Metabolomic Profiles in Patients with Cervical Cancer Undergoing Cisplatin and Radiation Therapy.

This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q ExactiveTM Focus Hybrid Quadrupole-OrbitrapTM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 µm) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40°C. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.

Safety Assessment of Levilactobacillus brevis KU15006: A Comprehensive Analysis of its Phenotypic and Genotypic Properties.

Levilactobacillus brevis KU15006, isolated from kimchi, exhibits pathogen-antagonistic and anti-diabetic activities; however, the safety of this strain has not been assessed. In the present study, L. brevis KU15006 was evaluated to elucidate its safety as a probiotic strain using phenotypic and genotypic analyses. Its safety was assessed using a minimum inhibitory concentration test comprising nine antibiotics, 26 antibiotic resistance genes, a single conjugative element, virulence gene analysis, hemolysis, cell cytotoxicity, mucin degradation, and toxic metabolite production. L. brevis KU15006 exhibited equal or lower minimum inhibitory concentration for the nine antibiotics than the cut-off value established by the European Food Safety Authority. It did not harbor antibiotic resistance and virulence genes. L. brevis KU15006 lacked ß-hemolysis, mucin degradation, cytotoxicity against Caco-2 cells, gelatin liquefaction, bile salt deconjugation, and toxic metabolite production abilities. Based on the results, L. brevis KU15006, which has antagonistic and anti-diabetic effects, could be marketed as a probiotic in the future.

Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration.

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

Mediating effects of workgroup processes on the relationship between nurse turnover and nurse outcomes in hospitals.

Background: Nurse turnover is often considered to be an outcome, and few studies have investigated its consequences in nursing care. The underlying mechanism of the nurse turnover-nurse outcome relationship has not been empirically investigated. Therefore, this study examines workgroup processes and nurse outcomes as the consequences of nurse turnover and the mediating effect of workgroup processes on the nurse turnover-nurse outcomes relationship. Methods: A cross-sectional design was adopted to investigate the data collected from 264 staff nurses. Furthermore, six-month turnover rates, workgroup processes (nurse-nurse collaboration, team cohesion), and nurse outcomes (job satisfaction, intent to leave) were utilized in the multivariate regression models. Results: Overall, 53 (24.4%) nurses had worked in nursing units with a zero six-month turnover rate. The average mean six-month turnover rate was 15.5%. Nurse turnover adversely affected nurses' job satisfaction and several subscales of team cohesion including task cohesion and social cohesion. Team cohesion partially mediated the relationship between nurse turnover and job satisfaction. Conclusion: Nurse turnover decreased job satisfaction and team cohesion, and team cohesion partially mediated the nurse turnover-nurse outcomes relationship. These findings provide evidence supporting the significant adverse effects of nurse turnover and suggest the potential role of workgroup processes in explaining the underlying mechanism of the relationship between nurse turnover and nurse outcomes. Implications for nursing and health policy: Healthcare organizations must create a positive work environment to reduce nurse turnover. Further, states and countries should try to develop and establish nursing and health policies to prevent turnover.

Immunostimulatory Activity of Lactococcus lactis subsp. lactis CAB701 Isolated from Jeju Cabbage.

This study explored the potential of Lactococcus lactis subsp. lactis CAB701 as a probiotic strain, focusing on its immunostimulatory properties. Despite adverse conditions in the gastrointestinal environment, this strain exhibited remarkable survivability, as evidenced by its tolerance to acid, bile, and pancreatin, coupled with its impressive ability to adhere to Caco-2 cells. It also exhibited significant antioxidant activity, similar to the established probiotic Lacticaseibacillus rhamnosus GG (LGG). Our research elucidates the potent immunostimulatory effects of L. lactis subsp. lactis CAB701. This strain significantly enhanced nitric oxide production in RAW 264.7, far exceeding that obtained with LGG. An in-depth examination revealed elevated expression of key inflammatory mediators, including inducible nitric oxide synthase, tumor necrosis factor-alpha, cyclooxygenase-2, interleukin (IL)-1 beta, and IL-6. L. lactis subsp. lactis CAB701 increases the expression of critical signaling proteins in the mitogen-activated protein kinase pathway. This prompted a substantial increase in the expression of phosphorylated c-Jun N-terminal kinases and extracellular signal-regulated kinases, suggesting their role in modulating these immune-related pathways. Overall, these findings demonstrate the significant immunostimulatory capacity of L. lactis subsp. lactis CAB701, positioning it as a potential candidate for probiotic use, especially in applications that enhance immune responses.

Structural analysis and prebiotic activity of exopolysaccharide produced by probiotic strain Bifidobacterium bifidum EPS DA-LAIM.

Exopolysaccharide (EPS)-producing Bifidobacterium bifidum EPS DA-LAIM was isolated from healthy human feces, the structure of purified EPS from the strain was analyzed, and its prebiotic activity was evaluated. The EPS from B. bifidum EPS DA-LAIM is a glucomannan-type heteropolysaccharide with a molecular weight of 407-1007 kDa, and its structure comprises 2-mannosyl, 6-mannosyl, and 2,6-mannosyl residues. The purified EPS promoted the growth of representative lactic acid bacteria and bifidobacterial strains. Bifidobacterium bifidum EPS DA-LAIM increased nitric oxide production in RAW 264.7 macrophage cells, indicating its immunostimulatory activity. Bifidobacterium bifidum EPS DA-LAIM also exhibited high gastrointestinal tract tolerance, gut adhesion ability, and antioxidant activity. These results suggest that EPS from B. bifidum EPS DA-LAIM is a potentially useful prebiotic material, and B. bifidum EPS DA-LAIM could be applied as a probiotic candidate. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01213-w.

Potential Probiotic Properties of Exopolysaccharide-Producing Lacticaseibacillus paracasei EPS DA-BACS and Prebiotic Activity of Its Exopolysaccharide.

Exopolysaccharide (EPS)-producing Lacticaseibacillus paracasei EPS DA-BACS was isolated from healthy human feces and its probiotic properties, as well as the structure and prebiotic activity of the EPS from this strain were examined. EPS from L. paracasei EPS DA-BACS had a ropy phenotype, which is known to have potential health benefits and is identified as loosely cell-bounded glucomannan-type EPS with a molecular size of 3.7 × 106 Da. EPS promoted the acid tolerance of L. paracasei EPS DA-BACS and provided cells with tolerance to gastrointestinal stress. The purified EPS showed growth inhibitory activity against Clostridium difficile. L. paracasei EPS DA-BACS cells completely inhibited the growth of Bacillus subtilis, Pseudomonas aeruginosa, and Aspergillus brasiliensis, as well as showed high growth inhibitory activity against Staphylococcus aureus and Escherichia coli. Treatment of lipopolysaccharide-stimulated RAW 264.7 cells with heat-killed L. paracasei EPS DA-BACS cells led to a decrease in the production of nitric oxide, indicating the anti-inflammatory activity of L. paracasei EPS DA-BACS. Purified EPS promoted the growth of Lactobacillus gasseri, Bifidobacterium bifidum, B. animalis, and B. faecale which showed high prebiotic activity. L. paracasei EPS DA-BACS harbors no antibiotic resistance genes or virulence factors. Therefore, L. paracasei EPS DA-BACS exhibits anti-inflammatory and antimicrobial activities with high gut adhesion ability and gastrointestinal tolerance and can be used as a potential probiotic.

Environmental Risk and Credit Ratings, and the Moderating Effect of Market Competition.

This study examines the relationship between environmental risk and corporate bond credit ratings, and the moderating effect of market competition. We focus on Korean firms that are facing increasing risk of environmental crisis after the COVID-19 pandemic. Recently, the Korean government has been controlling businesses while promoting policies to transform the economy into a low-energy, low-carbon economy. We find that a firm's greenhouse gas emission and energy consumption, which are direct indicators of environmental risk, are negatively associated with bond credit ratings. We also report that the negative effect of environmental risk on credit ratings is stronger in firms with low market competition. This study contributes to prior research by improving the understanding of the effect of environmental risk on credit ratings. In particular, it is significant to examine the effect of environmental risk, measured as direct environmental performance not affected by green washing, on credit rating. Therefore, we shed light on environment-oriented management beyond the determinants of credit ratings, which have been discussed in previous studies. We also suggest that policymakers need to manage market competition in terms of environmental justice, given that market competition has a significant moderating effect on the relationship between environmental risk and credit ratings.

Real-world evidence of levofloxacin prophylaxis in elderly patients with newly diagnosed multiple myeloma who received bortezomib, melphalan, and prednisone regimen.

BACKGROUND: Although survival outcomes of multiple myeloma (MM) have improved with the development of new and effective agents, infection remains the major cause of morbidity and mortality. Here, we evaluated the efficacy of levofloxacin prophylaxis (in a real-world setting) during bortezomib, melphalan, and prednisone (VMP) therapy in elderly patients with newly diagnosed MM. METHODS: This study retrospectively analyzed the records of patients with newly diagnosed MM treated with the VMP regimen between February 2011 and September 2020 at three institutes of the Republic of Korea. RESULTS: Of a total of 258 patients, 204 (79.1%) received levofloxacin prophylaxis during VMP therapy. The median number of levofloxacin prophylaxis cycles was 4 (range, 1‒9), but 10 patients did not complete the planned prophylaxis because of side effects. Sixty-six patients (25.5%) experienced severe infections during VMP therapy, most of which (74.7%) occurred within the first four cycles of VMP therapy regardless of levofloxacin prophylaxis status. Early severe infection was significantly associated with poor survival. In multivariate analysis, levofloxacin prophylaxis was significantly associated with a lower risk in early severe infection. CONCLUSION: Our findings suggest that levofloxacin prophylaxis should be considered at least during the first four cycles of VMP therapy in elderly patients with newly diagnosed MM.

Direct Wiring of Eutectic Gallium-Indium to a Metal Electrode for Soft Sensor Systems.

For wider applications of liquid metal-based stretchable electronics, electrical interface has remained a crucial issue due to its fragile electromechanical stability and complex fabrication steps. In this study, a direct writing-based technique is introduced to form the writing paths of conductive liquid metal (eutectic gallium-indium, eGaIn) and electrical connections to off-the-shelf metal electrodes in a single process. Specifically, by extending eGaIn wires written on a silicone substrate, the eGaIn wires were physically connected to five different metal electrodes, of which stability as an electrical connection was investigated. Among the five different surface materials, the metal electrode finished by electroless nickel immersion gold (ENIG) was reproducible and had low contact resistance without time-dependent variation. In our experiments, it was verified that the electrode part made by an ENIG-finished flexible flat cable (FFC) was mechanically (strain, ≤100%; pressure, ≤600 kPa) and thermally (temperature, ≤180 °C) durable. By modifying the trajectories of eGaIn wires, soft sensor systems composed of 10 sensing units were fabricated and tested to measure finger joint angles and ground reaction forces, respectively. The proposed method enables eGaIn-based soft sensors or circuits to be connected to typical electronic components through FFCs or weldable surfaces, using only off-the-shelf materials without additional mechanical or chemical treatments.

Consistent and Reproducible Direct Ink Writing of Eutectic Gallium-Indium for High-Quality Soft Sensors.

Given the need for stretchable sensors, many studies have been conducted on eutectic gallium-indium, which has superior properties as a conductive ink. However, it has remained a challenge to manufacture sensors in a consistent and reproducible manner because conventional mold-based fabrication still depends highly on manual techniques. To overcome this limitation, the direct ink writing was used in this study, focusing on improving the stability of writing by exploring issues related to failure and ensuring the consistency of the microchannel by selecting appropriate process variables, including the syringe material. As a result, multiple sensors produced under the same manufacturing conditions had similar behaviors. This fabrication technique improved the accuracy of manufacturing a microchannel, and its behavior was predicted successfully by a simple mathematical model, which was confirmed by nondestructive inspections of the microchannel. In developing a one-piece glove-type sensor without an assembly process, the efficiency of the fabrication technique was also emphasized.

Quantitative evaluation of hand functions using a wearable hand exoskeleton system.

To investigate, improve, and observe the effect of rehabilitation therapy, many studies have been conducted on evaluating the motor function quantitatively by developing various types of robotic systems. Even though the robotic systems have been developed, functional evaluation of the hand has been rarely investigated, because it is difficult to install a number of actuators or sensors to the hand due to limited space around the fingers. Therefore, in this study, a hand exoskeleton was developed to satisfy the required specifications for evaluating the hand functions including spasticity of finger flexors, finger independence, and multi-digit synergy and algorithms to evaluate such functions were proposed. The hand exoskeleton was composed with the four 4-bar linkages, two motors, and three loadcells for each finger, and it was able to flex/extend the metacarpal (MCP) and proximal interphalangeal(PIP) joints independently while measuring the pulling force at each phalanx. Using the hand exoskeleton, the hand functions of the three healthy subject were evaluated and the experimental results were analyzed.

A Soft Sensor-Based Three-Dimensional (3-D) Finger Motion Measurement System.

In this study, a soft sensor-based three-dimensional (3-D) finger motion measurement system is proposed. The sensors, made of the soft material Ecoflex, comprise embedded microchannels filled with a conductive liquid metal (EGaln). The superior elasticity, light weight, and sensitivity of soft sensors allows them to be embedded in environments in which conventional sensors cannot. Complicated finger joints, such as the carpometacarpal (CMC) joint of the thumb are modeled to specify the location of the sensors. Algorithms to decouple the signals from soft sensors are proposed to extract the pure flexion, extension, abduction, and adduction joint angles. The performance of the proposed system and algorithms are verified by comparison with a camera-based motion capture system.

Understanding Editing Behaviors in Multilingual Wikipedia.

Multilingualism is common offline, but we have a more limited understanding of the ways multilingualism is displayed online and the roles that multilinguals play in the spread of content between speakers of different languages. We take a computational approach to studying multilingualism using one of the largest user-generated content platforms, Wikipedia. We study multilingualism by collecting and analyzing a large dataset of the content written by multilingual editors of the English, German, and Spanish editions of Wikipedia. This dataset contains over two million paragraphs edited by over 15,000 multilingual users from July 8 to August 9, 2013. We analyze these multilingual editors in terms of their engagement, interests, and language proficiency in their primary and non-primary (secondary) languages and find that the English edition of Wikipedia displays different dynamics from the Spanish and German editions. Users primarily editing the Spanish and German editions make more complex edits than users who edit these editions as a second language. In contrast, users editing the English edition as a second language make edits that are just as complex as the edits by users who primarily edit the English edition. In this way, English serves a special role bringing together content written by multilinguals from many language editions. Nonetheless, language remains a formidable hurdle to the spread of content: we find evidence for a complexity barrier whereby editors are less likely to edit complex content in a second language. In addition, we find that multilinguals are less engaged and show lower levels of language proficiency in their second languages. We also examine the topical interests of multilingual editors and find that there is no significant difference between primary and non-primary editors in each language.