Hyperspectral dark-field microscopy of human breast lumpectomy samples for tumor margin detection in breast-conserving surgery.

Significance: Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human post-lumpectomy breast tissues excised during breast-conserving surgeries. Aim: We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples. Approach: Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed. The performance of the HSDFM is evaluated by comparing the backscattering intensity spectra of polystyrene microbead solutions with the Monte Carlo simulation of the experimental data. For classification algorithms, two analysis approaches, a supervised technique based on the spectral angle mapper (SAM) algorithm and an unsupervised technique based on the K-means algorithm are applied to classify various tissue types including carcinoma subtypes. In the supervised technique, the SAM algorithm with manually extracted endmembers guided by H&E annotations is used as reference spectra, allowing for segmentation maps with classified tissue types including carcinoma subtypes. Results: The manually extracted endmembers of known tissue types and their corresponding threshold spectral correlation angles for classification make a good reference library that validates endmembers computed by the unsupervised K-means algorithm. The unsupervised K-means algorithm, with no a priori information, produces abundance maps with dominant endmembers of various tissue types, including carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma. The two carcinomas' unique endmembers produced by the two methods agree with each other within <2% residual error margin. Conclusions: Our report demonstrates a robust procedure for the validation of an unsupervised algorithm with the essential set of parameters based on the ground truth, histopathological information. We have demonstrated that a trained library of the histopathology-guided endmembers and associated threshold spectral correlation angles computed against well-defined reference data cubes serve such parameters. Two classification algorithms, supervised and unsupervised algorithms, are employed to identify regions with carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma present in the tissues. The two carcinomas' unique endmembers used by the two methods agree to <2% residual error margin. This library of high quality and collected under an environment with no ambient background may be instrumental to develop or validate more advanced unsupervised data cube analysis algorithms, such as effective neural networks for efficient subtype classification.

The effects of free trade agreements on the stock market: Evidence from Vietnam.

This study examines the effects of news events related to the European Union-Vietnam Free Trade Agreement (EVFTA) on the Vietnam stock market from 2010 to 2020. We calculate sectoral abnormal returns prior to, during, and after announcements and find that the Vietnamese stock market is susceptible to these events. We discovered that the announcement had a negative impact on the market, which might diminish the effectiveness of the Agreement. The findings show that more than half of Vietnam's sectors had an immediate reaction to EVFTA announcements, with fourteen reacting negatively and six responding positively. Two of the ten events did not have any immediate impact on these industries but all events resulted in either early or delayed reactions. We also find market scepticism and major changes in the deal led to the emergence of a diamond risk structure. We run multiple robustness tests to account for market integration and other factors that may affect stock returns. In addition, we explore potential sectoral systematic risk changes following these occurrences using different ARCH-type models. These additional tests confirm the robustness of our findings.

Investigating the effects of ultrafine bubbles on bacterial growth.

Several previous studies have considered ultrafine bubbles as a potential research target because their properties can be applied in many different research areas. In particular, the interaction between UFBs and microorganisms has always been one of the aspects that receives much attention due to the high difficulty in controlling a living system. The properties of UFBs, as mobile air-water interfaces, are greatly determined by their gas cores which play a critical role in regulating microbial growth. This study aims to investigate the effects of ultrafine bubbles on bacterial growth. Two well-studied organisms were chosen as models - Escherichia coli and Staphylococcus aureus. Their growing behavior was examined based on the growth rate, phenotype and biomass. Three types of Luria-Bertani cultures were tested, including a standard culture containing distilled water, an air ultrafine bubble culture, and a hydrogen ultrafine bubble culture. The UFBs were generated via ultrasonic cavitation and stabilized by 50 µM SDS, which was proven to have negligible effects on bacterial growth. By comparing among the three cultivation conditions, the bacterial growth rates were observed to be the highest in exposure to HUFBs. The results also signified that UFBs had an enhancement on cell proliferation. On the other hand, while proposing an increase in cell density, bacteria cultured in HUFB media have their sizes decreased uniformly and significantly (p-value < 0.05). This study confirmed that bacterial growth was promoted by UFBs; and better effects recorded were due to the HUFB present in the culture media. However, the average morphological size of bacteria was in negative correlation with their population size.

Review on the Significant Interactions between Ultrafine Gas Bubbles and Biological Systems.

Having sizes comparable with living cells and high abundance, ultrafine bubbles (UBs) are prone to inevitable interactions with different types of cells and facilitate alterations in physiological properties. The interactions of four typical cell types (e.g., bacterial, fungal, plant, and mammalian cells) with UBs have been studied over recent years. For bacterial cells, UBs have been utilized in creating the capillary force to tear down biofilms. The release of high amounts of heat, pressure, and free radicals during bubble rupture is also found to affect bacterial cell growth. Similarly, the bubble gas core identity plays an important role in the development of fungal cells. By the proposed mechanism of attachment of UBs on hydrophobin proteins in the fungal cell wall, oxygen and ozone gas-filled ultrafine bubbles can either promote or hinder the cell growth rate. On the other hand, reactive oxygen species (ROS) formation and mass transfer facilitation are two means of indirect interactions between UBs and plant cells. Likewise, the use of different gas cores in generating bubbles can produce different physical effects on these cells, for example, hydrogen gas for antioxidation against infections and oxygen for oxidation of toxic metal ions. For mammalian cells, the importance of investigating their interactions with UBs lies in the bubbles' action on cell viability as membrane poration for drug delivery can greatly affect cells' survival. UBs have been utilized and tested in forming the pores by different methods, ranging from bubble oscillation and microstream generation through acoustic cavitation to bubble implosion.

Derivation of Ultra-High Gain Hybrid Converter Families for HASEL Actuators Used in Soft Mobile Robots.

This work proposes, analyzes, designs, and validates superior topologies of UHGH converters that are capable of supporting extremely large conversion ratios up to ∼2000× and output voltage up to ∼4-12 kV for future mobile soft robots from an input voltage as low as the range of a 1-cell battery pack. Thus, the converter makes soft robots standalone systems that can be untethered and mobile. The extremely large voltage gain is enabled by a unique hybrid combination of a high-gain switched magnetic element (HGSME) and a capacitor-based voltage multiplier rectifier (CVMR) that, together, achieve small overall size, efficient operation, and output voltage regulation and shaping with simple duty-cycle modulation. With superior performance, power density, and compact size, the UHGH converters prove to be a promising candidate for future untethered soft robots.

Preparation of High-quality Oil from Vegetable Oil with High-free Fatty Acid (FFA) Content Using an Ammonia/Methanol Solution.

There are significant concerns regarding the quality of vegetable oils in the food and biofuel industries. In this study, we explored the preparation of high- quality oil from high-free fatty acid (FFA) vegetable oil using an ammonia/MeOH solvent as an alkali base. Among the six tested solvents, MeOH was the most suitable for the separation of the oil and FFAs. Among the three alkali bases, ammonia enhanced the miscibility of FFAs in MeOH by forming ammonium salts. The amounts of FFAs in the upper layer and oil in the lower layer were positively correlated (r = 0.9348 and 0.9617, respectively) with MeOH. With increasing MeOH concentration, the amount of oil in the lower layer increased along with the FFAs in the upper layer. Using the molar ratio of ammonia to FFA 1:1 and the ratio (v/w) of MeOH to oil 4:3, 91.6% FFAs and 97.8% oil in the upper and lower layers, respectively, were produced from 50% FFA oil. Using a relational expression of FFAs and oil in the upper layer, 97.1% FFAs and 99.6% oil in each layer was obtained from 10% FFA oil. The oil in the lower layer was further purified by extraction with MeOH. This method is easy and efficient for the separation and purification of oil, accompanied by the reuse of reagents with almost no loss of raw materials.

An Ultra High Gain Converter for Driving HASEL Actuator Used in Soft Mobile Robots.

Soft robots have the potential to fundamentally change interactions between robots and the surrounding environment, and between robots and animals, and robots and humans in ways that today's hard robots are incapable of doing. However, to realize this potential, soft robot actuators require extremely high voltage supplies of more than 4 kV. The electronics that can satisfy this need currently are either too large and bulky or unable to achieve the high power efficiency required for mobile systems. To meet this challenge, this paper conceptualizes, analyzes, designs, and validates a hardware prototype of an ultra-high gain (UHG) converter that can support extremely large conversion ratios up to ∼1000× to provide up to 5 kV output voltage from an input voltage of ∼5-10 V. This converter is demonstrated to be able to drive HASEL (Hydraulically Amplified Self-Healing Electrostatic) actuators, a promising candidate to realize future soft mobile robotic fishes, from an input voltage range of a 1-cell battery pack. The circuit topology employs a unique hybrid combination of a high-gain switched magnetic element (HGSME) and a diode and capacitor-based voltage multiplier rectifier (DCVMR) to enable compact magnetic elements, efficient soft-charging in all flying capacitors, and adjustable output voltage capability with simple duty-cycle modulation. Achieving an efficiency of 78.2% at 15 W output power, while providing 3.85 kV output from 8.5 V input, the proposed UGH converter proves to be a promising candidate for future untethered soft robots.

Long-Term North American Trend in Patch Test Reactions: A 32-Year Statistical Overview (1984-2016).

Background: Allergic contact dermatitis (ACD) remains a public health issue worldwide, despite regulations intended to minimize sensitization. With up-to-date knowledge about which chemicals continue to have high allergenicity, the government/industry can refocus their efforts to be most effective. Objective: We reviewed updated data showing common allergens that elicit ACD to determine the progress in reducing sensitization to inform public health policy, government regulation, and industry standards. Methods: We compiled data from the North American Contact Dermatitis Group showing patch test results from 1984 to 2016 for 153 compounds. Using these data, we analyzed the trends over time of positive test reactions to determine whether they are increasing or decreasing. Results: Of the 47 compounds with sufficient data to analyze, 23 had a decreasing proportion of positive patch test results over the whole period. An additional 5 had a decreasing proportion over a shorter period. Finally, 4 had an increasing proportion over any period: compositae mix, methylchloroisothiazolinone/methylisothiazolinone, nickel sulfate, and thimerosal mix. Conclusions: The data strongly indicate decreasing and increasing frequency trends and challenge us to seek explanations, which are not yet clear. It is hoped that these data can be valuable in informing public health policy, government, and industry.

Experience and insights from the emergency multiday take-home dose methadone dispensing in Ho Chi Minh City in context of COVID-19.

Introduction: We aimed to assess the uptake of the pilot multiday take-home dose methadone program during COVID-19 by the patients and document the experience with this novel approach to Methadone Maintenance Treatment (MMT) in Vietnam through this operational research.Materials and methods: A total of 10 clinics were identified randomly using the PPS method. A total of 502 patients were selected from the clinics using a simple randomization technique. The information was collected from the administrative and treatment records and direct face-to-face interview with the patients.Results: None of the clinics reported an incidence of overdose. A large majority of the patients reported that take home methadone program as being convenient (79.6%) and agreed that they shall like to join the multiday take-home dose in future (98.7%).Conclusions: The findings of the current study suggested that the multiday take-home methadone program was feasible and well accepted by the patients in Ho Chi Minh City. It helped ensure continuity of care to patients on MMT during the COVID-19 pandemic.

Long-Term North American Trend in Patch Test Reactions: A 32-Year Statistical Overview (1984-2016).

BACKGROUND: Allergic contact dermatitis (ACD) remains a public health issue worldwide, despite regulations intended to minimize sensitization. With up-to-date knowledge about which chemicals continue to have high allergenicity, the government/industry can refocus their efforts to be most effective. OBJECTIVE: We reviewed updated data showing common allergens that elicit ACD to determine the progress in reducing sensitization to inform public health policy, government regulation, and industry standards. METHODS: We compiled data from the North American Contact Dermatitis Group showing patch test results from 1984 to 2016 for 153 compounds. Using these data, we analyzed the trends over time of positive test reactions to determine whether they are increasing or decreasing. RESULTS: Of the 47 compounds with sufficient data to analyze, 23 had a decreasing proportion of positive patch test results over the whole period. An additional 5 had a decreasing proportion over a shorter period. Finally, 4 had an increasing proportion over any period: compositae mix, methylchloroisothiazolinone/methylisothiazolinone, nickel sulfate, and thimerosal mix. CONCLUSIONS: The data strongly indicate decreasing and increasing frequency trends and challenge us to seek explanations, which are not yet clear. It is hoped that these data can be valuable in informing public health policy, government, and industry.

A spectrum of preferential flow alters solute mobility in soils.

Preferential flow reduces water residence times and allows rapid transport of pollutants such as organic contaminants. Thus, preferential flow is considered to reduce the influence of soil matrix-solute interactions during solute transport. While this claim may be true when rainfall directly follows solute application, forcing rapid chemical and physical disequilibrium, it has been perpetuated as a general feature of solute transport-regardless of the magnitude preferential flow. A small number of studies have alternatively shown that preferential transport of strongly sorbing solutes is reduced when solutes have time to diffuse and equilibrate within the soil matrix. Here we expand this inference by allowing solute sorption equilibrium to occur and exploring how physiochemical properties affect solute transport across a vast range of preferential flow. We applied deuterium-labeled rainfall to field plots containing manure spiked with eight common antibiotics with a range of affinity for the soil after 7 days of equilibration with the soil matrix and quantified preferential flow and solute transport using 48 soil pore water samplers spread along a hillslope. Based on > 700 measurements, our data showed that solute transport to lysimeters was similar-regardless of antibiotic affinity for soil-when preferential flow represented less than 15% of the total water flow. When preferential flow exceeded 15%, however, concentrations were higher for compounds with relatively low affinity for soil. We provide evidence that (1) bypassing water flow can select for compounds that are more easily released from the soil matrix, and (2) this phenomenon becomes more evident as the magnitude of preferential flow increases. We argue that considering the natural spectrum preferential flow as an explanatory variable to gauge the influence of soil matrix-solute interactions may improve parsimonious transport models.

Hypoxia, Serum Starvation, and TNF-α Can Modify the Immunomodulation Potency of Human Adipose-Derived Stem Cells.

INTRODUCTION: Adipose-derived stem cells (ADSCs) are mesenchymal stem cells (MSCs) that are found in adipose tissues, which are easily obtained from liposuction procedures using an enzyme mixture. The adhering cells are then selectively cultivated. ADSCs have great potential in regenerative medicine because they are plentiful, easily accessible, and less invasive. They also have an impressive proliferation ability and can be differentiated into mesenchymal lineages and trans-differentiating into many other cell types. In particular, they have extraordinary abilities in immunomodulation. This study aimed to investigate the effects of culture conditions (hypoxia, starvation, and TNF-α treatment) on the immunomodulation of human ADSCs. METHODS: Human ADSCs were expanded in vitro in the standard condition before they were cultured in different stress conditions. ADSCs from passages fifth were confirmed as MSCs by some standard assays suggested by the International Society for Cell and Gene Therapy. These MSCs were used to culture in four different stress conditions: hypoxia, serum starvation, and TNF-α treatment in 48 h. After treatments, MSCs were used to evaluate their immunomodulation capacity using MSCs mixed lymphocyte reaction assay, and the concentrations of IDO, PGE2, IL-6, and IL-10 were secreted in the culture medium. RESULTS: In different stress conditions, ADSCs exhibited different responses related to their immunomodulation. In serum starvation, ADSCs exerted a strong secretion of IDO and PGE2, whereas they showed strong IL-6 secretion in the TNF-α-supplemented medium. When exposed to lymphocytes, ADSCs caused an increase in the ratio of regulatory T cells (Tregs), and co-culture lymphocytes with ADSCs induced in hypoxic malnutrition conditions increased the IL-10 level the most. In addition, when exposed to dendritic cells (DCs), ADSCs inhibited the mature marker expressions of the DCs. CONCLUSION: The current research showed that ADSCs change their immunomodulation properties to survive in in vitro culture environments. Treatment of ADSCs in the starvation medium for 48 h can increase the immunomodulation of ADSCs.

Engineering conversion of Asteraceae plants into biochars for exploring potential applications: A review.

Asteraceae presents one of the most globally prevalent, cultivated, and fundamental plant families. However, a large amount of agricultural wastes has been yearly released from Asteraceae crops, causing adverse impacts on the environment. The objective of this work is to have insights into their biomass potentials and technical possibility of conversion into biochars. Physicochemical properties are systematically articulated to orientate environmental application, soil amendment, and other utilizations. Utilizations of Asteraceae biochars in wastewater treatment can be categorized by heavy metal ions, organic dyes, antibiotics, persistent organic pollutants (POPs), and explosive compounds. Some efforts were made to analyze the production cost, as well as the challenges and prospects of Asteraceae-based biochars.

Multifunctional ZnO nanoparticles bio-fabricated from Canna indica L. flowers for seed germination, adsorption, and photocatalytic degradation of organic dyes.

The potential of green nanomaterials for environmental and agricultural fields is emerging due to their biocompatible, eco-friendly, and cost-effective performance. We report the use of Canna indica flowers extract as new capping and stabilizing source to bio-fabricate ZnO nanoparticles (ZnO NPs for dyes removal, seed germination. ZnO NPs was biosynthesized by ultrasound-assisted alkaline-free route to reach the critical green strategy. The physicochemical findings of ZnO revealed small crystallite size (27.82 nm), sufficient band-gap energy (3.08 eV), and diverse functional groups. Minimum­run resolution IV approach found the most pivotal factors influencing on removal of Coomassie Brilliant Blue G-250. Uptake studies pointed out that pseudo second-order, and Langmuir were the best fitted models. Dye molecules behaved monolayer adsorption on ZnO surface layers, and controlled by chemisorption. Natural solar light was used as effective source for photocatalytic degradation of methylene blue (94.23% of removal and 31.09 mg/g of uptake capacity). Compared with H2O and ZnSO4, ZnO NPs positively affected the growth of shoot and root lengths (10.2-27.8%) of bean seedlings in most cases. ZnO acts an agrochemical for boosting weight gain, and germination ratio. This study may be promising for developing the recyclable, multifunctional ZnO nanoparticles for environmental and agricultural applications.

Multiyear Group and Medical Center Patch Test Frequency Data: Confounding Variables.

Patch test frequency data have been extensively published by research groups, such as the International Contact Dermatitis Research Group, North American Contact Dermatitis Group, Dermato-Allergology Study and Research Group, and European Environmental Contact Dermatitis Research Group. As this knowledge accumulation is widely applied in clinical and public health settings, we describe confounding factors to consider when using such data for medical policy considerations. These concepts can also be used in individual reports of new allergens or series of cases. Some of these confounders may have been reported in current literature (until October 2020), whereas others have not been mentioned/considered in most group publications.

Osteochondral Autograft Plugs versus Paste Graft: Ex Vivo Morselization Increases Chondral Matrix Production.

OBJECTIVE: Patients undergoing articular cartilage paste grafting have been shown in studies to have significant improvement in pain and function in long-term follow-ups. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte matrix production versus intact osteochondral autograft plugs. DESIGN: This institutional review board-approved study characterizes the effects of impacting osteochondral plugs harvested from the intercondylar notch of 16 patients into a paste, leaving one graft intact as a control. Cell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR (quantitative reverse transcription-polymerase chain reaction) were analyzed at 24 and 48 hours. Matrix production and cell morphology were evaluated using histology. RESULTS: Paste samples from patients (mean age 39.7) with moderate (19%) to severe (81%) cartilage lesions displayed 34% and 80% greater cell proliferation compared to plugs at 24 and 48 hours post processing, respectively (P = 0.015 and P = 0.021). qRT-PCR analysis yielded a significant (P = 0.000) increase of aggrecan, SOX-9, collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division throughout paste samples, with accumulation of aggrecan around multiple chondrocyte lacunae. CONCLUSIONS: Paste graft preparation resulted in increased mobility of chondrocytes by matrix disruption without loss of cell viability. The impaction procedure stimulated chondrocyte proliferation resulting in a cellular response to reestablish native extracellular matrix. Analysis of gene expression supports a regenerative process of cartilage tissue formation and contradicts long-held beliefs that impaction trauma leads to immediate cell death. This mechanism of action translates into clinical benefit for patients with moderate to severe cartilage damage.

Spatial distribution and temporal change of antibiotics in soils amended with manure using two field application methods.

Compared to surface application, manure subsurface injection significantly reduces transport of manure-associated antibiotics via surface runoff. However, the environmental fate of antibiotics in manure injection slits is unknown. A field investigation was conducted to monitor distribution and dissipation of pirlimycin, tylosin, chlortetracycline, and sulfamerazine in soil following either surface application or subsurface injection of liquid dairy manure. A simulated rainfall was conducted on days 0, 3, and 7 after manure application. Soil samples were collected before, on the day of, and 5, 14, 60, and 180 days after the simulated rainfall. Around an hour after manure application, antibiotic concentrations in injection slits were 4-49 and 4-26 times higher than those outside the slits and in surface application plots, respectively. Antibiotics concentrated in the injection slits for an extended time with limited horizontal and vertical movement, exposing the microbial community inside the slits to an elevated level of antibiotics. Dissipation of antibiotics was the fastest during the first 14 d after manure application before slowing down. There were no significant differences in antibiotic dissipation patterns in soils amended with manure using two application methods. Although the half-lives ranged from 3-11 d for pirlimycin, 3-10 d for sulfamerazine, 5-12 d for tylosin, and 3-21 day for chlortetracycline; pirlimycin, sulfamerazine, and tylosin remained detectable in soil even 180 d after the single manure application, indicating that soils could be a long-term source for antibiotics to the surrounding environment. Overall, in addition to resulting in less surface runoff of antibiotics from the fields, manure subsurface injection can also retain antibiotics in the injection slits and limit their movement overtime. However, more studies are needed to better understand if elevated levels of antibiotics, nutrients, organic matter, and water would result in "hot zones" for antibiotic resistance development in the manure subsurface injected fields.

Optimization, equilibrium, adsorption behavior and role of surface functional groups on graphene oxide-based nanocomposite towards diclofenac drug.

Aquatic contamination of diclofenac (DCF), an emergent non-steroidal anti-inflammatory drug (NSAIDs), can result in adverse effects to many ecosystems through biomagnification. Hence, introducing effective remediation techniques to sequester the pharmaceutical wastes is highly fundamental to prevent their accumulation in the environment. Generally, adsorption has been presented as a green and efficient approach. Herein, we report the characterization and application of the novel magnetic nanocomposite (GO@CoFe2O4) derived from cobalt-based ferrite (CoFe2O4) and graphene oxide (GO) for DCF adsorption. For the optimization procedure, the response surface methodology (RSM) was adopted to investigate the impacts of DCF concentration (1.6-18.4 mg/L), DCF dosage (0.08-0.92 g/L), and solution pH (2.6-9.4) to find the optimum conditions for DCF removal, at 10.5 mg/L, 0.74 g/L, and pH 4, respectively. For the adsorption experiments, the kinetic, isotherm, thermodynamic, and intraparticle diffusion models were systematically studied. Moreover, we have elucidated the role of functional groups on the surface of GO@CoFe2O4 in enhancing the adsorption of DCF drug. With good removal efficiency (up to 86.1%), high maximum adsorption capacity (32.4 mg/g), GO@CoFe2O4 can be a potential candidate to eliminate DCF drug from water.

Real-time, functional intra-operative localization of rat cavernous nerve network using near-infrared cyanine voltage-sensitive dye imaging.

Despite current progress achieved in the surgical technique of radical prostatectomy, post-operative complications such as erectile dysfunction and urinary incontinence persist at high incidence rates. In this paper, we present a methodology for functional intra-operative localization of the cavernous nerve (CN) network for nerve-sparing radical prostatectomy using near-infrared cyanine voltage-sensitive dye (VSD) imaging, which visualizes membrane potential variations in the CN and its branches (CNB) in real time. As a proof-of-concept experiment, we demonstrate a functioning complex nerve network in response to electrical stimulation of the CN, which was clearly differentiated from surrounding tissues in an in vivo rat prostate model. Stimulation of an erection was confirmed by correlative intracavernosal pressure (ICP) monitoring. Within 10 minutes, we performed trans-fascial staining of the CN by direct VSD administration. Our findings suggest the applicability of VSD imaging for real-time, functional imaging guidance during nerve-sparing radical prostatectomy.