Smart contact lenses for continuous glucose monitoring (CGM) have great potential for huge clinical impact. To date, their development has been limited by challenges in accurate detection of glucose ...without hysteresis for tear glucose monitoring to track the blood glucose levels. Here, long‐term robust CGM in diabetic rabbits is demonstrated by using bimetallic nanocatalysts immobilized in nanoporous hydrogels in smart contact lenses. After redox reaction of glucose oxidase, the nanocatalysts facilitate rapid decomposition of hydrogen peroxide and nanoparticle‐mediated charge transfer with drastically improved diffusion via rapid swelling of nanoporous hydrogels. The ocular glucose sensors result in high sensitivity, fast response time, low detection limit, low hysteresis, and rapid sensor warming‐up time. In diabetic rabbits, smart contact lens can detect tear glucose levels consistent with blood glucose levels measured by a glucometer and a CGM device, reflecting rapid concentration changes without hysteresis. The CGM in a human demonstrates the feasibility of smart contact lenses for further clinical applications.
Smart contact lenses containing bimetallic nanocatalysts immobilized in nanoporous hydrogels are developed for long‐term and robust continuous glucose monitoring. The smart contact lenses can accurately monitor increasing and decreasing blood glucose levels with 92.2% acceptable data in diabetic and normal rabbits. Finally, the clinical feasibility and safety of smart contact lenses are evaluated on the eyes of a human patient.
In this paper, we propose a doubly robust method to estimate the heterogeneity of the average treatment effect with respect to observed covariates of interest. We consider a situation where a large ...number of covariates are needed for identifying the average treatment effect but the covariates of interest for analyzing heterogeneity are of much lower dimension. Our proposed estimator is doubly robust and avoids the curse of dimensionality. We propose a uniform confidence band that is easy to compute, and we illustrate its usefulness via Monte Carlo experiments and an application to the effects of smoking on birth weights.
Background
As the world is becoming increasingly connected by the World Wide Web, the internet is becoming the main source of health information. With the novel COVID-19 pandemic, ubiquitous use of ...the internet has changed the daily lives of individuals, from working from home to seeking and meeting with health care providers through web-based sites. Such heavy reliance on internet-based technologies raises concerns regarding the accessibility of the internet for minority populations who are likely to already face barriers when seeking health information.
Objective
This study aims to examine the level of technology access and common modes of technology used by Korean American women and to investigate how key psychosocial determinants of health such as age, education, English proficiency, and health literacy are correlated with sources of health information used by Korean American women and by their use of the internet.
Methods
We used data from a subsample of Korean American women (N=157) who participated in a community-based randomized trial designed to test a health literacy–focused cancer screening intervention. In addition to descriptive statistics to summarize Korean American women’s internet access and common modes of technology use, we conducted backward stepwise logistic regression analyses to substantiate the association between the psychosocial determinants of health and internet use.
Results
Approximately two-thirds (103/157, 65.6%) of the sample had access to the internet, and nearly all had access to a mobile phone. The internet was the most commonly used channel to obtain health information 63% (99/157), and 70% (110/157) of the sample used text messaging. Nevertheless, only approximately 38.8% (40/103) of the sample were very confident in using the internet, and only 29.9% (47/157) were very confident in using text messaging. Multivariate analyses revealed that older age (>50 years) was associated with 79% lower odds of using the internet to seek health information (adjusted odds ratio AOR 0.21, 95% CI 0.10-0.46). The higher health literacy group (19+ on Rapid Estimate of Adult Literacy in Medicine) had 56% lower odds of using the internet to acquire health information (AOR 0.44, 95% CI 1.13-11.18). Higher education (college+) was associated with both internet use (AOR 4.42, 95% CI 1.88-9.21) and text messaging (AOR 3.42, 95% CI 1.55-7.54). Finally, English proficiency was associated with text messaging (AOR 4.20, 95% CI 1.44-12.24).
Conclusions
The differences in modes of technology access, use, and confidence by some of the key psychosocial determinants, as observed in our study sample, have important implications when health care teams develop dissemination plans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Tumor metastasis remains the cause of 90% of cancer‐related deaths. Cancer stem cells (CSC) are thought to be responsible for the aggressive and metastatic nature of triple‐negative breast cancers ...(TNBC), and new therapeutic strategies are being devised to target them. Flubendazole (FLU) is a widely used anthelmintic agent that also exhibits anticancer activity in several cancer types. The aim of this study was to characterize the mechanism of action of FLU on breast cancer stem cell (BCSC)‐like properties and metastasis in TNBC. FLU treatment caused a significant induction of apoptosis, accompanied by G2/M phase accumulation, caspase‐3/‐7 activation and the dysregulation of STAT3 activation in TNBC cells. The latter phenomenon was associated with impairment of cancer stem‐like traits, concomitant with a reduction in the CD24low/CD44high, CD24high/CD49fhigh subpopulation, ALDH1 activity and mammosphere formation. The BCSC‐enriched populations exhibited enhanced metastasis with higher STAT3 activation, while FLU administration inhibited tumor growth, angiogenesis and lung and liver metastasis, coinciding with decreased MMP‐2 and MMP‐9 levels in circulating blood. FLU kills not only rapid proliferating tumor cells but also effectively eradicates BCSC‐like cells in vitro and in vivo. Our findings warrant further investigation of FLU as a treatment for metastatic TNBC.
What's new?
Triple‐negative breast cancers (TNBCs) with high levels of cancer stem‐like properties have aggressive metastatic phenotypes and are difficult to treat. Despite chemotherapy, many patients with TNBC die within five years of diagnosis. Here, the authors show that breast cancer cell populations enriched with cancer stem cells (CSCs) exhibit enhanced metastasis and increased STAT3 activation and that STAT3 activation can be inhibited in vitro following administration of the anthelmintic drug flubendazole. In mice with CSC‐enriched TNBC tumors, flubendazole inhibited tumor growth, angiogenesis and lung and liver metastasis. The data warrant additional study of the potential clinical value of flubendazole in TNBC.
Purpose
We introduced a novel reconstruction network, jointly unrolled cross‐domain optimization‐based spatio‐temporal reconstruction network (JUST‐Net), aimed at accelerating 3D multi‐echo ...gradient‐echo (mGRE) data acquisition and improving the quality of resulting myelin water imaging (MWI) maps.
Method
An unrolled cross‐domain spatio‐temporal reconstruction network was designed. The main idea is to combine frequency and spatio‐temporal image feature representations and to sequentially implement convolution layers in both domains. The k‐space subnetwork utilizes shared information from adjacent frames, whereas the image subnetwork applies separate convolutions in both spatial and temporal dimensions. The proposed reconstruction network was evaluated for both retrospectively and prospectively accelerated acquisition. Furthermore, it was assessed in simulation studies and real‐world cases with k‐space corruptions to evaluate its potential for motion artifact reduction.
Results
The proposed JUST‐Net enabled highly reproducible and accelerated 3D mGRE acquisition for whole‐brain MWI, reducing the acquisition time from fully sampled 15:23 to 2:22 min within a 3‐min reconstruction time. The normalized root mean squared error of the reconstructed mGRE images increased by less than 4.0%, and the correlation coefficients for MWI showed a value of over 0.68 when compared to the fully sampled reference. Additionally, the proposed method demonstrated a mitigating effect on both simulated and clinical motion‐corrupted cases.
Conclusion
The proposed JUST‐Net has demonstrated the capability to achieve high acceleration factors for 3D mGRE‐based MWI, which is expected to facilitate widespread clinical applications of MWI.
Excavating the molecular details of many diverse enzymes from metagenomes remains challenging in agriculture, food, health, and environmental fields. We present a versatile method that accelerates ...metabolic enzyme discovery for highly selective gene capture in metagenomes using next‐generation sequencing. Culture‐independent enzyme mining of environmental DNA is based on a set of short identifying degenerate sequences specific for a wide range of enzyme superfamilies, followed by multiplexed DNA barcode sequencing. A strategy of ‘focused identification of next‐generation sequencing‐based definitive enzyme research’ enabled us to generate targeted enzyme datasets from metagenomes, resulting in minimal hands‐on obtention of high‐throughput biological diversity and potential function profiles, without being time‐consuming. This method also provided a targeted inventory of predicted proteins and molecular features of metabolic activities from several metagenomic samples. We suggest that the efficiency and sensitivity of this method will accelerate the decryption of microbial diversity and the signature of proteins and their metabolism from environmental samples.
Focused identification of next‐generation sequencing‐based definitive enzyme research (FINDER), as a culture‐independent high‐throughput enzyme screening platform technology, enabled us to quickly determine the value of metagenomic samples and to collect a large amount of information regarding useful enzyme profiles. FINDER could also allow us to rapidly characterize environmental microbiota at any given time, and yield established catalogs of functional genes in situ. This large‐scale screening method is a versatile approach for identifying novel biocatalysts and excavating natural deposits of novel enzymes at a metagenomic scale.
Peptides exhibit lower affinity and a shorter half-life in the body than antibodies. Conversely, peptides demonstrate higher efficiency in tissue penetration and cell internalization than antibodies. ...Regardless of the pros and cons of peptides, they have been used as tumor-homing ligands for delivering carriers (such as nanoparticles, extracellular vesicles, and cells) and cargoes (such as cytotoxic peptides and radioisotopes) to tumors. Additionally, tumor-homing peptides have been conjugated with cargoes such as small-molecule or chemotherapeutic drugs via linkers to synthesize peptide-drug conjugates. In addition, peptides selectively bind to cell surface receptors and proteins, such as immune checkpoints, receptor kinases, and hormone receptors, subsequently blocking their biological activity or serving as hormone analogs. Furthermore, peptides internalized into cells bind to intracellular proteins and interfere with protein-protein interactions. Thus, peptides demonstrate great application potential as multifunctional players in cancer therapy.
Abstract
Trastuzumab resistance in HER2-positive breast cancer is associated with a poorer prognosis. HSP90 is thought to play a major role in such resistance, but N-terminal inhibitors of this ...target have had little success. We sought to investigate the utility of NCT-547, a novel, rationally-designed C-terminal HSP90 inhibitor in the context of overcoming trastuzumab resistance. NCT-547 treatment significantly induced apoptosis without triggering the heat shock response (HSR), accompanied by caspase-3/− 7 activation in both trastuzumab-sensitive and -resistant cells. NCT-547 effectively promoted the degradation of full-length HER2 and truncated p95HER2, while also attenuating hetero-dimerization of HER2 family members. The impairment of cancer stem-like traits was observed with reductions in ALDH1 activity, the CD24
low
/CD44
high
subpopulation, and mammosphere formation in vitro and in vivo. NCT-547 was an effective inhibitor of tumor growth and angiogenesis, and no toxic outcomes were found in initial hepatic and renal analysis. Our findings suggest that NCT-547 may have applications in addressing trastuzumab resistance in HER2-positive breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metabolic syndrome (MetS) arises from complex interactions between host genetic and environmental factors. Although it is now widely accepted that the gut microbiota plays a crucial role in host ...metabolism, current knowledge on the effect of host genetics on specific gut microbes related to MetS status remains limited. Here, we investigated the links among host genetic factors, gut microbiota and MetS in humans.
We characterised the gut microbial community composition of 655 monozygotic (n=306) and dizygotic (n=74) twins and their families (n=275), of which approximately 18% (121 individuals) had MetS. We evaluated the association of MetS status with the gut microbiota and estimated the heritability of each taxon. For the MetS-related and heritable taxa, we further investigated their associations with the apolipoprotein A-V gene (
) single nucleotide polymorphism (SNP) rs651821, which is known to be associated with triglyceride levels and MetS.
Individuals with MetS had a lower gut microbiota diversity than healthy individuals. The abundances of several taxa were associated with MetS status;
,
and
were enriched in the MetS group, whereas
,
and
were enriched in the healthy group. Among the taxa associated with MetS status, the phylum Actinobacteria, to which
belongs, had the highest heritability (45.7%). Even after adjustment for MetS status, reduced abundances of Actinobacteria and
were significantly linked to the minor allele at the
SNP rs651821.
Our results suggest that an altered microbiota composition mediated by a specific host genotype can contribute to the development of MetS.
A smart contact lens can be used as an excellent interface between the human body and an electronic device for wearable healthcare applications. Despite wide investigations of smart contact lenses ...for diagnostic applications, there has been no report on electrically controlled drug delivery in combination with real-time biometric analysis. Here, we developed smart contact lenses for both continuous glucose monitoring and treatment of diabetic retinopathy. The smart contact lens device, built on a biocompatible polymer, contains ultrathin, flexible electrical circuits and a microcontroller chip for real-time electrochemical biosensing, on-demand controlled drug delivery, wireless power management, and data communication. In diabetic rabbit models, we could measure tear glucose levels to be validated by the conventional invasive blood glucose tests and trigger drugs to be released from reservoirs for treating diabetic retinopathy. Together, we successfully demonstrated the feasibility of smart contact lenses for noninvasive and continuous diabetic diagnosis and diabetic retinopathy therapy.
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