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Vietnam is among the countries with the highest prevalence of chronic hepatitis B (CHB) and individuals who suffer from CHB oftentimes perceive high levels of stigma and discrimination. Our study aimed to provide evidence on the prevalence of stigma against hepatitis B virus (HBV), HBV infection, and social determinants of stigma and discrimination in patients. A cross-sectional study was conducted at Viet-Tiep Hospital, Hai Phong, Vietnam. Stigma and discrimination against CHB in the last month were measured via four dimensions: (1) Blame/Judgment; (2) Shame; (3) Discrimination in different settings; (4) Disclosure of CHB status. Multivariate Logistic and Tobit regressions were used to identify factors associated with CHB-related stigma and discrimination. Among 298 enrolled patients, 4.8% experienced blame/judgement, 10.2% perceived shame, 48.5% felt discriminated in healthcare facilities, and 90.6% disclosed their health status with spouses/partners. Factors associated with lower odds of CHB-related stigma/discrimination included living with spouses/partners, old age, being employed, and the existence of comorbidities was linked with higher odds of stigma. Anti-stigma programs should target those who are younger and have comorbidities. This could be done by community-based interventions which focus on inaccurate beliefs about viral hepatitis. Furthermore, families, healthcare providers, and society should play a crucial role in supporting CHB patients.
Two commercially available enzymes, Dextrozyme (α-amylase) and Esperase (protease), were covalently immobilized on non-woven electrospun poly(styrene-co-maleic anhydride) nanofiber mats with partial retention of their catalytic activity. Immobilization was achieved for the enzymes on their own as well as in different combinations with an additional enzyme, β-galactosidase, on the same non-woven nanofiber mat. This experiment yielded a universal method for immobilizing different combinations of enzymes with nanofibrous mats containing maleic anhydride (MAnh) residues in the polymer backbone.
To define the links between paramyxovirus budding and cellular ESCRT machinery, we previously identified angiomotin-like 1 (AMOTL1) in a screen for host factors that bind to the matrix (M) protein of parainfluenza virus 5 (PIV5). This protein harbors three L/PPXY sequences, allowing it to interact with WW domain containing proteins including NEDD4 family members. We hypothesize that paramyxoviruses use AMOTL1 as a linker to indirectly recruit the same NEDD4 ubiquitin ligases for budding that other enveloped viruses recruit directly through their PPXY late domains. In support of this hypothesis, we found that AMOTL1 could link together M proteins and NEDD4 family proteins in three-way co-IP experiments. Both PIV5 and mumps virus M proteins could be linked to the NEDD4 family proteins NEDD4-1, NEDD4L, and NEDL1, provided that AMOTL1 was co-expressed as a bridging protein. AMOT and AMOTL2 could not substitute for AMOTL1, as they lacked the ability to bind with paramyxovirus M proteins. Attachment of a PPXY late domain sequence to PIV5 M protein obviated the need for AMOTL1 as a linker between M and NEDD4 proteins. Together, these results suggest a novel host factor recruitment strategy for paramyxoviruses to achieve particle release.
Organic phosphates and phosphonates are present in a number of cellular components that can be damaged by exposure to ionizing radiation. This work reports femtosecond time-resolved mass spectrometry (FTRMS) studies of three organic phosphonate radical cations that model the DNA sugar-phosphate backbone: dimethyl methylphosphonate (DMMP), diethyl methylphosphonate (DEMP), and diisopropyl methylphosphonate (DIMP). Upon ionization, each molecular radical cation exhibits unique oscillatory dynamics in its ion yields resulting from coherent vibrational excitation. DMMP has particularly well-resolved 45 fs ( 732 ± 28 cm - 1 ) oscillations with a weak feature at 610⁻650 cm - 1 , while DIMP exhibits bimodal oscillations with a period of ∼55 fs and two frequency features at 554 ± 28 and 670⁻720 cm - 1 . In contrast, the oscillations in DEMP decay too rapidly for effective resolution. The low- and high-frequency oscillations in DMMP and DIMP are assigned to coherent excitation of the symmetric O⁻P⁻O bend and P⁻C stretch, respectively. The observation of the same ionization-induced coherently excited vibrations in related molecules suggests a possible common excitation pathway in ionized organophosphorus compounds of biological relevance, while the distinct oscillatory dynamics in each molecule points to the potential use of FTRMS to distinguish among fragment ions produced by related molecules.
Sample preparation is an important step when testing the mechanical properties of materials. Especially, when carbon nanotubes (CNT) are added to epoxy resin, the increase in viscosity complicates the casting of testing specimens. We present a vacuum casting approach for different geometries in order to produce specimens from functional nanocomposites that consist of epoxy matrix and oxidized multi-walled carbon nanotubes (MWCNTs). The nanocomposites were characterized with various mechanical tests that showed improved fracture toughness, bending and tensile properties performance by addition of oxidized MWCNTs. Strengthening mechanisms were analyzed by SEM images of fracture surfaces and in-situ imaging by digital image correlation (DIC).
Aedes aegypti (L.) is the primary vector of chikungunya, dengue, yellow fever, and Zika viruses. The leucine-rich repeats (LRR)-containing domain is evolutionarily conserved in many proteins associated with innate immunity in invertebrates and vertebrates, as well as plants. We focused on the AaeLRIM1 and AaeAPL1 gene expressions in response to Zika virus (ZIKV) and chikungunya virus (CHIKV) infection using a time course study, as well as the developmental expressions in the eggs, larvae, pupae, and adults. RNA-seq analysis data provided 60 leucine-rich repeat related transcriptions in Ae. aegypti in response to Zika virus (Accession number: GSE118858, accessed on: August 22, 2018, GEO DataSets). RNA-seq analysis data showed that AaeLRIM1 (AAEL012086-RA) and AaeAPL1 (AAEL009520-RA) were significantly upregulated 2.5 and 3-fold during infection by ZIKV 7-days post infection (dpi) of an Ae. aegypti Key West strain compared to an Orlando strain. The qPCR data showed that LRR-containing proteins related genes, AaeLRIM1 and AaeAPL1, and five paralogues were expressed 100-fold lower than other nuclear genes, such as defensin, during all developmental stages examined. Together, these data provide insights into the transcription profiles of LRR proteins of Ae. aegypti during its development and in response to infection with emergent arboviruses.
In biomedical signal processing, we often face the problem of artifacts that distort the original signals. This concerns also sleep recordings, such as EEG. Artifacts may severely affect or even make impossible visual inspection, as well as automatic processing. Many proposed methods concentrate on certain artifact types. Therefore, artifact-free data are often obtained after sequential application of different methods. Moreover, single-channel approaches must be applied to all channels alternately. The aim of this study is to develop a multichannel artifact detection method for multichannel sleep EEG capable of rejecting different artifact types at once. The inspiration for the study is gained from recent advances in the field of Riemannian geometry. The method we propose is tested on real datasets. The performance of the proposed method is measured by comparing detection results with the expert labeling as a reference and evaluated against a simpler method based on Riemannian geometry that has previously been proposed, as well as against the state-of-the-art method FASTER. The obtained results prove the effectiveness of the proposed method.
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, and despite optimized treatment options, median survival remains dismal. Contemporary evidence suggests disease recurrence results from expansion of a robustly radioresistant subset of GBM progenitor cells, termed GBM stem cells (GSCs). In this study, we utilized transmission electron microscopy to uncover ultrastructural effects on patient-derived GSC lines exposed to supratherapeutic radiotherapy levels. Elevated autophagosome formation and increased endoplasmic reticulum (ER) internal diameter, a surrogate for ER stress and activation of unfolded protein response (UPR), was uncovered. These observations were confirmed via protein expression through Western blot. Upon interrogating genomic data from an open-access GBM patient database, overexpression of UPR-related chaperone protein genes was inversely correlated with patient survival. This indicated controlled UPR may play a role in promoting radioresistance. To determine if potentiating UPR further can induce apoptosis, we exposed GSCs to radiation with an ER stress-inducing drug, 2-deoxy-D-glucose (2-DG), and found dose-dependent decreases in viability and increased apoptotic marker expression. Taken together, our results indicate GSC radioresistance is, in part, achieved by overexpression and overactivation of ER stress-related pathways, and this effect can be overcome via potentiation of UPR, leading to loss of GSC viability.
Metagenomics can be used to identify potential biocontrol agents for invasive species and was used here to identify candidate species for biocontrol of an invasive club moss in New Zealand. Profiles were obtained for Selaginella kraussiana collected from nine geographically disjunct locations in Northern New Zealand. These profiles were distinct from those obtained for the exotic club moss Selaginella moellendorffii and the native club mosses Lycopodium deuterodensum and Lycopodium volubile also collected in Northern New Zealand. Fungi and bacteria implicated elsewhere in causing plant disease were identified on plants of Selaginella that exhibited signs of necrosis. Most notably, high densities of sequence reads from Xanthomonas translucens and Pseudomonas syringae were associated with some populations of Selaginella but not Lycopodium. Since these bacteria are already in use as biocontrol agents elsewhere, further investigation into their potential as biocontrol of Selaginella in New Zealand is suggested.
The distribution of pyrethroid insecticide deltamethrin (DLM) in goat milk and cheese (caciotta) following pour-on administration at the sheep dosage (DLMS-10 mL/60 kg body weight) and double dosage (DLMD-20 mL/60 kg body weight) was studied. DLM concentrations were measured in milk collected from study animals (No.14) before treatment and at 2, 4, 8, 12, 16, 24, 30, 36, 48, 56, until 168 h (7 days) post treatment and in caciotta cheese at 12 and 24 h post treatment. At both dosages, the maximum level of DLM residues in goat milk and cheese was below the maximum residue limit (MRL) of 20 μg kg-1 established for bovine milk (EU No 37/2010) at all time points. However, in terms of public health, higher DLM residues in cheese show that further specific studies should be performed on double dosage efficacy and pharmacokinetic and pharmacodynamics properties of ectoparasites in lactating goats.
The electron-transfer flavoprotein dehydrogenase gene (ETFDH) that encodes the ETF-ubiquinone oxidoreductase (ETF-QO) has been reported to be the major cause of multiple acyl-CoA dehydrogenase deficiency (MADD). ETF-QO is an electron carrier that mainly functions in mitochondrial fatty acid β-oxidation and the delivery of electrons to the ubiquinone pool in the mitochondrial respiratory chain. A high frequency of c.250G>A has been found in Taiwanese patients with late-onset MADD. We postulated that the ETFDH c.250G>A mutation may concomitantly impair fatty acid β-oxidation and mitochondrial function. Using MADD patient-derived lymphoblastoid cells and specifically overexpressed ETFDH c.92C>T, c.250G>A, or coexisted c.92C>T and c.250G>A (c.92C>T + c.250G>A) mutated lymphoblastoid cells, we addressed the genotype-phenotype relationship of ETFDH variation in the pathogenesis of MADD. The decreased adenosine triphosphate synthesis, dissipated mitochondrial membrane potentials, reduced mitochondrial bioenergetics, and increased neutral lipid droplets and lipid peroxides were found in the MADD patient-derived lymphoblastoid cells. Riboflavin and/or coenzyme Q10 supplementation rescued cells from lipid droplet accumulation. All three mutant types, c.92C>T, c.250G>A, or c.92C>T + c.250G>A, had increased lipid droplet accumulation after treatment with palmitic acid. These results help to clarify the molecular pathogenesis of MADD as a result of the high frequency of the ETFDH c.250G>A and c.92C>T mutations.
Benefiting from big data, powerful computation and new algorithmic techniques, we have been witnessing the renaissance of deep learning, particularly the combination of natural language processing (NLP) and deep neural networks. The advent of electronic medical records (EMRs) has not only changed the format of medical records but also helped users to obtain information faster. However, there are many challenges regarding researching directly using Chinese EMRs, such as low quality, huge quantity, imbalance, semi-structure and non-structure, particularly the high density of the Chinese language compared with English. Therefore, effective word segmentation, word representation and model architecture are the core technologies in the literature on Chinese EMRs.
Signal transducer and activator of transcription 3 (STAT3) is an oncogene constitutively activated in hepatocellular carcinoma (HCC) cells and HCC cancer stem cells (CSCs). Constitutively activated STAT3 plays a pivotal role in holding cancer stemness of HCC CSCs, which are essential for hepatoma initiation, relapse, metastasis and drug resistance. Therefore, STAT3 has been validated as a novel anti-cancer drug target and the strategies targeting HCC CSCs may bring new hopes to HCC therapy. This study aimed to isolate and identify small-molecule STAT3 signaling inhibitors targeting CSCs from the ethyl acetate (EtOAc) extract of the roots of Polygonum cuspidatum and to evaluate their in vitro anti-cancer activities.
Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), causing large economical losses of the global swine industry. Nitric oxide (NO), as an important signaling molecule, has antiviral activity on some viruses. To date, there is little information on the role of NO during PCV2 infection.
Bartonella henselae, Bartonella clarridgeiae and the rare Bartonella koehlerae are zoonotic pathogens, with cats being regarded as the main reservoir hosts. The spread of the infection among cats occurs mainly via fleas and specific preventive measures need to be implemented. The effectiveness of a 10% imidacloprid/4.5% flumethrin polymer matrix collar (Seresto®, Bayer Animal Health), registered to prevent flea and tick infestations, in reducing the risk of Bartonella spp. infection in privately owned cats, was assessed in a prospective longitudinal study.
Functionality and versatility of microprocessor-controlled stance-control knee-ankle-foot orthoses (M-SCKAFO) are dictated by their embedded control systems. Proper gait phase recognition (GPR) is required to enable these devices to provide sufficient knee-control at the appropriate time, thereby reducing the incidence of knee-collapse and fall events. Ideally, the M-SCKAFO sensor system would be local to the thigh and knee, to facilitate innovative orthosis designs that allow more flexibility for ankle joint selection and other orthosis components. We hypothesized that machine learning with local sensor signals from the thigh and knee could effectively distinguish gait phases across different walking conditions (i.e., surface levels, walking speeds) and that performance would improve with gait phase transition criteria (i.e., current states depend on previous states).
Carbon ion radiotherapy (CIRT) has been delivered to more than 20,000 patients worldwide. International trials have been recommended in order to emphasize the actual benefits. The ULICE program (Union of Light Ion Centers in Europe) addressed the need for harmonization of CIRT practices. A comparative knowledge of the sources and magnitudes of uncertainties altering dose distribution and clinical effects during the whole CIRT procedure is required in that aim.
Although the role of axillary imaging has been redirected for predicting high nodal burden rather than predicting nodal metastases since ACOSOG Z1011 trial, it remains unclear whether and how axillary lymph node (ALN) characteristics predicts high nodal burden. Our study was aimed to evaluate the predictive value of imaging characteristics of ALNs at ultrasound and magnetic resonance imaging (MRI) for prediction of high nodal burden (≥3 metastatic ALNs) in clinically node-negative breast cancer patients.
Crimean Congo Hemorrhagic Fever (CCHF) is a highly infectious zoonotic disease of humans transmitted by Hyalomma ticks. Earlier studies have shown CCHF seroprevalence in livestock throughout India, yet sporadic outbreaks have been recorded mostly from the Gujarat state of India since 2011. Occupational vulnerability to CCHF for animal handlers, veterinarians, abattoir workers, and healthcare workers has been documented. The current study was planned to determine the seroprevalence of CCHF with an intention to identify the high -risk population and high -risk areas from Gujarat state, India.
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