The growing commercial interest in indoor location-based services (ILBS) has spurred recent development of many indoor positioning techniques. Due to the absence of Global Positioning System (GPS) ...signal, many other signals have been proposed for indoor usage. Among them, Wi-Fi (802.11) emerges as a promising one due to the pervasive deployment of wireless LANs (WLANs). In particular, Wi-Fi fingerprinting has been attracting much attention recently because it does not require line-of-sight measurement of access points (APs) and achieves high applicability in complex indoor environment. This survey overviews recent advances on two major areas of Wi-Fi fingerprint localization: advanced localization techniques and efficient system deployment. Regarding advanced techniques to localize users, we present how to make use of temporal or spatial signal patterns, user collaboration, and motion sensors. Regarding efficient system deployment, we discuss recent advances on reducing offline labor-intensive survey, adapting to fingerprint changes, calibrating heterogeneous devices for signal collection, and achieving energy efficiency for smartphones. We study and compare the approaches through our deployment experiences, and discuss some future directions.
Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for ...precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.
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•Living biobank includes 17 normal and 46 gastric cancer organoid lines•Organoid biobank encompasses most of the known molecular subtypes of gastric cancer•Organoids recapitulate the genomic and transcriptomic features of original tumors•High-throughput screen revealed potential target drugs for personalized therapy
Leung and colleagues established a biobank of patient-derived gastric cancer organoids that encompasses a diverse array of subtypes and maintained long-term similarity to the original tumors. They used the organoids to perform large-scale drug screening that identified potential target drugs and could guide patient drug selection.
Skin antisepsis is a simple and effective measure to prevent infections. The efficacy of chlorhexidine is actively discussed in the literature on skin antisepsis. However, study outcomes due to ...chlorhexidine-alcohol combinations are often attributed to chlorhexidine alone. Thus, we sought to review the efficacy of chlorhexidine for skin antisepsis and the extent of a possible misinterpretation of evidence.
We performed a systematic literature review of clinical trials and systematic reviews investigating chlorhexidine compounds for blood culture collection, vascular catheter insertion and surgical skin preparation. We searched PubMed, CINAHL, the Cochrane Library, the Agency for Healthcare Research and Quality website, several clinical trials registries and a manufacturer website. We extracted data on study design, antiseptic composition, and the following outcomes: blood culture contamination, catheter colonisation, catheter-related bloodstream infection and surgical site infection. We conducted meta-analyses of the clinical efficacy of chlorhexidine compounds and reviewed the appropriateness of the authors' attribution.
In all three application areas and for all outcomes, we found good evidence favouring chlorhexidine-alcohol over aqueous competitors, but not over competitors combined with alcohols. For blood cultures and surgery, we found no evidence supporting chlorhexidine alone. For catheters, we found evidence in support of chlorhexidine alone for preventing catheter colonisation, but not for preventing bloodstream infection. A range of 29 to 43% of articles attributed outcomes solely to chlorhexidine when the combination with alcohol was in fact used. Articles with ambiguous attribution were common (8-35%). Unsubstantiated recommendations for chlorhexidine alone instead of chlorhexidine-alcohol were identified in several practice recommendations and evidence-based guidelines.
Perceived efficacy of chlorhexidine is often in fact based on evidence for the efficacy of the chlorhexidine-alcohol combination. The role of alcohol has frequently been overlooked in evidence assessments. This has broader implications for knowledge translation as well as potential implications for patient safety.
Summary
Background
The rs738409 GG variant in patatin‐like phospholipase 3 (PNPLA3) is associated with non‐alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if ...it contributes to the development of NAFLD through affecting dietary pattern.
Aim
To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD.
Methods
Liver fat and fibrosis were assessed by proton‐magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food‐frequency questionnaire.
Results
The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern.
Conclusions
The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.
We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS).
We followed up 75 patients for 3 ...weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods.
Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days.
The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage.
Published online May 9, 2003 http://image.thelancet.com/extras/03art4432web.pdf
Nanomaterials (NMs) have gained prominence in technological advancements due to their tunable physical, chemical and biological properties with enhanced performance over their bulk counterparts. NMs ...are categorized depending on their size, composition, shape, and origin. The ability to predict the unique properties of NMs increases the value of each classification. Due to increased growth of production of NMs and their industrial applications, issues relating to toxicity are inevitable. The aim of this review is to compare synthetic (engineered) and naturally occurring nanoparticles (NPs) and nanostructured materials (NSMs) to identify their nanoscale properties and to define the specific knowledge gaps related to the risk assessment of NPs and NSMs in the environment. The review presents an overview of the history and classifications of NMs and gives an overview of the various sources of NPs and NSMs, from natural to synthetic, and their toxic effects towards mammalian cells and tissue. Additionally, the types of toxic reactions associated with NPs and NSMs and the regulations implemented by different countries to reduce the associated risks are also discussed.
The penetration of renewable energy sources is expected to rapidly increase from 15% to 50% in 2050 due to their vital contribution to the global energy requirements, sustainability and quality of ...life in economical, environmental and health aspects. This huge rise highlights the necessity of development of energy storage systems, especially for intermittency renewable energies such as solar photovoltaic and wind turbine, in order to balance the energy network. In this study, renewable energy options including pumped hydro, pressurized air, flywheels, Li ion batteries, hydrogen and super-capacitors are compared based on a specific set of criteria. The criteria considered are energy/power density, ease of integration with the existing energy network, cost effectiveness, durability, efficiency and safety. Our study showed that storing renewable energy sources in the form of hydrogen through the electrolysis process is ranked as the most promising option considering the mentioned criteria. It brings about several benefits suggesting that hydrogen and fuel cells are promising contributors towards a more sustainable future, both in energy demand and environmental sustainability.
•Energy storage technologies provide the balance in modern energy networks.•Storing renewable energy in the form of hydrogen via the electrolysis process is concluded to be the most promising option.•Hydrogen energy provides high energy density, low capital cost and easy integration with the existing energy network.•Hydrogen and fuel cell contribute to a more sustainable future.
Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank ...enriched in EOCRCs.
We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed.
We observed a striking diversity of molecular phenotypes, including
fusions. Transcriptionally,
fusion organoids resembled normal colon organoids and were distinct from
mutant organoids, with high
and low
expression. Single cell transcriptome analysis confirmed the similarity between
fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the
mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of
in normal human colon organoids led to upregulation of PTK7 protein and suppression of
, but less so with an engineered
mutation. The frequent co-occurrence of
fusions with
or
mutation was confirmed in TCGA database searches.
mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time.
These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.
Fatigue failure in the high-cycle and ultrahigh-cycle regimes is often dominated by the crack initiation processes, which are strongly influenced by the salient features and defects in the ...microstructure. Competing fatigue mechanisms involving crack initiation at persistent slipbands, grain boundaries, pores, and non-metallic inclusions or particles, have been reported to occur at surface sites in the high-cycle fatigue regime (10
6–10
7 cycles), but shift to interior sites in the ultrahigh-cycle fatigue regime (10
9–10
10 cycles). The changes in fatigue mechanism and crack initiation site result in large variations in fatigue life. This overview article examines the roles of microstructural features such as grain size, texture, porosity, non-metallic inclusion in the fatigue crack initiation process and the manners by which these microstructural effects affect the shape of the stress–life curves.
Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression ...and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and epigenetic perturbations and unique mutational signatures. We identified previously known (TP53, ARID1A and CDH1) and new (MUC6, CTNNA2, GLI3, RNF43 and others) significantly mutated driver genes. Specifically, we found RHOA mutations in 14.3% of diffuse-type tumors but not in intestinal-type tumors (P < 0.001). The mutations clustered in recurrent hotspots affecting functional domains and caused defective RHOA signaling, promoting escape from anoikis in organoid cultures. The top perturbed pathways in gastric cancer included adherens junction and focal adhesion, in which RHOA and other mutated genes we identified participate as key players. These findings illustrate a multidimensional and comprehensive genomic landscape that highlights the molecular complexity of gastric cancer and provides a road map to facilitate genome-guided personalized therapy.
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