Development of predictive models for lymphedema by using blood tests and therapy data.

Lymphedema is a disease that refers to tissue swelling caused by an accumulation of protein-rich fluid that is usually drained through the lymphatic system. Detection of lymphedema is often based on expensive diagnoses such as bioimpedance spectroscopy, shear wave elastography, computed tomography, etc. In current machine learning models for lymphedema prediction, reliance on observable symptoms reported by patients introduces the possibility of errors in patient-input data. Moreover, these symptoms are often absent during the initial stages of lymphedema, creating challenges in its early detection. Identifying lymphedema before these observable symptoms manifest would greatly benefit patients by potentially minimizing the discomfort caused by these symptoms. In this study, we propose to use new data, such as complete blood count, serum, and therapy data, to develop predictive models for lymphedema. This approach aims to compensate for the limitations of using only observable symptoms data. We collected data from 2137 patients, including 356 patients with lymphedema and 1781 patients without lymphedema, with the lymphedema status of each patient confirmed by clinicians. The data for each patient included: (1) a complete blood count (CBC) test, (2) a serum test, and (3) therapy information. We used various machine learning algorithms (i.e. random forest, gradient boosting, decision tree, logistic regression, and artificial neural network) to develop predictive models on the training dataset (i.e. 80% of the data) and evaluated the models on the external validation dataset (i.e. 20% of the data). After selecting the best predictive models, we created a web application to aid medical doctors and clinicians in the rapid screening of lymphedema patients. A dataset of 2137 patients was assembled from Seoul National University Bundang Hospital. Predictive models based on the random forest algorithm exhibited satisfactory performance (balanced accuracy = 87.0 ± 0.7%, sensitivity = 84.3 ± 0.6%, specificity = 89.1 ± 1.5%, precision = 97.4 ± 0.7%, F1 score = 90.4 ± 0.4%, and AUC = 0.931 ± 0.007). We developed a web application to facilitate the swift screening of lymphedema among medical practitioners: https://snubhtxt.shinyapps.io/SNUBH_Lymphedema . Our study introduces a novel tool for the early detection of lymphedema and establishes the foundation for future investigations into predicting different stages of the condition.

Enhancement of Wound Healing Efficacy by Chitosan-based Hydrocolloid on Sprague Dawley Rats.

BACKGROUND/AIM: Chitosan-based functional materials have attracted considerable attention worldwide for applications in wound healing, especially in skin wound healing, due to their efficiency in hemostasis, anti-bacterial, and skin regeneration. Various chitosan-based products have been developed for skin wound healing applications, but most of these face limitations in either efficacy or cost-effectiveness. Therefore, there is a need to develop a unique material that can handle all of these concerns and be utilized for acute and chronic wounds. This study investigated mechanisms of new chitosan-based hydrocolloid patches in inflammatory reduction and skin formation by using wound-induced Sprague Dawley Rats. MATERIALS AND METHODS: Our study combined a hydrocolloid patch with chitosan to achieve a practical and accessible medical patch that would enhance skin wound healing. Our chitosan-embedded patch has shown a significant influence by preventing wound expansion and inflammation increment on Sprague Dawley rat models. RESULTS: The chitosan patch significantly increased the wound healing rate and accelerated the inflammatory stage by suppressing pro-inflammatory cytokines activity (e.g., TNF-α, IL-6, MCP-1, and IL-1ß). Moreover, the product was effective in promoting skin regeneration, demonstrated by the increase in the number of fibroblasts through specific biomarkers (e.g., vimentin, α-SMA, Ki-67, collagen I, and TGF-ß1). CONCLUSION: Our study on the chitosan-based hydrocolloid patches not only elucidated mechanisms of reducing inflammation and enhancing proliferation, but also provided a cost-effective method for skin wound dressing.

One Health Surveillance Highlights Circulation of Viruses with Zoonotic Potential in Bats, Pigs, and Humans in Viet Nam.

A One Health cross-sectoral surveillance approach was implemented to screen biological samples from bats, pigs, and humans at high-risk interfaces for zoonotic viral spillover for five viral families with zoonotic potential in Viet Nam. Over 1600 animal and human samples from bat guano harvesting sites, natural bat roosts, and pig farming operations were tested for coronaviruses (CoVs), paramyxoviruses, influenza viruses, filoviruses and flaviviruses using consensus PCR assays. Human samples were also tested using immunoassays to detect antibodies against eight virus groups. Significant viral diversity, including CoVs closely related to ancestors of pig pathogens, was detected in bats roosting at the human-animal interfaces, illustrating the high risk for CoV spillover from bats to pigs in Viet Nam, where pig density is very high. Season and reproductive period were significantly associated with the detection of bat CoVs, with site-specific effects. Phylogeographic analysis indicated localized viral transmission among pig farms. Our limited human sampling did not detect any known zoonotic bat viruses in human communities living close to the bat cave and harvesting bat guano, but our serological assays showed possible previous exposure to Marburg virus-like (Filoviridae), Crimean-Congo hemorrhagic fever virus-like (Bunyaviridae) viruses and flaviviruses. Targeted and coordinated One Health surveillance helped uncover this viral pathogen emergence hotspot.

A Comprehensive Review of Natural Compounds for Wound Healing: Targeting Bioactivity Perspective.

Wound healing is a recovering process of damaged tissues by replacing dysfunctional injured cellular structures. Natural compounds for wound treatment have been widely used for centuries. Numerous published works provided reviews of natural compounds for wound healing applications, which separated the approaches based on different categories such as characteristics, bioactivities, and modes of action. However, current studies provide reviews of natural compounds that originated from only plants or animals. In this work, we provide a comprehensive review of natural compounds sourced from both plants and animals that target the different bioactivities of healing to promote wound resolution. The compounds were classified into four main groups (i.e., anti-inflammation, anti-oxidant, anti-bacterial, and collagen promotion), mostly studied in current literature from 1992 to 2022. Those compounds are listed in tables for readers to search for their origin, bioactivity, and targeting phases in wound healing. We also reviewed the trend in using natural compounds for wound healing.

Nanomicelle-generating Microneedles Loaded With Tranilast for Treatment of Hypertrophic Scars in a Rabbit Model.

BACKGROUND/AIM: Hypertrophic scars (HS) are the result of pathological wound healing characterized by a red, raised scar formation. The goal of this research was development of a new method for treatment of HS formation. MATERIALS AND METHODS: A tranilast-loaded microneedle (TMN) was developed and applied in a rabbit ear model to treat an induced HS. Scar elevation index, the thickness of dorsal skin by hematoxylin and eosin staining, collagen deposition by Masson trichrome staining and expression of myofibroblast biomarker proteins were evaluated. RESULTS: The 12×12 array of the TMN containing 2.9 µg tranilast per needle released more than 80% of the drug within 30 min. During the procedure, control, non-loaded MN and TMN loaded with three different doses of tranilast (low: 2.5-3, medium: 25-30, and high: 100-150 µg) were applied to the HS in rabbit ears. High-level TMN led to a clear and natural appearance of skin, a decrease in scar elevation index by 47% and decline in the thickness of the epidermis from 69.27 to 15.92 µm when compared to the control group. Moreover, the collagen density also decreased in groups treated with medium- or high-level TMNs, by 10.2% and 9.06%, respectively. Furthermore, the expression of transforming growth factor-ß, collagen-1, and α-smooth muscle actin proteins was reduced in TMN-treated HSs compared to the control. CONCLUSION: The findings show the overall efficacy of TMNs in inhibiting HS. Thus, use of TMN is a simple and cosmetic remedy for HS, with good protection and reliability.

Evidence of SARS-CoV-2 Related Coronaviruses Circulating in Sunda pangolins (Manis javanica) Confiscated From the Illegal Wildlife Trade in Viet Nam.

Despite the discovery of several closely related viruses in bats, the direct evolutionary progenitor of SARS-CoV-2 has not yet been identified. In this study, we investigated potential animal sources of SARS-related coronaviruses using archived specimens from Sunda pangolins (Manis javanica) and Chinese pangolins (Manis pentadactyla) confiscated from the illegal wildlife trade, and from common palm civets (Paradoxurus hermaphroditus) raised on wildlife farms in Viet Nam. A total of 696 pangolin and civet specimens were screened for the presence of viral RNA from five zoonotic viral families and from Sarbecoviruses using primers specifically designed for pangolin coronaviruses. We also performed a curated data collection of media reports of wildlife confiscation events involving pangolins in Viet Nam between January 2016 and December 2020, to illustrate the global pangolin supply chain in the context of Viet Nam where the trade confiscated pangolins were sampled for this study. All specimens from pangolins and civets sampled along the wildlife supply chains between February 2017 and July 2018, in Viet Nam and tested with conventional PCR assays designed to detect flavivirus, paramyxovirus, filovirus, coronavirus, and orthomyxovirus RNA were negative. Civet samples were also negative for Sarbecoviruses, but 12 specimens from seven live pangolins confiscated in Hung Yen province, northern Viet Nam, in 2018 were positive for Sarbecoviruses. Our phylogenetic trees based on two fragments of the RdRp gene revealed that the Sarbecoviruses identified in these pangolins were closely related to pangolin coronaviruses detected in pangolins confiscated from the illegal wildlife trade in Yunnan and Guangxi provinces, China. Our curated data collection of media reports of wildlife confiscation events involving pangolins in Viet Nam between January 2016 and December 2020, reflected what is known about pangolin trafficking globally. Pangolins confiscated in Viet Nam were largely in transit, moving toward downstream consumers in China. Confiscations included pangolin scales sourced originally from Africa (and African species of pangolins), or pangolin carcasses and live pangolins native to Southeast Asia (predominately the Sunda pangolin) sourced from neighboring range countries and moving through Viet Nam toward provinces bordering China.

Portable Rabies Virus Sequencing in Canine Rabies Endemic Countries Using the Oxford Nanopore MinION.

As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION's potential for low-cost, high volume sequencing of pathogens in locations with limited resources.

Coronavirus testing indicates transmission risk increases along wildlife supply chains for human consumption in Viet Nam, 2013-2014.

Outbreaks of emerging coronaviruses in the past two decades and the current pandemic of a novel coronavirus (SARS-CoV-2) that emerged in China highlight the importance of this viral family as a zoonotic public health threat. To gain a better understanding of coronavirus presence and diversity in wildlife at wildlife-human interfaces in three southern provinces in Viet Nam 2013-2014, we used consensus Polymerase Chain Reactions to detect coronavirus sequences. In comparison to previous studies, we observed high proportions of positive samples among field rats (34.0%, 239/702) destined for human consumption and insectivorous bats in guano farms (74.8%, 234/313) adjacent to human dwellings. Most notably among field rats, the odds of coronavirus RNA detection significantly increased along the supply chain from field rats sold by traders (reference group; 20.7% positivity, 39/188) by a factor of 2.2 for field rats sold in large markets (32.0%, 116/363) and 10.0 for field rats sold and served in restaurants (55.6%, 84/151). Coronaviruses were also detected in rodents on the majority of wildlife farms sampled (60.7%, 17/28). These coronaviruses were found in the Malayan porcupines (6.0%, 20/331) and bamboo rats (6.3%, 6/96) that are raised on wildlife farms for human consumption as food. We identified six known coronaviruses in bats and rodents, clustered in three Coronaviridae genera, including the Alpha-, Beta-, and Gammacoronaviruses. Our analysis also suggested either mixing of animal excreta in the environment or interspecies transmission of coronaviruses, as both bat and avian coronaviruses were detected in rodent feces on wildlife farms. The mixing of multiple coronaviruses, and their apparent amplification along the wildlife supply chain into restaurants, suggests maximal risk for end consumers and likely underpins the mechanisms of zoonotic spillover to people.

Genetically and Antigenically Divergent Influenza A(H9N2) Viruses Exhibit Differential Replication and Transmission Phenotypes in Mammalian Models.

Low-pathogenicity avian influenza A(H9N2) viruses, enzootic in poultry populations in Asia, are associated with fewer confirmed human infections but higher rates of seropositivity compared to A(H5) or A(H7) subtype viruses. Cocirculation of A(H5) and A(H7) viruses leads to the generation of reassortant viruses bearing A(H9N2) internal genes with markers of mammalian adaptation, warranting continued surveillance in both avian and human populations. Here, we describe active surveillance efforts in live poultry markets in Vietnam in 2018 and compare representative viruses to G1 and Y280 lineage viruses that have infected humans. Receptor binding properties, pH thresholds for HA activation, in vitro replication in human respiratory tract cells, and in vivo mammalian pathogenicity and transmissibility were investigated. While A(H9N2) viruses from both poultry and humans exhibited features associated with mammalian adaptation, one human isolate from 2018, A/Anhui-Lujiang/39/2018, exhibited increased capacity for replication and transmission, demonstrating the pandemic potential of A(H9N2) viruses.IMPORTANCE A(H9N2) influenza viruses are widespread in poultry in many parts of the world and for over 20 years have sporadically jumped species barriers to cause human infection. As these viruses continue to diversify genetically and antigenically, it is critical to closely monitor viruses responsible for human infections, to ascertain if A(H9N2) viruses are acquiring properties that make them better suited to infect and spread among humans. In this study, we describe an active poultry surveillance system established in Vietnam to identify the scope of influenza viruses present in live bird markets and the threat they pose to human health. Assessment of a recent A(H9N2) virus isolated from an individual in China in 2018 is also reported, and it was found to exhibit properties of adaptation to humans and, importantly, it shows similarities to strains isolated from the live bird markets of Vietnam.

Complementary Hybrid Semiconducting Superlattices with Multiple Channels and Mutual Stabilization.

An organic-inorganic hybrid superlattice with near perfect synergistic integration of organic and inorganic constituents was developed to produce properties vastly superior to those of either moiety alone. The complementary hybrid superlattice is composed of multiple quantum wells of 4-mercaptophenol organic monolayers and amorphous ZnO nanolayers. Within the superlattice, multichannel formation was demonstrated at the organic-inorganic interfaces to produce an excellent-performance field effect transistor exhibiting outstanding field-effect mobility with band-like transport and steep subthreshold swing. Furthermore, mutual stabilizations between organic monolayers and ZnO effectively reduced the performance degradation notorious in exclusively organic and ZnO transistors.

Techno-economic assessment of hybrid extraction and distillation processes for furfural production from lignocellulosic biomass.

BACKGROUND: Lignocellulosic biomass is one of the most promising alternatives for replacing mineral resources to overcome global warming, which has become the most important environmental issue in recent years. Furfural was listed by the National Renewable Energy Laboratory as one of the top 30 potential chemicals arising from biomass. However, the current production of furfural is energy intensive and uses inefficient technology. Thus, a hybrid purification process that combines extraction and distillation to produce furfural from lignocellulosic biomass was considered and investigated in detail to improve the process efficiency. This effective hybrid process depends on the extracting solvent, which was selected based on a comprehensive procedure that ranged from solvent screening to complete process design. RESULTS: Various solvents were first evaluated in terms of their extraction ability. Then, the most promising solvents were selected to study the separation feasibility. Eventually, processes that used the three best solvents (toluene, benzene, and butyl chloride) were designed and optimized in detail using Aspen Plus. Sustainability analysis was performed to evaluate these processes in terms of their energy requirements, total annual costs (TAC), and carbon dioxide (CO2) emissions. The results showed that butyl chloride was the most suitable solvent for the hybrid furfural process because it could save 44.7% of the TAC while reducing the CO2 emissions by 45.5% compared to the toluene process. In comparison with the traditional purification process using distillation, this suggested hybrid extraction/distillation process can save up to 19.2% of the TAC and reduce 58.3% total annual CO2 emissions. Furthermore, a sensitivity analysis of the feed composition and its effect on the performance of the proposed hybrid system was conducted. CONCLUSIONS: Butyl chloride was found to be the most suitable solvent for the hybrid extraction/distillation process of furfural production. The proposed hybrid sequence was more favorable than the traditional distillation process when the methanol fraction of the feed stream was <3% and more benefit could be obtained when that fraction decreased.

Multiple component quantitative analysis for the pattern recognition and quality evaluation of Kalopanacis Cortex using HPLC.

A quantitative and pattern recognition analyses were conducted for quality evaluation of Kalopanacis Cortex (KC) using HPLC. For quantitative analysis, four bioactive compounds, liriodendrin, pinoresinol O-ß-D-glucopyranoside, acanthoside B and kalopanaxin B, were determined. The analysis method was optimized and validated using ODS column with mobile phase of methanol and aqueous phosphoric acid. The validation gave acceptable linearities (r > 0.9995), recoveries (98.4% to 101.9%) and precisions (RSD < 2.20). The limit of detection of compounds ranged from 0.4 to 0.9 µg/mL. Among the four compounds, liriodendrin was recommended as a marker compound for the quality control of KC. The pattern analysis was successfully carried out by analyzing thirty two samples from four species, and the authentic KC samples were completely discriminated from other inauthentic species by linear discriminant analysis. The results indicated that the method was suitable for the quantitative analysis of liriodendrin and the quality evaluation of KC.