articles+ search results

Female, Humans, Pilot Projects, Endoscopes, Fallopian Tubes, Ovarian Neoplasms diagnostic imaging, and Ovarian Neoplasms pathology

Significance: High grade serous ovarian cancer is the most deadly gynecological cancer, and it is now believed that most cases originate in the fallopian tubes (FTs). Early detection of ovarian cancer could double the 5-year survival rate compared with late-stage diagnosis. Autofluorescence imaging can detect serous-origin precancerous and cancerous lesions in ex vivo FT and ovaries with good sensitivity and specificity. Multispectral fluorescence imaging (MFI) can differentiate healthy, benign, and malignant ovarian and FT tissues. Optical coherence tomography (OCT) reveals subsurface microstructural information and can distinguish normal and cancerous structure in ovaries and FTs.
Aim: We developed an FT endoscope, the falloposcope, as a method for detecting ovarian cancer with MFI and OCT. The falloposcope clinical prototype was tested in a pilot study with 12 volunteers to date to evaluate the safety and feasibility of FT imaging prior to standard of care salpingectomy in normal-risk volunteers. In this manuscript, we describe the multiple modifications made to the falloposcope to enhance robustness, usability, and image quality based on lessons learned in the clinical setting.
Approach: The ∼ 0.8    mm diameter falloposcope was introduced via a minimally invasive approach through a commercially available hysteroscope and introducing a catheter. A navigation video, MFI, and OCT of human FTs were obtained. Feedback from stakeholders on image quality and procedural difficulty was obtained.
Results: The falloposcope successfully obtained images in vivo . Considerable feedback was obtained, motivating iterative improvements, including accommodating the operating room environment, modifying the hysteroscope accessories, decreasing endoscope fragility and fiber breaks, optimizing software, improving fiber bundle images, decreasing gradient-index lens stray light, optimizing the proximal imaging system, and improving the illumination.
Conclusions: The initial clinical prototype falloposcope was able to image the FTs, and iterative prototyping has increased its robustness, functionality, and ease of use for future trials.
(© 2023 The Authors.)

Image reconstruction from data collected over full-angular range (FAR) in dual-energy CT (DECT) is well-studied. There exists interest in DECT with advanced scan configurations in which data are collected only over limited-angular ranges (LARs) for meeting unique workflow needs in certain practical imaging applications, and thus in the algorithm development for image reconstruction from such LAR data. The objective of the work is to investigate and prototype image reconstructions in DECT with LAR scans. We investigate and prototype optimization programs with various designs of constraints on the directional-total-variations (DTVs) of virtual monochromatic images and/or basis images, and derive the DTV algorithms to numerically solve the optimization programs for achieving accurate image reconstruction from data collected in a slew of different LAR scans. Using simulated and real data acquired with low- and high-kV spectra over LARs, we conduct quantitative studies to demonstrate and evaluate the optimization programs and their DTV algorithms developed. As the results of the numerical studies reveal, while the DTV algorithms yield images of visual quality and quantitative accuracy comparable to that of the existing algorithms from FAR data, the former reconstruct images with improved visualization, reduced artifacts, and also enhanced quantitative accuracy when applied to LAR data in DECT. Optimization-based, one-step algorithms, including the DTV algorithms demonstrated, can be developed for quantitative image reconstruction from spectral data collected over LARs of extents that are considerably smaller than the FAR in DECT. The theoretical and numerical results obtained can be exploited for prototyping designs of optimization-based reconstructions and LAR scans in DECT, and they may also yield insights into the development of reconstruction procedures in practical DECT applications. The approach and algorithms developed can naturally be applied to investigating image reconstruction from LAR data in multi-spectral and photon-counting CT.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)

Acetyl Coenzyme A metabolism, Cell Extracts, Escherichia coli metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, and Metabolic Engineering

Building and optimizing biosynthetic pathways in engineered cells holds promise to address societal needs in energy, materials, and medicine, but it is often time-consuming. Cell-free synthetic biology has emerged as a powerful tool to accelerate design-build-test-learn cycles for pathway engineering with increased tolerance to toxic compounds. However, most cell-free pathway prototyping to date has been performed in extracts from wildtype cells which often do not have sufficient flux towards the pathways of interest, which can be enhanced by engineering. Here, to address this gap, we create a set of engineered Escherichia coli and Saccharomyces cerevisiae strains rewired via CRISPR-dCas9 to achieve high-flux toward key metabolic precursors; namely, acetyl-CoA, shikimate, triose-phosphate, oxaloacetate, α-ketoglutarate, and glucose-6-phosphate. Cell-free extracts generated from these strains are used for targeted enzyme screening in vitro. As model systems, we assess in vivo and in vitro production of triacetic acid lactone from acetyl-CoA and muconic acid from the shikimate pathway. The need for these platforms is exemplified by the fact that muconic acid cannot be detected in wildtype extracts provided with the same biosynthetic enzymes. We also perform metabolomic comparison to understand biochemical differences between the cellular and cell-free muconic acid synthesis systems (E. coli and S. cerevisiae cells and cell extracts with and without metabolic rewiring). While any given pathway has different interfaces with metabolism, we anticipate that this set of pre-optimized, flux enhanced cell extracts will enable prototyping efforts for new biosynthetic pathways and the discovery of biochemical functions of enzymes.
(Copyright © 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Microfluidic 3D cell culture devices that enable the recapitulation of key aspects of organ structures and functions in vivo represent a promising preclinical platform to improve translational success during drug discovery. Essential to these engineered devices is the spatial patterning of cells from different tissue types within a confined microenvironment. Traditional fabrication strategies lack the scalability, cost-effectiveness, and rapid prototyping capabilities required for industrial applications, especially for processes involving thermoplastic materials. Here, an approach to pattern fluid guides inside microchannels is introduced by establishing differential hydrophilicity using pressure-sensitive adhesives as masks and a subsequent selective coating with a biocompatible polymer. Optimal coating conditions are identified using polyvinylpyrrolidone, which resulted in rapid and consistent hydrogel flow in both the open-chip prototype and the fully bonded device containing additional features for medium perfusion. The suitability of the device for dynamic 3D cell culture is tested by growing human hepatocytes in the device under controlled fluid flow for a 14-day period. Additionally, the study demonstrated the potential of using the device for pharmaceutical high-throughput screening applications, such as predicting drug-induced liver injury. The approach offers a facile strategy of rapid prototyping thermoplastic microfluidic organ chips with varying geometries, microstructures, and substrate materials.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Caregivers play a critical role in the treatment and recovery of youth and young adults at risk for psychosis. Caregivers often report feeling isolated, overwhelmed, and lacking in resources. Mobile health (mHealth) has the potential to provide scalable, accessible, and in-the-moment support to caregivers. To date, few if any mHealth resources have been developed specifically for this population.
Objective: The aim of this study was to conduct user-centered design and testing of an mHealth intervention to support early psychosis caregivers.
Methods: We conducted a multiphase user-centered development process to develop the Bolster mobile app. In phase 1, a total of 21 caregivers were recruited to participate in a qualitative needs assessment and respond to an initial prototype of the Bolster platform. Content analysis was used to identify key needs and design objectives, which guided the development of the Bolster mobile app. In phase 2, a total of 11 caregivers were recruited to participate in a 1-week field trial wherein they provided qualitative and quantitative feedback regarding the usability and acceptability of Bolster; in addition, they provided baseline and posttest assessments of the measures of distress, illness appraisals, and family communication.
Results: In phase 1, participants identified psychoeducation, communication coaching, a guide to seeking services, and support for coping as areas to address. Live prototype interaction sessions led to multiple design objectives, including ensuring that messages from the platform were actionable and tailored to the caregiver experience, delivering messages in multiple modalities (eg, video and text), and eliminating a messaging-style interface. These conclusions were used to develop the final version of Bolster tested in the field trial. In phase 2, of the 11 caregivers, 10 (91%) reported that they would use Bolster if they had access to it and would recommend it to another caregiver. They also reported marked changes in their appraisals of illness (Cohen d=0.55-0.68), distress (Cohen d=1.77), and expressed emotion (Cohen d=0.52).
Conclusions: To our knowledge, this study is the first to design an mHealth intervention specifically for early psychosis caregivers. Preliminary data suggest that Bolster is usable, acceptable, and promising to improve key targets and outcomes. A future fully powered clinical trial will help determine whether mHealth can reduce caregiver burdens and increase engagement in services among individuals affected by psychosis.
(©Benjamin Buck, Mary Wingerson, Erica Whiting, Jaime Snyder, Maria Monroe-DeVita, Dror Ben-Zeev. Originally published in JMIR Mental Health (https://mental.jmir.org), 30.11.2023.)

Nanotechnology, Microfluidics, Bioreactors, Microfluidic Analytical Techniques, and Nanopores

While injection molding is becoming the fabrication modality of choice for high-scale production of microfluidic devices, especially those used for in vitro diagnostics, its translation into the growing area of nanofluidics (structures with at least one dimension <100 nm) has not been well established. Another prevailing issue with injection molding is the high startup costs and the relatively long time between device iterations making it in many cases impractical for device prototyping. We report, for the first time, functional nanofluidic devices with dimensions of critical structures below 30 nm fabricated by injection molding for the manipulation, identification, and detection of single molecules. UV-resin molds replicated from Si masters served as mold inserts, negating the need for generating Ni-mold inserts via electroplating. Using assembled devices with a cover plate via hybrid thermal fusion bonding, we demonstrated two functional thermoplastic nanofluidic devices. The first device consisted of dual in-plane nanopores placed at either end of a nanochannel and was used to detect and identify single ribonucleotide monophosphate molecules via resistive pulse sensing and obtain the effective mobility of the molecule through nanoscale electrophoresis to allow its identification. The second device demonstrated selective binding of a single RNA molecule to a solid phase bioreactor decorated with a processive exoribonuclease, XRN1. Our results provide a simple path towards the use of injection molding for device prototyping in the development stage of any nanofluidic or even microfluidic application, through which rapid scale-up is made possible by transitioning from prototyping to high throughput production using conventional Ni mold inserts.

Premature birth and neonatal mortality are significant global health challenges, with 15 million premature births annually and an estimated 2.5 million neonatal deaths. Approximately 90% of preterm births occur in low/middle income countries, particularly within the global regions of sub-Saharan Africa and South Asia. Neonatal hypothermia is a common and significant cause of morbidity and mortality among premature and low birth weight infants, particularly in low/middle-income countries where rates of premature delivery are high, and access to health workers, medical commodities, and other resources is limited. Kangaroo Mother Care/Skin-to-Skin care has been shown to significantly reduce the incidence of neonatal hypothermia and improve survival rates among premature infants, but there are significant barriers to its implementation, especially in low/middle-income countries (LMICs). The paper proposes the use of a multidisciplinary approach to develop an integrated mHealth solution to overcome the barriers and challenges to the implementation of Kangaroo Mother Care/Skin-to-skin care (KMC/STS) in LMICs. The innovation is an integrated mHealth platform that features a wearable biomedical device (NeoWarm) and an Android-based mobile application (NeoRoo) with customized user interfaces that are targeted specifically to parents/family stakeholders and healthcare providers, respectively. This publication describes the iterative, human-centered design and participatory development of a high-fidelity prototype of the NeoRoo mobile application. The aim of this study was to design and develop an initial ("A") version of the Android-based NeoRoo mobile app specifically to support the use case of KMC/STS in health facilities in Kenya. Key functions and features are highlighted. The proposed solution leverages the promise of digital health to overcome identified barriers and challenges to the implementation of KMC/STS in LMICs and aims to equip parents and healthcare providers of prematurely born infants with the tools and resources needed to improve the care provided to premature and low birthweight babies. It is hoped that, when implemented and scaled as part of a thoughtful, strategic, cross-disciplinary approach to reduction of global rates of neonatal mortality, NeoRoo will prove to be a useful tool within the toolkit of parents, health workers, and program implementors.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Sherri Bucher has been awarded intellectual property protection for invention of the NeoWarm biomedical device. This includes US patent US10390630B2, Nigeria NG/PT/C/2018/2802 and ARIPO patent PT/C/2018/2802. The authors declare no other potential conflicts of interest with respect to research, authorship, financial relationships, and/or publication of the article.
(Copyright: © 2023 Bucher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Humans, SARS-CoV-2, Australia epidemiology, Disease Outbreaks prevention control, Workplace, and COVID-19 epidemiology

Early case detection is critical to preventing onward transmission of COVID-19 by enabling prompt isolation of index infections, and identification and quarantining of contacts. Timeliness and completeness of ascertainment depend on the surveillance strategy employed. This paper presents modelling used to inform workplace testing strategies for the Australian government in early 2021. We use rapid prototype modelling to quickly investigate the effectiveness of testing strategies to aid decision making. Models are developed with a focus on providing relevant results to policy makers, and these models are continually updated and improved as new questions are posed. Developed to support the implementation of testing strategies in high risk workplace settings in Australia, our modelling explores the effects of test frequency and sensitivity on outbreak detection. We start with an exponential growth model, which demonstrates how outbreak detection changes depending on growth rate, test frequency and sensitivity. From the exponential model, we learn that low sensitivity tests can produce high probabilities of detection when testing occurs frequently. We then develop a more complex Agent Based Model, which was used to test the robustness of the results from the exponential model, and extend it to include intermittent workplace scheduling. These models help our fundamental understanding of disease detectability through routine surveillance in workplaces and evaluate the impact of testing strategies and workplace characteristics on the effectiveness of surveillance. This analysis highlights the risks of particular work patterns while also identifying key testing strategies to best improve outbreak detection in high risk workplaces.
(© 2023. BioMed Central Ltd., part of Springer Nature.)

LoRa technology has gained popularity as one of the most widely used standards for device interconnection due to its ability to cover long distances and energy efficiency, making it a suitable choice for various Internet of Things (IoT) monitoring and control applications. In this sense, this work presents the development of a visual support tool for creating IoT devices with LoRa and LoRaWAN connectivity. This work significantly advances the state of the art in LoRa technology by introducing a novel visual support tool tailored for creating IoT devices with LoRa and LoRaWAN connectivity. By simplifying the development process and offering compatibility with multiple hardware solutions, this research not only facilitates the integration of LoRaWAN technology within educational settings but also paves the way for rapid prototyping of IoT nodes. The incorporation of block programming for LoRa and LoRaWAN using the Arduinoblocks framework as a graphical environment enhances the capabilities of the tool, positioning it as a comprehensive solution for efficient firmware generation. In addition to the visual tool for firmware generation, multiple compatible hardware solutions enable easy, economical, and stable development, offering a comprehensive hardware and software solution. The hardware proposal is based on an ESP32 microcontroller, known for its power and low cost, in conjunction with an RFM9x module that is based on SX127x LoRa transceivers. Finally, three successfully tested use cases and a discussion are presented.

The transfer from batch to flow chemistry is often based on commercial microfluidic equipment, such as costly complete reactor systems, which cannot be easily tailored to specific requirements of technologies such as DNA-encoded library technology (DELT), in particular for increasingly important photochemical reactions. Customized photoreactor concepts using rapid prototyping technology offer a modular, flexible, and affordable design that allows for adaptation to various applications. In order to validate the prototype reactors, a photochemical pinacol coupling reaction at 368 nm was conducted to demonstrate the transfer from batch to flow chemistry. The conversion rates were optimized by adapting the design parameters of the microfluidic flow photoreactor module. Subsequently, the photoreactor module has been extended to an application with DNA-tagged substrates by switching to LEDs with a wavelength of 454 nm. The successful recovery of DNA confirmed the feasibility of the modular-designed flow photo reactor. This collaborative approach holds enormous potential to drive the development of DELT and flow equipment design.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Dinter, Willems, Nissalk, Hastürk, Brunschweiger and Kockmann.)