The Expression Patterns of Immune Checkpoint Molecules in Colorectal Cancer: An Analysis Based on Microsatellite Status.

Recently, immunotherapy has arisen as a novel treatment approach for patients with colorectal cancer (CRC), but the effectiveness of immunotherapy varies in these patients. We hypothesized that immune checkpoint molecules (ICMs), which are the targets of immunotherapy, are often exhibited concomitantly. Our objective was to investigate the patterns of ICM expression in patients with CRC and the differences in ICM expression based on microsatellite instability status. The immunohistochemical expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and lymphocyte-activation gene 3 (LAG-3) in the tumor center and periphery was assessed in patients with non-metastatic colorectal cancer. We enrolled 83 patients with CRC: a total of 40 microsatellite-stable (MSS) and 43 microsatellite-instability-high (MSI-H) cancer patients. PD-L1 was more frequently expressed in the tumor center in the MSI-H patients with than that in the MSS patients (18 [41.9%] vs. 3 [7.5%], respectively; p < 0.001), and the same trend was observed for TIM-3 expression (30 [69.8%] vs. 19 [47.5%], respectively; p = 0.047). The concomitant expression of two or more ICMs was more frequently observed than no expression or the expression of a single molecule in both the MSS and MSI-H groups; a total of 34 (79.7%) patients with MSI-H cancer and 23 (57.5%) with MSS cancer showed ICM expression at the tumor center, whereas 34 (79.7%) patients with MSI-H cancer and 22 (55%) with MSS cancer showed expression at the tumor periphery. Patients with the genetic characteristics of MSI-H cancer showed higher expression levels of ICMs than those in patients with MSS cancer, and predominantly, two or more ICMs were concurrently expressed. Our findings highlight the potential efficacy of the dual-blockade approach in immunotherapy, particularly in patients with MSI-H CRC.

Development of a novel, high-efficacy oncolytic herpes simplex virus type 1 platform equipped with two distinct retargeting modalities.

To retarget oncolytic herpes simplex virus (oHSV) to cancer-specific antigens, we designed a novel, double-retargeted oHSV platform that uses single-chain antibodies (scFvs) incorporated into both glycoprotein H and a bispecific adapter expressed from the viral genome to mediate infection predominantly via tumor-associated antigens. Successful retargeting was achieved using a nectin-1-detargeted HSV that remains capable of interacting with herpesvirus entry mediator (HVEM), the second canonical HSV entry receptor, and is, therefore, recognized by the adapter consisting of the virus-binding N-terminal 82 residues of HVEM fused to the target-specific scFv. We tested both an epithelial cell adhesion molecule (EpCAM)- and a human epidermal growth factor receptor 2-specific scFv separately and together to target cells expressing one, the other, or both receptors. Our results show not only dose-dependent, target receptor-specific infection in vitro, but also enhanced virus spread compared with single-retargeted virus. In addition, we observed effective infection and spreading of the EpCAM double-retargeted virus in vivo. Remarkably, a single intravenous dose of the EpCAM-specific virus eliminated all detectable tumors in a subcutaneous xenograft model, and the same intravenous dose seemed to be harmless in immunocompetent FVB/N mice. Our findings suggest that our double-retargeted oHSV platform can provide a potent, versatile, and systemically deliverable class of anti-cancer therapeutics that specifically target cancer cells while ensuring safety.

Sporosarcina jeotgali sp. nov., Sporosarcina oncorhynchi sp. nov., and Sporosarcina trichiuri sp. nov., Isolated from Jeotgal, a Traditional Korean Fermented Seafood.

Three novel, Gram-stain-positive, obligate aerobic, catalase- and oxidase-positive bacterial strains, designated B2O-1T, T2O-4T, and 0.2-SM1T-5T, were isolated from jeotgal, a traditional Korean fermented seafood. Strains B2O-1T, T2O-4T, and 0.2-SM1T-5T exhibited distinct colony colors, characterized by pink, yellow, and red opaque circular colonies, respectively. Phylogenetic analysis revealed that three strains formed a paraphyletic clade within the genus Sporosarcina and shared < 99.0% similarity with Sporosarcina aquimarina KCTC 3840T and Sporosarcina saromensis KCTC 13119T in their 16S rRNA gene sequences. The three strains exhibiting Orthologous Average Nucleotide Identity values < 79.3% and digital DNA-DNA hybridization values < 23.1% within the genus Sporosarcina affirmed their distinctiveness. Strains B2O-1T, T2O-4T, and 0.2-SM1T-5T contained MK-7 as a sole respiratory menaquinone and A4α type peptidoglycan based on lysine with alanine, glutamic acid, and aspartic acid. The common polar lipids include diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. Strain T2O-4T contained one unidentified phospholipid, whereas strain 0.2-SM1T-5T contained two unidentified phospholipids. Cellular fatty acid profiles, with C15:0 anteiso as the major fatty acid, supported the affiliation of the three strains to the genus Sporosarcina. Based on the polyphasic characteristics, strains B2O-1T (= KCTC 43506T = JCM 36032T), T2O-4T (= KCTC 43489T = JCM 36031T), and 0.2-SM1T-5T (= KCTC 43519T = JCM 36034T) represent three novel species within the genus Sporosarcina, named Sporosarcina jeotgali sp. nov., Sporosarcina oncorhynchi sp. nov., and Sporosarcina trichiuri sp. nov., respectively.

Supportive Communication Between Emerging Adults With Cancer and Nurses During Diagnosis and Cancer Treatment: An Exploratory Qualitative Study Using Interviews.

BACKGROUND: Having a cancer diagnosis during early adulthood can be a significant challenge for an individual. Nurses' supportive communication plays a vital role during the diagnosis and treatment period to lessen psychological distress and promote coping. OBJECTIVE: This exploratory study aimed to examine (1) the experiences of emerging adults with cancer (EAs) aged between 18 and 25 years in communicating with nurses during diagnosis and treatment and (2) nurses' experiences of providing supportive communication with this patient group. METHODS: Semistructured interviews were conducted with EAs and nurses with experience caring for this patient group. Thematic analysis was conducted, guided by interpretive hermeneutic perspectives. RESULTS: Eight EA participants and 7 nurse participants participated in interviews. Five themes emerged: (1) having casual conversations with nurses helped EAs cope during cancer treatment and (2) helped EAs fulfill the need for social connectedness, (3) nurses as a different form of peer-like support, (4) nurses used themselves as a therapeutic tool to foster trust and emotional safety of EAs, and (5) nurses needed to maintain professional boundaries while being compassionate. CONCLUSIONS: This study highlighted a rather underdocumented aspect of supportive communication: meeting psychosocial needs through casual, day-to-day conversations. IMPLICATIONS FOR PRACTICE: Having casual conversations with nurses appeared to help EAs' psychological coping during cancer treatment. These casual conversations, which on the surface seemed clinically insignificant, fulfilled their psychosocial needs. Considering the valuable interpersonal engagement that led to emotional benefits for EAs, communication training for cancer nurses needs to build their capacity to maintain both relational and emotional boundaries.

Experiences and perspectives of colorectal cancer survivors and general practitioners on the delivery of survivorship care in general practice: a mixed methods study.

BACKGROUND: Many colorectal cancer (CRC) survivors experience ongoing sequelae from their cancer treatment. Limited evidence exists regarding how CRC survivors and general practitioners (GPs) manage these sequelae in the community. This study aimed to explore the experiences and perspectives of CRC survivors and GPs on current approaches to monitoring and managing sequelae of CRC treatment. METHODS: We conducted a mixed-methods study using cross-sectional national surveys and qualitative interviews with CRC survivors and GPs to explore: (1) treatment sequelae experienced by CRC survivors, (2) how these were monitored and managed by general practitioners, and (3) suggestions to improve ongoing management of the treatment sequelae. Survey responses were reported descriptively. Qualitative data were thematically analysed using an interpretive descriptive approach. RESULTS: Seventy participants completed surveys: 51 CRC survivors and 19 GPs, and four interviews were conducted with GPs. CRC survivors experienced a range of treatment sequelae, but often did not discuss these with their GPs (experienced vs discussed: 86% vs 47% for fatigue/lack of energy, 78% vs 27% for psychological/emotional concern, 63% vs 22% for impaired sleep, 69% vs 29% for weight loss/gain, 59% vs 16% for sexual and intimacy concerns). GPs reported inadequate information transfer from cancer services and workload as major barriers to optimal care. CONCLUSIONS: System-level changes that facilitate adequate information transfer from cancer services to GPs upon CRC treatment completion, as well as addressing time constraint issues essential for comprehensive monitoring and management of CRC treatment sequelae, could enhance the care of CRC survivors in the community setting.

Serum lipids as predictive markers for death by suicide.

Serum lipid levels have been associated with an increased risk of suicidal behaviors. This retrospective cohort study aimed to investigate the association between serum lipid levels and death by suicide among suicide attempters according to sex. Suicide attempters visiting emergency departments between 2007 and 2011 were followed up until the date of all-cause death or December 31, 2012. Sex-stratified Cox proportional hazards regression and competing risk models were constructed to obtain the hazard ratios (HR) of serum lipid measures and suicide. For each significant lipid variable in the final models, Kaplan-Meier survival analysis and cumulative incidence function (CIF) were employed to compare the time to suicide between the high- and low-lipid groups based on the best cutoff point from the receiver operating characteristic curve. In 408 female attempters (65.8 %), the HR in the Cox regression model and subdistribution HR in the competing risk model for increased total cholesterol (TC) were 0.968 and 0.970, respectively. In the Kaplan-Meier survival analysis and CIF, increased death by suicide was demonstrated in the low-TC group (< 165 mg/dL). Lower serum TC levels among female suicide attempters may predict suicide. More careful monitoring is warranted in women with lower TC levels who recently attempted suicide.

Association of periodontal disease treatment with mortality in patients with dementia: a population-based retrospective cohort study (2002-2018).

Dementia is one of the leading causes of death worldwide. In this study, we analyzed the association of periodontal treatment with the risk of death in patients with dementia. The analyzed data were obtained by linking the National Health Insurance Corporation claims data between 2002 and 2018 to the Statistics Korea death registry. In total, 1,131,406 patients with dementia aged ≥ 65 years had undergone dental treatment during the study period. Time-dependent Cox proportional hazards model was performed. The mortality rate was approximately 10% among the patients with dementia. The 17-years cumulative survival rates for patients who received periodontal treatment and their untreated counterparts were 83.5% and 71.5%, respectively. The crude hazard ratio of the periodontal group was approximately twice as high as that of the non-periodontal group (1.99; P < 0.001). Furthermore, in the regression model that was adjusted for socio-demographic variables and systematic chronic diseases, the risk of death in the non-periodontal group was approximately 1.83 times higher than that of the periodontal group (P < 0.00). These findings suggest that preventive periodontal treatment may decrease mortality risk in older people with dementia.

Evaluating a shared care pathway intervention for people receiving chemotherapy to reduce post-treatment unplanned hospital presentations: a randomised controlled trial.

PURPOSE: The aim of this randomised controlled trial (RCT) was to explore whether a community nursing intervention for outpatients receiving systemic therapy reduced unplanned hospital presentations and improved physical and psychosocial health outcomes over the first three cycles of treatment compared to a control group receiving standard care. METHODS: The number of and reasons for unplanned presentations were obtained for 170 intervention and 176 control group adult patients with solid tumours starting outpatient chemotherapy. Poisson regression was used to compare the number of presentations between the intervention and control groups. Patients self-completed the Hospital Anxiety and Depression Scale, the Cancer Behavior Inventory and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) at the start of the first four cycles. Linear regression techniques were used to compare quality of life outcomes. RESULTS: The reduction in unplanned presentations in the intervention group relative to the control group was 12% (95% CI, - 25%, 37%; P = 0.48). At the start of cycle 4, there was no difference in anxiety (difference = 0.47 (95% CI, - 0.28, 1.22; P = 0.22)), depression (difference = 0.57 (95% CI, - 0.18, 1.31; P = 0.13)) or EORTC QLQ-C30 summary score (difference = 0.16 (95% CI, - 2.67, 3.00; P = 0.91)). Scores for self-efficacy as measured by the Cancer Behavior Inventory were higher in the intervention group (difference = 4.3 (95% CI, 0.7, 7.9; P = 0.02)). CONCLUSION: This RCT did not demonstrate a benefit in reducing unplanned presentations to hospital. The trial identified improved cancer-based self-efficacy in patients receiving the intervention. TRIAL REGISTRATION: Registered at Australian and New Zealand Clinical Trials Registry: ACTRN12614001113640, registered 21/10/2014.

Quantitative Analysis and Molecular Docking Simulation of Flavonols from Eruca sativa Mill. and Their Effect on Skin Barrier Function.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents, including n-hexane (EHex), chloroform (ECHCl3), ethyl acetate (EEA), n-butyl alcohol (EBuOH), and water (EDW). Ethyl acetate fraction (EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-and di-glycoside of each aglycone. The main flavonol form of EEA is the mono-glycoside of each aglycone detected, and the most abundant flavonol mono-glycoside is kaempferol 3-glucoside 7.4%, followed by quercetin-3-glucoside 2.3% and isorhamnetin 3-glucoside 1.4%. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that the flavonol composition of E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Effects of Parallel Contact Cooling on Pulsed-Type, Bipolar Radiofrequency-Induced Tissue Reactions in an in vivo Porcine Model.

Background: Skin cooling during laser or radiofrequency (RF) treatments is a method to minimize thermal damage to the epidermis, reduce pain, and decrease post-treatment downtime. We evaluated the effect of parallel contact cooling (PCC) on RF-induced thermal reactions in minipig skin in vivo after bipolar microneedling RF treatment. Methods: RF treatments were administered at frequencies of 0.5, 1, and 2 MHz with single (500 ms), six (1000 ms), and ten (5000 ms) sub-pulse packs to minipig skin with or without PCC. Subsequently, thermometric imaging and histology were used to analyze skin reactions to RF. Results: Thermometric images showed that PCC promptly lowered skin temperature in the RF-treated area, with this effect persisting for over 60s. Regardless of the PCC, RF treatments lasting for 500 ms with a single pulse pack resulted in peri-electrode coagulative necrosis (PECN) zones and inter-electrode non-necrotic thermal reaction (IENT) zones in the dermis. In contrast, treatment lasting 5000 ms with 10 sub-pulse packs produced distinct IENT without notable PECN over a wide dermal area. Skin specimens obtained at 1 h and 3, 7, and 14 days after PCC-assisted RF treatments showed a higher degree of thermal tissue reactions in the deeper dermal regions compared to those after RF treatments without PCC. Conclusion: PCC-assisted RF treatment, utilizing an invasive bipolar microneedling device, enhanced RF-induced skin reactions in the mid to deep dermis while preserving the epidermis and upper papillary dermis from excessive thermal tissue injury.

Genomic attributes and characterization of novel exopolysaccharide-producing bacterium Halomonas piscis sp. nov. isolated from jeotgal.

Halophilic bacterial strains, designated SG2L-4T, SB1M4, and SB2L-5, were isolated from jeotgal, a traditional Korean fermented food. Cells are Gram-stain-negative, aerobic, non-motile, rod-shaped, catalase-positive, and oxidase-negative. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain SG2L-4T is closely related to Halomonas garicola KACC 18117T with a similarity of 96.2%. The complete genome sequence of strain SG2L-4T was 3,227,066 bp in size, with a genomic G + C content of 63.3 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain SG2L-4T and H. garicola KACC 18117T were 90.5 and 40.7%, respectively. The optimal growth conditions for strain SG2L-4T were temperatures between 30 and 37°C, a pH value of 7, and the presence of 10% (w/v) NaCl. The polar lipids identified included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unknown phospholipid, an unknown glycolipid, and an unknown polar lipid. The major cellular fatty acids were C16:0, summed features 8 (C18:1ω6c and/or C18:1ω7c), C19:0 cyclo ω8c, and summed features 3 (C16:1ω6c and/or C16:1ω7c). The predominant respiratory quinone was ubiquinone with nine isoprene units (Q-9). Based on the phenotypic, genotypic, and chemotaxonomic results, strain SG2L-4T represents a novel species within the genus Halomonas, for which the name Halomonas piscis sp. nov. is proposed. The type strain is SG2L-4T (=KCTC 92842T = JCM 35929T). Functional annotation of the genome of strain SG2L-4T confirmed the presence of exopolysaccharide synthesis protein (ExoD) and capsular polysaccharide-related genes. Strain SG2L-4T also exhibited positive results in Molisch's test, indicating the presence of extracellular carbohydrates and exopolysaccharides (EPS) production. These findings provide valuable insights into the EPS-producing capabilities of H. piscis sp. nov. isolated from jeotgal, contributing to understanding its potential roles in food and biotechnological applications.

P. mirabilis-derived pore-forming haemolysin, HpmA drives intestinal alpha-synuclein aggregation in a mouse model of neurodegeneration.

BACKGROUND: Recent studies suggesting the importance of the gut-microbiome in intestinal aggregated alpha synuclein (α-syn) have led to the exploration of the possible role of the gut-brain axis in central nervous system degeneration. Proteus mirabilis (P. mirabilis), a gram-negative facultative anaerobic bacterium, has been linked to brain neurodegeneration in animal studies. We hypothesised that P. mirabilis-derived virulence factors aggregate intestinal α-synuclein and could prompt the pathogenesis of dopaminergic neurodegeneration in the brain. METHODS: We used vagotomised- and antibiotic-treated male murine models to determine the pathogenesis of P. mirabilis during brain neurodegeneration. The neurodegenerative factor that is driven by P. mirabilis was determined using genetically mutated P. mirabilis. The pathological functions and interactions of the virulence factors were determined in vitro. FINDINGS: The results showed that P. mirabilis-induced motor dysfunction and neurodegeneration are regulated by intestinal α-syn aggregation in vagotomised- or antibiotic-treated murine models. We deduced that the specific virulence factor, haemolysin A (HpmA), plays a role in the pathogenesis of P. mirabilis. HpmA is involved in α-synuclein oligomerisation and membrane pore formation, resulting in the activation of mTOR-mediated autophagy signalling in intestinal neuroendocrine cells. INTERPRETATION: Taken together, the results of the present study suggest that HpmA can interact with α-syn and act as a possible indicator of brain neurodegenerative diseases that are induced by P. mirabilis. FUNDING: This study was supported by a grant from the National Research Foundation of Korea.

Ptychographic lens-less birefringence microscopy using a mask-modulated polarization image sensor.

Birefringence, an inherent characteristic of optically anisotropic materials, is widely utilized in various imaging applications ranging from material characterizations to clinical diagnosis. Polarized light microscopy enables high-resolution, high-contrast imaging of optically anisotropic specimens, but it is associated with mechanical rotations of polarizer/analyzer and relatively complex optical designs. Here, we present a form of lens-less polarization-sensitive microscopy capable of complex and birefringence imaging of transparent objects without an optical lens and any moving parts. Our method exploits an optical mask-modulated polarization image sensor and single-input-state LED illumination design to obtain complex and birefringence images of the object via ptychographic phase retrieval. Using a camera with a pixel size of 3.45 µm, the method achieves birefringence imaging with a half-pitch resolution of 2.46 µm over a 59.74 mm2 field-of-view, which corresponds to a space-bandwidth product of 9.9 megapixels. We demonstrate the high-resolution, large-area, phase and birefringence imaging capability of our method by presenting the phase and birefringence images of various anisotropic objects, including a monosodium urate crystal, and excised mouse eye and heart tissues.

Analysis of the Status and Future Direction for Digital Therapeutics in Children and Adolescent Psychiatry.

Digital therapeutics based on software, such as artificial intelligence, virtual reality, games, and smartphone applications, are in the spotlight as new therapeutic alternatives in child and adolescent psychiatry. It draws attention to overcoming conventional therapeutics' limitations, such as toxicity, cost, and accessibility, and encourages patients to participate in the treatment attractively. The growth potential of the digital therapeutics market for psychiatric disorders in children and adolescents in Korea and abroad has been highlighted. Clinical studies and Food and Drug Administration approvals for digital therapeutics have increased, and cases approved by the Ministry of Food and Drug Safety have emerged in Korea. As seen above, digital transformation in child and adolescent psychiatry will change treatment paradigms significantly. Therefore, as this new field has just begun to emerge, it is necessary to verify the effectiveness and scope of the application of digital therapeutics and consider preparing a compensation system and institutional arrangements. Accordingly, this study analyzed the development trends and application status of digital therapeutics in children and adolescents and presented limitations and development directions from the perspective of application in healthcare. Further, the study is expected to identify the utility and limitations of digital therapeutics for children and adolescents and establish effective application measures.

Euglena gracilis (Euglena) powder supplementation enhanced immune function through natural killer cell activity in apparently healthy participants: A randomized, double-blind, placebo-controlled trial.

Euglena gracilis (Euglena) is a microalgae found in most freshwater environments that produces paramylon, an insoluble ß-1,3-glucan linked to human immunity. We hypothesized that Euglena powder has effects on immune function in apparently healthy adults. The study included male or female volunteers between the ages of 20 and 70 years who had white blood cell counts ranging from 4 × 103/µL to 10 × 103/µL, a "severe" rating on the stress questionnaire from the Korea National Health and Nutrition Examination Survey, and at least 2 upper respiratory infections with cold-like symptoms in the previous year. Participants received either a placebo or 700 mg of Euglena powder daily for 8 weeks. The study measured natural killer cell activity, cytokine concentrations, and blood lipid profiles to confirm the immune effect of Euglena consumption. In conclusion, Euglena improved immunological function through natural killer cell activity. Safety assessment showed no significant changes in vital signs or clinical chemistry indicators, and there were no adverse events associated with Euglena consumption. Euglena supplementation may help boost the immune systems of healthy individuals.

Alkalimarinus alittae sp. nov., isolated from gut of marine sandworm (Alitta virens) and emended description of the genus Alkalimarinus.

A novel, Gram-stain-negative, aerobic, motile, catalase- and oxidase-negative bacterial strain, designated A2M4T, was isolated from the gut contents of a marine sandworm Alitta virens, collected from the eastern coast of the Republic of Korea. Strain A2M4T formed translucent circular colonies and showed rod-shaped cells with peritrichous flagella. Optimal growth of strain A2M4T occurred at 25 °C, pH 7.0 and in the presence of 2 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain A2M4T was closely related to Alkalimarinus sediminis FA028T, with the highest sequence similarity of 98.9 %. The complete genome sequence of strain A2M4T was 4.25 Mbp in size and the genomic G+C content, calculated from the genome sequence, was 43.2 mol%. A comparison between the genome sequence of strain A2M4T and that of its closest relative, A. sediminis FA028T, showed an average nucleotide identity value of 76.63 % and a digital DNA-DNA hybridization value of 22.2 %. Strain A2M4T contained Q-9 as the sole respiratory isoprenoid quinone and the major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The major cellular fatty acids of strain A2M4T were C14 : 0, C16 : 0 and summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c). Based on its phenotypic, chemotaxonomic and genomic characteristics, strain A2M4T represents a novel species of the genus Alkalimarinus, for which the name Alkalimarinus alittae sp. nov. is proposed. The type is strain A2M4T (=KCTC 92030T=JCM 35924T). The description of the genus Alkalimarinus has also been emended.

Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients.

The tumor microenvironment of colorectal cancer (CRC) is heterogenous; thus, it is likely that multiple immune-related and inflammatory markers are simultaneously expressed in the tumor. The aim of this study was to identify immune-related and inflammatory markers expressed in freshly frozen CRC tissues and to investigate whether they are related to the clinicopathological features and prognosis of CRC. Seventy patients with CRC who underwent curative surgical resection between December 2014 and January 2017 were included in this study. Tissue samples were obtained from tumor and non-tumor areas in the patients' colons. The concentrations of immune-related markers (APRIL/TNFSF13, BAFF, LAG-3, PD-1, PD-L1, and CTLA-4) and inflammatory markers (CHIT, MMP-3, osteocalcin, pentraxin-3, sTNF-R1, and sTNF-R2) in the samples were measured using the Bio-plex Multiplex Immunoassay system. The concentrations of APRIL/TNFSF13, BAFF, and MMP-3 in the samples were significantly high; thus, we conducted analyses based on the cut-off values for these three markers. The high-APRIL/TNFSH13-expression group showed a significantly higher rate of metastatic lesions than the low-expression group, whereas the high-MMP-3-expression group had higher CEA levels, more lymph node metastases, and more advanced disease stages than the low-expression group. The five-year disease-free survival of the high-MMP-3-expression group was significantly shorter than that of the low-expression group (65.1% vs. 90.2%, p = 0.033). This study provides evidence that the APRIL/TNFSF13, BAFF, and MMP-3 pathway is overexpressed in CRC tissues and is associated with unfavorable clinicopathological features and poor prognosis in CRC patients. These markers could serve as diagnostic or prognostic biomarkers for CRC.

Impact of customer incivility on restaurant employee stress spread and turnover: COVID-19 vaccination mandate.

In response to the unprecedented pandemic in recent history, COVID-19 vaccination mandates in the U.S. caused significant changes and disruption in hospitality operations and customer experiences. The primary goal of this study is to examine whether and how customer incivility induced by the COVID-19 vaccine mandate in the U.S. affects employees' behavioral outcomes (i.e., stress spread between employees and turnover intention) via psychological mechanisms (i.e., stress and negative emotion) and when the relationship is moderated by personal (employee prosocial motivation) and organizational (supervisor support) characteristics. Findings show that customer incivility increases employee turnover intention as well as interpersonal conflicts at work via increased stress and negative emotions. These relationships are weakened when prosocial motivation of employees and the level of supervisor support is high. Findings expand the occupational stress model by specifically incorporating the context of the COVID-19 vaccine mandate and further provide implications for restaurant managers and policy makers.

In vivo Guinea Pig Model Study for Evaluating Antifungal Effect of a Dual-Diode Laser with Wavelengths of 405 Nm and 635 Nm on Dermatophytosis.

Background: Various laser- and light-based devices have been introduced as complementary or alternative treatment modalities for dermatophytosis, particularly for finger or toenail onychomycosis. Objective: This study aimed to comparatively evaluate the antifungal effects of 405-nm and 635-nm dual-band diode lasers using an in vivo guinea pig model of dermatophytosis. Materials and Methods: A guinea pig model was developed by the repetitive application of fungal spore preparations to the back skin of guinea pigs. Dual-diode laser treatment was delivered to the guinea pig skin at a power of 24 mW at a wavelength of 405 nm and 18 mW at 635 nm for 12 min. The treatments were administered three times weekly for 2 weeks, and a mycological study was performed. Results: Mycological studies using scraped samples obtained from treatment groups A (N = 8) and B (N = 8) after dual-diode laser treatment revealed that seven of eight (87.5%) samples in each group had negative results for direct potassium hydroxide microscopy and fungal culture studies. Skin specimens from each infected laser-untreated guinea pig exhibited spongiotic psoriasiform epidermis with parakeratosis. Meanwhile, skin specimens from infected laser-treated guinea pigs in groups A and B demonstrated thinner epidermal thickness than those from infected untreated controls but thicker than those from uninfected treated controls without noticeable inflammatory cell infiltration in the dermis. Conclusion: The guinea pig dermatophytosis model can be used to comparatively evaluate the efficacy and safety of various treatment modalities, including dual-diode lasers, for superficial fungal skin infection.