Deletion of the TMEM30A gene enables leukemic cell evasion of NK cell cytotoxicity.

Natural killer (NK) cell immunotherapy has gained attention as a promising strategy for treatment of various malignancies. In this study, we used a genome-wide CRISPR screen to identify genes that provide protection or susceptibility to NK cell cytotoxicity. The screen confirmed the role of several genes in NK cell regulation, such as genes involved in interferon-γ signaling and antigen presentation, as well as genes encoding the NK cell receptor ligands B7-H6 and CD58. Notably, the gene TMEM30A, encoding CDC50A-beta-subunit of the flippase shuttling phospholipids in the plasma membrane, emerged as crucial for NK cell killing. Accordingly, a broad range of TMEM30A knock-out (KO) leukemia and lymphoma cells displayed increased surface levels of phosphatidylserine (PtdSer). TMEM30A KO cells triggered less NK cell degranulation, cytokine production and displayed lower susceptibility to NK cell cytotoxicity. Blockade of PtdSer or the inhibitory receptor TIM-3, restored the NK cell ability to eliminate TMEM30A-mutated cells. The key role of the TIM-3 - PtdSer interaction for NK cell regulation was further substantiated by disruption of the receptor gene in primary NK cells, which significantly reduced the impact of elevated PtdSer in TMEM30A KO leukemic cells. Our study underscores the potential significance of agents targeting the interaction between PtdSer and TIM-3 in the realm of cancer immunotherapy.

Landscape of Epstein-Barr virus gene expression and perturbations in cancer.

Epstein-Barr virus (EBV) is the causative agent for multiple neoplastic diseases of epithelial and lymphocytic origin1-3. The heterogeneity of the viral elements expressed and the mechanisms by which these coding and non-coding genes maintain cancer cell properties in vivo remain elusive4,5. Here we conducted a multi-modal transcriptomic analysis of EBV-associated neoplasms and identified that the ubiquitously expressed RPMS1 non-coding RNAs support cancer cell properties by disruption of the interferon response. Our map of EBV expression shows a variable, but pervasive expression of BNLF2 discerned from the overlapping LMP1 RNA in bulk sequencing data. Using long-read single-molecule sequencing, we identified three new viral elements within the RPMS1 gene. Furthermore, single-cell sequencing datasets allowed for the separation of cancer cells and healthy cells from the same tissue biopsy and the characterization of a microenvironment containing interferon gamma excreted by EBV-stimulated T-lymphocytes. In comparison with healthy epithelium, EBV-transformed cancer cells exhibited increased proliferation and inhibited immune response induced by the RPMS1-encoded microRNAs. Our atlas of EBV expression shows that the EBV-transformed cancer cells express high levels of non-coding RNAs originating from RPMS1 and that the oncogenic properties are maintained by RPMS1 microRNAs. Through bioinformatic disentanglement of single cells from cancer tissues we identified a positive feedback loop where EBV-activated immune cells stimulate cancer cells to proliferate, which in turn undergo viral reactivation and trigger an immune response.

Comparison of assistance preferences of older adults with different functional dependence levels on domestic tasks performed by robots.

BACKGROUND: Robots have the potential to assist older adults in their home-based daily living tasks. Previous studies indicated that older adults generally accept robot assistance. However, the preferences of older adults with different functional dependence levels are lacking. These older adults encounter varying levels of difficulty in daily living and may have distinct preferences for robot assistance. This study aimed to describe and compare the preferences for robot assistance on domestic tasks in older adults with different functional dependence levels. METHODS: This cross-sectional descriptive study recruited a convenience sample of 385 older adults in Hong Kong. They were categorized as independent, partially dependent, and dependent using the Katz Index of Independence in Activities of Daily Living. Their preferences for robot assistance on a list of 48 domestic tasks under six categories were assessed through the Assistance Preference Checklist. Differences in preferences between the three groups were compared using one-way ANOVA test. RESULTS: Findings revealed the differences and similarities in preferences between participants with different dependence levels. In most domestic tasks under the personal care category, dependent and partially dependent older adults reported a significantly lower preferences for human assistance or a higher preferences for robot assistance (p < 0.001), compared with the independent ones. The effect size varied from medium to large (eta squared = 0.07 to 0.52). However, participants, regardless of functional dependence levels, preferred human to assist in some domestic tasks under the health and leisure activities category and preferred robot to assist in most of the domestic tasks under the chores, information management, and manipulating objects category. CONCLUSIONS: Older adults with different levels of functional dependence exhibit different preferences for robotic assistance. To effectively use robots and assist older adults as they age, the specific preferences of older adults must be considered before designing and introducing robots in domestic care.

Improving health literacy of antibiotic use in people with cystic fibrosis (CF)-comparison of the readability of patient information leaflets (PILs) from the EU, USA and UK of 23 CF-related antibiotics used in the treatment of CF respiratory infections.

Background: Antibiotic adherence is poor amongst people with cystic fibrosis (CF). Low-quality patient information leaflets (PILs), which accompany prescription antibiotics, with poor readability may contribute to poor antibiotic adherence, with the potential for antimicrobial resistance (AMR) development. The aim of this study was to examine the readability of antibiotic PILs used to treat CF lung infections. Methods: CF-related antibiotics (n = 23; seven classes: aminoglycosides, ß-lactams, fluoroquinolones, macrolides/lincosamides, oxazolidinones, tetracyclines, trimethoprim/sulfamethoxazole) were investigated. Readability of PILs (n = 141; 23 antibiotics) from the EU (n = 40), USA (n = 42) and UK (n = 59) was calculated. Results: Mean [± standard error of mean (SEM)] values for the Flesch Reading Ease (FRE) for EU, USA and UK were 50.0 ±â€Š1.1, 56.2 ±â€Š1.3 and 51.7 ±â€Š1.1, respectively (FRE target ≥60). Mean (± SEM) values for the Flesch Kinkaid Grade Level (FKGL) for the EU, USA and UK were 9.0 ±â€Š0.2, 7.5 ±â€Š0.2 and 9.6 ±â€Š0.2, respectively (FKGL target ≤8). US PILs were significantly shorter (P < 0.0001) in words (mean ±â€ŠSEM = 1365 ±â€Š52), than either UK or EU PILs, with fewer sentences (P < 0.0001), fewer words per sentence (P < 0.0001) and fewer syllables per word. The mean ( ±â€ŠSEM) reading time of UK PILs (n = 59) was 12.7 ±â€Š0.55 mins . Conclusions: Readability of antibiotic PILs is poor. Improving PIL readability may lead to improved health literacy, which may translate to increased antibiotic adherence and AMR avoidance. Authors preparing written materials for the lay/patient CF community are encouraged to employ readability calculators, so that final materials are within recommended readability reference parameters, to support the health (antibiotic) literacy of their readers.

NKG2A gene variant predicts outcome of immunotherapy in AML and modulates the repertoire and function of NK cells.

BACKGROUND: The natural killer (NK) complex (NKC) harbors multiple genes such as KLRC1 (encoding NKG2A) and KLRK1 (encoding NKG2D) that are central to regulation of NK cell function. We aimed at determining to what extent NKC haplotypes impact on NK cell repertoire and function, and whether such gene variants impact on outcome of IL-2-based immunotherapy in acute myeloid leukemia (AML). METHODS: Genotype status of NKG2D rs1049174 and NKG2A rs1983526 was determined using the TaqMan-Allelic discrimination approach. To dissect the impact of single nucloetide polymorphim (SNP) on NK cell function, we engineered the K562 cell line with CRISPR to be killed in a highly NKG2D-dependent fashion. NK cells were assayed for degranulation, intracellular cytokine production and cytotoxicity using flow cytometry. RESULTS: In AML patients receiving immunotherapy, the NKG2A gene variant, rs1983526, was associated with superior leukemia-free survival and overall survival. We observed that superior NK degranulation from individuals with the high-cytotoxicity NKG2D variant was explained by presence of a larger, highly responsive NKG2A+ subset. Notably, NK cells from donors homozygous for a favorable allele encoding NKG2A mounted stronger cytokine responses when challenged with leukemic cells, and NK cells from AML patients with this genotype displayed higher accumulation of granzyme B during histamine dihydrochloride/IL-2 immunotherapy. Additionally, among AML patients, the NKG2A SNP defined a subset of patients with HLA-B-21 TT with a strikingly favorable outcome. CONCLUSIONS: The study results imply that a dimorphism in the NKG2A gene is associated with enhanced NK cell effector function and improved outcome of IL-2-based immunotherapy in AML.

Improving health literacy of antifungal use-Comparison of the readability of antifungal medicines information from Australia, EU, UK, and US of 16 antifungal agents across 5 classes (allylamines, azoles, echinocandins, polyenes, and others).

Adherence to antifungals is poor in high endemic regions where antifungal resistance is high. Poor readability of prescription/over-the-counter (OTC) antifungals may contribute to poor adherence, due to the patient not fully understanding the purpose, importance, and dosage of their antifungal medicine. As there are no reports on the readability of antifungals, this study examined the readability of patient-facing antifungal information. Antifungals (n = 16; five classes [allylamines, azoles, echinocandins, polyenes, and others-flucytosine and griseofulvin]) were selected. Readability of four sources of information, (i) summary of product characteristics, (ii) patient information leaflets (PILs), (iii) OTC patient information, and (iv) patient web-based information, was calculated using Readable software, to obtain readability scores [(i) Flesch Reading Ease [FRE], (ii) Flesch-Kinkaid Grade Level [FKGL], (iii) Gunning Fog Index, and (iv) Simple Measure of Gobbledygook (SMOG) Index) and text metrics [word count, sentence count, words/sentence, and syllables/word]. PILs, web-based resources, and OTC patient information had good readability (FRE mean ± sd = 52.8 ± 6.7, 58.6 ± 6.9, and 57.3 ± 7.4, respectively), just falling short of the ≥ 60 target. For FKGL (target ≤ 8.0), PILs, web-based resources, and OTC patient information also had good readability (mean ± sd = 8.5 ± 1.0, 7.2 ± 0.86, and 7.8 ± 0.1, respectively). Improved readability scores observed correlate with reduced words, words/sentence and syllables/word. Improving readability may lead to improved patient health literacy. Healthcare professionals, academics, and publishers preparing written materials regarding antifungals for the lay/patient community are encouraged to employ readability calculators to check the readability of their work, so that the final material is within recommended readability reference parameters, to support the health literacy of their patients/readers.

Yeast and mould infections can be difficult-to-treat, due to resistance. Our study shows that patient information on antifungals is fairly easy-to-read. Such information helps the patient know how best to take the medicine and help avoid resistance. Authors should always try to write clearly for patients.

Antimicrobial Resistance (AMR).

Antimicrobial resistance (AMR) has now emerged as a chronic public health problem globally, with the forecast of 10 million deaths per year globally by 2050. AMR occurs when viruses, bacteria, fungi and parasites do not respond to antimicrobial treatments in humans and animals, thus allowing the survival of the microorganism within the host. The prominent cause contributing to the current crisis remains to be the overuse and misuse of antimicrobials, particularly the inappropriate usage of antibiotics, increasing the global burden of antimicrobial resistance. The global consumption and usage of antibiotics are therefore closely monitored at all times. This review provides a current overview of the implications of strategies used by international governmental organisations, including the UN's 17 Sustainable Development Goals (SDGs), to address the problem of antibiotic resistance, as well as the "One Health Approach," a system incorporating a multidisciplinary effort to achieve the best possible health outcome by acknowledging the clear connections between humans, animals and their shared environment. The importance of public awareness and health literacy of lay audiences still needs to be further emphasised as part of global and local action plans. Antimicrobial resistance continues to be a major global public health dilemma of the 21st century. Already this topic is receiving substantial political input from the G7 countries and continues to be on the agenda of numerous political conferences. The consequences of failure to adequately address AMR are profound, with estimations of a return to the pre-antibiotic era, where everyday infections relating to childbirth, surgery and open fractured limbs could be potentially life-threatening. AMR itself represents a microcosm of factors, including social anthropology, civil unrest/war, diasporas, ethnic displacement, political systems, healthcare, economics, societal behaviour both at a population and individual level, health literacy, geoclimatic events, global travel and pharmaceutical innovation and investment, thus finding a solution that adequately addresses AMR and which helps stem further AMR emergence is complicated. Success will involve individuals, communities and nations all working together to ensure that the world continues to possess a sufficient armamentarium of effective antimicrobials that will sustain human and animal health, both now and in the future.

A metropolitan-scale, three-dimensional agent-based model to assess the effectiveness of the COVID-19 Omicron wave interventions in a hyperdense city: a case study of Hong Kong.

We simulated the COVID-19 Omicron spread in Hong Kong, China, by building a novel three-dimensional agent-based model that incorporates its vertically expanded, hyperdense urban environment. The model examined the effectiveness of the 'zero-COVID' interventions (i.e., Compulsory Universal Testing (CUT) and citywide lockdown) that were for debate during the Omicron wave in Hong Kong. We found that such stringent interventions would be effective only with even faster and stricter implementation. Therefore, flexible long-term strategies should also be considered to contain and prevent future infectious diseases.

Optimization of cerebrospinal fluid microbial DNA metagenomic sequencing diagnostics.

Infection in the central nervous system is a severe condition associated with high morbidity and mortality. Despite ample testing, the majority of encephalitis and meningitis cases remain undiagnosed. Metagenomic sequencing of cerebrospinal fluid has emerged as an unbiased approach to identify rare microbes and novel pathogens. However, several major hurdles remain, including establishment of individual limits of detection, removal of false positives and implementation of universal controls. Twenty-one cerebrospinal fluid samples, in which a known pathogen had been positively identified by available clinical techniques, were subjected to metagenomic DNA sequencing. Fourteen samples contained minute levels of Epstein-Barr virus. The detection threshold for each sample was calculated by using the total leukocyte content in the sample and environmental contaminants found in the bioinformatic classifiers. Virus sequences were detected in all ten samples, in which more than one read was expected according to the calculations. Conversely, no viral reads were detected in seven out of eight samples, in which less than one read was expected according to the calculations. False positive pathogens of computational or environmental origin were readily identified, by using a commonly available cell control. For bacteria, additional filters including a comparison between classifiers removed the remaining false positives and alleviated pathogen identification. Here we show a generalizable method for identification of pathogen species using DNA metagenomic sequencing. The choice of bioinformatic method mainly affected the efficiency of pathogen identification, but not the sensitivity of detection. Identification of pathogens requires multiple filtering steps including read distribution, sequence diversity and complementary verification of pathogen reads.

Predicting standardized absolute returns using rolling-sample textual modelling.

Understanding how textual information impacts financial market volatility has been one of the growing topics in financial econometric research. In this paper, we aim to examine the relationship between the volatility measure that is extracted from GARCH modelling and textual news information both publicly available and from subscription, and the performances of the two datasets are compared. We utilize a latent Dirichlet allocation method to capture the dynamic features of the textual data overtime by summarizing their statistical outputs, such as topic distributions in documents and word distributions in topics. In addition, we transform various measures representing the popularity and diversity of topics to form predictors for a rolling regression model to assess the usefulness of textual information. The proposed method captures the statistical properties of textual information over different time periods and its performance is evaluated in an out-of-sample analysis. Our results show that the topic measures are more useful for predicting our volatility proxy, the unexplained variance from the GARCH model than the simple moving average. The finding indicates that our method is helpful in extracting significant textual information to improve the prediction of stock market volatility.

Out-of-field dose and its constituent components for a 1.5 T MR-Linac.

This study aims to quantify the relative contributions of phantom scatter, collimator scatter and head leakage to the out-of-field doses (OFDs) of both static fields and clinical intensity-modulated radiation therapy (IMRT) treatments in a 1.5 T MR-Linac. The OFDs of static fields were measured at increasing distances from the field edge in an MR-conditional water phantom. Inline scans at depths of dmax (14 mm), 50 and 100 mm were performed for static fields of 5 × 5, 10 × 10 and 15 × 15 cm2under three different conditions: full scatter, with phantom scatter prevented, and head leakage only. Crossline scans at isocenter and offset positions were performed in full scatter condition. EBT3 radiochromic films were placed at 100 mm depth of solid water phantom to measure the OFD of clinical IMRT plans. All water tank data were normalized to Dmax of a 10 × 10 cm2field and the film results were presented as a fraction of the target mean dose.The OFD in the inline direction varied from 3.5% (15 × 15 cm2, 100 mm depth, 50 mm distance) to 0.014% (5 × 5 cm2, dmax, 400 mm distance). For all static fields, the collimator scatter was higher than the phantom scatter and head leakage at a distance of 100-400 mm. Head leakage remained the smallest among the three components, except at long distances (>375 mm) with small field size. Compared to the inline scans, the crossline scans at the isocenter showed higher doses at distances longer than 80 mm. All crossline profiles at longitudinal offset positions showed a cone shape with laterally shifted maxima. The OFD of IMRT deliveries varied with different target size. For prostate stereotactic body radiation therapy (SBRT) treatment, the OFD decreased from 2% to 0.03% at a distance of 50-500 mm. The OFDs have been measured for a 1.5 T MR-Linac. The presented dosimetric data are valuable for radiation safety assessments on patients treated with the MR-Linac, such as evaluating carcinogenic risk and radiation exposure to cardiac implantable electronic devices.

FLAME: long-read bioinformatics tool for comprehensive spliceome characterization.

Comprehensive characterization of differentially spliced RNA transcripts with nanopore sequencing is limited by bioinformatics tools that are reliant on existing annotations. We have developed FLAME, a bioinformatics pipeline for alternative splicing analysis of gene-specific or transcriptome-wide long-read sequencing data. FLAME is a Python-based tool aimed at providing comprehensible quantification of full-length splice variants, reliable de novo recognition of splice sites and exons, and representation of consecutive exon connectivity in the form of a weighted adjacency matrix. Notably, this workflow circumvents issues related to inadequate reference annotations and allows for incorporation of short-read sequencing data to improve the confidence of nanopore sequencing reads. In this study, the Epstein-Barr virus long noncoding RNA RPMS1 was used to demonstrate the utility of the pipeline. RPMS1 is ubiquitously expressed in Epstein-Barr virus associated cancer and known to undergo ample differential splicing. To fully resolve the RPMS1 spliceome, we combined gene-specific nanopore sequencing reads from a primary gastric adenocarcinoma and a nasopharyngeal carcinoma cell line with matched publicly available short-read sequencing data sets. All previously reported splice variants, including putative ORFs, were detected using FLAME. In addition, 32 novel exons, including two intron retentions and a cassette exon, were discovered within the RPMS1 gene.

Geographic Clustering of Fast-Food Restaurants Around Secondary Schools in Hong Kong.

INTRODUCTION: Clustering of fast-food restaurants around schools facilitates fast-food consumption among students, which may cause obesity. We examined the prevalence of fast-food restaurants and identified the clusters of fast-food restaurants near secondary schools in Hong Kong. METHODS: We collected data of Western fast-food chain restaurants and 490 secondary schools in Hong Kong. Descriptive statistics and buffer analysis identified the prevalence of fast-food restaurants around the secondary schools within 400-m and 800-m buffers. Additional analyses compared schools stratified by the 3 main regions in Hong Kong, district-level population density, and median monthly household income. We used Getis-Ord GI* hot spot analysis to measure spatial clusters of fast-food restaurants around schools and Global Moran's I to measure the spatial autocorrelation based on each school and the number of fast-food restaurants within the 400-m buffer. RESULTS: The average number of fast-food restaurants within 400 m and 800 m of a school was 2.0 and 6.3, respectively. Seven in 10 secondary schools had at least 1 fast-food restaurant within 400 m. The number of schools with no fast-food restaurants was higher in Hong Kong Island, considered the "rich region" in Hong Kong. Hot spots of clusters were significantly located in the high-density downtown areas. We observed significant spatial autocorrelation between fast-food restaurants and secondary schools in the areas with high density, low income, and high income (P < .001, z > 2.58). CONCLUSION: Fast-food restaurants were substantially clustered around secondary schools in Hong Kong. Territory-wide studies about the health effect of fast-food clusters around schools on children and adolescents are warranted in Hong Kong.

A primary nasopharyngeal three-dimensional air-liquid interface cell culture model of the pseudostratified epithelium reveals differential donor- and cell type-specific susceptibility to Epstein-Barr virus infection.

Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection. Donors varied in susceptibility to de novo EBV infection, but susceptible cultures also displayed differences with respect to pathogenesis. The cultures from one donor yielded lytic infection but cells from two other donors were positive for EBV-encoded EBERs and negative for other lytic infection markers. All cultures stained positive for the pseudostratified markers CK7, MUC5AC, α-tubulin in cilia, and the EBV epithelial cell receptor Ephrin receptor A2. To define EBV transcriptional programs by cell type and to elucidate latent/lytic infection-differential changes, we performed single cell RNA-sequencing on one EBV-infected culture that resulted in alignment with many EBV transcripts. EBV transcripts represented a small portion of the total transcriptome (~0.17%). All cell types in the pseudostratified epithelium had detectable EBV transcripts with suprabasal cells showing the highest number of reads aligning to many EBV genes. Several restriction factors (IRF1, MX1, STAT1, C18orf25) known to limit lytic infection were expressed at lower levels in the lytic subcluster. A third of the differentially-expressed genes in NPC tumors compared to an uninfected pseudostratified ALI culture overlapped with the differentially-expressed genes in the latent subcluster. A third of these commonly perturbed genes were specific to EBV infection and changed in the same direction. Collectively, these findings suggest that the pseudostratified epithelium could harbor EBV infection and that the pseudostratified infection model mirrors many of the transcriptional changes imposed by EBV infection in NPC.

Effects on skin dose from unwanted air gaps under bolus in an MR-guided linear accelerator (MR-linac) system.

Bolus is commonly used in MV photon radiotherapy to increase superficial dose and improve dose uniformity for treating shallow lesions. However, irregular patient body contours can cause unwanted air gaps between a bolus and patient skin. The resulting dosimetric errors could be exacerbated in MR-Linac treatments, as secondary electrons generated by photons are affected by the magnetic field. This study aimed to quantify the dosimetric effect of unwanted gaps between bolus and skin surface in an MR-Linac. A parallel-plate ionization chamber and EBT3 films were utilized to evaluate the surface dose under bolus with various gantry angles, field sizes, and different air gaps. The results of surface dose measurements were then compared to Monaco 5.40 Treatment Planning System (TPS) calculations. The suitability of using a parallel-plate chamber in MR-Linac measurement was validated by benchmarking the percentage depth dose and output factors with the microDiamond detector and air-filled ionization chamber measurements in water. A non-symmetric response of the parallel-plate chamber to oblique beams in the magnetic field was characterized. Unwanted air gaps significantly reduced the skin dose. For a frontal beam, skin dose was halved when there was a 5 mm gap, a much larger difference than in a conventional linac. Skin dose manifested a non-symmetric pattern in terms of gantry angle and gap size. The TPS overestimated skin dose in general, but shared the same trend with measurement when there was no air gap, or the gap size was larger than 5 mm. However, the calculated and measured results had a large discrepancy when the bolus-skin gap was below 5 mm. When treating superficial lesions, unwanted air gaps under the bolus will compromise the dosimetric goals. Our results highlight the importance of avoiding air gaps between bolus and skin when treating superficial lesions using an MR-Linac system.

Effect of Contacting Surface on the Performance of Thin-Film Force and Pressure Sensors.

Flexible force and pressure sensors are important for assessing the wear comfort of tightly fitting apparel. Their accuracy and repeatability depend on the sensor itself and the contacting surface. Measurements of the contact pressure on soft surfaces like human skin tend to be erroneous, which could be due to incorrect sensor calibrations. This study aims to examine the effects of human body parameters such as the hardness and temperature of the contacting surface by using a custom-made calibration setup and investigating the incorporation of rigid discs on the sensor surface. Two commercial force sensors, FlexiForce and SingleTact, and one pressure sensor, Pliance X, are used in the investigation. The findings reveal that adding rigid discs on both sides of the force sensors improves their sensitivity. Systematic calibration has been performed on the surfaces with different temperatures and hardness. The results show that FlexiForce and Pliance X tend to be affected by the changes in surface temperature and surface hardness. Prolonged testing time shows that the time dependence of SingleTact and Pliance X sensor is lower, which suggests that they are more suitable for lengthier evaluations in which interface pressure is exerted on the human body. In brief, sensor attachment and proper calibration should be thoroughly considered before using sensors for applications on soft surfaces, like the human body.

Efficient Deep Learning-based Wound-bed Segmentation For Mobile Applications.

This paper proposes a deep learning image segmentation method for the purpose of segmenting wound-bed regions from the background. Our contributions include proposing a fast and efficient convolutional neural networks (CNN)-based segmentation network that has much smaller number of parameters than U-Net (only 18.1% that of U-Net, and hence the trained model has much smaller file size as well). In addition, the training time of our proposed segmentation network (for the base model) is only about 40.2% of that needed to train a U-Net. Furthermore, our proposed base model also achieved better performance compared to that of the U-Net in terms of both pixel accuracy and intersection-over-union segmentation evaluation metrics. We also showed that because of the small footprint of our efficient CNN-based segmentation model, it could be deployed to run in real-time on portable and mobile devices such as an iPad.

Chinese Medicinal Herbs Targeting the Gut-Liver Axis and Adipose Tissue-Liver Axis for Non-Alcoholic Fatty Liver Disease Treatments: The Ancient Wisdom and Modern Science.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The pathogenesis of NAFLD is complex. Frontline western medicines only ameliorate the symptoms of NAFLD. On the contrary, the uniqueness of Chinese medicine in its interpretation of NAFLD and the holistic therapeutic approach lead to a promising therapeutic efficacy. Recent studies reveal that the gut-liver axis and adipose tissue-liver axis play important roles in the development of NAFLD. Interestingly, with advanced technology, many herbal formulae are found to target the gut-liver axis and adipose tissue-liver axis and resolve the inflammation in NAFLD. This is the first review summarizes the current findings on the Chinese herbal formulae that target the two axes in NAFLD treatment. This review not only demonstrates how the ancient wisdom of Chinese medicine is being interpreted by modern pharmacological studies, but also provides valuable information for the further development of the herbal-based treatment for NAFLD.

Deep sequencing of liver explant transcriptomes reveals extensive expression from integrated hepatitis B virus DNA.

Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Integration of HBV DNA into the human genome may contribute to oncogenesis and to the production of the hepatitis B surface antigen (HBsAg). Whether integrations contribute to HBsAg levels in the blood is poorly known. Here, we characterize the HBV RNA profile of HBV integrations in liver tissue in patients with chronic HBV infection, with or without concurrent hepatitis D infection, by transcriptome deep sequencing. Transcriptomes were determined in liver tissue by deep sequencing providing 200 million reads per sample. Integration points were identified using a bioinformatic pipeline. Explanted liver tissue from five patients with end-stage liver disease caused by HBV or HBV/HDV was studied along with publicly available transcriptomes from 21 patients. Almost all HBV RNA profiles were devoid of reads in the core and the 3' redundancy (nt 1830-1927) regions, and contained a large number of chimeric viral/human reads. Hence, HBV transcripts from integrated HBV DNA rather than from covalently closed circular HBV DNA (cccDNA) predominated in late-stage HBV infection, in particular in cases with hepatitis D virus co-infection. The findings support the suggestion that integrated HBV DNA can be a significant source of HBsAg in humans.

Effect of material property, surface temperature and contact duration on the thermal sensation when contacting shell materials of electronic devices.

Heat generated in electronic devices is generally unevenly distributed across the casing. Contacting the hot areas may cause thermal discomfort and possibly skin burn. This study aims at better understanding the interrelationship between the thermal sensation, material properties and surface temperature for enhancing the user experience of electronic devices. A Thermal Simulation System was developed in this study to precisely control the surface temperature of shell materials to simulate various end-use conditions. Seventeen participants were asked to contact the plates with their fingers and rate their thermal sensation using the magnitude estimation approach. Results showed that thermal sensation magnitude and plate temperature followed a power function. The differences in sensation magnitude can be attributed to the thermal inertias of different materials. The findings suggested that laminated plate was generally perceived cooler when heated. Given that the surface temperature of plate is higher than skin, the thermal sensation magnitude increases with contact duration.