Wireless, flexible, ion-selective electrodes (ISEs) are of great interest in the development of wearable health monitors and clinical systems. Existing film-based electrochemical sensors, however, still have practical limitations due to poor electrical contact and material–interfacial leakage. Here, we introduce a wireless, flexible film-based system with a highly selective, stable, and reliable sodium sensor. A flexible and hydrophobic composite with carbon black and soft elastomer serves as an ion-to-electron transducer offering cost efficiency, design simplicity, and long-term stability. The sensor package demonstrates repeatable analysis of selective sodium detection in saliva with good sensitivity (56.1 mV/decade), stability (0.53 mV/h), and selectivity coefficient of sodium against potassium (−3.0). The film ISEs have an additional membrane coating that provides reinforced stability for the sensor upon mechanical bending. Collectively, the comprehensive study of materials, surface chemistry, and sensor design in this work shows the potential of the wireless flexible sensor system for low-profile wearable applications.
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Maximilian O Schaettler;
Rupen Desai;
Anthony Z Wang;
Alexandra J Livingstone;
Dale K Kobayashi;
Andrew T Coxon;
Jay A Bowman-Kirigin;
Connor J Liu;
Mao Li;
Diane E Bender;
Michael J White;
David M Kranz;
Tanner M Johanns;
Gavin P Dunn
Background Adoptive cellular therapies with chimeric antigen receptor T cells have revolutionized the treatment of some malignancies but have shown limited efficacy in solid tumors such as glioblastoma and face a scarcity of safe therapeutic targets. As an alternative, T cell receptor (TCR)-engineered cellular therapy against tumor-specific neoantigens has generated significant excitement, but there exist no preclinical systems to rigorously model this approach in glioblastoma. Methods We employed single-cell PCR to isolate a TCR specific for the Imp3 D81N neoantigen (mImp3) previously identified within the murine glioblastoma model GL261. This TCR was used to generate the Mutant Imp3-Specific TCR TransgenIC (MISTIC) mouse in which all CD8 T cells are specific for mImp3. The therapeutic efficacy of neoantigen-specific T cells was assessed through a model of cellular therapy consisting of the transfer of activated MISTIC T cells and interleukin 2 into lymphodepleted tumor-bearing mice. We employed flow cytometry, single-cell RNA sequencing, and whole-exome and RNA sequencing to examine the factors underlying treatment response. Results We isolated and characterized the 3×1.1C TCR that displayed a high affinity for mImp3 but no wild-type cross-reactivity. To provide a source of mImp3-specific T cells, we generated the MISTIC mouse. In a model of adoptive cellular therapy, the infusion of activated MISTIC T cells resulted in rapid intratumoral infiltration and profound antitumor effects with long-term cures in a majority of GL261-bearing mice. The subset of mice that did not respond to the adoptive cell therapy showed evidence of retained neoantigen expression but intratumoral MISTIC T cell dysfunction. The efficacy of MISTIC T cell therapy was lost in mice bearing a tumor with heterogeneous mImp3 expression, showcasing the barriers to targeted therapy in polyclonal human tumors. Conclusions We generated and characterized the first TCR transgenic against an endogenous neoantigen within a preclinical glioma model and demonstrated the therapeutic potential of adoptively transferred neoantigen-specific T cells. The MISTIC mouse provides a powerful novel platform for basic and translational studies of antitumor T-cell responses in glioblastoma.
Saliva can be used for health monitoring with non-invasive wearable systems. Such devices, including electrochemical sensors, may provide a safe, fast, and cost-efficient way of detecting target ions. Although salivary ions are known to reflect those in blood, no available clinical device can detect essential ions directly from saliva. Here, we introduce an all-solid-state, flexible film sensor that allows highly accurate detection of sodium levels in saliva, comparable to those in blood. The wireless film sensor system can successfully measure sodium ions from a small volume of infants’ saliva (<400 µL), demonstrating its potential as a continuous health monitor. This study includes the structural characterization and error analysis of a carbon/elastomer-based ion-selective electrode and a reference electrode to confirm the signal reliability. The sensor, composed of a pair of the electrodes, shows good sensitivity (58.9 mV/decade) and selectivity (log K = −2.68 for potassium), along with a broad detection range of 5 × 10−5 ≈ 1 M with a low detection limit of 4.27 × 10−5 M. The simultaneous comparison between the film sensor and a commercial electrochemical sensor demonstrates the accuracy of the flexible sensor and a positive correlation in saliva-to-blood sodium levels. Collectively, the presented study shows the potential of the wireless ion-selective sensor system for a non-invasive, early disease diagnosis with saliva.
Airborne microbiome alterations, an emerging global health concern, have been linked to anthropogenic activities in numerous studies. However, these studies have not reached a consensus. To reveal general trends, we conducted a meta-analysis using 3226 air samples from 42 studies, including 29 samples of our own. We found that samples in anthropogenic activity-related categories showed increased microbial diversity, increased relative abundance of pathogens, increased co-occurrence network complexity, and decreased positive edge proportions in the network compared with the natural environment category. Most of the above conclusions were confirmed using the samples we collected in a particular period with restricted anthropogenic activities. Additionally, unlike most previous studies, we used 15 human-production process factors to quantitatively describe anthropogenic activities. We found that microbial richness was positively correlated with fine particulate matter concentration, NH3emissions, and agricultural land proportion and negatively correlated with the gross domestic product per capita. Airborne pathogens showed preferences for different factors, indicating potential health implications. SourceTracker analysis showed that the human body surface was a more likely source of airborne pathogens than other environments. Our results advance the understanding of relationships between anthropogenic activities and airborne bacteria and highlight the role of airborne pathogens in public health.
In science, technology, engineering, and mathematics (STEM) fields, disabled people remain a significantly underrepresented part of the workforce. Recent data suggests that about 20% of undergraduates in the United States have disabilities, but representation in STEM fields is consistently lower than in the general population. Of those earning STEM degrees, only about 10% of undergraduates, 6% of graduate students, and 2% of doctoral students identify as disabled. This suggests that STEM fields have difficulty recruiting and retaining disabled students, which ultimately hurts the field, because disabled scientists bring unique problem-solving perspectives and input. This essay briefly explores the ways in which ableism - prejudice against disabled people based on the assumption that they are "less than"their nondisabled peers - in research contributes to the exclusion of disabled scientists and suggests ways in which the scientific community can improve accessibility and promote the inclusion of disabled scientists in academic science.
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Ngoc Do Ha;
Milkie Vu;
Anh Tuan Nguyen;
Quynh Thi Nguyen Hoa;
Phuong Bui Thanh;
Van Nguyen Quy;
Thu Thi Tran Ngan;
Bac Thi La Ly;
Thu Thi Nguyen Nga;
Quang N Nguyen;
Thanh Phan Hai;
Thi Hoang Men;
Gia Vu Linh;
Minh Thi Vu Thuc;
Xuan Tran Bach;
Carl A Latkin;
Cyrus SH Ho;
Roger CM Ho
Background: While internal migrants in Vietnam have been a key driving force in the country's rapid economic development, they also face many vulnerabilities. Our study seeks to explore possible inequalities in housing and working conditions between local and internal migrant industrial workers in Vietnam. Methods: Cross-sectional surveys were conducted with 1200 industrial workers in four regions of Vietnam. Dependent variables included housing conditions (satisfaction with convenience of accommodation, sanitation and water of accommodation, and accommodation in general) and working conditions (satisfaction with income, monthly income, number of hazardous working conditions, and work-related stress measured through the modified Effort-Reward Imbalance Questionnaire). The primary independent variable is migrant status. Covariates included region, gender, education, marital status, accommodation status, living arrangements, industry, age, monthly income, experience, and working hours. Results: Of the sample, 24.7% (n = 296) were migrants. Overall, no differences were found regarding housing conditions by migrant status. In adjusted regression models, migrants reported higher numbers of hazardous working conditions (β = 0.07, 95 %CI = 0.01–0.13, p = 0.01) and higher monthly income (β = 0.05, 95 %CI = 0.01–0.09, p = 0.02). Discussion: Recent state-level changes in the Vietnamese household registration system may explain the lack of differences in housing conditions by migrant status. Future research should utilize longitudinal designs to examine impacts over time of state policy on migrants’ housing conditions as well as well-being. Regarding working conditions, findings highlight the need for stronger social protection policy and better information channels on occupational health and safety for migrants. Further research, including qualitative studies, is needed to explore why migrants face more hazardous working conditions.
We present a color segmentation approach based on a two-dimensional color map derived from the input image. Pathologists stain tissue biopsies with various colored dyes to see the expression of biomarkers. In these images, because of color variation due to inconsistencies in experimental procedures and lighting conditions, the segmentation used to analyze biological features is usually ad-hoc. Many algorithms like K-means use a single metric to segment the image into different color classes and rarely provide users with powerful color control. Our 2D color map interactive segmentation technique based on human color perception information and the color distribution of the input image, enables user control without noticeable delay. Our methodology works for different staining types and different types of cancer tissue images. Our proposed method's results show good accuracy with low response and computational time making it a feasible method for user interactive applications involving segmentation of histological images.
This paper presents a novel, fast and semi-automatic method for accurate cell cluster segmentation and cell counting of digital tissue image samples. In pathological conditions, complex cell clusters are a prominent feature in tissue samples. Segmentation of these clusters is a major challenge for development of an accurate cell counting methodology. We address the issue of cluster segmentation by following a three step process. The first step involves pre-processing required to obtain the appropriate nuclei cluster boundary image from the RGB tissue samples. The second step involves concavity detection at the edge of a cluster to find the points of overlap between two nuclei. The third step involves segmentation at these concavities by using an ellipse-fitting technique. Once the clusters are segmented, individual nuclei are counted to give the cell count. The method was tested on four different types of cancerous tissue samples and shows promising results with a low percentage error, high true positive rate and low false discovery rate.
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Kristin Beima-Sofie;
Anjuli D Wagner;
Caroline Soi;
Wenjia Liu;
Deanna Tollefson;
Irene N Njuguna;
Emily Ogutu;
Douglas Gaitho;
Nancy Mburu;
Geoffrey Oluoch;
Peter Mwaura;
Peter Cherutich;
Laura Oyiengo;
Grace C John-Stewart;
Ruth Nduati;
Kenneth Sherr;
Sarah Gimbel
Background
Children and adolescents living with HIV have poorer rates of HIV testing, treatment, and virologic suppression than adults. Strategies that use a systems approach to optimize these multiple, linked steps simultaneously are critical to close these gaps.
Methods
The Systems Analysis and Improvement Approach (SAIA) was adapted and piloted for the pediatric and adolescent HIV care and treatment cascade (SAIA-PEDS) at 6 facilities in Kenya. SAIA-PEDS includes three tools: continuous quality improvement (CQI), flow mapping, and pediatric cascade analysis (PedCAT). A predominately qualitative evaluation utilizing focus group discussions (N = 6) and in-depth interviews (N = 19) was conducted with healthcare workers after implementation to identify determinants of implementation. Data collection and analysis were grounded in the Consolidated Framework for Implementation Research (CFIR).
Results
Overall, the adapted SAIA-PEDS strategy was acceptable, and the three tools complemented one another and provided a relative advantage over existing processes. The flow mapping and CQI tools were compatible with existing workflows and resonated with team priorities and goals while providing a structure for group problem solving that transcended a single department’s focus. The PedCAT was overly complex, making it difficult to use. Leadership and hierarchy were complex determinants. All teams reported supportive leadership, with some describing in detail how their leadership was engaged and enthusiastic about the SAIA-PEDS process, by providing recognition, time, and resources. Hierarchy was similarly complex: in some facilities, leadership stifled rapid innovation by insisting on approving each change, while at other facilities, leadership had strong and supportive oversight of processes, checking on the progress frequently and empowering teams to test innovative ideas.
Conclusion
CQI and flow mapping were core components of SAIA-PEDS, with high acceptability and consistent use, but the PedCAT was too complex. Leadership and hierarchy had a nuanced role in implementation. Future SAIA-PEDS testing should address PedCAT complexity and further explore the modifiability of leadership engagement to maximize implementation.
This study describes the effect of zinc on monocyte adhesion to endothelial cells under different shear stress regimens, which may trigger atherogenesis. Human umbilical vein endothelial cells were exposed to steady shear stress (15 dynes/cm 2 or 1 dyne/cm 2) or reversing shear stress (time average 1 dyne/cm 2) for 24 h. In all shear stress regimes, zinc deficiency enhanced THP-1 cell adhesion, while heparinase III reduced monocyte adhesion following reversing shear stress exposure. Unlike other shear stress regimes, reversing shear stress alone enhanced monocyte adhesion, which may be associated with increased H 2O 2 and superoxide together with relatively low levels of nitric oxide (NO) production. L-N G-Nitroarginine methyl ester (L-NAME) treatment increased monocyte adhesion under 15 dynes/cm 2 and under reversing shear stress. After reversing shear stress, monocyte adhesion dramatically increased with heparinase III treatment followed by a zinc scavenger. Static culture experiments supported the reduction of monocyte adhesion by zinc following endothelial cell cytokine activation. These results suggest that endothelial cell zinc levels are important for the inhibition of monocyte adhesion to endothelial cells, and may be one of the key factors in the early stages of atherogenesis.