We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer–specific gene expressions were evaluated using ...mRNA from the isolated CTCs. A CTC‐based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone‐sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration‐resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate‐specific antigen (PSA), prostate‐specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR‐V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC‐based genetic signatures may guide the early diagnosis of advanced prostate cancer.
CTCs have useful biological information for understanding the prostate cancer aggressiveness. CTC‐based gene signatures have potential for early diagnosis of metastatic prostate cancer. Multigene profile (AR, AR‐V7, PSA, PSMA, EpCAM, and KRT19) may guide the diagnosis and treatment of metastatic prostate cancer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
► Identified factors leading to preference for social interaction in online support groups (OSGs) over offline interaction. ► Conducted an online survey of current users of health-related OSGs. ► ...Found that those who were dissatisfied with support from offline contacts tended to prefer social interaction in OSGs. ► Found that preference for social interaction in OSGs was prominent among those who developed intimate relationships in OSGs.
The purpose of the current study was to identify potential factors leading to preference for social interaction in online support groups (OSGs) over offline interaction. By identifying such factors, the current study advances understanding of the way patients use the Internet as a supportive resource and integrate support from offline and online relationships. An online survey was conducted with current users of health-related OSGs (N=158). Findings show that those who were dissatisfied with the support they received from their current offline contacts were more likely to prefer social interaction in OSGs. Such a preference was prominent among those who built deeper social relationships in OSGs. Results suggest that some people develop a preference for social interaction in OSGs over offline interaction and use computer-mediated relationships as a possible alternative to offline support networks. Healthcare professionals and users as well as designers of OSGs must acknowledge the limits of online support and caution against the possibility of developing excessive reliance on online support resources.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Inhibition and eradication of Staphylococcus aureus biofilms with conventional antibiotic is difficult, and the treatment is further complicated by the rise of antibiotic resistance among ...staphylococci. Consequently, there is a need for novel antimicrobials that can treat biofilm-related infections and decrease antibiotics burden. Natural compounds such as eugenol with anti-microbial properties are attractive agents that could reduce the use of conventional antibiotics. In this study we evaluated the effect of eugenol on MRSA and MSSA biofilms in vitro and bacterial colonization in vivo.
Effect of eugenol on in vitro biofilm and in vivo colonization were studied using microtiter plate assay and otitis media-rat model respectively. The architecture of in vitro biofilms and in vivo colonization of bacteria was viewed with SEM. Real-time RT-PCR was used to study gene expression. Check board method was used to study the synergistic effects of eugenol and carvacrol on established biofilms. Eugenol significantly inhibited biofilms growth of MRSA and MSSA in vitro in a concentration-dependent manner. Eugenol at MIC or 2×MIC effectively eradicated the pre-established biofilms of MRSA and MSSA clinical strains. In vivo, sub-MIC of eugenol significantly decreased 88% S. aureus colonization in rat middle ear. Eugenol was observed to damage the cell-membrane and cause a leakage of the cell contents. At sub-inhibitory concentration, it decreases the expression of biofilm-and enterotoxin-related genes. Eugenol showed a synergistic effect with carvacrol on the eradication of pre-established biofilms.
This study demonstrated that eugenol exhibits notable activity against MRSA and MSSA clinical strains biofilms. Eugenol inhibited biofilm formation, disrupted the cell-to-cell connections, detached the existing biofilms, and killed the bacteria in biofilms of both MRSA and MSSA with equal effectiveness. Therefore, eugenol may be used to control or eradicate S. aureus biofilm-related infections.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The proposed paper presents the design of a leaky‐wave antenna inspired by holographic metasurfaces employing thin film. Leveraging the holographic principle, this metasurface showcases its ...transformative capacity by converting an omnidirectionally radiating monopole into a highly directional antenna emitting leaky waves. The holographic metasurface is constructed using a thin film of polyimide (PI) (Df = 0.008; Dk = 3.5), measuring 50 μm in thickness. The antenna structure comprises multiple layers, commencing with the top PI layer, succeeded by a 40 μm thick adhesive layer (Df = 0.004; Dk = 6). Subsequent layer includes the Rogers RT/duroid 5880 substrate (Df = 0.0009; Dk = 2.20), grounded at the bottom and has a thickness of 1.6 mm. The meticulously tailored design of the proposed antenna ensures optimal performance at 15 GHz, facilitating directional radiation and precise beam steering at 10 degrees (ϴ = 10°). This innovative design, incorporating the holographic metasurface on thin film, significantly enhances the antenna's performance, increasing gain from 1.5 dBi to 13.8 dBi.
Holographic Measurface Inspired Leaky‐wave antenna.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Intermediate phase shifting is a footprint- and cost-reduction technique for reconfigurable feed networks. These feed networks are utilized in antenna arrays to perform electrical beam steering. In ...intermediate phase shifting, a phase shifter is shared between two adjacent antennas. Conventionally, antennas only have individual phase shifters. With shared phase shifters, we reduce the number of components and the footprint by 25%. Consequently, this decreases the price and enables designs at millimeter-wave frequencies where space is limited due to frequency-dependent antenna spacing. This intermediate phase shifting is demonstrated by designing a reconfigurable feed network for the
-band that generates a continuous phase shift profile for beam steering. Due to the use of varactors and a novel biasing method, it does not require expensive beamformer integrated chips or lumped components for biasing. The feed network is combined with a 4 × 4 antenna array to demonstrate its beam-steering capabilities. The result is a high-density and minimalistic design that fits in a small volume of 25.6 × 25.6 × 0.95 mm
. With this small antenna array, the main beam is steered at ±40∘ broadside, providing full 1D and restricted 2D steering. It is a potential candidate for wireless sensor and mobile networks.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In two-dimensional honeycomb ferromagnets, bosonic magnon quasiparticles (spin waves) may either behave as massless Dirac fermions or form topologically protected edge states. The key ingredient ...defining their nature is the next-nearest-neighbor Dzyaloshinskii-Moriya interaction that breaks the inversion symmetry of the lattice and discriminates chirality of the associated spin-wave excitations. Using inelastic neutron scattering, we find that spin waves of the insulating honeycomb ferromagnetCrI3(TC=61K) have two distinctive bands of ferromagnetic excitations separated by a∼4meVgap at the Dirac points. These results can only be understood by considering a Heisenberg Hamiltonian with Dzyaloshinskii-Moriya interaction, thus providing experimental evidence that spin waves inCrI3can have robust topological properties potentially useful for dissipationless spintronic applications.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM, UPUK
The transition of fleshy fruit maturation to ripening is regulated by exogenous and endogenous signals that coordinate the transition of the fruit to a final state of attractiveness to seed ...dispersing organisms. Tomato is a model for biology and genetics regulating specific ripening pathways including ethylene, carotenoids and cell wall metabolism in addition to upstream signaling and transcriptional regulators. Ripening‐associated transcription factors described to date including the RIN‐MADS, CLEAR NON‐RIPENING, TAGL1 and LeHB‐1 genes all encode positive regulators of ripening phenomena. Here we describe an APETALA2 transcription factor (SlAP2a) identified through transcriptional profiling of fruit maturation that is induced during, and which negatively regulates, tomato fruit ripening. RNAi repression of SlAP2a results in fruits that over‐produce ethylene, ripen early and modify carotenoid accumulation profiles by altering carotenoid pathway flux. These results suggest that SlAP2a functions during normal tomato fruit ripening as a modulator of ripening activity and acts to balance the activities of positive ripening regulators.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Given the long-term survival of most patients with thyroid cancer, it is very important to distinguish patients who need aggressive treatment from those who do not. Conventional clinicopathological ...prognostic parameters could not completely predict the final outcome of each patient. Recently, molecular marker-based risk stratification of thyroid cancer has been proposed to better estimate the cancer risk. Although BRAF mutation has drawn much attention based on its high prevalence, its association with recurrence or mortality is not clear. Recently, telomerase reverse transcriptase (TERT) promoter mutation has been identified in thyroid cancer. It increases telomerase activity, which allows cancer cells to immortalize. It was found in 10 to 20% of differentiated thyroid carcinoma and 40% of dedifferentiated thyroid carcinoma. It is highly prevalent in old age, large tumor, aggressive histology, advanced stages, and distant metastasis. It is associated with increased recurrence and mortality. Concomitant BRAF and TERT promoter mutations worsen the survival rate. Inclusion of TERT promoter mutation analysis with conventional clinicopathological evaluation can lead to better prognostication and management for individual patients.
Phenylboronic acid‐functionalized chondroitin sulfate A (CSA)–deoxycholic‐acid (DOCA)‐based nanoparticles (NPs) are prepared for tumor targeting and penetration. (3‐Aminomethylphenyl)boronic acid ...(AMPB) is conjugated to CSA–DOCA conjugate via amide bond formation, and its successful synthesis is confirmed using proton nuclear magnetic resonance spectroscopy (1H‐NMR). Doxorubicin (DOX)‐loaded CSA–DOCA–AMPB NPs with a mean diameter of ≈200 nm, a narrow size distribution, negative zeta potential, and spherical morphology are prepared. DOX release from NPs is enhanced at acidic pH compared to physiological pH. CSA–DOCA–AMPB NPs exhibit improved cellular uptake in A549 (human lung adenocarcinoma) cells and penetration into A549 multicellular spheroids compared to CSA–DOCA NPs as evidenced by confocal laser scanning microscopy and flow cytometry. In vivo tumor targeting and penetrating by CSA–DOCA–AMPB NPs, based on both CSA–CD44 receptor and boronic acid–sialic acid interactions, is revealed using near‐infrared fluorescence (NIRF) imaging. Penetration of NPs to the core of the tumor mass is observed in an A549 tumor xenografted mouse model and verified by three‐dimensional NIRF imaging. Multiple intravenous injections of DOX‐loaded CSA–DOCA–AMPB NPs efficiently inhibit the growth of A549 tumor in the xenografted mouse model and increase apoptosis. These boronic acid‐rich NPs are promising candidates for cancer therapy and imaging.
(3‐Aminomethylphenyl)boronic acid
(AMPB)‐functionalized chondroitin sulfate A (CSA)–deoxycholic acid (DOCA)‐based nanoparticles (NPs) are prepared for anticancer drug delivery and cancer diagnosis. Doxorubicin (DOX)‐loaded CSA–DOCA–AMPB NPs exhibit improved targeting, penetration, and therapeutic efficacies for CD44 receptor‐expressed tumors, compared to CSA–DOCA NPs, via CSA–CD44 receptor and boronic‐acid–sialic‐acid interactions.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
An end-fire radiating implantable antenna with a small footprint and broadband operation at the frequency range of 3–5 GHz is proposed for high-data-rate wireless communication in a brain–machine ...interface. The proposed Vivaldi antenna was implanted vertically along the height of the skull to avoid deformation in the radiation pattern and to compensate for a gain–loss caused by surrounding lossy brain tissues. It was shown that the vertically implanted end-fire antenna had a 3 dB higher antenna gain than a horizontally implanted broadside radiating antenna discussed in recent literature. Additionally, comb-shaped slot arrays imprinted on the Vivaldi antenna lowered the resonant frequency by approximately 2 GHz and improved the antenna gain by more than 2 dB compared to an ordinary Vivaldi antenna. An antenna prototype was fabricated and then tested for verification inside a seven-layered semi-solid brain phantom where each layer had similar electromagnetic material properties as actual brain tissues. The measured data showed that the antenna radiated toward the end-fire direction with an average gain of −15.7 dBi under the frequency of interest, 3–5 GHz. A link budget analysis shows that reliable wireless communication can be achieved over a distance of 10.8 cm despite the electromagnetically harsh environment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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