Uptake of tumour necrosis factor-alpha inhibitor biosimilars for psoriasis: a drug utilization study from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR).

BACKGROUND: Tumour necrosis factor-alpha inhibitors (TNFi) have revolutionized the treatment of moderate-to-severe psoriasis. Following patent expiry of the originator biologics, TNFi biosimilars became available, presenting the opportunity for significant reductions in drug costs. OBJECTIVES: To describe the uptake of TNFi biosimilars for psoriasis treatment in the UK and Ireland. METHODS: This observational cohort study utilizes data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR), a national pharmacovigilance study register for patients with psoriasis on systemic treatments. We analysed biosimilar uptake trends over time in nine geographical regions of England along with Wales, Scotland, Northern Ireland and the Republic of Ireland. We assessed the incidence of switching to biosimilars in an originator-user cohort (switchers). Patients on originators infliximab, etanercept and adalimumab at the time originator patents expired, entered the cohort on 1 February 2015, August 2015 and October 2018, respectively, and were followed up until 31 October 2021. Trends in biosimilar initiations were assessed in an adalimumab-naïve cohort who started adalimumab between 1 October 2018 and 31 July 2019 (starters). We assessed the associations between patient factors and originator-to-biosimilar switching and biosimilar initiation using a multivariable Cox regression model and a multivariable logistic regression model, respectively. RESULTS: Included in the originator-user cohort were 4202 patients (209 on infliximab, 742 on etanercept and 3251 on adalimumab). For infliximab, etanercept and adalimumab, respectively, the cumulative incidence of originator-to-biosimilar switching increased with time to 14.8%, 23.6% and 66.6% after 3 years. Across geographical regions, 3-year switching rates varied from 0% to 43.7% for infliximab; from 0% to 40.4% for etanercept; and from 12.5% to 84.3% for adalimumab. Out of the 528 patients included in the adalimumab-naïve cohort, 67.8% started on biosimilars. Originator-to-biosimilar switching and biosimilar initiation were more common in men and in patients who had lower Psoriasis Area and Severity Index at cohort entry. CONCLUSIONS: The uptake of biosimilars increased over time and varied considerably across the UK and Ireland; adalimumab had the highest biosimilar uptake rate compared with that of other TNFi drugs.

Skull Fracture Patterns and Morphologies Among Fatal Motorcycle Traffic Accident Victims in Vietnam.

ABSTRACT: We aim to describe morphological structures of skull fractures and relevant factors in motorcycle accident victims in Vietnam. This work represents a retrospective cross-sectional study based on forensic reports of fatal motorcycle accident victims. Between January 2013 and August 2019, a total of 226 fatal motorcycle accident patients with skull fracture diagnoses were enrolled. Linear and depressed fractures were the common patterns (46.0% and 37.2% of cases, respectively), whereas stellate (11.5%) fractures were rare. Fractures of the temporal bone (68.6% of cases) and basilar skull (60.6%) were the most common, whereas fractures of the parietal bone were the least common (9.7%). Two or more patterns of skull fracture were recorded in 25.5% of cases, and 2 or more fracture locations were recorded in 76.6% of cases. Fractures of the parietal bone were associated with victims not wearing a helmet. In addition, fractures of the basilar skull were more likely to occur among victims with alcohol consumption. We found the common pattern of skull fractures was linear and depressed fractures, and the common location of skull fractures was temporal and basilar bone. Further studies that include larger sample sizes and collect more information should be conducted to better understand relationships between skull fractures and related factors.

Detection of human fecal pollution in environmental waters using human mitochondrial DNA and correlation with general and human-associated fecal genetic markers.

Human mitochondrial DNA (mtDNA) genetic markers are abundant in sewage and highly human-specific, suggesting a great potential for the environmental application as human fecal pollution indicators. Limited data are available on the occurrence and co-occurrence of human mtDNA with fecal bacterial markers in surface waters, and how the abundance of these markers is influenced by rain events. A 1-year sampling study was conducted in a suburban watershed impacted by human sewage contamination to evaluate the performance of a human mtDNA-based marker along with the bacterial genetic markers for human-associated Bacteroidales (BacHum and HF183) and Escherichia coli. Additionally, the human mtDNA-based assay was correlated with rain events and other markers. The mtDNA marker was detected in 92% of samples (n = 140) with a mean concentration of 2.96 log10 copies/100 ml throughout the study period. Human mtDNA was detected with greater abundance than human-associated Bacteroidales that could be attributed to differences in the decay of these markers in the environment. The abundance of all markers was positively correlated with rain events, and human mtDNA abundance was significantly correlated with various bacterial markers. In general, these results should support future risk assessment for impacted watersheds, particularly those affected by human fecal pollution, by evaluating the performance of these markers during rain events.

Dual Genotype Orientia tsutsugamushi Infection in Patient with Rash and Eschar, Vietnam, 2016.

We report a dual genotype Orientia tsutsugamushi infection in Vietnam in 2016. The patient had fever, rash, and an eschar. The Kawasaki genotype was identified in the eschar specimen and Karp genotype in the whole blood specimen. The genotype co-infection rate for scrub typhus is unknown and should be further evaluated.

Effects of metal oxide nanoparticles on nitrification in wastewater treatment systems: A systematic review.

While the variety of engineered nanoparticles used in consumer products continues to grow, the use of metal oxide nanoparticles in electronics, textiles, cosmetics and food packaging industry has grown exponentially in recent years, which will inevitably result in their release into wastewater streams in turn impacting the important biological processes in wastewater treatment plants. Among these processes, nitrification play a critical role in nitrogen removal during wastewater treatment, however, it is sensitive to a wide range of inhibitory substances including metal oxide nanoparticles. Therefore, it is essential to systematically asses the effects of metal oxide nanoparticles on nitrification in biological wastewater treatment systems. In this review we discuss the present scenario of metal oxide nanoparticles and their impact on biological wastewater treatment processes, specifically nitrogen removal through nitrification. We also summarize the various methods used to measure nitrification inhibition by metal oxide nanoparticles and highlight corresponding results obtained using those methods. Finally, the key research gaps that need to be addressed in future are discussed.

Analysis of stromal cell secretomes reveals a critical role for stromal cell-derived hepatocyte growth factor and fibronectin in angiogenesis.

OBJECTIVE: Angiogenesis requires tightly coordinated crosstalk between endothelial cells (ECs) and stromal cells, such as fibroblasts and smooth muscle cells. The specific molecular mechanisms moderating this process are still poorly understood. METHODS AND RESULTS: Stromal cell-derived factors are essential for EC sprouting and lumen formation. We therefore compared the abilities of 2 primary fibroblast isolates and a primary smooth muscle cell isolate to promote in vitro angiogenesis, and analyzed their secretomes using a combination of nano liquid chromatography-mass spectrometry/mass spectrometry, quantitative PCR, and ELISA. Each isolate exhibited a different level of angiogenic ability. Using quantitative MS, we then compared the secretomes of a fibroblast isolate exhibiting low angiogenic activity, a fibroblast isolate exhibiting high angiogenic activity, and human umbilical vein ECs. High angiogenic fibroblast supernatants exhibited an overabundance of proteins associated with extracellular matrix constituents compared with low angiogenic fibroblasts or ECs. Finally, small interfering RNA technology and purified protein were used to confirm a role for stromal cell-derived hepatocyte growth factor and fibronectin in inducing EC sprouting. CONCLUSIONS: Differences in stromal cell ability to induce angiogenesis are a result of differences in the secreted proteomes of both extracellular matrix proteins and proangiogenic growth factors.

Dissemination of antimicrobial resistance in agricultural ecosystems following irrigation with treated municipal wastewater.

The spread of antimicrobial resistance (AMR) in agricultural systems via irrigation water is a serious public health issue as it can be transmitted to humans through the food chain. Therefore, understanding the dissemination routes of antibiotic resistance genes (ARGs) in agricultural systems is crucial for the assessment of health risks associated with eating fresh vegetables such as spinach and radish irrigated with treated municipal wastewater (TMW). In this study, we investigated the bacterial community structure and resistome in the soil-plant-earthworm continuum after irrigation of spinach and radish with TMW containing the antibiotics trimethoprim (TMP), sulfamethoxazole (SMZ), and sulfapyridine (SPD) using 16S rRNA gene sequencing and high throughput quantitative PCR (HT-qPCR). The study was conducted in two phases: Phase I involved eight weeks of spinach and radish production using TMW for irrigation, whereas Phase II entailed three weeks of earthworm exposure to contaminated plant material obtained in Phase I. The 16S data indicated that the rhizosphere bacterial community composition and structure were more resilient to antibiotic residuals in the irrigated water, with radish showing less susceptibility than spinach than those of bulk soils. The HT-qPCR analysis revealed that a total of 271 ARGs (out of 285) and 9 mobile genetic elements (MGEs) (out of 10) were detected in all samples. Higher diversity and abundance of ARGs were observed for samples irrigated with higher concentrations of antibiotics in both spinach and radish treatments. However, compared to spinach, radish ARG dynamics in the soil biome were more stable due to the change of antibiotic introduction to the soil. At the class level, multi-drug resistance (MDR) class was altered significantly by the presence of antibiotics in irrigation water. Compared to earthworm fecal samples, their corresponding soil environments showed a higher number of detected ARGs, suggesting that earthworms could play a role in reducing ARG dissemination in the soil environments. These findings will not only provide insight into the dissemination of ARGs in agricultural environments due to antibiotic residuals in irrigated water but could help understand the potential human health risks associated with ARGs.

Dissemination of antibiotic resistance genes through soil-plant-earthworm continuum in the food production environment.

Treated municipal wastewater (TMW) can provide a reliable source of irrigation water for crops, which is especially important in arid areas where water resources are limited or prone to drought. Nonetheless, TMW may contain residual antibiotics, potentially exposing the crops to these substances. The goal of this study was to investigate the dissemination of antibiotics resistance genes (ARGs) in the soil-plant-earthworm continuum after irrigation of spinach and radish plants with TMW containing trimethoprim, sulfamethoxazole, and sulfapyridine in a greenhouse experiment, followed by feeding of earthworms with harvested plant materials. Our results showed that antibiotic resistance genes (ARGs) were enriched in the soil-plant-earthworm microbiomes irrigated with TMW and TMW spiked with higher concentrations of antibiotics. The number of ARGs and antibiotic-resistant bacteria (ARB) enrichment varied with plant type, with spinach harboring a significantly higher amount of ARGs and ARB compared to radish. Our data showed that bulk and rhizosphere soils of spinach and radish plants irrigated with MilliQ water, TMW, TMW10, or TMW100 had significant differences in bacterial community (p < 0.001), ARG (p < 0.001), and virulence factor gene (VFG) (p < 0.001) diversities. The abundance of ARGs significantly decreased from bulk soil to rhizosphere to phyllosphere and endosphere. Using metagenome assembled genomes (MAGs), we recovered many bacterial MAGs and a near complete genome (>90 %) of bacterial MAG of genus Leclercia adecarboxylata B from the fecal microbiome of earthworm that was fed harvested radish tubers and spinach leaves grown on TMW10 irrigated waters, and this bacterium has been shown to be an emerging pathogen causing infection in immunocompromised patients that may lead to health complications and death. Therefore, crops irrigated with TMW containing residual antibiotics and ARGs may lead to increased incidences of enrichment of ARB in the soil-plant-earthworm continuum.

Biosimilars for the Treatment of Psoriasis: A Systematic Review of Clinical Trials and Observational Studies.

Importance: Biosimilars have the potential to reduce costs for the management of moderate-to-severe psoriasis compared with originators. However, the extrapolation of evidence enables the approval of a biosimilar for use in indications held by the originator without directly being studied in clinical trials. Thus, biosimilars can be approved for psoriasis based on extrapolated evidence from other diseases. The availability of evidence for the effectiveness and safety of biosimilars for the treatment of psoriasis is therefore unclear. Objective: To compare the efficacy/effectiveness and safety of biosimilars with originator biologics for the treatment of patients with psoriasis. Evidence Review: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and The European Union Clinical Trials Register were searched in August 2022. Eligible studies were appraised using the Cochrane Risk of Bias 2 and ROBINS-I tools. All analyses were conducted from September 2022 to November 2022. Findings: Fourteen trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) were included. Twelve trials compared biosimilars with originators in originator-naive patients (starters), and 11 trials compared switching from originator to biosimilar (switchers) with continuous originator treatments. There was no clinically or statistically significant difference in rates of achieving 75% improvement in Psoriasis Area and Severity Index scores and risks of adverse events (AEs) at week 16 and week 52 between the comparators. Two cohort studies showed no difference in effectiveness and safety outcomes between originators and biosimilars, whereas 1 study reported more AEs in patients who switched to biosimilars of adalimumab at 12 months. Three trials showed low risk of bias, whereas 11 trials had moderate risk of bias. All cohort studies had moderate to high risk of bias. Conclusions and Relevance: In this systematic review, there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators for the treatment of patients with psoriasis. Most of the available evidence was based on randomized clinical trials, although high-quality real-world evidence was lacking. Future studies are needed to examine the long-term effectiveness and safety of biosimilars for the treatment of patients with psoriasis.

Simple and cost-effective way to make mobile antibiotic cement spacer: hand-made silicone mold.

BACKGROUND: Two-stage exchange arthroplasty is considered the most common approach for the management of prosthetic joint infections. There has been plentiful evidence to support the superiority of the mobile spacers over the static ones. Unfortunately, articulating options are not available in our low-resource environment, which motivated us to come up with an affordable way to create a mobile cement spacer. After experimenting with a variety of materials and producing methods, we realized that silicone is a favorable material for mold building and established a simple process of making a handmade silicone mold. We demonstrate the clinical outcomes of three prosthetic joint infections by using these spacers in the hope of spreading the idea to our colleagues who work in the circumstances of a developing country. Construction of the spacer molds: The molds, consisting of two parts, were shaped by using high viscosity addition silicone (elite HD+ putty soft, Zhermack SpA, Italy) as material, and previously removed implants as template. They were sterilized using ethylene oxide treatment before being ready for casting antibiotic-loaded bone cement spacer. CASE REPORT: Three cases of prosthetic infection were treated with two-stage revision, using antibiotic-impregnated cement spacer cast in hand-made silicone molds. We sought to determine intraoperative complications, postoperative range of motion, and functional scores. All the patients were regularly followed up to identify fractures or dislocation of the spacer, and reinfection. RESULTS: At the end of the follow-up, all three patients had the infection eradicated. The three patients could sit comfortably with bent knees, walk with partial weight-bearing, and achieve 75-80 degrees of knee flexion in the first week after surgery. Follow-up X-rays revealed no fractures or dislocation in any of the spacers. CONCLUSION: Silicone molds offer a simple and cost-effective alternative to costly commercial products in producing articulating spacers. Treating infected joints arthroplasty with these spacers allows for early motion and partial weight bearing and improves patient satisfaction and life quality before reimplantation without significant complications.

The Role of Quorum Sensing in the Development of Microcystis aeruginosa Blooms: Gene Expression.

Microcystis aeruginosa (M. aeruginosa) is the dominant cyanobacterial species causing harmful algal blooms in water bodies worldwide. The blooms release potent toxins and pose severe public health hazards to water bodies, animals, and humans who are in contact with or consume this water. The interaction between M. aeruginosa and heterotrophic bacteria is thought to contribute to the development of the blooms. This study strives to provide a specific answer to whether quorum sensing is also a potential mechanism mediating the interaction of different strains/species and the expression by gene luxS or gene mcyB in M. aeruginosa growth. The luxS gene in M. aeruginosa PCC7806 is associated with quorum sensing and was tested by q-PCR throughout a 30-day growth period. The same was performed for the mcyB gene. Heterotrophic bacteria were collected from local water bodies: Cibolo Creek and Leon Creek in San Antonio, Texas. Results revealed that in algal bloom scenarios, there is a similar concentration of gene luxS that is expressed by the cyanobacteria. Gene mcyB, however, is not directly associated with algal blooms, but it is related to cyanotoxin production. Toxicity levels increased in experiments with multiple algal strains, and the HSL treatment was not effective at reducing microcystin levels.

Smart Low Level Laser Therapy System for Automatic Facial Dermatological Disorder Diagnosis.

Computer-aided diagnosis using dermoscopy images is a promising technique for improving the efficiency of facial skin disorder diagnosis and treatment. Hence, in this study, we propose a low-level laser therapy (LLLT) system with a deep neural network and medical internet of things (MIoT) assistance. The main contributions of this study are to (1) provide a comprehensive hardware and software design for an automatic phototherapy system, (2) propose a modified-U2Net deep learning model for facial dermatological disorder segmentation, and (3) develop a synthetic data generation process for the proposed models to address the issue of the limited and imbalanced dataset. Finally, a MIoT-assisted LLLT platform for remote healthcare monitoring and management is proposed. The trained U2-Net model achieved a better performance on untrained dataset than other recent models, with an average Accuracy of 97.5%, Jaccard index of 74.7%, and Dice coefficient of 80.6%. The experimental results demonstrated that our proposed LLLT system can accurately segment facial skin diseases and automatically apply for phototherapy. The integration of artificial intelligence and MIoT-based healthcare platforms is a significant step toward the development of medical assistant tools in the near future.

Superiority of left heart deformation in early anthracycline-related cardiac dysfunction detection.

OBJECTIVE: This study aimed to assess the incidence of early cancer therapy-related cardiac dysfunction (CTRCD) and the characteristics of left and right heart deformations during anthracycline chemotherapy. METHODS: We prospectively enrolled a cohort of 351 chemotherapy-naïve women with breast cancer and cardiovascular risk factors who were scheduled to receive anthracycline. The left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS) and right ventricular and left atrial longitudinal strains were evaluated using echocardiography at baseline, before every subsequent cycles and at 3 weeks after the final anthracycline dose. CTRCD was defined as a new LVEF reduction by ≥10 percentage points to an LVEF<50% and/or a new relative decline in GLS by >15% from the baseline value. RESULTS: Eighteen (5.1%) patients had evidence of asymptomatic CTRCD during anthracycline treatment, and 50% developed CTRCD before completing the chemotherapy regimen. In the CTRCD group, while LV-GLS decrease significantly after the first dose of anthracycline, the reduction of right ventricular free-wall longitudinal strain and left atrial reservoir strain were observed after the second dose. Other strain indices could not be used to identify early CTRCD. CONCLUSIONS: Cardiotoxicity appeared soon after the initiation of anthracycline chemotherapy. Among the left-heart and right-heart mechanics, LV-GLS remains the best deformation indicator for detecting early CTRCD.

Potential reservoirs of antimicrobial resistance in livestock waste and treated wastewater that can be disseminated to agricultural land.

Livestock manure, dairy lagoon effluent, and treated wastewater are known reservoirs of antibiotic resistance genes (ARGs), antibiotic-resistant bacteria (ARB), and virulence factor genes (VFGs), and their application to agricultural farmland could be a serious public health threat. However, their dissemination to agricultural lands and impact on important geochemical pathways such as the nitrogen (N) cycle have not been jointly explored. In this study, shotgun metagenomic sequencing and analyses were performed to examine the diversity and composition of microbial communities, ARGs, VFGs, and N cycling genes in different livestock manure/lagoon and treated wastewater collected from concentrated animal feeding operations (CAFOs) and a municipal wastewater treatment plant along the west coast of the United States. Multivariate analysis showed that diversity indices of bacterial taxa from the different microbiomes were not significantly different based on InvSimpson (P = 0.05), but differences in ARG mechanisms were observed between swine manure and other microbiome sources. Comparative resistome profiling showed that ARGs in microbiome samples belonged to four core resistance classes: aminoglycosides (40-55 %), tetracyclines (30-45 %), beta-lactam-resistance (20-35 %), macrolides (18-30 %), and >50 % of the VFGs that the 24 microbiomes harbored were phyletically affiliated with two bacteria, Bacteroidetes fragilis and Enterobacter aerogenes. Network analysis based on Spearman correlation showed co-occurrence patterns between several genes such as transporter-gene and regulator, efflux pump and involved-in-polymyxin- resistance, aminoglycoside, beta-lactam, and macrolide with VFGs and bacterial taxa such as Firmicutes, Candidatus Themoplasmatota, Actinobacteria, and Bacteroidetes. Metabolic reconstruction of metagenome-assembled genome (MAGs) analysis showed that the most prevalent drug resistance mechanisms were associated with carbapenem resistance, multidrug resistance (MDR), and efflux pump. Bacteroidales was the main taxa involved in dissimilatory nitrate reduction (DNRA) in dairy lagoon effluent. This study demonstrates that the dissemination of waste from these sources can increase the spread of ARGs, ARB, and VFGs into agricultural lands, negatively impacting both soil and human health.

Drug survival and safety of biosimilars and originator adalimumab in the treatment of psoriasis: a multinational cohort study.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease. Adalimumab is an effective but previously expensive biological treatment for psoriasis. The introduction of biosimilars following the patent expiry of the originator adalimumab Humira has reduced the unit cost of treatment. However, the long-term effectiveness and safety of adalimumab biosimilars for treating psoriasis in real-world settings are uncertain and may be a barrier to widespread usage. METHODS AND ANALYSIS: This study aims to compare the drug survival and safety of adalimumab biosimilars to adalimumab originator for the treatment of psoriasis. We will use both routinely collected healthcare databases and dedicated pharmacovigilance registries from the PsoNet initiative, including data from the UK, France and Spain. We will conduct a cohort study using a prevalent new user design. We will match patients on previous adalimumab exposure time to create two equal-sized cohorts of biosimilar and originator users. The coprimary outcomes are drug survival, defined by the time from cohort entry to discontinuation of the drug of interest; and risk of serious adverse events, defined by adverse events leading to hospitalisation or death. Cox proportional hazards models will be fitted to calculate HRs as the effect estimate for the outcomes. ETHICS AND DISSEMINATION: The participating registries agree with the Declaration of Helsinki and received approval from local ethics committees. The results of the study will be published in scientific journals and presented at international dermatology conferences by the end of 2023.

Bridging the gap between tumor-on-chip and clinics: a systematic review of 15 years of studies.

Over the past 15 years, the field of oncology research has witnessed significant progress in the development of new cell culture models, such as tumor-on-chip (ToC) systems. In this comprehensive overview, we present a multidisciplinary perspective by bringing together physicists, biologists, clinicians, and experts from pharmaceutical companies to highlight the current state of ToC research, its unique features, and the challenges it faces. To offer readers a clear and quantitative understanding of the ToC field, we conducted an extensive systematic analysis of more than 300 publications related to ToC from 2005 to 2022. ToC offer key advantages over other in vitro models by enabling precise control over various parameters. These parameters include the properties of the extracellular matrix, mechanical forces exerted on cells, the physico-chemical environment, cell composition, and the architecture of the tumor microenvironment. Such fine control allows ToC to closely replicate the complex microenvironment and interactions within tumors, facilitating the study of cancer progression and therapeutic responses in a highly representative manner. Importantly, by incorporating patient-derived cells or tumor xenografts, ToC models have demonstrated promising results in terms of clinical validation. We also examined the potential of ToC for pharmaceutical industries in which ToC adoption is expected to occur gradually. Looking ahead, given the high failure rate of clinical trials and the increasing emphasis on the 3Rs principles (replacement, reduction, refinement of animal experimentation), ToC models hold immense potential for cancer research. In the next decade, data generated from ToC models could potentially be employed for discovering new therapeutic targets, contributing to regulatory purposes, refining preclinical drug testing and reducing reliance on animal models.

Wastewater surveillance for SARS-CoV-2 to support return to campus: Methodological considerations and data interpretation.

The COVID-19 pandemic has been challenging for various institutions such as school systems due to widespread closures. As schools re-open their campuses to in-person education, there is a need for frequent screening and monitoring of the virus to ensure the safety of students and staff and to limit risk to the surrounding community. Wastewater surveillance (WWS) of SARS-CoV-2 is a rapid and economical approach to determine the extent of COVID-19 in the community. The focus of this review is on the emergence of WWS as a tool for safe return to school campuses, taking into account methodological considerations such as site selection, sample collection and processing, SARS-CoV-2 quantification, and data interpretation. Recently published studies on the implementation of COVID-19 WWS on school and college campuses were reviewed. While there are several logistical and technical challenges, WWS can be used to inform decision-making at the school campus and/or building level.

A Flexible, Wearable, and Wireless Biosensor Patch with Internet of Medical Things Applications.

Monitoring the vital signs and physiological responses of the human body in daily activities is particularly useful for the early diagnosis and prevention of cardiovascular diseases. Here, we proposed a wireless and flexible biosensor patch for continuous and longitudinal monitoring of different physiological signals, including body temperature, blood pressure (BP), and electrocardiography. Moreover, these modalities for tracking body movement and GPS locations for emergency rescue have been included in biosensor devices. We optimized the flexible patch design with high mechanical stretchability and compatibility that can provide reliable and long-term attachment to the curved skin surface. Regarding smart healthcare applications, this research presents an Internet of Things-connected healthcare platform consisting of a smartphone application, website service, database server, and mobile gateway. The IoT platform has the potential to reduce the demand for medical resources and enhance the quality of healthcare services. To further address the advances in non-invasive continuous BP monitoring, an optimized deep learning architecture with one-channel electrocardiogram signals is introduced. The performance of the BP estimation model was verified using an independent dataset; this experimental result satisfied the Association for the Advancement of Medical Instrumentation, and the British Hypertension Society standards for BP monitoring devices. The experimental results demonstrated the practical application of the wireless and flexible biosensor patch for continuous physiological signal monitoring with Internet of Medical Things-connected healthcare applications.

Fecal pollution source characterization in the surface waters of recharge and contributing zones of a karst aquifer using general and host-associated fecal genetic markers.

Fecal pollution of surface waters in the karst-dominated Edwards aquifer is a serious concern as contaminated waters can rapidly transmit to groundwaters, which are used for domestic purposes. Although microbial source tracking (MST) detects sources of fecal pollution, integrating data related to environmental processes (precipitation) and land management practices (septic tanks) with MST can provide better understanding of fecal contamination fluxes to implement effective mitigation strategies. Here, we investigated fecal sources and their spatial origins at recharge and contributing zones of the Edwards aquifer and identified their relationship with nutrients in different environmental/land-use conditions. During March 2019 to March 2020, water samples (n = 295) were collected biweekly from 11 sampling sites across four creeks and analyzed for six physico-chemical parameters and ten fecal indicator bacteria (FIB) and MST-based qPCR assays targeting general (E. coli, Enterococcus, and universal Bacteroidales), human (BacHum and HF183), ruminant (Rum2Bac), cattle (BacCow), canine (BacCan), and avian (Chicken/Duck-Bac and GFD) fecal markers. Among physico-chemical parameters, nitrate-N (NO3-N) concentrations at several sites were higher than estimated national background concentrations for streams. General fecal markers were detected in the majority of water samples, and among host-associated MST markers, GFD, BacCow, and Rum2Bac were more frequently detected than BacCan, BacHum, and HF183, indicating avian and ruminant fecal contamination is a major concern. Cluster analysis results indicated that sampling sites clustered based on precipitation and septic tank density showed significant correlation (p < 0.05) between nutrients and FIB/MST markers, indicating these factors are influencing the spatial and temporal variations of fecal sources. Overall, results emphasize that integration of environmental/land-use data with MST is crucial for a better understanding of nutrient loading and fecal contamination.

Enhanced precision of real-time control photothermal therapy using cost-effective infrared sensor array and artificial neural network.

Photothermal therapy (PTT) requires tight thermal dose control to achieve tumor ablation with minimal thermal injury on surrounding healthy tissues. In this study, we proposed a real-time closed-loop system for monitoring and controlling the temperature of PTT using a non-contact infrared thermal sensor array and an artificial neural network (ANN) to induce a predetermined area of thermal damage on the tissue. A cost-effective infrared thermal sensor array was used to monitor the temperature development for feedback control during the treatment. The measured and predicted temperatures were used as inputs of fuzzy control logic controllers that were implemented on an embedded platform (Jetson Nano) for real-time thermal control. Three treatment groups (continuous wave = CW, conventional fuzzy logic = C-Fuzzy, and ANN-based predictive fuzzy logic = P-Fuzzy) were examined and compared to investigate the laser heating performance and collect temperature data for ANN model training. The ex vivo experiments validated the efficiency of fuzzy control with temperature method on maintaining the constant interstitial tissue temperature (80 ± 1.4 °C) at a targeted surface of the tissue. The linear relationship between coagulation areas and the treatment time was indicated in this study, with the averaged coagulation rate of 0.0196 cm2/s. A thermal damage area of 1.32 cm2 (diameter ∼1.3 cm) was observed under P-Fuzzy condition for 200 s, which covered the predetermined thermal damage area (diameter ∼1 cm). The integration of real-time feedback temperature control with predictive ANN could be a feasible approach to precisely induce the preset extent of thermal coagulation for treating papillary thyroid microcarcinoma.