugular vein. Its presentation is non-specific but may represent in severe clinical consequences including venous thrombosis and intracranial haemorrhage. Thorough understanding of local anatomy is important in understanding the pathogenesis and establishing the diagnosis. Our case reported here illustrates the use of multimodality imaging, including dynamic Computer tomography manoeuvre, in identifying the site of obstruction and guidance towards successful surgical treatment.

Drosophila tweety facilitates autophagy to regulate mitochondrial homeostasis and bioenergetics in Glia.

Mitochondria support the energetic demands of the cells. Autophagic turnover of mitochondria serves as a critical pathway for mitochondrial homeostasis. It is unclear how bioenergetics and autophagy are functionally connected. Here, we identify an endolysosomal membrane protein that facilitates autophagy to regulate ATP production in glia. We determined that Drosophila tweety (tty) is highly expressed in glia and localized to endolysosomes. Diminished fusion between autophagosomes and endolysosomes in tty-deficient glia was rescued by expressing the human Tweety Homolog 1 (TTYH1). Loss of tty in glia attenuated mitochondrial turnover, elevated mitochondrial oxidative stress, and impaired locomotor functions. The cellular and organismal defects were partially reversed by antioxidant treatment. We performed live-cell imaging of genetically encoded metabolite sensors to determine the impact of tty and autophagy deficiencies on glial bioenergetics. We found that tty-deficient glia exhibited reduced mitochondrial pyruvate consumption accompanied by a shift toward glycolysis for ATP production. Likewise, genetic inhibition of autophagy in glia resulted in a similar glycolytic shift in bioenergetics. Furthermore, the survival of mutant flies became more sensitive to starvation, underlining the significance of tty in the crosstalk between autophagy and bioenergetics. Together, our findings uncover the role for tty in mitochondrial homeostasis via facilitating autophagy, which determines bioenergetic balance in glia.

WRAPPER study: Real-world effectiveness and tolerability of adjunctive perampanel for people with drug-resistant epilepsy in Hong Kong.

OBJECTIVE: The Prince of Wales Hospital (PWH) Real-world Analysis of People with Drug-Resistant Epilepsy (DRE) on PERampanel (WRAPPER) study assessed effectiveness and tolerability of adjunctive perampanel in people with DRE attending PWH. METHODS: This was a prospective single-center real-world observational study involving 70 people with DRE between July 2016 and June 2021. A post hoc analysis after the initial study period of 16 weeks assessed outcomes for an extended period up to 52 weeks. RESULTS: After 16 weeks, median dose of perampanel was 2 mg (IQR 24 mg). 50% responder rates were 40.0%, 41.5%, and 48.7% at 16, 26, and 52 weeks. Seizure freedom was 12.9%, 20.7%, and 25.6% at 16, 26, and 52 weeks. Monthly seizure frequency reduced from 3.0 (IQR 3.0-6.6) at baseline to 2.0 (IQR 2.0-6.0, p = 0.005) at 16 weeks; 2.0 (IQR 2.0-5.0, p = 0.01) at 26 weeks; and 2.0 (IQR 0.0-4.0, p = 0.018) at 52 weeks. Older age predicted 50% responders (OR 1.08, 95% CI 1.01-1.14, p = 0.048). At 16 weeks, 51.4% (36/70) had treatment-emergent adverse effects (TEAEs). Most common was seizure exacerbation at 35.7% (25/70) followed by fatigue at 15.7% (11/70). NPI-12 and ZBI scores indicated no increase in neuropsychiatric symptoms on perampanel. SIGNIFICANCE: Low-dose 2-4 mg adjunctive perampanel for people with DRE conferred appreciable improvements in seizure reduction without significant neuropsychiatric adverse effects in the real-world setting at a tertiary center in Hong Kong and had better antiseizure effect with advancing age. PLAIN LANGUAGE SUMMARY: This real-world study from Hong Kong found low-dose perampanel was effective and tolerable for people with drug-resistant epilepsy. Furthermore, perampanel was also potentially more effective with advancing age.

Comparison of the 12-month impact of COVID-19 and SARS on physiological capacity and health-related quality of life.

BACKGROUND: Little is known about the differences in medium to long-term recovery on spirometry, 6-minute walking distance (6MWD) and health-related quality of life (HRQoL) between COVID-19 and SARS. METHODS: We performed a 12-month prospective study on COVID-19 survivors. The changes in dynamic lung volumes at spirometry (%predicted FEV1, %predicted FVC), 6MWD and HRQoL at 1-3, 6 to 12 months were compared against a historical cohort of SARS survivors using the same study protocol. The residual radiological changes in HRCT in COVID-19 survivors were correlated with their functional capacity. RESULTS: 108 COVID-19 survivors of various disease severity (asymptomatic 2.9%, mild 33.3%, moderate 47.2%, severe 8.3%, critical 8.3%) were recruited. When compared with 97 SARS survivors, 108 COVID-19 survivors were older (48.1 ± 16.4 vs. 36.1 ± 9.5 years, p < 0.001) and required less additional support during hospitalization; with lower dynamic lung volumes, shorter 6MWD and better physical component score. Both groups of survivors had comparable changes in these parameters at subsequent follow-ups. Both COVID-19 and SARS survivors had similar mental component score (MCS) at 6 and 12 months. COVID-19 survivors initially experienced less (between-group difference, -3.1, 95% confidence interval [CI] -5.5 to -0.7, p = 0.012) and then more improvement (between-group difference 2.9, 95%, CI 0.8 to 5.1, p = 0.007) than SARS survivors in the MCS at 1-3 to 6 months and 6 to 12 months respectively. Forty (44.0%) out of 91 COVID-19 survivors had residual abnormalities on HRCT at 12 months, with a negative correlation between the severity scores of parenchymal changes and 6MWD (r=-0.239, p < 0.05). CONCLUSIONS: COVID-19 survivors demonstrated a similar recovery speed in dynamic lung volumes and exercise capacity, but different paces of psychological recovery as SARS survivors in the convalescent phase. The severity of parenchymal changes in HRCT is negatively correlated with the 6MWD of COVID-19 survivors. TRIAL REGISTRATION: This prospective study was registered at ClinicalTrials.gov on 2 November 2020 (Identifier: NCT04611243).

Human Prune Regulates the Metabolism of Mammalian Inorganic Polyphosphate and Bioenergetics.

Inorganic polyphosphate (polyP) is an evolutionarily conserved and ubiquitous polymer that is present in all studied organisms. PolyP consists of orthophosphates (Pi) linked together by phosphoanhydride bonds. The metabolism of polyP still remains poorly understood in higher eukaryotes. Currently, only F0F1-ATP synthase, Nudt3, and Prune have been proposed to be involved in this metabolism, although their exact roles and regulation in the context of polyP biology have not been fully elucidated. In the case of Prune, in vitro studies have shown that it exhibits exopolyphosphatase activity on very short-chain polyP (up to four units of Pi), in addition to its known cAMP phosphodiesterase (PDE) activity. Here, we expand upon studies regarding the effects of human Prune (h-Prune) on polyP metabolism. Our data show that recombinant h-Prune is unable to hydrolyze short (13-33 Pi) and medium (45-160 Pi) chains of polyP, which are the most common chain lengths of the polymer in mammalian cells. Moreover, we found that the knockdown of h-Prune (h-Prune KD) results in significantly decreased levels of polyP in HEK293 cells. Likewise, a reduction in the levels of polyP is also observed in Drosophila melanogaster loss-of-function mutants of the h-Prune ortholog. Furthermore, while the activity of ATP synthase, and the levels of ATP, are decreased in h-Prune KD HEK293 cells, the expression of ATP5A, which is a main component of the catalytic subunit of ATP synthase, is upregulated in the same cells, likely as a compensatory mechanism. Our results also show that the effects of h-Prune on mitochondrial bioenergetics are not a result of a loss of mitochondrial membrane potential or of significant changes in mitochondrial biomass. Overall, our work corroborates the role of polyP in mitochondrial bioenergetics. It also demonstrates a conserved effect of h-Prune on the metabolism of short- and medium-chain polyP (which are the predominant chain lengths found in mammalian cells). The effects of Prune in polyP are most likely exerted via the regulation of the activity of ATP synthase. Our findings pave the way for modifying the levels of polyP in mammalian cells, which could have pharmacological implications in many diseases where dysregulated bioenergetics has been demonstrated.

Noninvasive Glucose Sensing In Vivo.

Blood glucose monitoring is an essential aspect of disease management for individuals with diabetes. Unfortunately, traditional methods require collecting a blood sample and thus are invasive and inconvenient. Recent developments in minimally invasive continuous glucose monitors have provided a more convenient alternative for people with diabetes to track their glucose levels 24/7. Despite this progress, many challenges remain to establish a noninvasive monitoring technique that works accurately and reliably in the wild. This review encompasses the current advancements in noninvasive glucose sensing technology in vivo, delves into the common challenges faced by these systems, and offers an insightful outlook on existing and future solutions.

Retinal Vein Occlusion after COVID-19 Vaccination-A Review.

Background Retinal vein occlusion (RVO) occurring after COVID-19 vaccination has been reported worldwide. Such a sight-threatening condition occurring after COVID-19 vaccination is a menace to ophthalmic health. This article reviews current evidence related to post-COVID-19 vaccination RVO. Method A total of 29 relevant articles identified on PubMed in January 2023 were selected for review. Observation All cases presented to ophthalmologists with visual loss shortly after COVID-19 vaccination. Mean and median age were both 58. No sex predominance was observed. RVO was diagnosed from findings on dilated fundal examination and ophthalmic imaging. AstraZeneca and BNT vaccines accounted for most cases. Vascular risk factors, e.g., diabetes mellitus and hypertension, were common. Most laboratory tests requested came back unremarkable. Most patients responded well to standard treatment, except those with ophthalmic comorbidities. Visual prognosis was excellent on short-term follow-up. Discussion The causality between RVO and COVID-19 vaccination is undeterminable because of the nature of articles, heterogenous reporting styles, contradicting laboratory findings and co-existing vascular risk factors. Vaccine-induced immune thrombotic thrombocytopenia, retinal vasculitis and homocysteinaemia were proposed to explain post-vaccination RVO. Large-scale studies have demonstrated that the incidence of RVO following COVID vaccination is very low. Nevertheless, the effects of boosters on retinal vasculature and ophthalmic health are still unclear. Conclusions The benefits of COVID-19 vaccination are believed to outweigh its ophthalmic risks. To ensure safe vaccination, the prior optimisation of comorbidities and post-vaccination monitoring are important. COVID-19 vaccines (including boosters) should be offered with reasonable confidence. Further studies are warranted to elucidate the ophthalmic impact of vaccines.

An efficient approach to estimate the risk of coronary artery disease for people living with HIV using machine-learning-based retinal image analysis.

BACKGROUND: People living with HIV (PLWH) have increased risks of non-communicable diseases, especially cardiovascular diseases. Current HIV clinical management guidelines recommend regular cardiovascular risk screening, but the risk equation models are not specific for PLWH. Better tools are needed to assess cardiovascular risk among PLWH accurately. METHODS: We performed a prospective study to determine the performance of automatic retinal image analysis in assessing coronary artery disease (CAD) in PLWH. We enrolled PLWH with ≥1 cardiovascular risk factor. All participants had computerized tomography (CT) coronary angiogram and digital fundus photographs. The primary outcome was coronary atherosclerosis; secondary outcomes included obstructive CAD. In addition, we compared the performances of three models (traditional cardiovascular risk factors alone; retinal characteristics alone; and both traditional and retinal characteristics) by comparing the area under the curve (AUC) of receiver operating characteristic curves. RESULTS: Among the 115 participants included in the analyses, with a mean age of 54 years, 89% were male, 95% had undetectable HIV RNA, 45% had hypertension, 40% had diabetes, 45% had dyslipidemia, and 55% had obesity, 71 (61.7%) had coronary atherosclerosis, and 23 (20.0%) had obstructive CAD. The machine-learning models, including retinal characteristics with and without traditional cardiovascular risk factors, had AUC of 0.987 and 0.979, respectively and had significantly better performance than the model including traditional cardiovascular risk factors alone (AUC 0.746) in assessing coronary artery disease atherosclerosis. The sensitivity and specificity for risk of coronary atherosclerosis in the combined model were 93.0% and 93.2%, respectively. For the assessment of obstructive CAD, models using retinal characteristics alone (AUC 0.986) or in combination with traditional risk factors (AUC 0.991) performed significantly better than traditional risk factors alone (AUC 0.777). The sensitivity and specificity for risk of obstructive CAD in the combined model were 95.7% and 97.8%, respectively. CONCLUSION: In this cohort of Asian PLWH at risk of cardiovascular diseases, retinal characteristics, either alone or combined with traditional risk factors, had superior performance in assessing coronary atherosclerosis and obstructive CAD. SUMMARY: People living with HIV in an Asian cohort with risk factors for cardiovascular disease had a high prevalence of coronary artery disease (CAD). A machine-learning-based retinal image analysis could increase the accuracy in assessing the risk of coronary atherosclerosis and obstructive CAD.

Multi-center validation of an artificial intelligence system for detection of COVID-19 on chest radiographs in symptomatic patients.

OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR. METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases. RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong's test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar's test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001). CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR. KEY POINTS: • An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. • Differences in AI model performance were seen across region, disease severity, gender, and age. • Prevalence simulations on the international test set demonstrate the model's NPV is greater than 98.5% at any prevalence below 4.5%.

Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in a Drosophila Model of ALS.

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapbP58S ) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapbP58S -induced changes in NMJ morphology by either a loss of endoplasmic reticulum (ER) Ca2+ release channels or the inhibition Ca2+/calmodulin (CaM)-activated kinase II (CaMKII). These data suggest that decreased stability of presynaptic microtubules at vapbP58S NMJs results from hyperactivation of CaMKII because of elevated cytosolic [Ca2+]. We attribute the Ca2+ dyshomeostasis to delayed extrusion of cytosolic Ca2+ Suggesting that this defect in Ca2+ extrusion arose from an insufficient response to the bioenergetic demand of neural activity, depolarization-induced mitochondrial ATP production was diminished in vapbP58S neurons. These findings point to bioenergetic dysfunction as a potential cause for the synaptic defects in vapbP58S -expressing motor neurons.SIGNIFICANCE STATEMENT Whether the synchrony between the rates of ATP production and demand is lost in degenerating neurons remains poorly understood. We report that expression of a gene equivalent to an amyotrophic lateral sclerosis (ALS)-causing variant of vesicle-associated membrane protein B (VAPB) in fly neurons decouples mitochondrial ATP production from neuronal activity. Consequently, levels of ATP in mutant neurons are unable to keep up with the bioenergetic burden of neuronal activity. Reduced rate of Ca2+ extrusion, which could result from insufficient energy to power Ca2+ ATPases, results in the accumulation of residual Ca2+ in mutant neurons and leads to alterations in synaptic vesicle (SV) release and synapse development. These findings suggest that synaptic defects in a model of ALS arise from the loss of activity-induced ATP production.

Knowledge Mapping of Enterprise Network Research in China: A Visual Analysis Using CiteSpace.

Enterprise Network (EN) has increasingly gained popularity in academia. Over the past few decades, a substantial amount of EN studies have been published in China. Drawing upon a sample of 603 papers retrieved from the Chinese Social Sciences Citation Index database (CSSCI) between 1998 and 2020, this study aims to delve into the status quo, knowledge base, research focus, and evolutionary trends of EN research in China. A multifaceted bibliometric analysis was performed using CiteSpace. The findings mainly indicate that the research on EN in China has a clear development context, and the research content gradually changes from macro to micro. In addition to foreign Social Network theories, the research results of domestic scholars have become the basic knowledge in this field. The research includes these topics: the conceptualization of EN, EN as indicators of enterprise development, EN's impact on start-ups, mechanisms of EN's effect and governance of EN. The potential direction for future research has been identified as the integration between EN and other forms of networks, and the structure of EN.

Evaluating seasonal variations of fecal coliform colonization in Magallana hongkongensis and Crassostrea rhizophorae: A preliminary study of oyster quality grown in Hong Kong aquacultural farms.

The objective of this research is to investigate the spatial and temporal patterns of bacteriological quality in raw oysters sampled from different aquacultural farms located in Aberdeen Typhoon Shelter, Carp Gates, Lau Fau Shan, Ma Wan, and Mui Wo in Hong Kong. Magallana hongkongensis and Crassostrea rhizophorae were collected and analyzed for fecal coliforms. Throughout the 13-month monitoring period, all samples had generally high bacterial loads, ranging from 1.4 × 107 cfu/g to 8.9 × 107 cfu/g and exceeded the guideline suggested by the HKSAR government (i.e. 700 MPN/100 g). Besides, a linear regression analysis showed that the amount of fecal coliforms in raw oysters had strong correlations (p < 0.05) to the monthly rainfall records throughout the monitoring period. Such findings illustrate the high loading of pathogenic microorganisms in the tissue of oysters which represent a potential threat of people contracting foodborne diseases.

Transmembrane H+ fluxes and the regulation of neural induction in Xenopus laevis.

It has previously been reported that in ex vivo planar explants prepared from Xenopus laevis embryos, the intracellular pH (pHi) increases in cells of the dorsal ectoderm from stage 10.5 to 11.5 (i.e. 11-12.5 hpf). It was proposed that such increases (potentially due to H+ being extruded, sequestered, or buffered in some manner), play a role in regulating neural induction. Here, we used an extracellular ion-selective electrode to non-invasively measure H+ fluxes at eight locations around the equatorial circumference of intact X. laevis embryos between stages 9-12 (˜7-13.25 hpf). We showed that at stages 9-11, there was a small H+ efflux recorded from all the measuring positions. At stage 12 there was a small, but significant, increase in the efflux of H+ from most locations, but the efflux from the dorsal side of the embryo was significantly greater than from the other positions. Embryos were also treated from stages 9-12 with bafilomycin A1, to block the activity of the ATP-driven H+ pump. By stage 22 (24 hpf), these embryos displayed retarded development, arresting before the end of gastrulation and therefore did not display the usual anterior and neural structures, which were observed in the solvent-control embryos. In addition, expression of the early neural gene, Zic3, was absent in treated embryos compared with the solvent controls. Together, our new in vivo data corroborated and extended the earlier explant-derived report describing changes in pHi that were suggested to play a role during neural induction in X. laevis embryos.

Teaching psychiatry to medical students in the time of COVID-19: experiences from UK medical schools.

AIMS AND METHOD: Education leads for undergraduate psychiatry in UK medical schools completed questionnaires on adaptations made to undergraduate psychiatry education, their impact and what lessons could be learnt for the future. RESULTS: Respondents from 24 medical schools across the UK reported a major shift to online teaching delivery, with reduced workplace learning and increased use of teleconferencing, online tasks and self-directed learning. Changes were implemented with some faculty training provided, but little additional funding or resources from medical schools or National Health Service trusts. A variety of challenges and opportunities were reported. CLINICAL IMPLICATIONS: Despite the extraordinary efforts of education leads to maintain undergraduate psychiatry education, the pandemic may affect the development of students' professional competencies and recruitment into psychiatry. Individual clinicians, trusts and medical and foundation schools have much to offer, and need to work with students to replace what has been lost during the pandemic.

Improving the accuracy of chloride measurements through participation in regular external quality assessment programme.

BACKGROUND: A chloride test is an integral part of a basic metabolic panel that is essential for the assessment of a patient's acid-base and electrolyte status. While many methods are available commercially for the routine measurement of chloride, there is a need to address the accuracy and variability among the measurement results, especially with the prevalence of patients seeking treatment across different healthcare providers for alternative opinions. METHOD: A method based on sector field inductively coupled plasma isotope dilution mass spectrometry (SF-ICP-IDMS) was developed for the measurement of chloride in human serum. The SF-ICP-IDMS method was then used to assign the target values in the Health Sciences Authority (HSA) External Quality Assessment (EQA) Programme to evaluate the results of chloride test from participating clinical laboratories. RESULTS: The accuracy of the measurements was evaluated by comparing the results with the certified values of Electrolytes in Frozen Human Serum Certified Reference Materials (SRM 956c and SRM 956d) from the National Institute of Standards and Technology (NIST) at different chloride concentration levels. Over a five-year period from 2014-2018, the number of clinical laboratories which participated in the EQA Programme increased from 23 to 33. Comparison of robust means from the laboratories' results with our assigned target values revealed a reduction in relative deviation over time. The relationship between the deviation of each brand of clinical analysers and the chloride levels was established, where a larger deviation was uncovered at low chloride concentration. The SF-ICP-IDMS method was further demonstrated to be comparable with methods used by other metrology institutes in an international comparison organised by HSA under the auspice of the Consultative Committee for Amount of Substance - Metrology in Chemistry and Biology (CCQM). CONCLUSION: The use of metrologically traceable assigned target values enabled the study of method biasness from a small pool of dataset in each of the four brands of clinical analysers in HSA EQA Programme. This work underscores the need to improve the accuracy of chloride measurements by regular participation in an accuracy-based EQA Programme.

Pten Regulates Cardiomyocyte Differentiation by Modulating Non-CG Methylation via Dnmt3.

The regulation of cardiomyocyte differentiation is a fundamental aspect of cardiac development and regenerative medicine. PTEN plays important roles during embryonic development. However, its role in cardiomyocyte differentiation remains unknown. In this study, a low-cost protocol for cardiomyocyte differentiation from mouse embryonic stem cells (ESCs) is presented and it is shown that Pten deletion potently suppresses cardiomyocyte differentiation. Transcriptome analysis shows that the expression of a series of cardiomyocyte marker genes is downregulated in Pten-/- cardiomyocytes. Pten ablation induces Dnmt3b expression via the AKT/FoxO3a pathway and regulates the expression of a series of imprinted genes, including Igf2. Double knockout of Dnmt3l and Dnmt3b rescues the deficiency of cardiomyocyte differentiation of Pten-/- ESCs. The DNA methylomes from wild-type and Pten-/- embryoid bodies and cardiomyocytes are analyzed by whole-genome bisulfite sequencing. Pten deletion significantly promotes the non-CG (CHG and CHH) methylation levels of genomic DNA during cardiomyocyte differentiation, and the non-CG methylation levels of cardiomyocyte genes and Igf2 are increased in Pten-/- cardiomyocytes. Igf2 or Igf1r deletion also suppresses cardiomyocyte differentiation through the MAPK/ERK signaling pathway, and IGF2 supplementation partially rescues the cardiomyocyte differentiation. Finally, Pten conditional knockout mice are generated and the role of PTEN in cardiomyocyte differentiation is verified in vivo.

Candidate region aware nested named entity recognition.

Named entity recognition (NER) is crucial in various natural language processing (NLP) tasks. However, the nested entities which are common in practical corpus are often ignored in most of current NER models. To extract the nested entities, two categories of models (i.e., feature-based and neural network-based approaches) are proposed. However, the feature-based models suffer from the complicated feature engineering and often heavily rely on the external resources. Discarding the heavy feature engineering, recent neural network-based methods which treat the nested NER as a classification task are designed but still suffer from the heavy class imbalance issue and the high computational cost. To solve these problems, we propose a neural multi-task model with two modules: Binary Sequence Labeling and Candidate Region Classification to extract the nested entities. Extensive experiments are conducted on the public datasets. Comparing with recent neural network-based approaches, our proposed model achieves the better performance and obtains the higher efficiency.

An assessment of heavy metal contamination in the marine soil/sediment of Coles Bay Area, Svalbard, and Greater Bay Area, China: a baseline survey from a rapidly developing bay.

The objective of this research is to investigate the pollution levels of tin (Sn), arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), mercury (Hg), and zinc (Zn) of soil/sediment taken in Coles Bay Area (CBA), Svalbard, and Great Bay Area (GBA), China, in an attempt to evaluate the pollution potential related to recent development in the areas. A total of 150 soil/sediment samples were collected in each location. Heavy metal concentrations were detectable levels at all sites and the values of Cd of all soil/sediment samples were higher than Dutch Target and Intervention Values. Heavy metal concentration in soil/sediment was further analyzed by principal component analysis (PCA). It was revealed that three components were found in two studying sites and contributed 60.2% and 75.9% of variations to reflect soil/sediment quality in CBA and GBA, respectively. Based on the results of KMO (0.52) and Bartlett's test (p < 0.000), there are 32.1%, 15.6%, and 11.1% and 39.45%, 19.01%, and 17.52% of the variance in the first, second, and third component explained that the metal concentration of Pb, Cd, and Sn was highly correlated with the soil/sediment quality in CBA and GBA, respectively. Among these three heavy metals, Cd concentration was the common dominant factor to affect soil/sediment quality in these two study sites. It is recommended that investigation of the sources of pollution (either point or non-point source) during CBA or GBA development and management together with consideration of abiotic (soil)-biotic (organisms) interactions should be taken into account when choosing suitable remediation strategies in the future.