Personalized Drug Therapy: Innovative Concept Guided With Proteoformics.

Personalized medicine can reduce adverse effects, enhance drug efficacy, and optimize treatment outcomes, which represents the essence of personalized medicine in the pharmacy field. Protein drugs are crucial in the field of personalized drug therapy and are currently the mainstay, which possess higher target specificity and biological activity than small-molecule chemical drugs, making them efficient in regulating disease-related biological processes, and have significant potential in the development of personalized drugs. Currently, protein drugs are designed and developed for specific protein targets based on patient-specific protein data. However, due to the rapid development of two-dimensional gel electrophoresis and mass spectrometry, it is now widely recognized that a canonical protein actually includes multiple proteoforms, and the differences between these proteoforms will result in varying responses to drugs. The variation in the effects of different proteoforms can be significant and the impact can even alter the intended benefit of a drug, potentially making it harmful instead of lifesaving. As a result, we propose that protein drugs should shift from being targeted through the lens of protein (proteomics) to being targeted through the lens of proteoform (proteoformics). This will enable the development of personalized protein drugs that are better equipped to meet patients' specific needs and disease characteristics. With further development in the field of proteoformics, individualized drug therapy, especially personalized protein drugs aimed at proteoforms as a drug target, will improve the understanding of disease mechanisms, discovery of new drug targets and signaling pathways, provide a theoretical basis for the development of new drugs, aid doctors in conducting health risk assessments and making more cost-effective targeted prevention strategies conducted by artificial intelligence/machine learning, promote technological innovation, and provide more convenient treatment tailored to individualized patient profile, which will benefit the affected individuals and society at large.

Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India.

BACKGROUND: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. RESULTS: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. CONCLUSION: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.

Floatable Termination-Vacant MXene Architecture for High-Performance and Cost-Effective Photothermal Dehydrogenation.

Liquid hydrogen carriers have garnered considerable interest in long-distance and large-scale hydrogen storage owing to their exceptional hydrogen storage density, safety, and compatibility. Nonetheless, their practical application is hampered by the low hydrogen production rate and high cost, stemming from poor thermal utilization and heavy reliance on noble metals in solar bulk dehydrogenation platforms. To conquer these challenges, we devise an economical all-in-one architecture comprising the photothermal catalytic termination-vacant MXene and a highly insulated melamine substrate. This design floats on the air-reactant interface to efficiently drive solar interfacial dehydrogenation. The melamine enables interfacial heat localization to improve the thermal utilization, providing a high reaction temperature. Meanwhile, the MXene with termination vacancies exposes rich active sites for formic acid dehydrogenation, and simultaneously high performance and cost-effectiveness can be realized. This work offers fresh perspectives on the design and application of photothermal catalytic MXene, broadening the prospects for hydrogen storage using liquid hydrogen carriers.

Risk-based lung cancer screening in heavy smokers: a benefit-harm and cost-effectiveness modeling study.

BACKGROUND: Annual screening through low-dose computed tomography (LDCT) is recommended for heavy smokers. However, it is questionable whether all individuals require annual screening given the potential harms of LDCT screening. This study examines the benefit-harm and cost-effectiveness of risk-based screening in heavy smokers and determines the optimal risk threshold for screening and risk-stratified screening intervals. METHODS: We conducted a comparative cost-effectiveness analysis in China, using a cohort-based Markov model which simulated a lung cancer screening cohort of 19,146 heavy smokers aged 50 ~ 74 years old, who had a smoking history of at least 30 pack-years and were either current smokers or had quit for < 15 years. A total of 34 risk-based screening strategies, varying by different risk groups for screening eligibility and screening intervals (1-year, 2-year, 3-year, one-off, non-screening), were evaluated and were compared with annual screening for all heavy smokers (the status quo strategy). The analysis was undertaken from the health service perspective with a 30-year time horizon. The willingness-to-pay (WTP) threshold was adopted as three times the gross domestic product (GDP) of China in 2021 (CNY 242,928) per quality-adjusted life year (QALY) gained. RESULTS: Compared with the status quo strategy, nine risk-based screening strategies were found to be cost-effective, with two of them even resulting in cost-saving. The most cost-effective strategy was the risk-based approach of annual screening for individuals with a 5-year risk threshold of ≥ 1.70%, biennial screening for individuals with a 5-year risk threshold of 1.03 ~ 1.69%, and triennial screening for individuals with a 5-year risk threshold of < 1.03%. This strategy had the highest incremental net monetary benefit (iNMB) of CNY 1032. All risk-based screening strategies were more efficient than the status quo strategy, requiring 129 ~ 656 fewer screenings per lung cancer death avoided, and 0.5 ~ 28 fewer screenings per life-year gained. The cost-effectiveness of risk-based screening was further improved when individual adherence to screening improved and individuals quit smoking after being screened. CONCLUSIONS: Risk-based screening strategies are more efficient in reducing lung cancer deaths and gaining life years compared to the status quo strategy. Risk-stratified screening intervals can potentially balance long-term benefit-harm trade-offs and improve the cost-effectiveness of lung cancer screenings.

Molecular Characterization of Lineage-IV Peste Des Petits Ruminants Virus and the Development of In-House Indirect Enzyme-Linked Immunosorbent Assay (IELISA) for its Rapid Detection".

Peste des petits ruminants (PPRV), a highly contagious viral disease, causes significant economic losses concerning sheep and goats. Recently, PPR viruses (PPRVs), have adopted new hosts and lineage IV of PPRVs represents genetic diversity within the same lineage. 350 samples, including blood, swabs, and tissues from sheep/goats, were collected during the 2020-2021 disease outbreaks in Pakistan. These samples were analysed through RT-PCR and three isolates of PPRV with accession numbers, MW600920, MW600921, and MW600922, were submitted to GenBank, based on the partial N-gene sequencing. This analysis provides a better understanding of genetic characterizations and a targeted RT-PCR approach for rapid PPRV diagnosis. An IELISA test was developed using the semi-purified antigen MW600922 isolate grown in Vero cells. The PPRV isolates currently present high divergence with the Turkish strain; conversely, similarities equivalent to 99.73% were observed for isolates collected from Pakistan. The developed indirect ELISA (IELISA) test demonstrated antibody detection rates at dilutions of 1:200 for antibodies (serum) and 1:32 for antigens. In comparison to cELISA, high specificity (85.23%) and sensitivity (90.60%) rates were observed. In contrast to the virus neutralization test (VNT), IELISA was observed to be 100% specific and 82.14% sensitive in its results. Based on these results, serological surveys conducted for PPR antibodies using IELISA can be a more effective strategy on a larger scale. Furthermore, our results demonstrate a significant breakthrough in the research in terms of cost-effectiveness and storage efficiency, and the developed IELISA test is highly recommended for use in developing countries.

Peste des petits ruminants (PPRV) is a transboundary, highly contagious, and economically significant viral disease affecting small ruminants and wildlife. PPRV, a disease that only targets animals, is the focus of the Global Eradication Programme (PPRV GEP), which aims to eradicate the disease by 2030. Following the completion of the first phase of the GEP (2017­2021), Pakistan has initiated the second phase: PPRV presence and the implementation of a control strategy. Rapid and accurate laboratory diagnosis is vital to the disease's effective control and eradication. In the present study, we have improved diagnosis by reverse transcriptase polymerase chain reaction (RT-PCR), which not only can detect low viral concentrations but also contributes to the genetic analysis of lineage-IV viruses. However, the development of cost-effective indirect ELISA (iELISA) may allow for the analysis of serum samples obtained from larger populations of small ruminants.

The cost-effectiveness of osteoporosis medications for preventing periprosthetic fractures following femoral neck fracture indicated hip arthroplasty: a break-even analysis.

Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF. INTRODUCTION: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs. METHODS: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates. RESULTS: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500. CONCLUSION: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced.

Flexible cost-penalized Bayesian model selection: Developing inclusion paths with an application to diagnosis of heart disease.

We propose a Bayesian model selection approach that allows medical practitioners to select among predictor variables while taking their respective costs into account. Medical procedures almost always incur costs in time and/or money. These costs might exceed their usefulness for modeling the outcome of interest. We develop Bayesian model selection that uses flexible model priors to penalize costly predictors a priori and select a subset of predictors useful relative to their costs. Our approach (i) gives the practitioner control over the magnitude of cost penalization, (ii) enables the prior to scale well with sample size, and (iii) enables the creation of our proposed inclusion path visualization, which can be used to make decisions about individual candidate predictors using both probabilistic and visual tools. We demonstrate the effectiveness of our inclusion path approach and the importance of being able to adjust the magnitude of the prior's cost penalization through a dataset pertaining to heart disease diagnosis in patients at the Cleveland Clinic Foundation, where several candidate predictors with various costs were recorded for patients, and through simulated data.

Which Localizing Strategy is the Most Cost-Effective in Reoperative Primary Hyperparathyroidism?

INTRODUCTION: 2%-10% of patients with primary hyperparathyroidism (PHPT) who undergo parathyroidectomy develop persistent/recurrent disease. The aim of this study was to determine which preoperative localization method is most cost-effective in reoperative PHPT. METHODS: Clinical decision analytic models comparing cost-effectiveness of localizing studies in reoperative PHPT were constructed using TreeAge Pro. Cost and probability assumptions were varied via Probabilistic Sensitivity Analysis (PSA) to test the robustness of the base case models. RESULTS: Base case analysis of model 1 revealed ultrasound (US)-guided fine-needle aspiration with PTH assay as most cost-effective after localizing US. This was confirmed on PSA of model 1. Model 2 showed four-dimensional computed tomography (4D-CT) as most cost-effective after negative US. If not localized by US, on PSA, 4D-CT was the next most cost-effective test. CONCLUSIONS: US-guided FNA with PTH is the most cost-effective confirmatory test after US localization. 4D-CT should be considered as the next best test after negative US.

Stable fixation using absorbable sutures in craniofacial surgery in patients over 24 months of age-a retrospective study.

PURPOSE: In craniofacial surgery, the stable fixation of transposed bone segments is crucial in order to ensure good long-term results. The use of absorbable material in fixation avoids the need for a second surgery, which would otherwise be required to remove osteosynthesis material. The authors of the present manuscript have already demonstrated that absorbable sutures ensure the stable fixation of bone segments in patients up to 24 months of age. However, it has thus far remained unclear whether stable fixation is possible in older patients by using only absorbable sutures due to the slower bone remodelling and prolonged healing time in this cohort. METHOD: For the present study, osteosynthesis was performed in 50 patients ranging from 25.7 to 192.1 months of age (mean, 61.4 ± 21.7 months) using solely absorbable sutures (PDS II®, Ethicon, Germany). Post-operative stability and possible restrictions-such as foreign body reactions-were evaluated within clinical and radiological routine follow-ups. RESULTS: All children demonstrated clinically and radiologically stable osteosynthesis both directly post-operatively and in follow-ups. No significant foreign body reaction could be seen. CONCLUSION: The present study demonstrates-for the first time-that absorbable sutures with a longer absorption period are also very well suited for the fixation of bone segments in patients over 24 months of age. The sole use of absorbable sutures in children over 24 months of age is a safe procedure with nearly no foreign body reactions. The procedure enables stable and highly cost-effective osteosynthesis without altering the osteotomy design.

Production and SERS characterization of bacteriocin-like inhibitory substances by latilactobacillus sakei in whey permeate powder: exploring natural antibacterial potential.

Bacteriocins are antimicrobial compounds that have awakened interest across several industries due to their effectiveness. However, their large-scale production often becomes unfeasible on an industrial scale, primarily because of high process costs. Addressing this challenge, this work analyzes the potential of using low-cost whey permeate powder, without any supplementation, to produce bacteriocin-like inhibitory substances (BLIS) through the fermentation of Latilactobacillus sakei. For this purpose, different concentrations of whey permeate powder (55.15 gL-1, 41.3 gL-1 and 27.5 gL-1) were used. The ability of L. sakei to produce BLIS was evaluated, as well as the potential of crude cell-free supernatant to act as a preservative. Raman spectroscopy and surface-enhanced Raman scattering (SERS) provided detailed insights into the composition and changes occurring during fermentation. SERS, in particular, enhanced peak definition significantly, allowing for the identification of key components, such as lactose, proteins, and phenylalanine, which are crucial in understanding the fermentation process and BLIS characteristics. The results revealed that the concentration of 55.15 gL-1 of whey permeate powder, in flasks without agitation and a culture temperature of 32.5 °C, presented the highest biological activity of BLIS, reaching 99% of inhibition of Escherichia coli and Staphylococcus aureus with minimum inhibitory concentration of 36-45%, respectively. BLIS production began within 60 h of cultivation and was associated with class II bacteriocins. The results demonstrate a promising approach for producing BLIS in an economical and environmentally sustainable manner, with potential implications for various industries.

Deep Reinforcement Learning-Empowered Cost-Effective Federated Video Surveillance Management Framework.

Video surveillance systems are integral to bolstering safety and security across multiple settings. With the advent of deep learning (DL), a specialization within machine learning (ML), these systems have been significantly augmented to facilitate DL-based video surveillance services with notable precision. Nevertheless, DL-based video surveillance services, which necessitate the tracking of object movement and motion tracking (e.g., to identify unusual object behaviors), can demand a significant portion of computational and memory resources. This includes utilizing GPU computing power for model inference and allocating GPU memory for model loading. To tackle the computational demands inherent in DL-based video surveillance, this study introduces a novel video surveillance management system designed to optimize operational efficiency. At its core, the system is built on a two-tiered edge computing architecture (i.e., client and server through socket transmission). In this architecture, the primary edge (i.e., client side) handles the initial processing tasks, such as object detection, and is connected via a Universal Serial Bus (USB) cable to the Closed-Circuit Television (CCTV) camera, directly at the source of the video feed. This immediate processing reduces the latency of data transfer by detecting objects in real time. Meanwhile, the secondary edge (i.e., server side) plays a vital role by hosting a dynamically controlling threshold module targeted at releasing DL-based models, reducing needless GPU usage. This module is a novel addition that dynamically adjusts the threshold time value required to release DL models. By dynamically optimizing this threshold, the system can effectively manage GPU usage, ensuring resources are allocated efficiently. Moreover, we utilize federated learning (FL) to streamline the training of a Long Short-Term Memory (LSTM) network for predicting imminent object appearances by amalgamating data from diverse camera sources while ensuring data privacy and optimized resource allocation. Furthermore, in contrast to the static threshold values or moving average techniques used in previous approaches for the controlling threshold module, we employ a Deep Q-Network (DQN) methodology to manage threshold values dynamically. This approach efficiently balances the trade-off between GPU memory conservation and the reloading latency of the DL model, which is enabled by incorporating LSTM-derived predictions as inputs to determine the optimal timing for releasing the DL model. The results highlight the potential of our approach to significantly improve the efficiency and effective usage of computational resources in video surveillance systems, opening the door to enhanced security in various domains.

Affordable 3D Orientation Visualization Solution for Working Class Remotely Operated Vehicles (ROV).

ROV operators often encounter challenges with orientation awareness while operating underwater, primarily due to relying solely on 2D camera feeds to manually control the ROV robot arm. This limitation in underwater visibility and orientation awareness, as observed among Malaysian ROV operators, can compromise the accuracy of arm placement, and pose a risk of tool damage if not handle with care. To address this, a 3D orientation monitoring system for ROVs has been developed, leveraging measurement sensors with nine degrees of freedom (DOF). These sensors capture crucial parameters such as roll, pitch, yaw, and heading, providing real-time data on the ROV's position along the X, Y, and Z axes to ensure precise orientation. These data are then utilized to generate and process 3D imaging and develop a corresponding 3D model of the operational ROV underwater, accurately reflecting its orientation in a visual representation by using an open-source platform. Due to constraints set by an agreement with the working class ROV operators, only short-term tests (up to 1 min) could be performed at the dockyard. A video demonstration of a working class ROV replica moving and reflecting in a 3D simulation in real-time was also presented. Despite these limitations, our findings demonstrate the feasibility and potential of a cost-effective 3D orientation visualization system for working class ROVs. With mean absolute error (MAE) error less than 2%, the results align with the performance expectations of the actual working ROV.

Cost-Effective Data Acquisition Systems for Advanced Structural Health Monitoring.

With the growing demand for infrastructure and transportation facilities, the need for advanced structural health monitoring (SHM) systems is critical. This study introduces two innovative, cost-effective, standalone, and open-source data acquisition devices designed to enhance SHM through the latest sensing technologies. The first device, termed CEDAS_acc, integrates the ADXL355 MEMS accelerometer with a RaspberryPi mini-computer, ideal for measuring strong ground motions and assessing structural modal properties during forced vibration tests and structural monitoring of mid-rise buildings. The second device, CEDAS_geo, incorporates the SM24 geophone sensor with a Raspberry Pi, designed for weak ground motion measurements, making it suitable for seismograph networks, seismological research, and early warning systems. Both devices function as acceleration/velocity Data Acquisition Systems (DAS) and standalone data loggers, featuring hardware components such as a single-board mini-computer, sensors, Analog-to-Digital Converters (ADCs), and micro-SD cards housed in protective casings. The CEDAS_acc includes a triaxial MEMS accelerometer with three ADCs, while the CEDAS_geo uses horizontal and vertical geophone elements with an ADC board. To validate these devices, rigorous tests were conducted. Offset Test, conducted by placing the sensor on a leveled flat surface in six orientations, demonstrating the accelerometer's ability to provide accurate measurements using gravity as a reference; Frequency Response Test, performed at the Gebze Technical University Earthquake and Structure Laboratory (GTU-ESL), comparing the devices' responses to the GURALP-5TDE reference sensor, with CEDAS_acc evaluated on a shaking table and CEDAS_geo's performance assessed using ambient vibration records; and Noise Test, executed in a low-noise rural area to determine the intrinsic noise of CEDAS_geo, showing its capability to capture vibrations lower than ambient noise levels. Further field tests were conducted on a 10-story reinforced concrete building in Gaziantep, Turkey, instrumented with 8 CEDAS_acc and 1 CEDAS_geo devices. The building's response to a magnitude 3.2 earthquake and ambient vibrations was analyzed, comparing results to the GURALP-5TDE reference sensors and demonstrating the devices' accuracy in capturing peak accelerations and modal frequencies with minimal deviations. The study also introduced the Record Analyzer (RECANA) web application for managing data analysis on CEDAS devices, supporting various data formats, and providing tools for filtering, calibrating, and exporting data. This comprehensive study presents valuable, practical solutions for SHM, enhancing accessibility, reliability, and efficiency in structural and seismic monitoring applications and offering robust alternatives to traditional, costlier systems.

Efficient AAV9 Purification Using a Single-Step AAV9 Magnetic Affinity Beads Isolation.

Adeno-associated viruses (AAVs) have emerged as promising tools for gene therapy due to their safety and efficacy in delivering therapeutic genes or gene editing sequences to various tissues and organs. AAV serotype 9 (AAV9), among AAV serotypes, stands out for its ability to efficiently target multiple tissues, thus holding significant potential for clinical applications. However, existing methods for purifying AAVs are cumbersome, expensive, and often yield inconsistent results. In this study, we explore a novel purification strategy utilizing Dynabeads™ CaptureSelect™ magnetic beads. The AAV9 magnetic beads capture AAV9 with high specificity and recovery between 70 and 90%, whereas the AAVX magnetic beads did not bind to the AAV9. Through continuous interaction with AAVs in solution, these beads offer enhanced clearance of genomic DNA and plasmids even in the absence of endonuclease. The beads could be regenerated at least eight times, and the used beads could be stored for up to six months and reused without a significant reduction in recovery. The potency of the AAV9-purified vectors in vivo was comparable to that of iodixanol purified vectors.

Comparative evaluation of drying methods for struvite produced from electrocoagulated source-separated urine: Implications for quality, energy and cost-effectiveness.

Struvite precipitation from source-separated urine is crucial for waste utilization and sustainability. However, after precipitation, the high moisture content of struvite necessitates an additional drying process that can be costly and inefficient. In the present study, the performance of different drying methods-open sun drying, air drying, conventional drying (20-100 °C), and microwave drying (180-720 W) on the quality of struvite obtained from source-separated urine through electrocoagulation using Mg-Mg electrodes were evaluated. It was found that higher temperatures and power in the convective oven and microwave resulted in higher diffusivity (10-9-10-7 m2s-1), leading to reduced drying times. Different models were employed to comprehend the drying mechanism, and the one with the highest correlation coefficient (R2 = 0.99) and the lowest statistical values was selected. The key findings indicated that higher power and temperature levels were more cost-effective. However, characterization of the dried struvite using X-ray diffraction and Fourier-transformed infrared spectroscopy, disintegration of struvite crystals at temperatures above 60 °C in the conventional oven and 180 W in the microwave oven was observed. Based on the results, we conclude that sun drying is a cost-effective and environmentally friendly alternative for drying struvite without compromising its quality.

Using evidence to identify teaching strategies to improve student competencies.

BACKGROUND: Organizational assessment revealed opportunities to develop a critical mass of faculty educated about EBP and integrate competencies into practice. The faculty orientation online program did not include information about the EBP process, teaching strategies, or student competencies. PURPOSE: The purpose of this EBP project was to investigate the best teaching strategies that foster student competencies. IMPLEMENTATION PLAN: Based on the evidence, an online EBP module was developed including the best teaching strategies for instruction of EBP, the student competencies that must be mastered and teaching barriers that must be overcome. The results and implementation plan were presented to leaders and faculty Online Council for feedback, approval, and buy-in. OUTCOMES: Twenty-five faculty completed the EBP online module over 1 year providing examples for teaching strategies that related EBP to clinical practice, teaching methods that engaged students and examples of assignments that promoted student competency. IMPLICATIONS FOR PRACTICE: Using evidence to develop an EBP module for faculty orientation to online teaching provided a cost-effective way to develop a critical mass of faculty educated in EBP teaching strategies and methods that foster student competencies.

Automatically transferring supervised targets method for segmenting lung lesion regions with CT imaging.

BACKGROUND: To present an approach that autonomously identifies and selects a self-selective optimal target for the purpose of enhancing learning efficiency to segment infected regions of the lung from chest computed tomography images. We designed a semi-supervised dual-branch framework for training, where the training set consisted of limited expert-annotated data and a large amount of coarsely annotated data that was automatically segmented based on Hu values, which were used to train both strong and weak branches. In addition, we employed the Lovasz scoring method to automatically switch the supervision target in the weak branch and select the optimal target as the supervision object for training. This method can use noisy labels for rapid localization during the early stages of training, and gradually use more accurate targets for supervised training as the training progresses. This approach can utilize a large number of samples that do not require manual annotation, and with the iterations of training, the supervised targets containing noise become closer and closer to the fine-annotated data, which significantly improves the accuracy of the final model. RESULTS: The proposed dual-branch deep learning network based on semi-supervision together with cost-effective samples achieved 83.56 ± 12.10 and 82.67 ± 8.04 on our internal and external test benchmarks measured by the mean Dice similarity coefficient (DSC). Through experimental comparison, the DSC value of the proposed algorithm was improved by 13.54% and 2.02% on the internal benchmark and 13.37% and 2.13% on the external benchmark compared with U-Net without extra sample assistance and the mean-teacher frontier algorithm, respectively. CONCLUSION: The cost-effective pseudolabeled samples assisted the training of DL models and achieved much better results compared with traditional DL models with manually labeled samples only. Furthermore, our method also achieved the best performance compared with other up-to-date dual branch structures.

Hematological, clinical, immunophenotypic characterization, and treatment outcomes of prognostically significant genetic subtypes of B-lineage acute lymphoblastic leukemia: A report of 1021 patients from India.

BACKGROUND: The published literature on hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low-income countries. For newer classifications such as BCR::ABL1-like ALLs, the scarcity of patient-level data is even more pronounced. METHODS: The authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1-like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n = 1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1-like ALL subtype and other genetic subtypes of ALL. RESULTS: Patients with BCR::ABL1-positive and BCR::ABL1-like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1-negative cases (p < .05). Logistic regression modeling of B-lineage-ALL (B-ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1-like ALL (p < .05). Furthermore, patients with BCR::ABL1-like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1-negative ALLs (p < .05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1-like ALLs compared to BCR::ABL1-negative ALL cases (p < .05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1-positive ALL cases were statistically significant (p < .05), and BCR::ABL1-like ALL cases had high MRD-positivity as compared to BCR::ABL1-negative ALL cases but did not show statistical significance. CONCLUSIONS: The findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B-ALLs. This is the first report characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India. PLAIN LANGUAGE SUMMARY: Characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n = 1021) of acute lymphoblastic leukemia (ALLs) in patients from India. We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs. Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1-like ALL cases compared to BCR::ABL1-negative ALL cases. Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1-like ALLs (p < .05). In terms of treatment outcomes, BCR::ABL1-positive ALL had statistically significant minimal residual disease (MRD) (p < .05), and BCR::ABL1-like ALL cases had high MRD-positivity but did not show statistical significance as compared to BCR::ABL1-negative ALLs.

Cost-effectiveness of history-indicated cerclage vs cervical length assessment for prevention of preterm birth.

BACKGROUND: Preterm birth is one of the major causes of neonatal morbidity and mortality. Preterm delivery is a large burden to our health care system, and a history of preterm birth is one of the most common risk factors for subsequent preterm birth. OBJECTIVE: We sought to examine the cost-effectiveness of the history-indicated cerclage strategy compared with the transvaginal ultrasound cervical length assessment strategy in individuals with a history of preterm birth. STUDY DESIGN: We developed a decision analysis model to compare history-indicated cerclage and cervical length assessment. The primary outcome was the net monetary benefit from a maternal and neonatal perspective of both strategies, defined as the value of an intervention with a known willingness to pay threshold for a unit of benefit. The time horizon was set to be a lifetime. Costs (in 2022 USD) included those for the cerclage, serial transvaginal ultrasounds, maternal care for admission, neonatal care, and severe disability. Probabilities, utilities, and costs were derived from the literature. A cost-effectiveness threshold was set at $100,000 per QALY (quality-adjusted life year). We first conducted 1-way sensitivity analyses with associated variables as sensitivity analyses. We then performed a probabilistic sensitivity analysis using Monte Carlo simulation with 1000 trials to test the robustness of the results in the setting of simultaneous changes in probabilities, costs, and utilities. RESULTS: In our base-case analysis, the history-indicated cerclage strategy compared to transvaginal ultrasound cervical length assessment was associated with more cost ($85,038 vs $70,155), with slightly less effectiveness from the maternal perspective (26.74 QALY vs 26.78 QALY) and from the neonatal perspective (28.91 QALY vs 29.06 QALY), and with less maternal and neonatal net monetary benefit. Therefore, the history-indicated cerclage strategy was dominated. With the 1000 trials of Monte Carlo simulation, transvaginal ultrasound cervical length assessment was the preferred strategy 84% and 88% of the time from the maternal and neonatal perspectives, respectively. CONCLUSION: The history-indicated cerclage strategy was more expensive and slightly less effective than the transvaginal ultrasound cervical length assessment strategy with a lower net monetary benefit.