Thioamides antithyroid‐drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD‐induced agranulocytosis is important for clinical management. ...We performed a genome‐wide association study (GWAS) involving 20 patients with ATD‐induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single‐nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD‐induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8–103.7; P = 1.3 × 10‐24) and replication (OR = 37; 95% CI = 3.7–367.4; P = 9.6 × 10‐7). HLA‐B*38:02:01 was in complete linkage disequilibrium with rs185386680. High‐resolution HLA typing confirmed that HLA‐B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)‐induced agranulocytosis (OR = 265.5; 95% CI = 27.9–2528.0; P = 2.5 × 10‐14), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA‐B*38:02:01 in predicting CMZ/MMI‐induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
Colorectal cancer (CRC) development has been associated with increased proportions of Bacteroides fragilis and certain Streptococcus, Fusobacterium, and Peptostreptococcus species in the intestinal ...microbiota. We investigated associations between bacteremia from specific intestinal microbes and occurrence of CRC.
We performed a retrospective study after collecting data on 13,096 adult patients (exposed group) in Hong Kong hospitalized with bacteremia (identified by blood culture test) without a previous diagnosis of cancer from January 1, 2006 through December 31, 2015. We collected data on intestinal microbes previously associated with CRC (genera Bacteroides, Clostridium, Filifactor, Fusobacterium, Gemella, Granulicatella, Parvimonas, Peptostreptococcus, Prevotella, Solobacterium, and Streptococcus). Clinical information, including patient demographics, comorbid medical conditions, date of bacteremia, and bacterial species identified, were collected. The incidence of biopsy-proved CRC was compared between the exposed and unexposed (patients without bacteremia matched for age, sex, and comorbidities) groups.
The risk of CRC was increased in patients with bacteremia from B fragilis (hazard ratio HR = 3.85, 95% CI = 2.62–5.64, P = 5.5 × 10−12) or Streptococcus gallolyticus (HR = 5.73, 95% CI = 2.18–15.1, P = 4.1 × 10−4) compared with the unexposed group. In addition, the risk of CRC was increased in patients with bacteremia from Fusobacterium nucleatum (HR = 6.89, 95% CI = 1.70–27.9, P = .007), Peptostreptococcus species (HR = 3.06, 95% CI = 1.47–6.35, P = .003), Clostridium septicum (HR = 17.1, 95% CI = 1.82–160, P = .013), Clostridium perfringens (HR = 2.29, 95% CI = 1.16–4.52, P = .017), or Gemella morbillorum (HR = 15.2, 95% CI = 1.54–150, P = .020). We observed no increased risk in patients with bacteremia caused by microbes not previously associated with colorectal neoplasms.
In a retrospective analysis of patients hospitalized for bacteremia, we associated later diagnosis of CRC with B fragilis and S gallolyticus and other intestinal microbes. These bacteria might have entered the bloodstream from intestinal dysbiosis and perturbed barrier function. These findings support a model in which specific members of the intestinal microbiota promote colorectal carcinogenesis. Clinicians should evaluate patients with bacteremia from these species for neoplastic lesions in the colorectum.
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There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma.
We measured ...relative abundance of
(
),
(
) and
(
) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects.
The abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker
in patients with advanced adenoma than controls (p=0.022). The marker
, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively).
This study identified marker
as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.
•The optimum torrefaction condition for the production of high energy density biofuels was presented.•Reaction temperature had a strong impact on the energy density of torrefied biomass.•The energy ...analysis showed that heating values increased, with increased extend of treatment.•Each biomass has its own set of torrefaction conditions to achieve the same product quality.
Without appropriate treatment, lignocellulosic biomass is not suitable to be fed into existing combustion systems because of its high moisture content, low bulk energy density and difficulties in transport, handling and storage. The aim of this study was to investigate the effects of torrefaction treatment on the weight loss and energy properties of fast growing species in Malaysia (Acacia spp., and Macaranga spp.) as well as oil palm biomass (oil palm trunk and empty fruit bunch). The lignocellulosic biomass was torrefied at three different temperatures 200, 250 and 300°C for 15, 30 and 45min. Response surface methodology was used for optimization of torrefaction conditions, so that biofuel of high energy density, maximized energy properties and minimum weight loss could be manufactured. The analyses showed that increase in heating values was affected by treatment severity (cumulated effect of temperature and time). Our results clearly demonstrated an increased degradation of the material due to the combined effects of temperature and treatment time. While the reaction time had less impact on the energy density of torrefied biomass, the effect of reaction temperature was considerably stronger under the torrefaction conditions used in this study. It was demonstrated that each biomass type had its own unique set of operating conditions to achieve the same product quality. The optimized torrefaction conditions were verified empirically and applicability of the model was confirmed. The torrefied biomass occurred more suitable than raw biomass in terms of calorific value, physical and chemical properties. The results of this study could be used as a guide for the production of high energy density solid biofuel from lignocellulosic biomass available in Malaysia.
The new generation of bicycle-sharing is an O2O (online-to-offline) platform service that enables the users to access the bicycle with a smartphone App. This paper proposes a dynamic repositioning ...model with predicted demand, where the repositioning time interval is fixed. A data-driven Neural Network (NN) approach is introduced to forecast the bicycle-sharing demand. The repositioning objective function at each time interval is defined to simultaneously minimize the operator cost and penalty cost. In addition to the normal constraints in static repositioning problem, flow conservation, inventory-balance and travel time constraints are taken into account. Due to the non-deterministic polynomial-time hard (NP-hard) nature of this model, a hybrid metaheuristic approach of Adaptive Genetic Algorithm (AGA) and Granular Tabu Search (GTS) algorithm is applied to calculate the solution. Based on predicted demand, the initial repositioning plan is made by AGA statically at the beginning of study horizon, which ensures the global optimization of the first solution. As time goes on, repositioning plan is checked and updated according to the real-usage patterns using GTS algorithm, which has the advantage of high-performance local-search within a short computing time. Numerical analysis is conducted using the real cases. The simulation results reveal that the proposed methodology can effectively model the dynamic repositioning problem in response to real-time bicycle-sharing usage. The proposed methodology can be a value-added tool in enhancing the feasibility and sustainability of bicycle-sharing program.
The spray characteristics and heat transfer performance of pressure swirl nozzles were experimentally investigated in an open loop system. The spray flow structure, droplet Sauter mean diameter, and ...droplet impingement energy were characterized at predefined axial distances and pressure drops. It was found that the spray cone produced by the pressure swirl nozzles changes from hollow cone to full cone as the axial distance increases. The droplets size initially decreases with the increasing of axial distance but subsequently increases in the investigated range of axial distance, while the droplet impinging Weber number decreases monotonously. The surface temperature distribution was found to be solely dependent on the impinging droplet flux distribution in the non-boiling regime. High surface temperature expands the impinging spray cone and finally changes the impinging droplet flux distribution when the droplets impinge on the heated surface. The effect of nozzle-to-surface distance on heat transfer performance was found to be complex and surface temperature dependent. The heat transfer coefficient was investigated to be rather insensitive to the nozzle-to-surface distance at the full cone spray regime than that in the hollow cone spray regime. An empirical model that correlates the Nusselt number to the impinging Reynolds number, non-dimensional surface temperature and nozzle-to-surface distance was developed to fit the present experimental data with an average error of 14%.
► The flow structures of two pressure swirl nozzles were experimentally investigated. ► Surface temperature distribution is solely dependent on the impinging droplet flux. ► High surface temperature expands the spray cone near the heated surface. ► Nozzle-to-surface distance has complex influences on spray cooling performance. ► A concise and useful empirical correlation was developed.
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Microfluidics has been used to process self-assembling liposomal systems that are commonly considered for drug delivery applications. However, it has been found that the parameters of ...the process are not universally suited for all lipid types. We hypothesize here that size aggregation and instability of microfluidic liposomes are a direct consequence of the presence of interdigitation in these liposomes. Interdigitation refers to the phenomenon where two opposing leaflets of a bilayer interpenetrate into one another and form a single layer. When this happens, aggregation results as the single layer is not thermodynamically stable. Such interdigitation can be induced by pressure, chemicals or by the type of lipid structure. In this study, we systematically investigate the role of lipid composition on membrane interdigitation in order to understand the dependency of lipid interdigitation on liposome formation by microfluidics. By doing so, we use nano DSC and SAXS to probe the extent of lipid interdigitation by measuring the changes in thermodynamics and membrane thickness of the lipid bilayers. Our results show that microfluidic-fabricated liposomes undergo chemical interdigitation in the presence of ethanol, in particular saturated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Strategies to prevent interdigitation is to either remove ethanol above the lipid’s main transition temperature (Tm), preventing the formation of interdigitated structures and subsequent aggregated states or by the incorporation of the inhibiting additives, such as cholesterol.
Recent studies have shown that breast arterial calcification (BAC) detected on screening mammography is linked to cardiovascular diseases via medial calcification. However, its effect on ...cardiovascular outcomes remains unclear. Therefore, we conducted a meta-analysis to determine the effect of BAC on cardiovascular outcomes in patients.
Three electronic databases (Pubmed, Embase, and Scopus) were searched on May 1, 2022, for studies examining the relationship between BAC and cardiovascular outcomes including cardiac death, acute myocardial infarction, ischemic heart disease, stroke, peripheral artery disease, and heart failure. A random-effects meta-analysis model was used to summarise the studies.
A total of 5 longitudinal studies were included with a combined cohort of 87,865 patients. Significantly, the pooled risk ratio (RR) of the association between BAC and cardiac death was 2.06 (P < 0.00001). BAC was associated with a significantly increased risk of developing other cardiovascular diseases, such as ischemic/hemorrhagic stroke (RR 1.51; P = 0.003), ischemic stroke (RR 1.82; P < 0.00001), peripheral vascular disease (RR 1.24; P = 0.003), and heart failure (RR 1.84; P < 0.00001). There was no significant relationship for developing myocardial infarction or for total cardiovascular diseases.
Our findings suggest that BAC was associated with an increased risk of cardiovascular mortality, and certain cardiovascular outcomes. There is thus a potential to use BAC as a sex-specific cardiovascular risk assessment tool. Furthermore, there is a need for more widespread reporting of BAC to better understand the pathophysiologic mechanisms behind its correlation with cardiovascular disease and to apply it in clinical practice.
OBJECTIVE: To validate a Chinese version of the Diabetes Distress Scale (CDDS). RESEARCH DESIGN AND METHODS: The CDDS was derived using forward-backward translation and administered in 189 Chinese ...type 2 diabetic patients with evaluation of its psychometric properties. RESULTS: On the basis of principal-component analysis, three factors of the 15-item version of the CDDS (CDDS-15) accounted for 63% of the variance. The correlation coefficient between the original 17-item and 15-item scales was 0.99. The Cronbach α for internal consistency was 0.90, and the test-retest reliability coefficient was 0.74. The CDDS-15 score was significantly associated with glycemic control, obesity, depressive symptoms, and quality of life. CONCLUSIONS: The CDDS-15 is a valid and reliable instrument to assess diabetes-related distress.
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