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This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of Peperomia leptostachya leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (w/w). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), (E)-caryophyllene (17.4%), bicyclogermacrene (6.6%), α-pinene (6.2%), and β-pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC50 value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC50 value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC50 value of 37.45 ± 2.43 μg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that P. leptostachya leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions. [ABSTRACT FROM AUTHOR]

Germline mutations in Breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) cause breast, ovarian, and other cancers, and the chemotherapeutic drug doxorubicin (Dox) is widely used to treat these cancers. However, Dox use is limited by the latent induction of severe cardiotoxicity known as Dox-induced cardiomyopathy, for which there are no specific treatments currently available. Dox is administered into the systemic circulation, where it readily translocates into sub-cellular compartments and disrupts the integrity of DNA. Accumulating evidence indicates that oxidative stress, DNA damage, inflammation, and apoptosis all play a central role in Dox-induced cardiomyopathy. The BRCA1 and BRCA2 proteins are distinct as they perform crucial yet separate roles in the homologous recombination repair of DNA double-strand breaks, thereby maintaining genomic integrity. Additionally, both BRCA1 and BRCA2 mitigate oxidative stress and apoptosis in both cardiomyocytes and endothelial cells. Accordingly, BRCA1 and BRCA2 are essential regulators of pathways that are central to the development of cardiomyopathy induced by Doxorubicin. Despite extensive investigations, there exists a gap in knowledge about the role of BRCA1 and BRCA2 in Doxorubicin-induced cardiomyopathy. Here, we review the previous findings and associations about the expected role and associated mechanisms of BRCA1 and 2 in Dox-induced cardiomyopathy and future perspectives. [ABSTRACT FROM AUTHOR]

Prevalence of mental health disorders continue to increase worldwide. Over the past decades, suboptimal vitamin D (VD) levels and gut dysbiosis have been associated with neurological dysfunction and psychiatric disorders. In this review, we examined the available literature on VD and mental health disorders, particularly depression and anxiety, in both clinical and pre-clinical studies. Our extensive review failed to find a link between VD deficiency, depression, and anxiety-related behavior in preclinical animal models. However, strong evidence suggests that VD supplementation may alleviate symptoms in chronically stressed rodents, with some promising evidence from clinical studies. Further, fecal microbiota transplantations suggest a potential role of gut microbiota in neuropsychiatric disorders, although the underlying mechanisms remain to be fully elucidated. It has been postulated that serotonin, primarily produced by gut bacteria, may be a crucial factor. Hence, whether VD has the ability to impact gut microbiota and modulate serotonin synthesis warrants further investigation. Taken together, literature has suggested that VD may serve as a key regulator in the gut-brain axis to modulate gut microbiota and alleviate symptoms of depression and anxiety. The inconsistent results of VD supplementation in clinical studies, particularly among VD deficient participants, suggests that current intake recommendations may need to be re-evaluated for individuals at-risk (i.e. prior to diagnosis) of developing depression and/or anxiety. [ABSTRACT FROM AUTHOR]

Fifteen compounds containing benzothiazole have been synthesized successfully via Suzuki reaction of 2-(4-bromophenyl)benzothiazole 1 and phenylboronic acid derivatives in high yield. All samples display fluorescence emissions at wavelengths in the range of 380 to 450 nm under the excitation light of 330 nm. Compounds 2d, 2e, 2h and 2k exhibit quite good fluorescent property. [ABSTRACT FROM AUTHOR]

In recent years, empirical Bayesian (EB) inference has become an attractive approach for estimation in parametric models arising in a variety of real‐life problems, especially in complex and high‐dimensional scientific applications. However, compared to the relative abundance of available general methods for computing point estimators in the EB framework, the construction of confidence sets and hypothesis tests with good theoretical properties remains difficult and problem specific. Motivated by the Universal Inference framework, we propose a general and universal method, based on holdout likelihood ratios, and utilizing the hierarchical structure of the specified Bayesian model for constructing confidence sets and hypothesis tests that are finite sample valid. We illustrate our method through a range of numerical studies and real data applications, which demonstrate that the approach is able to generate useful and meaningful inferential statements in the relevant contexts. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (hMPV) can cause severe acute respiratory infection (ARI). We aimed to clarify the clinical and molecular epidemiological features of hMPV. We conducted an ARI surveillance targeting hospitalized children aged 1 month to 14 years in Nha Trang, Vietnam. Nasopharyngeal swabs were tested for respiratory viruses with PCR. We described the clinical characteristics of hMPV patients in comparison with those with respiratory syncytial virus (RSV) and those with neither RSV nor hMPV, and among different hMPV genotypes. Among 8822 patients, 278 (3.2%) were hMPV positive, with a median age of 21.0 months (interquartile range: 12.7–32.5). Among single virus-positive patients, hMPV cases were older than patients with RSV (p < 0.001) and without RSV (p = 0.003). The proportions of clinical pneumonia and wheezing in hMPV patients resembled those in RSV patients but were higher than in non-RSV non-hMPV patients. Seventy percent (n = 195) were genotyped (A2b: n = 40, 20.5%; A2c: n = 99, 50.8%; B1: n = 37, 19%; and B2: n = 19, 9.7%). The wheezing frequency was higher in A2b patients (76.7%) than in those with other genotypes (p = 0.033). In conclusion, we found a moderate variation in clinical features among hMPV patients with various genotypes. No seasonality was observed, and the multiple genotype co-circulation was evident. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (hMPV) can cause severe acute respiratory infection (ARI). We aimed to clarify the clinical and molecular epidemiological features of hMPV. We conducted an ARI surveillance targeting hospitalized children aged 1 month to 14 years in Nha Trang, Vietnam. Nasopharyngeal swabs were tested for respiratory viruses with PCR. We described the clinical characteristics of hMPV patients in comparison with those with respiratory syncytial virus (RSV) and those with neither RSV nor hMPV, and among different hMPV genotypes. Among 8822 patients, 278 (3.2%) were hMPV positive, with a median age of 21.0 months (interquartile range: 12.7–32.5). Among single virus-positive patients, hMPV cases were older than patients with RSV (p < 0.001) and without RSV (p = 0.003). The proportions of clinical pneumonia and wheezing in hMPV patients resembled those in RSV patients but were higher than in non-RSV non-hMPV patients. Seventy percent (n = 195) were genotyped (A2b: n = 40, 20.5%; A2c: n = 99, 50.8%; B1: n = 37, 19%; and B2: n = 19, 9.7%). The wheezing frequency was higher in A2b patients (76.7%) than in those with other genotypes (p = 0.033). In conclusion, we found a moderate variation in clinical features among hMPV patients with various genotypes. No seasonality was observed, and the multiple genotype co-circulation was evident. [ABSTRACT FROM AUTHOR]

Background It is not well known how reliably clinicians order reflex urinalysis to microscopy and culture (rUA-cx) for outpatient urinary tract infection (UTI) workup. Antibiotic appropriateness cannot be fully appreciated until the prevalence of UTIs and asymptomatic bacteriuria (ASB) are realized. Objective This quality improvement study has two major aims, first to determine UTI symptom accuracy for rUA-cx ordering and second, to confirm UTI and ASB cases by integrating rUA-cx and cascaded urinalysis results. Antibiotic utilization and diagnostic coding were secondarily linked to UTIs and ASB. Methods An electronic best-practice alert informed the ordering of two rUA-cx options: symptomatic - rUA-cx specifically for dysuria, frequency, urgency, costovertebral pain, suprapubic pain or fever versus non-specific -rUA-cx for vague complaints. UTI symptoms were verified by chart review. Confirmed UTI was defined as a significant culture with UTI symptoms and ASB as a significant culture without UTI symptoms. Results rUA-cx (2065) were prospectively collected over 6 months from female patients at risk for uncomplicated UTIs. Symptomatic -rUA-cx and non-specific -rUA-cx were associated with UTI symptoms for 53% (809/1527) and 20% (107/538), respectively. Overall, 44% (916/2065) of all rUA-cx had UTI symptoms. rUA-cx were overordered by a factor of 9 (2065/225) for every confirmed UTI. The UTI-to-ASB relative ratio was 2.6 (225/86). Regarding UTI-relevant antibiotics, 39% (214/553) were appropriately associated with UTI whereas only 22% (74/339) of inappropriate antibiotics were captured by the ASB definition, underestimating the problem 4-fold. Conclusions UTI and ASB remain challenging to categorize despite a meticulous method that applied acceptable criteria. [ABSTRACT FROM AUTHOR]

Mitigating the impacts of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and substance use requires comprehensive and systematic thinking in designing interventions and developing policies. This study describes the growth of research publications from 1991 to 2021 in the Web of Science database and points out current research landscapes in the fields of HIV/AIDS and substance use. Latent Dirichlet Allocation was used for classifying 21 359 papers into corresponding topics. The most common topics were HIV transmission, HIV infection, quality of life and mental health of substance users, and the biomedical effect of substance use. Emerging research landscapes include vulnerabilities of people who inject drugs to HIV transmission and related health problems. This study found a lack of research on health services, interdisciplinary and inter-sectoral in combination with clinical evaluation and treatment services. Future investment and implementation of HIV/AIDS and substance use programs should focus on research of health services and clinical evaluation, especially context-specific interventions. [ABSTRACT FROM AUTHOR]

Myopia prevention and anti-myopia treatment is of great importance in South East Asia. To evaluate the prevalence and related factors of myopic retinopathy in Vietnam. A cross-sectional study was conducted on 168 eyes of 88 patients with high myopia presenting to the Refraction Department of Vietnam National Eye Hospital. Inclusion criteria were high myopia (≤−6.00D with cycloplegic retinoscopy). Consecutive presenting patients recruited between January 2020 and August 2020 consented to participate. Participant age range was 12–47 years. Peripapillary atrophy was present in 70.2% of participants, most commonly atrophy of one-quarter of the disc (38.7%). Central retinal changes were present in 66.1% of participants, subclassified as tessellated fundus in 60.7%, diffuse chorioretinal atrophy in 4.2% and patchy chorioretinal atrophy in 1.2%. Peripheral retinal lesions were present in 43.5% of participants, consisting of white-without-pressure in 32.1%, lattice degeneration in 16.1%, snail track degeneration in 4.2% and microcystoid degeneration in 1.2%. Myopia ≤−8.00D and axial length ≥26.5 mm were associated with additional risk of posterior ocular complications. Furthermore, age ≥19 years increased risk of central myopic retinopathy and ≥10 years since initial myopia diagnosis increased the risk of peripapillary atrophy and central retinal changes. Other factors such as the age of onset of myopia and family myopia history did not appear to alter the risk of peripheral retina damage. Retinal disorders were common in Vietnamese people with high myopia. Within the current cohort with high myopia, myopia ≤−8.00D and axial length ≥26.5 mm were associated with a significant further elevation of risk. [ABSTRACT FROM AUTHOR]

A micellar hydrogel has long been considered an intelligent hydrophobic drug delivery material. In this study, synthesized PLA1750-PEG1750-PLA1750 micellar hydrogel aims to encapsulate ibuprofen (IBU) in the core PLA hydrophobic of the micelle and prolong the drug release time by an injectable route. The structure and morphology of the PLA1750-PEG1750-PLA1750 copolymer hydrogel were demonstrated by 1H NMR and TEM data. The hydrogel also achieved a gel state at a high concentration of 25 wt.% under the physiological conditions of the body (37°C, pH 7.4). Besides, the biocompatibility test displayed that the hydrogel slightly affected mice after injection one week and fully recovered after four weeks. Furthermore, the in vitro degradation of the hydrogel showed apparent gel erosion after the first three weeks, which is related to the IBU release rate: slow for the first three weeks and then fast. As a result, the total drug release after three and four weeks was 18 wt.% and 41 wt.%, respectively. However, in the first 24 hours, the amount of the drug released was 10 wt.%, suggesting that the IBU drug diffused from the surface hydrogel to the buffer solution. These show that PLA1750-PEG1750-PLA1750 hydrogel can be a potential IBU drug delivery candidate. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cells and PD-1 antibodies (PD-1 Ab) are emergent immunotherapies with unprecedented efficacy. The presence of PD-1 on T cells contributes to hypofunction of CAR-T therapy and inhibition of PD-1 enhances anti-cancer effect of CAR-T cells. Therefore, the combination of CAR-T cells and PD-1 antibody is a promissing strategy for cancer treatment. This study aims to establish our in-house CAR-T cells and evaluate the safety of CAR-T cells in combination with PD-1 antibody in animals. The toxicity of CD19-CAR-T cells was examined using Swiss Webster mice. Four mouse groups were treated with control, CAR-T, PD-1 antibody or CAR-T + PD-1 antibody. Mice's overall status was monitored and recorded. At the end-point, hematological and biochemical indices were quantified, histopathology of liver and kidney was evaluated by pathologists. The relative abnormal ratio and absolute values were compared between groups. We generated our in-house CAR-T cells and used them for safety evaluation in mice. The increase in mouse weight was observed in all groups after treatment and the weight was comparable between groups. The hematological, biochemical and histopathological parameters were equivalent between groups, except for liver grain degeneration occurred in treatment groups. Thus, CAR-T cells, PD-1 Ab and their combination were safe in mice. We successfully produced our in-house CAR-T cells and the combination of our CAR-T cells and PD-1 antibody was safe in mice with comparable values of hematopoietic indices, liver and kidney functions. Longer follow-up might be necessary to evaluate their effect on the liver. • We successfully produced our in-house CAR-T cells. • The combination of our in-house CAR-T cells and PD-1 antibody was safe in a mouse model. • The results support for further application of CAR-T cells combined with PD-1 Antibody. [ABSTRACT FROM AUTHOR]

A 31-year-old male was admitted to the hospital because of fever for 2 days. He also had chills, headaches, muscle aches, fatigue, and diarrhea. His vital signs were stable. Dengue virus nonstructural protein 1 (NS1) antigen was positive. Laboratory tests were significant for thrombocytopenia of 67.000/mm3 and high hematocrit of 45%. On the fifth day of the onset of fever, he experienced sudden epigastric pain. Laboratory results showed elevated serum amylase and lipase. Noncontrast abdominal CT findings were consistent with acute pancreatitis, Balthazar grade D. The patient was managed with supportive care and bowel rest. Two days later, his condition became stable, and he was discharged without complications. [ABSTRACT FROM AUTHOR]

Circulating fatty acid-binding protein 3 (FABP3) is an effective biomarker of myocardial injury and peripheral artery disease (PAD). The endothelium, which forms the inner most layer of every blood vessel, is exposed to higher levels of FABP3 in PAD or following myocardial injury, but the pathophysiological role of endothelial FABP3, the effect of FABP3 exposure on endothelial cells, and related mechanisms are unknown. Here, we aimed to evaluate the pathophysiological role of endothelial FABP3 and related mechanisms in vitro. Our molecular and functional in vitro analyses show that (1) FABP3 is basally expressed in endothelial cells; (2) inflammatory stress in the form of lipopolysaccharide (LPS) upregulated endothelial FABP3 expression; (3) loss of endogenous FABP3 protected endothelial cells against LPS-induced endothelial dysfunction; however, exogenous FABP3 exposure exacerbated LPS-induced inflammation; (4) loss of endogenous FABP3 protected against LPS-induced endothelial dysfunction by promoting cell survival and anti-inflammatory and pro-angiogenic signaling pathways. Together, these findings suggest that gain-of endothelial FABP3 exacerbates, whereas loss-of endothelial FABP3 inhibits LPS-induced endothelial dysfunction by promoting cell survival and anti-inflammatory and pro-angiogenic signaling. We propose that an increased circulating FABP3 in myocardial injury or PAD patients may be detrimental to endothelial function, and therefore, therapies aimed at inhibiting FABP3 may improve endothelial function in diseased states. [ABSTRACT FROM AUTHOR]

In examining the ageing-migration nexus from a Global South perspective, this paper explores the obligations, opportunities and constraints of caregiving performed by Vietnamese grandparent visitors during their sojourns in Australia. Employing a grounded theory approach and care circulation framework, we investigate how grandparent visitors and adult migrant children experience and understand care and ageing in contexts of mobility, including an analysis of how gender, age, socio-economic contexts and culture shape and affect their care norms and practices. The analysis emphasizes the critical contributions that Vietnamese grandparents make to the reproductive labour of their adult migrant children who often face challenges in balancing their family and work life. The resultant 'informal unpaid care mobility' of Vietnamese grandparents visitors creates 'informal care chains' that underscore the role of mobility as a care resource and the need for unpaid family care in migrant families due to the high cost of formal childcare in Australia. This analysis extends our understanding of the political economy of care, by highlighting the need for greater analysis of South–North informal care flows. [ABSTRACT FROM AUTHOR]

The current coronavirus disease 2019 (COVID-19) outbreak is alarmingly escalating and raises challenges in finding efficient compounds for treatment. Repurposing phytochemicals in herbs is an ideal and economical approach for screening potential herbal components against COVID-19. Andrographis paniculata, also known as Chuan Xin Lian, has traditionally been used as an anti-inflammatory and antibacterial herb for centuries and has recently been classified as a promising herbal remedy for adjuvant therapy in treating respiratory diseases. This study aimed to screen Chuan Xin Lian's bioactive components and elicit the potential pharmacological mechanisms and plausible pathways for treating COVID-19 using network pharmacology combined with molecular docking. The results found terpenoid (andrographolide) and flavonoid (luteolin, quercetin, kaempferol, and wogonin) derivatives had remarkable potential against COVID-19 and sequelae owing to their high degrees in the component-target-pathway network and strong binding capacities in docking scores. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the PI3K-AKT signaling pathway might be the most vital molecular pathway in the pathophysiology of COVID-19 and long-term sequelae whereby therapeutic strategies can intervene. [ABSTRACT FROM AUTHOR]

In this paper, TiO2 and Ag-doped TiO2 photocatalysts were coated on the cylindrical cordierite honeycomb monolith (CHM) to evaluate their photocatalytic disinfection against Escherichia coli (E. coli) bacteria under artificial sunlight irradiation. The X-ray diffraction (XRD) patterns showed a single-phase anatase structure for TiO2 samples calcined at 500 °C for 2 h. With the presence of Ag, the bandgap of TiO2 becomes narrower, and the absorption edge shifts toward the visible region. 6 mol% Ag-doped TiO2 (6Ag-T) showed a reduction of bandgap energy to 2.2 eV. TiO2 and Ag-doped TiO2 solutions were prepared and coated on the channels' surface of CHM for antibacterial applications. Although monolithic TiO2 caused a slight decrease in the number of alive E. coli, Ag dopant showed significant improvement in antibacterial properties. 6 mol% Ag-doped TiO2 coated on CHM (6Ag-T/S10/M) showed strong antibacterial effectiveness against E. coli that the bacterial cell concentration dropped to zero after 1 h of exposure. Impressively, reusability tests with these materials showed superior performance, where the antibacterial remains unchanged after five or seven successive operation cycles. [ABSTRACT FROM AUTHOR]

Vietnam has high rates of antibiotic use and resistance. Measuring resistance in commensal bacteria could provide an objective indicator for evaluating the impact of interventions to reduce antibiotic use and resistance. This study aimed to evaluate the feasibility, acceptability, and bacterial recovery for different sampling strategies. We conducted a cross-sectional mixed methods study in a rural community in Ha Nam Province, northern Vietnam, and collected structured interviews, samples, and in-depth interviews from households. Out of 389 households invited, 324 participated (83%), representing 1502 individuals. Samples were collected from these individuals (1498 stool, 1002 self-administered nasal swabs, and 496 HW-administered nasopharyngeal swabs). Pneumococci were recovered from 11.1% (128/1149) of the total population and 26.2% (48/183) of those under 5-years. Recovery was higher for health-worker (HW)-administered swabs (13.7%, 48/350) than self-administered swabs (10.0%, 80/799) (OR 2.06, 95% CI 1.07–3.96). Cost per swab was cheaper for self-administered ($7.26) than HW-administered ($8.63) swabs, but the overall cost for 100 positive samples was higher ($7260 and $6300 respectively). Qualitative interviews revealed that HW-administered nasopharyngeal swabs took longer to collect, caused more discomfort, and were more difficult to take from children. Factors affecting participation included sense of contribution, perceived trade-offs between benefits and effort, and peer influence. Reluctance was related to stool sampling and negative perceptions of research. This study provides important evidence for planning community-based carriage studies, including cost, logistics, and acceptability. Self-administered swabs had lower recovery, and though cheaper and quicker, this would translate to higher costs for large population-based studies. Recovery might be improved by swab-type, transport medium, and better cold-chain to lab. [ABSTRACT FROM AUTHOR]

Background. It has been widely assumed that TOETVA has demonstrated a new technique and a promising approach as it is both minimally invasive and optimally cosmetic. The objective of this study was to assess the surgical outcome, aesthetic satisfaction, and postoperative quality of life of TOETVA in comparison with open thyroid surgery. Patients and Methods. The study was designed as a prospective study, in which 121 patients from a single center in Vietnam underwent thyroid surgery, and the study was divided into two groups: 60 patients in the TOETVA group and 61 patients in the open surgery group. The patients have been followed up including surgical outcomes, cosmetic satisfaction, and quality of life. These criteria were assessed at 4 weeks, 8 weeks, and 12 weeks after the surgery using SF-36 and thyroid surgery-specific questionnaire. Results. Patients in the TOETVA group are significantly younger than patients in the open surgery group (35.8 + 10.3 vs 46.9 + 11.5, p < 0.001). The mean operating time was longer in the TOETVA group (102.9 ± 26.1 mins) than that in the open surgery group (66.8 ± 23.8 mins) with p = 0.0001. Cosmetic outcomes and overall satisfaction were significantly greater in the TOETVA group p = 0.0001. The SF-36 QOL scores of the patients in the TOETVA group were generally higher than the open surgery group. Conclusions. TOETVA has been widely used with a low complication rate, cosmetic appeal, and surgical efficacy. Postoperative quality of life, cosmetic outcomes, and overall satisfaction were significantly superior to the open surgery group. [ABSTRACT FROM AUTHOR]

A social network is one of the efficient tools for information propagation. The content is the bridge between the product and its customers. Evaluating the user's content creation is a valuable feature to improve information spreading on the social network. This paper proposes a method for extracting brand value with influencers by combining the user's amplification and content creation in influencer marketing. The amplification factors are studied based on the propagation of the posts on the social network in a duration time. Those factors are more valuable than before when using influencer marketing at a determined time. Moreover, the content creation score is also studied to measure content creation based on the passion point with a brand and its quality. The amplification factors and content creation score are combined to analyze posts' interest in detecting the emerging influent users for a product in the influencer marketing campaign. Using the amplification factors, the passion points, and the content creation score, a system to manage the influencer marketing on Facebook has been constructed and tested in the real-world campaign. The experimental results show that the proposed method's influencers bring the conversion rate's efficiency and revenue in the influencer marketing campaign. [ABSTRACT FROM AUTHOR]

Objective: Sparse representations have been utilized to identify functional connectivity (FC) of networks, while ICA employs the assumption of independence among the network sources to demonstrate FC. Here, we investigate a sparse decomposition method based on Morphological Component Analysis and K-SVD dictionary learning — MCA-KSVD — and contrast the effect of the sparsity constraint vs. the independency constraint on FC and denoising. Methods: Using a K-SVD algorithm, fMRI signals are decomposed into morphological components which have sparse spatial overlap. We present simulations when the independency assumption of ICA fails and MCA-KSVD recovers more accurate spatial-temporal structures. Denoising performance of both methods is investigated at various noise levels. A comprehensive experimental study was conducted on resting-state and task fMRI. Results: Validations show that ICA is advantageous when network components are well-separated and sparse. In such cases, the MCA-KSVD method has modest value over ICA in terms of network delineation but is significantly more effective in reducing spatial and temporal noise. Results demonstrate that the sparsity constraint yields sparser networks with higher spatial resolution while suppressing weak signals. Temporally, this localization effect yields higher contrast-to-noise ratios (CNRs) of time series. Conclusion: While marginally improving the spatial decomposition, MCA-KSVD denoises fMRI data much more effectively than ICA, preserving network structures and improving CNR, especially for weak networks. Significance: A sparsity-based decomposition approach may be useful for investigating functional connectivity in noisy cases. It may serve as an efficient decomposition method for reduced acquisition time and may prove useful for detecting weak network activations. [ABSTRACT FROM AUTHOR]

The endothelium maintains and regulates vascular homeostasis mainly by balancing interplay between vasorelaxation and vasoconstriction via regulating Nitric Oxide (NO) availability. Endothelial nitric oxide synthase (eNOS) is one of three NOS isoforms that catalyses the synthesis of NO to regulate endothelial function. However, eNOS's role in the regulation of endothelial function, such as cell proliferation and migration remain unclear. To gain a better understanding, we genetically knocked down eNOS in cultured endothelial cells using sieNOS and evaluated cell proliferation, migration and also tube forming potential in vitro. To our surprise, loss of eNOS significantly induced endothelial cell proliferation, which was associated with significant downregulation of both cell cycle inhibitor p21 and cell proliferation antigen Ki-67. Knockdown of eNOS induced cell migration but inhibited formation of tube-like structures in vitro. Mechanistically, loss of eNOS was associated with activation of MAPK/ERK and inhibition of PI3-K/AKT signaling pathway. On the contrary, pharmacologic inhibition of eNOS by inhibitors L-NAME or L-NMMA, inhibited cell proliferation. Genetic and pharmacologic inhibition of eNOS, both promoted endothelial cell migration but inhibited tube-forming potential. Our findings confirm that eNOS regulate endothelial function by inversely controlling endothelial cell proliferation and migration, and by directly regulating its tube-forming potential. Differential results obtained following pharmacologic versus genetic inhibition of eNOS indicates a more complex mechanism behind eNOS regulation and activity in endothelial cells, warranting further investigation. [ABSTRACT FROM AUTHOR]

Lung cancer remains a leading cause of death in cancer patients, and deregulation of apoptosis is a serious concern in clinical practice, even though therapeutic intervention has been greatly improved. Plants are a versatile source of biologically active compounds for anticancer drug discovery, and aspiletrein A (AA) is a steroidal saponin isolated from Aspidistra letreae that has a potent cytotoxic effect on various cancer cell lines. In this study, we investigated and determined the underlying molecular mechanism by which AA induces apoptosis. AA strongly induced apoptosis in NSCLC cells by mediating ROS generation and thereby activating AMP-activated protein kinase (AMPK) signaling. Consequently, downstream signaling and levels of phosphorylated mTOR and Bcl-2 were significantly decreased. Pretreatment with either an antioxidant, N-acetylcysteine, or an AMPK inhibitor, compound C, could reverse the apoptosis-inducing effect and counteract the effect of AA on the AMPK signaling pathway. Decreased levels of Bcl-2 were due to AA-mediating Bcl-2 degradation via a ROS/AMPK/mTOR axis-dependent proteasomal mechanism. Consistently, the apoptotic-inducing effect of AA was also observed in patient-derived malignant lung cancer cells, and it suppressed an in vitro 3D-tumorigenesis. This study identified the underlying mechanism of AA on lung cancer apoptosis, thereby facilitating potential research and development of this compound for further clinical implications. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is a rare neurovascular emergency that has been observed following COVID-19 infection, as well as following the use of non-mRNA COVID-19 vaccines. CASE PRESENTATION: The authors report a case of CVST in a 67-year-old woman, unvaccinated for COVID-19, who presented with acute otitis externa. It remains unclear whether the CVST was a following COVID-19 infection complication, otogenic CVST, or a combination of both. CONCLUSION: This case demonstrates the diagnostic and therapeutic dilemmas in managing this patient's challenging anticoagulation and antibiotic duration, as well as subsequent COVID-19 vaccination recommendations. [ABSTRACT FROM AUTHOR]

Summary: This article introduces a special issue of the Australian and New Zealand Journal of Statistics, dedicated as a Festschrift for Geoff McLachlan on the occasion of his 75th birthday. [ABSTRACT FROM AUTHOR]

Summary: The expectation–maximisation (EM) algorithm framework is an important tool for statistical computation. Due to the changing nature of data, online and mini‐batch variants of EM and EM‐like algorithms have become increasingly popular. The consistency of the estimator sequences that are produced by these EM variants often rely on an assumption regarding the continuous differentiability of a parameter update function. In many cases, the parameter update function is not in closed form and may only be defined implicitly, which makes the verification of the continuous differentiability property difficult. We demonstrate how a global implicit function theorem can be used to verify such properties in the cases of finite mixtures of distributions in the exponential family, and more generally, when the component‐specific distributions admit data augmentation schemes, within the exponential family. We then illustrate the use of such a theorem in the cases of mixtures of beta distributions, gamma distributions, fully visible Boltzmann machines and Student distributions. Via numerical simulations, we provide empirical evidence towards the consistency of the online EM algorithm parameter estimates in such cases. [ABSTRACT FROM AUTHOR]

Background: The transoral endoscopic thyroidectomy by vestibular approach (TOETVA) has been developed for early-stage thyroid cancer treatment as well as benign thyroid nodules worldwide including Viet Nam, with low rate of complications and excellent results. However, there has not been any comprehensive studies with a large number of patients and long-term follow-up in our country. Therefore, we conducted this study to evaluate the results of treatment by TOETVA for benign and malignant lesions of thyroid gland in Viet Nam. Methods: A prospective study was performed on 326 eligible patients who underwent TOETVA due to thyroid cancer and benign thyroid nodules in Department of Oncology and Palliative Care, Hanoi Medical University Hospital from July 2018 to April 2021. The clinical, surgical, and pathological characteristics, postoperative complications, and visual analog scale (VAS, 0–10 cm) score in day 1, 4, and 7 after surgery, long-term oncological and surgical outcomes were recorded. Results: The mean age was 36.9 ± 9.8 years. 231 patients (70.9%) were diagnosed with differentiated cancer and 95 patients (29.1%) were diagnosed benign tumors of thyroid gland. In the cancer group, 12 patients (5.2%) undergone TOETVA had T3b-intraoperative-stage diagnosis, 219 patients (92.2%) were diagnosed T1 according to AJCC 8th. After 1 month of surgery, among thyroid cancer patients, there was no abnormality reported by thyroid scintigraphy and neck ultrasound as well as in unstimulated-Tg and anti-Tg values. The mean number lymph-node dissected in the cancer group was 6.1 ± 4.1 (range 0–21 nodes). However, only 2.6 ± 1.8 metastasis nodes were discovered (range 1–8 nodes), and the maximum size of these nodes was less than 2 mm. 81 patients presented occult lymph-node metastasis among thyroid cancer patients with cN0 stage (account for 35%). The occult lymph-node metastasis was 34.2% and 50% in patients diagnosed with T1 and T3b groups, respectively. The median postoperative hospital stay was 5.4 ± 0.7 days. Postoperatively, transient hypoparathyroidism was recorded in 12 patients (4.8%), transient hoarse was noted in 9 patients (3.6%), and numb chin was identified in 7 patients (2.8%). No permanent complication was noted. VAS score on first postoperative day was 4.5 ± 0.8. Median follow-up time was 12 (3–25) months. No recurrence was recorded. Conclusions: TOETVA is an innovative and revolutionary technique in the treatment of benign thyroid nodules, as well as early-stage differentiated thyroid cancer. The results of oncology, postoperative complications, and satisfied outcomes supported the wide application of TOETVA in Viet Nam. [ABSTRACT FROM AUTHOR]

A qualitative inquiry study explores how religious vowed people experience forgiveness. Fourteen religious vowed men and women, living in relatively closed communities, shared their experiences of forgiveness over a lifetime of service. Grounded theory principals were utilized in data collection and analysis. Findings include a thematic description of how forgiveness is explained as an ongoing process involving offenses and transgressions, motivations, and challenges. Internal and social influences are discussed. Religious, spiritual, and family influences are identified, as well as community context. Forgiveness understanding is experienced as changing over time. Recommendations for counselors and other service providers are shared, and future qualitative exploration of the experiences of a wide range of cultural and religious groups is suggested. [ABSTRACT FROM AUTHOR]

Perfluorinated‐sulfonic‐acid‐based ionomers (PFSAs) are still the material of choice for electrochemical energy devices such as proton‐exchange membrane fuel cells or water electrolyzers. However, PFSAs show significant drawbacks ranging from a restricted temperature window of operation due to the insufficient thermomechanical stability, high cost, and questionable environmental properties. Recently, novel hydrocarbon‐based ionomers have been introduced, which not only have the potential to overcome these limitations, but also for the first time show promising performance, approaching that of PFSA‐based fuel cells and electrolyzers. This article summarizes the recent developments in this emerging field with a particular focus on the engineering of membrane‐electrode assemblies with hydrocarbon‐based polymer electrolytes. In the final part, the necessary key innovations are discussed, which are required for hydrocarbon ionomers to replace PFSAs in fuel cells and electrolyzers in the future. [ABSTRACT FROM AUTHOR]

Based on the solution of Young-Laplace equation using an inverse problem method for unknown capillary pressure, the exact parameterisation of the convex meridional profile of capillary bridges between two planar surfaces is presented in this paper. Mainly, two shapes of liquid bridges are discussed: nodoid and unduloid. In each case, from a set of observable data, we determine the exact parameterisation of the capillary bridges and their associated geometrical properties. The capillary pressure is recovered without direct measurements. The comparisons between the theory and the experiment demonstrate the accuracy of the analytical calculations. [ABSTRACT FROM AUTHOR]

[Display omitted] A series of complexes between bis(2-pyridyl)-di(4- n -butylphenyl)ethene (KT4) and bis(2-pyridyl)-di(3-methoxyphenyl)ethene (KT18) with transition metals Co(II), Cu(II), Zn(II), and Cd(II) were synthesized and crystallized. The structures of these compounds were confirmed based on IR, NMR, and MS spectra. Moreover, crystals were obtained for ZnKT18, CoKT18, CuKT18, CdKT18, and CdKT4. Single-crystal X-ray diffraction (XRD) demonstrated the ability of these pyridine-based ligands to coordinate to metal ions via two nitrogen atoms in the aromatic heterocycles. Depending on the central metal, they can form different structures. Zn(II) and Co(II) form mononuclear complexes with KT18 , where the metal coordinates to two N atoms and two chloride ions in a tetrahedral geometry (coordination number 4). The complexes CuKT18 , CdKT18 , and CdKT4 are binuclear complexes with one pendant chloride and two bridging chlorides coordinating with the metal ion (coordination number 5). The cytotoxic properties of free ligands and complexes were tested on four cancer lines, including KB, Hep-G2, Lu, and MCF-7. In general, the free ligands have no cytotoxic activity, while all complexes present strong to medium effects on these cancer lines. Several complexes are comparable in activity to cisplatin, a commercial drug used in the treatment of cancer. Specifically, ZnKT4 selectively inhibits the activities of the KB and Hep-G2 cell lines. CdKT4 has a high impact on Hep-G2 and Lu (IC 50 < 5 μM) while CdKT18 exhibits effective anticancer activity against the KB and MCF-7 cell lines. CuKT18 strongly inhibits the growth progress of the KB cancer cell (IC 50 = 9.52 μM). These IC 50 values are lower than those of cisplatin. [ABSTRACT FROM AUTHOR]

Topotactic transitions, that is, reversible crystal structure changes due to controllable stoichiometry of material, offer substantial potential to control a wide variety of functionality in transition metal oxides, especially in systems with high ionic mobility and correlated electrons. Here the authors report on topotactic electrochromism with prominent coloration efficiency in SrCo0.66Fe0.34O3−δ associated with changes of electrical conductivity and electronic structure of the material. Changes in electron correlation lead to significant coloration and light absorption, which provides a general approach for utilizing topotactic transitions in electrochromic applications. [ABSTRACT FROM AUTHOR]

A broadly applicable methodology for the regio‐ and enantioselective construction of branched allylic carbon‐heteroatom bonds from racemic, secondary allylic trichloroacetimidates has been developed. The branched allylic substrates undergo dynamic kinetic asymmetric substitution reactions with a number of unactivated anilines and carboxylic acids as well as unactivated aromatic thiols in the presence of a chiral bicyclo[3.3.0]octadiene‐ligated iridium catalyst. The allylic C−O, C−N, and C−S bond containing products are obtained in synthetically useful yield and selectivity. Mechanistic studies suggest that the iridium‐catalyzed enantioselective substitution reactions of heteroatom nucleophiles with allylic trichloroacetimidate substrates through an outer‐sphere nucleophilic addition mechanism. In addition, the chiral diene‐ligated iridium catalyst is effective at promoting asymmetric aminations of acyclic secondary anilines. Importantly, this catalytic iridium methodology enables the use of alkyl substituted allylic electrophiles. [ABSTRACT FROM AUTHOR]

Host-specific legume-rhizobium symbiosis is strictly controlled by rhizobial type III effectors (T3Es) in some cases. Here, we demonstrated that the symbiosis of Vigna radiata (mung bean) with Bradyrhizobium diazoefficiens USDA110 is determined by NopE, and this symbiosis is highly dependent on host genotype. NopE specifically triggered incompatibility with V. radiata cv. KPS2, but it promoted nodulation in other varieties of V. radiata, including KPS1. Interestingly, NopE1 and its paralogue NopE2, which exhibits calcium-dependent autocleavage, yield similar results in modulating KPS1 nodulation. Furthermore, NopE is required for early infection and nodule organogenesis in compatible plants. Evolutionary analysis revealed that NopE is highly conserved among bradyrhizobia and plant-associated endophytic and pathogenic bacteria. Our findings suggest that V. radiata and B. diazoefficiens USDA110 may use NopE to optimize their symbiotic interactions by reducing phytohormone-mediated ETI-type (PmETI) responses via salicylic acid (SA) biosynthesis suppression. [ABSTRACT FROM AUTHOR]

Phenanthroline, a rigid and planar compound with two fused pyridine rings, has been used as a powerful ligand for metals and a binding agent for DNA/RNA. We discovered that phenanthroline could be used as a nucleophilic catalyst to efficiently access high yielding and diastereoselective α‐1,2‐cis glycosides through the coupling of hydroxyl acceptors with α‐glycosyl bromide donors. We have conducted an extensive investigation into the reaction mechanism, wherein the two glycosyl phenanthrolinium ion intermediates, a 4C1 chair‐liked β‐conformer and a B2,5 boat‐like α‐conformer, have been detected in a ratio of 2:1 (β:α) using variable temperature NMR experiments. Furthermore, NMR studies illustrate that a hydrogen bonding is formed between the second nitrogen atom of phenanthroline and the C1‐anomeric hydrogen of sugar moiety to stabilize the phenanthrolinium ion intermediates. To obtain high α‐1,2‐cis stereoselectivity, a Curtin‐Hammett scenario was proposed wherein interconversion of the 4C1 chair‐like β‐conformer and B2,5 boat‐like α‐conformer is more rapid than nucleophilic addition. Hydroxyl attack takes place from the α‐face of the more reactive 4C1 β‐phenanthrolinium intermediate to give an α‐anomeric product. The utility of the phenanthroline catalysis is expanded to sterically hindered hydroxyl nucleophiles and chemoselective coupling of an alkyl hydroxyl group in the presence of a free C1‐hemiacetal. In addition, the phenanthroline‐based catalyst has a pronounced effect on site‐selective couplings of triol motifs and orthogonally activates the anomeric bromide leaving group over the anomeric fluoride and sulfide counterparts. [ABSTRACT FROM AUTHOR]

Fluid pressurization of critically stressed sheared zones can trigger slip mechanisms at work in many geological processes. Using discrete element modeling, we simulate pore‐pressure‐step creep test experiments on a sheared granular layer under a sub‐critical stress state to investigate the micromechanical processes at stake during fluid induced reactivation. The global response is consistent with available experiments. The progressive increase of pore pressure promotes slow steady creep at sub‐critical stress states, and fast accelerated dynamic slip once the critical strength is overcome. Our multi‐scale analyses show that these two emergent behaviors correlate to characteristic deformation modes: diffuse deformation during creep, and highly localized deformation during rupture. Creep corresponds to bulk deformation while rupture results from grain rotations initiating from overpressure induced unlocking of contacts located within the shear band which, consequently, acts as a roller bearing for the surrounding bulk. Plain Language Summary: Fluids can be at the origin of catastrophic disasters, e.g., earthquakes related to deep subsurface fluid injections or lanslides triggered by short‐term changes of hydrological conditions. It is now well assumed that these phenomena originate from mechanisms taking place in critically stressed shear zones found along tectonic faults, rock mass fractures or localized deformation bands. The increase of pore pressure promotes slip along these shear zones as confirmed by numerous experimental and numerical studies. In this work, we present computer simulations that reproduce the progressive reactivation of a granular shear zone as a result of fluid pressurization. Our simulations provide grain‐scale information that improves understanding of fluid induced slip behaviors and illuminate micromechanical details of phenomenological, macroscale observations. Key Points: Fluid induced reactivation can be either stable or unstable depending on the deformation modeSlow steady creep is accommodated through distributed bulk deformation at sub‐critical stress statesAccelerated dynamic slip results from intense grain rearrangements localized within the shear band [ABSTRACT FROM AUTHOR]

This study aimed to clarify the antidementia effects of ethanolic extract of Ocimum sanctum Linn. (OS) and its underlying mechanisms using olfactory bulbectomized (OBX) mice. OBX mice were treated daily with OS or a reference drug, donepezil (DNP). Spatial and nonspatial working memory performance was measured using a modified Y maze test and a novel object recognition test, respectively. Brain tissues of the animals were subjected to histochemical and neurochemical analysis. OS treatment attenuated OBX-induced impairment of spatial and nonspatial working memories. OBX induced degeneration of septal cholinergic neurons, enlargement of the lateral ventricles, and suppression of hippocampal neurogenesis. OS and DNP treatment also depressed these histological damages. OS administration reduced ex vivo activity of acetylcholinesterase in the brain. OBX diminished the expression levels of genes coding vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2). Treatment with OS and DNP reversed OBX-induced decrease in VEGF gene and protein expression levels without affecting the expression of the VEGFR2 gene. These results demonstrate that the administration of OS can lessen the cognitive deficits and neurohistological damages of OBX and that these actions are, at least in part, mediated by the enhancement of central cholinergic systems and VEGF expression. [ABSTRACT FROM AUTHOR]

Under different pathophysiological conditions, endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1, and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development; however, EndMT is also implicated in the pathogenesis of several genetically determined and acquired diseases, including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases, aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis, and cardiac fibrosis. Accordingly, understanding the mechanisms behind the cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy for treating aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and a lack of robust animal models and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Endothelial autophagy plays an important role in the regulation of endothelial function. The inhibition of endothelial autophagy is associated with the reduced expression of protein disulfide isomerase 4 (PDIA-4); however, its role in endothelial cells is not known. Here, we report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cell architecture, accompanied by the loss of endothelial markers and the gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). The loss of PDIA-4 activated TGFβ-signaling, and inhibition of TGFβ-signaling suppressed EndMT in PDIA-4-silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate endothelial function and/or limit autophagy and EndMT in (patho-)physiological conditions. [ABSTRACT FROM AUTHOR]

The rising adoption of agricultural technologies such as the Internet of Things (IoT) or "smart farming" aims to boost crop production in terms of both quantity and quality. This study compares the benefits of a smart farm employing an IoT-based hydroponic system with those of a conventional hydroponic farm, using Chinese cabbage (Brassica pekinensis L.) as the experimental crop. Our primary objective was to automate environmental monitoring, achieving pH level and electrical conductivity (EC) maintenance through smartphone or computer interfaces for nutrient and acid–base solution adjustments. Additionally, we evaluated plant growth and crop quality, finding superior results with the smart hydroponic system. On average, there were substantial increases in various parameters, including total fresh weight (27.14%), total dry weight (48.90%), plant height (11.14%), stem diameter (32.89%), leaf area (94.30%), leaf width (32.36%), leaf length (38.12%), and chlorophyll content (22.73%). Nitrate accumulation in the edible parts of Chinese cabbage remained within safe limits for both systems, reflecting careful nutrient management. These findings highlight the potential of IoT-based technology in enhancing productivity and quality in hydroponic farming, marking a significant step towards revolutionizing traditional agricultural practices for more efficient crop production systems. [ABSTRACT FROM AUTHOR]

A novel and efficient palladium-catalyzed direct mono and tetraarylation of tetrathienylethene with various arylbromides to synthesize donor-acceptor system of tetrathienylethene-arene (TTE-Ar) luminophores is reported. The mono- and tetra-arylated TTEs shown an emissive phenomenon, including photoluminescence in various organic solvents and aggregation induced emission (AIE) effect because TTE acts both as an electron-donor for intramolecular charge transfer (ICT) and as activator for AIE. The photoluminescence and AIE of these aryl-substituted TTEs are characterized. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] The effect of dextran molecular weight on the in vitro physicochemical and immune properties of cytosine-phosphate-guanine (CpG) oligodeoxynucleotide-amino-dextran conjugates is investigated. CpG-1668 was conjugated at the 3′-end to amino-dextran of differing molecular weight (20, 40, 70 or 110-kDa) via a stable bis-aryl hydrazone linkage. Conjugate formation was confirmed by agarose gel electrophoresis and dynamic light scattering measured the size and surface charge of conjugates. Uptake and immune-stimulatory activity of CpG-dextran by antigen-presenting cells was evaluated by flow cytometry and confocal microscopy. Degradation by DNase I was monitored by loss of the fluorescent signal from labelled CpG and changes in size and zeta potential. Hydrazone bond formation (UV 354 nm) showed on average four CpG molecules conjugated per polymer. CpG-dextran prepared from 20 or 40-kDa dextran had a size of 17 nm while 70 or 110-kDa was 30 nm. CpG-dextran was preferentially taken up by dendritic cells, followed by macrophages and then B-cells. Only the 20-kDa dextran conjugate significantly enhanced uptake by bone-marrow derived dendritic cells (BMDCs) compared to free CpG. Confocal microscopy showed that CpG and CpG-dextran accumulates in the endo -lysosomal compartment of BMDCs at 24 h. All conjugates upregulated activation markers (CD40, CD80 or CD86) of BMDCs to a similar level as for free CpG. CpG-dextran 40-kDa produced highest levels of cytokines (TNF-α, IL-6, and IL-12p70) secreted by BMDCs. Enzymatic protection assays showed that the conjugate made from dextran 20-kDa provided no protection for CpG while the higher molecular weight conjugates reduced degradation by DNase I. The 40-kDa dextran conjugate produced the greatest in vitro immune activity, this was due to the conjugate being relatively small in size for cell uptake while sufficiently large enough to protect CpG from nuclease attack. These in vitro studies identify the need to consider the molecular weight of the carrier in bioconjugate design. [ABSTRACT FROM AUTHOR]

Advanced services have caught the attention of industries and academics as a way to exploit new customer value propositions. However, the existing design methodologies for advanced services are limited to partially addressing one or some key design elements, hence causing confusion in practice. Moreover, human factors are not often addressed, even though the design for advanced services requires human-centered thinking. Aiming to advance the body of research, the current study aims to conceptually propose a multidimensional design methodology called DIMAND that captures the key design elements and their relations in a single-view structure in accordance with a human-centric approach. Specifically, DIMAND encapsulates the (i) life-cycle service design interrelated with other key design elements—(ii) stakeholder networks, (iii) new service development methods, and (iv) design skills—that must be considered to develop effective advanced service design. Based on a hybrid research design, DIMAND was conceptually developed through systematic reviews and structured analysis of existing design methodologies, as well as an elicitation of expert knowledge in the domain through the analytical hierarchy process (AHP). For validation, the average usability score of DIMAND as evaluated by 26 practitioners was 72.2, which falls into "excellence" on the simplified system usability scale (SUS), hence confirming its potential utility. As a result, DIMAND offers a novel and holistic guideline for design practitioners and engineers to obtain coherence in all the life-cycle design processes by simultaneously taking these key design elements and their relations into account, making the design of advanced services more practical. [ABSTRACT FROM AUTHOR]

The class of location-scale finite mixtures is of enduring interest both from applied and theoretical perspectives of probability and statistics. We establish and prove the following results: to an arbitrary degree of accuracy, (a) location-scale mixtures of a continuous probability density function (PDF) can approximate any continuous PDF, uniformly, on a compact set; and (b) for any finite p ≥ 1 , location-scale mixtures of an essentially bounded PDF can approximate any PDF in L p , in the L p norm. [ABSTRACT FROM AUTHOR]

Expectiles form a family of risk measures that have recently gained interest over the more common value-at-risk or return levels, primarily due to their capability to be determined by the probabilities of tail values and magnitudes of realizations at once. However, a prevalent and ongoing challenge of expectile inference is the problem of uncertainty quantification, which is especially critical in sensitive applications, such as in medical, environmental, or engineering tasks. We address this issue by developing a novel distribution, termed the multivariate expectile-based distribution (MED), that possesses an expectile as a closed-form parameter. Desirable properties of the distribution, such as log-concavity, make it an excellent fitting distribution in multivariate applications. Maximum likelihood estimation and Bayesian inference algorithms are described. Simulated examples and applications to expectile and mode estimation illustrate the usefulness of the MED for uncertainty quantification. • MED distribution is log-concave, unimodal, and its unique mode is an expectile. • It yields well-calibrated credible intervals for uncertainty quantification in expectile estimation. • MEDdist R package provides density, distribution, and quantile functions, and random sampling for the MED. [ABSTRACT FROM AUTHOR]

Porcine epidemic diarrhea (PED) virus (PEDV) is a highly contagious virus. PED was first identified in 2008 and has greatly affected the Vietnamese pig production economy. The aim of this study was to investigate the epidemiological and genetic characteristics of PEDV in piglet herds in the Mekong Delta, Vietnam. Diarrheal stool and intestinal samples from 2262 piglets from 191 herds in five provinces were collected to test for the presence of PEDV. Ten PEDV strains were randomly selected for sequencing, and four genes encoding PEDV structural proteins were analyzed. The rates of herds and samples positive for PEDV were 27.23% and 27.72%, respectively. In positive herds, the morbidity and mortality of PEDV-positive piglets were 97.97% and 79.06%, respectively, with most of the infected piglets under 7 days of age. Phylogenetic analysis showed that the 10 PEDV strains from this study clustered with genotype G2 strains from Vietnam and neighboring countries. Many amino acid substitutions were identified in important antigenic regions in the spike protein of the 10 strains when compared to four PEDV vaccine strains. This study provides novel insights into the epidemiology and genetic diversity of circulating PEDV strains, which could facilitate the development of an appropriate and proactive strategy for controlling PED. [ABSTRACT FROM AUTHOR]

L7652 --> 947.32 --> Background: Endothelial cells help maintain vascular homeostasis mainly by balancing interplay between vasorelaxation and vasoconstriction via regulating availability of Nitric Oxide (NO). Endothelial nitric oxide synthase (eNOS) is one of three NOS isoforms that catalyses the synthesis of NO to regulate endothelial function. To date, however, eNOS's role in endothelial cell proliferation, remains unclear. Methods and Results: To gain a better understanding about eNOS and cell proliferation, we genetically inhibited eNOS viasilencing by transfecting cultured human umbilical vein endothelial cells with sieNOS or scrambled control. Successful eNOS silencing was confirmed at transcript and protein levels, and then endothelial cell proliferation was evaluated. Surprisingly, loss of eNOS significantly induced endothelial cell proliferation, concomitant with significant downregulation of both cell cycle inhibitor p21 and cell proliferation antigen Ki‐67. To confirm the specificity of eNOS silencer, we used another sieNOS molecule, which also showed the similar results as endothelial proliferation was significantly induced in eNOS‐silenced endothelial cells. Later, to demonstrate that the induced endothelial cell proliferation is due to eNOS inhibition, we pharmacologically inhibited eNOS by treating endothelial cells with L‐NAME. Contrastingly, L‐NAME‐treatment significantly inhibited endothelial cell proliferation in a dose‐dependent manner. Conclusion: Our findings, for the first time, indicate that eNOS regulate endothelial function by directly controlling endothelial cell proliferation. Observed inhibition of endothelial cell proliferation by L‐NAME, may be due to its non‐specific effects. The findings also indicate that eNOS and L‐NAME might employ different pathways regulating endothelial cell proliferation warranting further investigation. [ABSTRACT FROM AUTHOR]

We report on efforts to improve the speed of low-G far-infrared transition-edged-sensed bolometers. We use a fabrication process that does not require any dry etch steps to reduce heat capacity on the suspended device and measure a reduction in the detector time constant. However, we also measure an increase in the temperature-normalized thermal conductance (G) and a corresponding increase in the noise-equivalent power (NEP). We employ a new near-IR photon-noise technique using a near-IR laser to calibrate the frequency-domain multiplexed AC system and compare the results to a well-understood DC circuit. We measure an NEP white noise level of 0.8 aW/rtHz with a 1/f knee below 0.1 Hz and a time constant of 3.2 ms. [ABSTRACT FROM AUTHOR]