Technology Platform Research Articles

OS Therapies to Develop ‘Tunable’ ADCs

OS Therapies is advancing a next-generation antibody-drug conjugate (ADC) technology platform, known as tunable ADCs (tADCs), which features tunable, tailored antibody-linker-payload candidates. This platform leverages the company’s proprietary silicone linker technology, enabling the delivery of multiple payloads per linker.

Abstract We103: Integration of deep learning assisted high-content screening and deep tissue-phenotyping to identify cardioprotective compounds in dilated cardiomyopathy

With a prevalence of 4:10,000, dilated cardiomyopathy (DCM) is the most common hereditary heart disease, characterized by dilatation of one or both ventricles and impaired systolic and diastolic function. Numerous mutations have been identified to cause DCM. TITIN-truncating variants (TTNtv) are commonly observed in 20% of the genetic DCM cases. Progress in drug discovery for DCM has been hampered by the lack of robust high-throughput/high-content analysis pipelines of disease-specific cell and tissue platforms for deep structural and functional phenotyping. To address this challenge, we have developed a two-tiered human induced pluripotent stem cell (iPSC)-based screening approach, comprised of high-content cardiomyocyte imaging with artificial intelligence (AI)-driven image and data analyses as well as deep tissue phenotyping in engineered heart muscle (EHM) models. As a DCM use case, we have developed several isogenic human iPSC-lines with and without a previously reported and pathologically relevant A-band-TTNtv mutation (c.70692_70693insAT; p.T23565SfsX5; Gerull et al. 11788824, Gramlich et al. 25759365, Fomin et al. 34731013) Using fixed weights from a convolutional deep neural network trained on ImageNet, we generated unbiased deep embeddings from each 2D cell model and applied these to train machine learning (ML) models to detect morphological disease phenotypes. Our ML model is able to confidently separate healthy controls from TTNtv cells with high accuracy (>93%), specificity (WT >79%) across different batches/plate layouts and generate concentration-response curves, demonstrating platform robustness and sensitivity. Building upon this work, we will present our latest efforts applying the platform technology for a chemogenomic screening campaign to identify novel cardioprotective drugs using a library of 7,100 bioactive compounds and validation assays, including measuring functional changes in EHMs. The phenotypic profiling platform, as presented here, can be readily adapted to other disease-relevant cell types and pathologies. Our results demonstrate the power of combining iPSC-CMs with cytological profiling and deep learning as well as tissue-level phenotyping to accelerate drug discovery for patients with DCM.

Antibody-Calixarene Drug Conjugate: A General Drug Delivery Platform for Tumor-Targeted Therapy.

Antibody-drug conjugates (ADCs), which combine the precise targeting capabilities of antibodies with the powerful cytotoxicity of small-molecule drugs, have evolved into a promising approach for tumor treatment. However, the traditional covalent coupling method requires the design of a specific linker tailored to the properties of the small-molecule drugs, which greatly limits the development of ADCs and the range of drugs that can be used. Herein, a novel type of antibody-calixarene drug conjugates (ACDCs) that function similarly to ADCs by delivering drugs to their targets using antibodies but without the requirement of covalent conjugation of the drugs with antibodies is presented. By replacement of conventional linkers with supramolecular linkers, the ACDCs can load various chemotherapeutic drugs through host-guest interactions. Furthermore, ACDCs are readily reduced upon reaching the hypoxic microenvironment, resulting in rapid release of the drugs. With this precise drug encapsulation and controlled release mechanism, ACDCs deliver drugs to tumor tissues effectively and achieve a significantly enhanced antitumor effect. Considering that the ACDCs can be easily prepared by combining antibody-calixarene conjugates derived from tumor-targeting antibodies with various small-molecule drugs, ACDCs may provide a promising platform technology to accelerate ADC development and thus improve the therapeutic efficacy of chemotherapy.

Smartbin Track

This project presents a sophisticated waste management system that combines IoT technology with an Android application to optimize garbage collection processes. The core infrastructure includes IoT-enabled smart trash cans equipped with sensors to detect fill levels autonomously. Complementing this hardware, the Android app serves as a comprehensive platform for managing various aspects of waste collection operations. Divided into modules for administration, employees, and truck drivers, the app offers functionalities such as real-time monitoring of trash levels, route optimization for collection trucks, and automated alerts for full bins. Through seamless integration of IoT capabilities and mobile technology, the system facilitates efficient and environmentally responsible waste management practices, contributing to a cleaner and more sustainable urban environment. Furthermore, the system enhances coordination and transparency within the municipal waste management framework. Municipal administrators gain valuable insights into waste collection efficiency through the app's dashboard. Employees can input data and perform tasks seamlessly, while truck drivers receive real-time updates on bin fill levels and optimized routes, improving overall operational efficiency. By harnessing IoT technology and mobile platforms, this innovative solution not only streamlines waste collection processes.

Tissue engineering and regenerative medicine approaches in colorectal surgery.

Tissue engineering and regenerative medicine (TERM) is an emerging field that has provided new therapeutic opportunities by delivering innovative solutions. The development of nontraditional therapies for previously unsolvable diseases and conditions has brought hope and excitement to countless individuals globally. Many regenerative medicine therapies have been developed and delivered to patients clinically. The technology platforms developed in regenerative medicine have been expanded to various medical areas; however, their applications in colorectal surgery remain limited. Applying TERM technologies to engineer biological tissue and organ substitutes may address the current therapeutic challenges and overcome some complications in colorectal surgery, such as inflammatory bowel diseases, short bowel syndrome, and diseases of motility and neuromuscular function. This review provides a comprehensive overview of TERM applications in colorectal surgery, highlighting the current state of the art, including preclinical and clinical studies, current challenges, and future perspectives. This article synthesizes the latest findings, providing a valuable resource for clinicians and researchers aiming to integrate TERM into colorectal surgical practice.

A theory of degrees in education

Degrees are presumably the most important institution in education markets. However, despite their high relevance, degrees and their design features remain poorly understood within the economics of education. This study addresses this gap. We provide an accurate formal definition of what constitutes a degree and formulate the first theory of degree design. This theory is based on a technological platform view that interprets degrees as modules within a hierarchical structure resembling that of software architectures. This approach provides new opportunities to address questions of degree optimization. Furthermore, a novel strategy to optimize the design of school degrees is proposed. This strategy is expected to improve the learning environment of weaker students across all school types, leaving higher-performing students rather unaffected. The implications and limitations of our approach are also discussed.

Utilizing a Virtual Reality Matrix in Medical Education.

Virtual reality (VR) is an emerging technology that has demonstrated incredible value within medical education. However, medical institutions adopting VR as a learning tool need to ensure that the immersive technology product they pick possesses standard usability criteria. The current literature is limited in defining what specific criteria institutions should look for, or how to select between various VR products. Since there have been little to no algorithms available to the medical education community to aid in this process, a reproducible matrix has been developed to evaluate multiple VR platforms at once which can help identify the best option for medical education programs. The matrix is a 10-point scoring system that includes what the research team considered to be the 10 most important factors when selecting a VR product for medical education. The scores of any two or more VR products can be quantitatively compared. Therefore, the matrix is to be used as a methodological framework to help objectively select the highest-rated immersive technology platform. The research team involved in the development of the matrix consistedof an associate dean for simulation and technology,a director of simulation and technology, and eight medical students.

Large-Scale Statistical Analysis of Defect Emission in hBN: Revealing Spectral Families and Influence of Flake Morphology.

Quantum emitters in two-dimensional layered hexagonal boron nitride are quickly emerging as a highly promising platform for next-generation quantum technologies. However, the precise identification and control of defects are key parameters to achieve the next step in their development. We conducted a comprehensive study by analyzing over 10,000 photoluminescence emission lines from liquid exfoliated hBN nanoflake samples, revealing 11 narrow sets of defect families within the 1.6 to 2.2 eV energy range. This challenges hypotheses of a random energy distribution. We also reported averaged defect parameters, including emission line widths, spatial density, phonon side bands, and Franck-Condon-related factors. These findings provide valuable insights into deciphering the microscopic origin of emitters in hBN hosts. We also explored the influence of the hBN host morphology on defect family formation, demonstrating its crucial impact. By tuning the flake size and arrangement, we achieve selective control of defect types while maintaining high spatial density. This offers a scalable approach to defect emission control, diverging from costly engineering methods. It emphasizes the significance of the morphological aspects of hBN hosts for gaining insights into defect origins and expanding their spectral control.

Enhanced recovery after surgery programs: Applying knowledge from the Covid-19 era to enhance rural surgery

Introduction: Enhanced Recovery After Surgery (ERAS) is a perioperative protocol proven to improve post-operative outcomes and reduce hospital length-of-stay. It has been implemented in both metropolitan and rural healthcare sites, with variable successful rates.Objective: In this review, we explore the evolution of the ERAS protocol and the unique challenges to its implementation within rural and regional settings: with a particular focus on the seismic impacts of the COVID-19 pandemic. We aim to identify current pitfalls in ERAS compliance, and lessons that can be learned and applied to rural clinical practice.Design: We conducted a systemized search of published literature regarding the impact of COVID-19 on ERAS pathways around the world in rural and metropolitan healthcare centres.Findings: Six observational studies and seven commentaries were included in this review.Discussion: The Covid 19 pandemic influenced elements of ERAS program both positively and negatively on the health care globally. There was an exponential uptake of technology and remote platforms during pandemic as a way to reduce transmission of COVID-19.Conclusion: The Covid-19 pandemic introduced an innovative approach to healthcare delivery. Novel approaches with inbuilt technological solutions should be applied to ERAS pathways, improving their versatility and expanding their reach to a wider patient community.

Mapping the Science World with Correlated Topic Modeling Analysis from Science-Related Posts on the Reddit Platform

The main source of technology in today's world is science. The world of science is being reshaped every day with the continuation of studies in the fields of science and technology. However, the development of technology causes the amount of data that cannot be processed with traditional methods on technological platforms to increase day by day. Making meaningful data meaningful by processing unmeaningful data will enable companies, institutions, and organizations to transform big data into highly beneficial tools. One of the most effective data mining techniques for processing and making sense of data is topic modeling. In this study, semantic content analysis of science-related posts on the Reddit platform was conducted using corelated topic modeling (CTM), one of the topic modeling techniques. In the first nine months of 2022, the hidden meanings in Reddit posts and the correlation between these meanings were revealed, and the relevant results were shared. It is thought that the results obtained will be a source of ideas for people interested in science and scientists for their research.

GIẢI PHÁP NÂNG CAO HIỆU QUẢ GIÁO DỤC ĐẠI HỌC TRONG KỶ NGUYÊN 4.0: TỐI ƯU HÌNH THỨC DẠY HỌC TRỰC TUYẾN VÀ ĐỔI MỚI, SÁNG TẠO TRONG CÔNG TÁC KIỂM TRA - ĐÁNH GIÁ

In the trend of globalization, under the impact of the Industrial Revolution 4.0, teaching activities at universities need to be thoroughly innovated and apply modern teaching methods and forms to meet the requirements of promoting students' positivity, initiative, and creativity; improve knowledge exploration and discovery skills, teamwork skills, self-study and self-research skills, etc. This suggests a modern form of teaching to be born: online teaching. Along with that is constant creativity and innovation in designing teaching materials as well as adjusting the assessment method of lecturers. However, reality shows that, due to many different reasons, the implementation of online teaching and the current teaching material design skills of most lecturers are still limited. The article will focus on analyzing the current situation of implementing online teaching, the causes of slow innovation in testing and assessment activities in the university teaching process. From there, contribute solutions to improve this situation. Keywords: Online teaching form; technological platform; online teaching channels and models; testing - evaluation

Impaired Visual Function in Posterior Vitreous Detachment Assessed With the Active-Learning Quantitative Contrast Sensitivity Function Test.

Introduction: To investigate whether there is visual function impairment in patients with posterior vitreous detachment (PVD) using the active-learning quantitative contrast sensitivity function test. Methods: In this cross-sectional study, contrast sensitivity was measured in eyes with PVD and eyes without PVD using the quantitative contrast sensitivity function algorithm on the Adaptive Sensory Technology platform. Outcomes included the area under the log contrast sensitivity function curve, contrast acuity, and contrast sensitivity thresholds at 1 to 18 cycles per degree (cpd). Snellen visual acuity (VA) was also measured. Mixed-effects multiple linear regression analyses were performed to evaluate the association between the presence of PVD and visual function, controlling for age and lens status. Results: The cohort comprised 232 healthy eyes of 205 participants; of these, 80 eyes of 69 patients had PVD. There was no significant association between VA and PVD presence. However, PVD was significantly associated with decreased contrast sensitivity thresholds at 1.5 cpd (β, -0.058; P = .003) and 3 cpd (β, -0.067; P = .004). Contrast sensitivity thresholds at lower (1 cpd) or higher (6, 12, 18 cpd) spatial frequencies did not significantly correlate with PVD presence. Even in the subgroup of symptomatic PVD eyes, VA was not significantly decreased, while quantitative contrast sensitivity function outcomes showed visual function deficits at low spatial frequencies (1.5 cpd and 3 cpd). Conclusions: Contrast sensitivity measured with the quantitative contrast sensitivity function test showed visual function deficits in eyes with PVD that would have been missed with VA testing alone. Incorporating this test in the retina clinic might offer a more comprehensive functional assessment of eyes with PVD, serving as an adjunct outcome metric in clinical decision-making.

Effectiveness of interventions on improving early-life dental care utilization: a systematic review and meta-analysis.

Although early-life dental care is crucial for preventing early childhood caries and has numerous benefits, the utilization rate of such care remains remarkably low worldwide, especially in families of low socioeconomic status. The aim of this study was to systematically review the scientific evidence relating to the effectiveness of interventions on improving early-life dental care utilization of very young children. We reviewed scientific evidence relating to these positive changes, with 7 randomized controlled trials after qualitative evaluation. Interventions assessed included prenatal oral health promotion, motivational interviewing, intraoral camera use alongside social work consultations to aid in decreasing barriers to care, monetary incentives for tooth brushing, fluoride varnish applications, and probiotic usage. The intervention was significantly effective in reducing the incidence of dental caries among children, especially in caries risk. Caries reduction was significant when oral health information was provided at frequent intervals prenatally. Caries increment was also reduced when probiotics were introduced when administered daily. Interventions that attempted to increase parental involvement in oral health care by increasing motivation and decreasing barriers had inconclusive results within the study groups. Considering high rates ECC, early establishment and preservation of a dental home should be a focus in public health measures. Continuous monitoring and parental involvement are key components to maintaining healthy oral conditions. Future studies could explore and test various innovative strategies that utilize technological platforms to engage with parents and promote early-life dental care utilization among the underserved population.

Operation warp speed: Harbinger of American industrial innovation policies

Abstract Operation warp speed (OWS) was a crash effort from 2020 to 2021 to undertake the late-stage development, production, and distribution of vaccines for the coronavirus pandemic. The vaccines were developed, approved, and available in a record time of 8 months using an industrial policy approach. Mainstream economists have long opposed industrial policy approaches as market interference, unless they can be justified by clear market failures. The nation has long had industrial economic policies in such areas as defense, health, transport, and agriculture. However, interventionist policies on the non-defense innovation side of the economy after the research stage have generally been avoided. OWS was a departure, an industrial innovation policy. OWS built a new organization with officials from major health science, regulatory, public health, and research agencies as well as the Defense Department. Elements of its program included: supporting a portfolio of different technology platforms, guaranteed contracts that enable production to evolve alongside development, flexible contracting mechanisms that enabled rapid procurement and intervention into supply chains, rapid technology certification that assured the new vaccines of rapid market entry, mapping supply chains and filling gaps to assure rapid production and distribution, and major product distribution. The elements applied in OWS amount to a new tool kit potentially relevant to other areas, and the USA is now pursuing a series of these in other technology fields.

COVID-19 Educational Side Effects: Pre-service EFL Teachers' Use of Digital Education Tools

Recent research has revealed the complexities of incorporating technology tools into lessons, despite the creation of several platforms and applications for education (Wen & Hua, 2020). The radical shift from traditional to online learning during the COVID-19 pandemic compelled teachers and students to develop technical skills to adapt to this new reality. This study explores the impact of this phenomenon on the perspectives of Pre-Service (PS) English language teachers (students in a teacher-training program), regarding the use of technology to support their own English language learning (ELL) process. To achieve this, an explanatory sequential mixed-method approach was employed. A questionnaire consisting of seven Likert scale statements and six open-ended questions was administered to 32 PS teachers from the English Language B.A program at a major public university in Southeast Mexico. Subsequently, eight participants were interviewed. The results indicated that despite most participants having prior knowledge of technological tools and educational platforms before the pandemic, they did not utilize them to support their ELL. However, the findings also revealed a positive response from participants towards continuing to use digital platforms due to perceived benefits experienced during Emergency Remote Teaching. These findings provide additional evidence concerning English learning and teaching and how classes can be more effective and significant using platforms and applications if classrooms are well equipped.

Strategy for Developing Lecturer Professionalism in Facing the Challenges of Distance Education in the Digital Era

Developments have opened the door to teaching without geographic boundaries, allowing students to access learning materials from anywhere, even in remote areas. This impacts demands for adaptation of teaching strategies and encourages the development of professionalism in lecturers who not only master technological aspects but also comprehensively understand the dynamics of distance education. Educational technology is essential in changing and improving education in this digital era. This research aims to identify strategies for developing lecturer professionalism in facing distance education challenges in the digital era. This type of research is qualitative research. Data collection techniques include interviews and observations of lecturer and student respondents at Al-Ihya Kuningan Islamic University—research results from strategies for developing professionalism in facing educational challenges in the digital era. To be more effective, you can apply several methods: mastery of technology and digital platforms, development of relevant and interactive learning materials, effective online communication skills, and time management skills. By implementing this strategy, lecturers can develop professionalism in facing distance education challenges in the digital era to provide a quality learning experience for students.

Collaborative strategies in the product-sharing market considering manufacturer's capital entry

Digital technology and online platforms have enabled large-scale business-to-consumer (B2C) sharing of normalized products. Recently, B2C sharing platforms have also become very popular. The impact of B2C sharing on traditional manufacturers can be very significant. With increased competition on the business end, many manufacturers (e.g., BYD and Didi; FAW and T3) have accessed the sharing market to provide customized products and technology services in addition to outright sales to platforms. This paper studies a capital-constrained sharing platform and manufacturer's optimal collaborative strategy in the sharing market and the economic implications of their collaboration. We propose a decomposition framework to establish three capital collaborative strategies based on a non-collaborative strategy (N-with-C), which is associated with different levels of the platform's capital and the manufacturer's capital entry. The three collaborative strategies are physical capital collaboration without service capital constraints (P-without-SC), physical capital collaboration with physical and service capital constraints (P-with-SC) and physical and service capital collaboration with physical and service capital constraints (PS-with-SC). We employ a game-theoretic analytical model for our analysis. Our results show that (i) the choice of a certain collaboration strategy depends on the platform's and manufacturer's decisions and how such interaction is affected by decision parameters such as initial capital level, claim proportion, spillover of product launch quantity, utilization efficiency and service efficiency; (ii) with a decrease in the platform's capital level, the N-with-C strategy gradually ceases to be the sharing platform's strategy choice; and (iii) with the manufacturer's service entry, the manufacturer suffers a complete reversal of the optimal strategy choices when choosing between the non-collaborative strategy and collaborative strategies, but P-with-SC is better than non-collaboration under a higher claim proportion and the sharing platform always prefers to collaborate. These results suggest that an increasing asymmetry of capital input and control rights influences the level of collaboration between the sharing platform and manufacturer.

ASSERT: A Platform Technology for Rapid Electrochemical Sensing of Soil Ammonium.

The world is facing a food shortage predicament largely fueled by inefficient, outdated farming conventions that are passed down from generation to generation. Overfertilization is one of the major byproducts of inadequate farming techniques. This leads to an imbalance in the soil ecosystem, affecting carbon sequestration, plant-available nutrients, and microorganisms. Sustainable agriculture, on the other hand, efficiently uses the soil with minimal fertilizer and crop rotation to prevent soil erosion. This method requires real-time information on the soil's health. An electrochemical ion-selective electrode (ISE) is presented to measure soil ammonium in situ. The sensor utilized electrochemical impedance spectroscopy for direct, continuous soil ammonium measurement without any soil pretreatment. The ISE is applied by drop-casting onto the working electrode. The sensor response was calibrated against the three main different soil textures (clay, sandy loam, and loamy clay) to cover the entirety of the soil texture triangle. The linear regression models showed an ammonium-dependent response with Pearson r > 0.991 for the various soil textures in the range of 2-32 ppm. The sensor response was validated against the gold standard spectrophotometric method after KCl extraction showed a less than 20% error rate between the measured ammonium and reference ammonium. A 16 day in situ soil study showed the capability of the sensor to measure soil ammonium in a temporally dynamic manner with a coefficient of variance of 11%, showing robust stability for in situ monitoring.

Efficacy of novel allogeneic cancer cells vaccine to treat colorectal cancer.

Colorectal cancer (CRC) remains a significant global health burden, emphasizing the need for innovative treatment strategies. 95% of the CRC population are microsatellite stable (MSS), insensitive to classical immunotherapies such as anti-PD-1; on the other hand, responders can become resistant and relapse. Recently, the use of cancer vaccines enhanced the immune response against tumor cells. In this context, we developed a therapeutic vaccine based on Stimulated Tumor Cells (STC) platform technology. This vaccine is composed of selected tumor cell lines stressed and haptenated in vitro to generate a factory of immunogenic cancer-related antigens validated by a proteomic cross analysis with patient's biopsies. This technology allows a multi-specific education of the immune system to target tumor cells harboring resistant clones. Here, we report safety and antitumor efficacy of the murine version of the STC vaccine on CT26 BALB/c CRC syngeneic murine models. We showed that one cell line (1CL)-based STC vaccine suppressed tumor growth and extended survival. In addition, three cell lines (3CL)-based STC vaccine significantly improves these parameters by presenting additional tumor-related antigens inducing a multi-specific anti-tumor immune response. Furthermore, proteomic analyses validated that the 3CL-based STC vaccine represents a wider quality range of tumor-related proteins than the 1CL-based STC vaccine covering key categories of tumor antigens related to tumor plasticity and treatment resistance. We also evaluated the efficacy of STC vaccine in an MC38 anti-PD-1 resistant syngeneic murine model. Vaccination with the 3CL-based STC vaccine significantly improved survival and showed a confirmed complete response with an antitumor activity carried by the increase of CD8+ lymphocyte T cells and M1 macrophage infiltration. These results demonstrate the potential of this technology to produce human vaccines for the treatment of patients with CRC.

Complete Circularized Genome Resources for Xylella fastidiosa subsp. sandyi Strains CO33 and CFBP8478

Xylella fastidiosa ( Xf) is a vascular phytopathogenic bacterium native to the Americas, known for causing severe diseases and significant economic losses in important crops. In Europe, Xf is considered a quarantine pathogen. Since its first detection in 2013 in Italy, mandatory surveys to search for Xf across Europe have revealed the presence of three Xf subspecies ( fastidiosa, multiplex, and pauca) in different outbreaks occurring in France, Spain, and Portugal. Xf subspecies sandyi and morus have not been associated with epidemic outbreaks in Europe; however, subspecies sandyi has been detected in intercepted plants imported from Costa Rica and Honduras. By combining data from the Oxford Nanopore Technologies and Illumina sequencing platforms, we obtained complete genomes for Xf strains CO33 and CFBP8478. Both strains belong to the subspecies sandyi and were isolated from coffee plants intercepted in Europe that were imported from Costa Rica. These two genome resources increase the scarce number of Xf genomes available belonging to the subspecies sandyi, which is crucial for comparative genomic analysis and population studies of this important plant-pathogenic bacterium. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .