Exploring novel immunotherapy biomarker candidates induced by cancer deformation

by Se Min Kim, Namu Park, Hye Bin Park, JuKyung Lee, Changho Chun, Kyung Hoon Kim, Jong Seob Choi, Hyung Jin Kim, Sekyu Choi, Jung Hyun Lee

Triple-negative breast cancer (TNBC) demands urgent attention for the development of effective treatment strategies due to its aggressiveness and limited therapeutic options [1]. This research is primarily focused on identifying new biomarkers vital for immunotherapy, with the aim of developing tailored treatments specifically for TNBC, such as those targeting the PD-1/PD-L1 pathway. To achieve this, the study places a strong emphasis on investigating Ig genes, a characteristic of immune checkpoint inhibitors, particularly genes expressing Ig-like domains with altered expression levels induced by "cancer deformation," a condition associated with cancer malignancy. Human cells can express approximately 800 Ig family genes, yet only a few Ig genes, including PD-1 and PD-L1, have been developed into immunotherapy drugs thus far. Therefore, we investigated the Ig genes that were either upregulated or downregulated by the artificial metastatic environment in TNBC cell line. As a result, we confirmed the upregulation of approximately 13 Ig genes and validated them using qPCR. In summary, our study proposes an approach for identifying new biomarkers applicable to future immunotherapies aimed at addressing challenging cases of TNBC where conventional treatments fall short.

YouTube as a source of information for pressure injury: Quality assessment and content analysis

Abstract

We aimed to assess the quality and reliability of pressure injury-related videos uploaded on YouTube, analyse the sources and contents, and examine the correlation between video parameters. We searched YouTube using two keywords, “pressure ulcer” and “pressure sore”, on August 20, 2022. We sorted the videos according to their number of views and included the top 100 videos for each keyword. The quality of videos was assessed using the Global Quality Scale (GQS), while their reliability was evaluated by the modified DISCERN (mDISCERN) tool. In addition, we evaluated the videos in which content was included, analysed the correlations and differences between GQS, mDISCERN, and video parameters. We initially found a total of 100 videos for each keyword and finally included and analysed 77 videos. The mean scores for the mDISCERN and GQS were 2.35 ± 0.98 and 3.09 ± 0.99, respectively. Both GQS and mDISCERN showed statistically significant correlations with each other (rho = 0.54, p < 0.0001*) and with the length of the videos, respectively (rho = 0.36, p = 0.001*), (rho = 0.29, p = 0.01*). Of the videos created by physicians, 8 (57.1%) included content related to treatment, while of the videos created by nonphysician health personnel, 22 (57.9%) included content related to prevention. Analysing whether there were differences in video parameters based on the sources, we observed significant differences between sources in GQS (p < 0.0001*), mDISCERN (p < 0.0001*), and video length (p = 0.001*). In the post-hoc analysis, videos uploaded by physicians or nonphysician health personnel showed higher quality and reliability than videos uploaded by other sources. Therefore, the results of this study could be useful for healthcare providers, as well as patients and caregivers, to search for high-quality and reliable YouTube videos related to pressure injury.

Enhancing care for transgender and gender diverse survivors of intimate partner violence: an Ontario-wide survey examining health and social service providers learning needs

Objectives

To better understand healthcare and social/community service providers’ learning needs associated with supporting transgender and gender diverse (trans) persons who have experienced intimate partner violence (IPV).

Setting

An online survey was distributed through the trans-LINK Network in Ontario, Canada.

Respondents

163 of 225 healthcare and social/community service providers completed the survey (72.4% response rate) between November 2022 and February 2023.

Main outcome measures

Expertise, training, workplace practices and learning needs related to supporting trans survivors of IPV.

Method

Quantitative survey results were analysed descriptively and open-ended responses were organised thematically. In March 2022, survey results were shared with 33 stakeholders who helped define goals and objectives for an e-learning curriculum using Jamboard, data from which were collated and organised into themes.

Results

Most (66.3%) survey respondents described having provided professional support to trans survivors of IPV, but only one-third (38.0%) reported having received relevant training, and many of the trainings cited were in fact focused on other forms of violence or trans health generally. The majority reported a mid (44.9%) or low-mid (28.5%) level of expertise and almost unanimously agreed that they would benefit from (further) training (99.4%). The most commonly recommended goal/objective for a curriculum emerging from the stakeholder consultation was to facilitate collaboration, knowledge sharing and (safe) referrals among organisations.

Conclusions

The results of this study highlight the critical need for an IPV curriculum specific to trans survivors and responsive to the needs of providers. As no one profession can address this complex issue in isolation, it is important that the curriculum aims to facilitate collaboration across sectors. In the absence of appropriate training and referrals, practitioners may perpetuate harm when caring for trans survivors of IPV.

A relationship analysis of the effects of COVID‐19 isolation on pressure sores in a tertiary hospital

Abstract

Management of pressure sores can have various environmental effects; moreover, the COVID-19 pandemic notably affected efforts towards effective management of pressure sores. Some cases of COVID-19 infections require long-term hospitalization in the intensive care unit. Moreover, special protective equipment worn by physicians owing to the pandemic complicate wound management. In this study, we compared the pressure ulcer characteristics between isolated patients with and those without COVID-19 and evaluated the effects of isolation on pressure sores. From November 2022 to February 2023, patients who had pressure sores were included and their medical records were reviewed retrospectively. The experimental group included patients with confirmed COVID-19 infections, who received clinical treatment in an isolated unit. Wound characteristics in each group and associated risk factors were analysed. Fifty-four isolated patients with COVID-19 and 58 control patients were included. The Braden Scale score and Korea patient classification system-1 did not vary significantly between the two groups. However, the number of Grade I pressure sores in the COVID-19 isolation group was significantly lower than those in the control group (p < 0.001), while the number of lesions was significantly higher (p = 0.034). The mortality rate in the COVID-19 isolation group was higher than that in the control group (p = 0.008), and more patients were discharged with unhealed wounds (p = 0.004). A higher treatment effect on pressure sores may be expected if the disease is more actively managed. Moreover, the wound care systems for isolated patients with COVID-19 require further attention.

Changes in instrumental activities daily living limitations and their associated factors according to gender in community-residing older adults: A longitudinal cohort study

by SeolHwa Moon, Eunmi Oh, Daum Chung, Gwi-Ryung Son Hong

Background

Increases in dependence among older adults cause increases in care needs and social care burden. Instrumental activities of daily living (IADL) are often used to assess the independence of older adults residing in communities. Various factors affect IADL limitations, but few studies confirm gender differences in IADL limitations in older adults. This study explored the changes in incidence of IADL limitations across 14 years and identified the factors associated with IADL limitations according to gender among older adults in Korea.

Method

This study uses secondary data analysis with 2006–2020 data from the Korean Longitudinal Study of Aging (KLoSA), a longitudinal cohort study. Among the total 10,254 participants, 1,230 adults aged 65 years and over who met the criteria were included in the final analysis. For each IADL item, a limitation was defined when the response was partial or complete dependence. Multivariate logistic regression was performed to identify the factors (in 2006) associated with IADL limitations in 2020.

Results

The mean age of the participants at baseline was 69.64 years (SD 3.93), and 61.0% of participants were female. Total scores for IADL limitations increased gradually across 14 years in all participants, and observed changes were statistically significant. The top three ranked items of IADL limitations differed according to gender in 2020: the top limitations in men were preparing meals, laundry, and using public transportation, and the top limitations in women were using public transportation, going out, and handling money. Factors associated with total IADL limitations were grip strength in men and age, dementia, fear of fall, and grip strength in women. Factors associated with the top three ranked items of IADL limitations differed according to gender.

Conclusion

The incidence of IADL limitations gradually increased in all participants over a 14-year period. In older adults in Korea, gender differences were confirmed in the factors associated with IADL limitations, as well as in the main limited activities. To minimize IADL limitations in community-residing older adults, it is necessary to plan tailored interventions.

Efficacy of preoperative lymphoscintigraphy in predicting surgical outcomes of lymphaticovenous anastomosis in lower extremity lymphedema: Clinical correlations in gynecological cancer-related lymphedema

by Min Young Yoo, Kyong-Je Woo, Seo Young Kang, Byung Seok Moon, Bom Sahn Kim, Hai-Jeon Yoon

Background

Lymphaticovenous anastomosis (LVA) is a promising microsurgical treatment for lower extremity lymphedema (LEL). Lymphoscintigraphy effectively assesses lower limb lymphatic systems before LVA, but its role in predicting the therapeutic outcomes of LVA is indeterminate. In this study we investigate the efficacy of preoperative lymphoscintigraphy using clinical findings to predict outcomes in gynecological cancer-related LEL patients who underwent LVA.

Methods

A retrospective review was conducted on consecutive gynecological cancer patients with LEL who had undergone LVA between June 2018 and June 2021. The therapeutic efficacy was assessed by measuring the change rate of the lower extremity lymphedema index (LELi) six months after surgery. Clinical data and lymphoscintigraphic findings were analyzed to assess therapeutic efficacy of LVA.

Results

Out of the 60 evaluated legs, 83.3% of the legs showed improved results after LVA. Univariable linear regression analysis revealed that higher preoperative LELi, and ovarian cancer were associated with superior LELi change rate (LC rate). Absence of dermal backflow (DBF) on lymphoscintigraphy was associated with inferior LC rate. Multivariable linear regression analysis identified ovarian cancer and higher preoperative LELi were independently correlated with favorable outcomes, while the absence of DBF was independently correlated with inferior outcomes.

Conclusion

The results of this study emphasizes the effectiveness of preoperative lymphoscintigraphy, preoperative LELi, and primary malignancy as predictors of LVA outcomes in gynecological cancer-related LEL patients.

ROS mediated anticandidal efficacy of 3-Bromopyruvate prevents vulvovaginal candidiasis in mice model

by Ravi Jothi, Seong-Tshool Hong, Munkhtur Enkhtsatsral, Shunmugiah Karutha Pandian, Shanmugaraj Gowrishankar

Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing Candida species viz., C. albicans, C. tropicalis and C. glabrata. Furthermore, the study validates 3BP’s therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing >99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 μg/mL against all tested Candida spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all Candida strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of Candida spp., achieving a maximum eradication level of 90%. Toxicity/safety profiling in both in vitro erythrocyte lysis and in vivo Galleria mellonella survival assay authenticated the non-toxic nature of 3BP up to 512 μg/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against Candida species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments.

A surfactant‐based dressing can reduce the appearance of Pseudomonas aeruginosa pigments and uncover the dermal extracellular matrix in an ex vivo porcine skin wound model

Abstract

From previous studies, we have shown that viable colony forming units of bacteria and bacterial biofilms are reduced after sequential treatment with a surfactant-based dressing. Here, we sought to test the impact on visible bacterial pigments and the ultrastructural impact following the sequential treatment of the same surfactant-based dressing. Mature Pseudomonas aeruginosa biofilms were grown on ex vivo porcine skin explants, and an imaging-based analysis was used to compare the skin with and without a concentrated surfactant. In explants naturally tinted by bacterial chromophores, wiping alone had no effect, while the use of a surfactant-based dressing reduced coloration. Similarly, daily wiping led to increased immunohistochemical staining for P. aeruginosa antigens, but not in the surfactant group. Confocal immunofluorescent imaging revealed limited bacterial penetration and coating of the dermis and loose pieces of sloughing material. Ultrastructural analysis confirmed that the biofilms were masking the extracellular matrix (ECM), but the surfactant could remove them, re-exposing the ECM. The masking of the ECM may provide another non-inflammatory explanation for delayed healing, as the ECM is no longer accessible for wound cell locomotion. The use of a poloxamer-based surfactant appears to be an effective way to remove bacterial chromophores and the biofilm coating the ECM fibres.

Evaluation of immunogenicity-induced DNA vaccines against different SARS-CoV-2 variants

by Se Eun Kim, So Hee Park, Woo-Jung Park, Gayeong Kim, Seo Yeon Kim, Hyeran Won, Yun-Ho Hwang, Heeji Lim, Hyeon Guk Kim, You-Jin Kim, Dokeun Kim, Jung-Ah Lee

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic worldwide. As of September 2023, the number of confirmed coronavirus cases has reached over 770 million and caused nearly 7 million deaths. The World Health Organization assigned and informed the characterization of variants of concern (VOCs) to help control the COVID-19 pandemic through global monitoring of circulating viruses. Although many vaccines have been proposed, developing an effective vaccine against variants is still essential to reach the endemic stage of COVID-19. We designed five DNA vaccine candidates composed of the first isolated genotype and major SARS-CoV-2 strains from isolated Korean patients classified as VOCs, such as Alpha, Beta, Gamma, and Delta. To evaluate the immunogenicity of each genotype via homologous and heterologous vaccination, mice were immunized twice within a 3-week interval, and the blood and spleen were collected 1 week after the final vaccination to analyze the immune responses. The group vaccinated with DNA vaccine candidates based on the S genotype and the Alpha and Beta variants elicited both humoral and cellular immune responses, with higher total IgG levels and neutralizing antibody responses than the other groups. In particular, the vaccine candidate based on the Alpha variant induced a highly diverse cytokine response. Additionally, we found that the group subjected to homologous vaccination with the S genotype and heterologous vaccination with S/Alpha induced high total IgG levels and a neutralization antibody response. Homologous vaccination with the S genotype and heterologous vaccination with S/Alpha and S/Beta significantly induced IFN-γ immune responses. The immunogenicity after homologous vaccination with S and Alpha and heterologous vaccination with the S/Alpha candidate was better than that of the other groups, indicating the potential for developing novel DNA vaccines against different SARS-CoV-2 variants.

Application of Skyline software for detecting prohibited substances in doping control analysis

by Hyeon-Jeong Lee, Mijin Jeon, Yoondam Seo, Inseon Kang, Wooyeon Jeong, Junghyun Son, Eugene C. Yi, Hophil Min

As the number of prohibited drugs has been progressively increasing and analytical methods for detecting such substances are renewed continuously for doping control, the need for more sensitive and accurate doping analysis has increased. To address the urgent need for high throughput and accurate analysis, liquid chromatography with tandem mass spectrometry is actively utilized in case of most of the newly designated prohibited substances. However, because all mass spectrometer vendors provide data processing software that is incapable of handling other instrumental data, it is difficult to cover all doping analysis procedures, from method development to result reporting, on one platform. Skyline is an open-source and vendor-neutral software program invented for the method development and data processing of targeted proteomics. Recently, the utilization of Skyline has been expanding for the quantitative analysis of small molecules and lipids. Herein, we demonstrated Skyline as a simple platform for unifying overall doping control, including the optimization of analytical methods, monitoring of data quality, discovery of suspected doping samples, and validation of analytical methods for detecting newly prohibited substances. For method optimization, we selected the optimal collision energies for 339 prohibited substances. Notably, 195 substances exhibited a signal intensity increase of >110% compared with the signal intensity of the original collision energy. All data related to method validation and quantitative analysis were efficiently visualized, extracted, or calculated using Skyline. Moreover, a comparison of the time consumed and the number of suspicious samples screened in the initial test procedure highlighted the advantages of using Skyline over the commercially available software TraceFinder in doping control.

A Semantic Segment Encoder (SSE): Improving human face inversion quality through minimized learning space

by Byungseok Kang, Youngjae Jo

Recently, Generative Adversarial Networks (GAN) has been greatly developed and widely used in image synthesis. A Style-Based Generator Architecture for Generative Adversarial Networks (StyleGAN) which is the foremost, continues to develop human face inversion domain. StyleGAN uses insufficient vector space to express more than one million pixels. It is difficult to apply in real business due to distortion-edit tradeoff problem in latent space. To overcome this, we propose a novel semantic segment encoder (SSE) with improved face inversion quality by narrowing the size of restoration latent space. Encoder’s learning area is minimized to logical semantic-segment units that can be recognized by humans. The proposed encoder does not affect other segments because only one segment is edited at a time. To verify the face inversion quality, we compared with the latest encoders both Pixel2style2Pixel and RestyleEncoder. Experimental result shows that the proposed encoder improved distortion quality around 20% while maintain editing performance.

Healthcare data quality assessment for improving the quality of the Korea Biobank Network

by Ki-Hoon Kim, Seol Whan Oh, Soo Jeong Ko, Kang Hyuck Lee, Wona Choi, In Young Choi

Numerous studies make extensive use of healthcare data, including human materials and clinical information, and acknowledge its significance. However, limitations in data collection methods can impact the quality of healthcare data obtained from multiple institutions. In order to secure high-quality data related to human materials, research focused on data quality is necessary. This study validated the quality of data collected in 2020 from 16 institutions constituting the Korea Biobank Network using 104 validation rules. The validation rules were developed based on the DQ4HEALTH model and were divided into four dimensions: completeness, validity, accuracy, and uniqueness. Korea Biobank Network collects and manages human materials and clinical information from multiple biobanks, and is in the process of developing a common data model for data integration. The results of the data quality verification revealed an error rate of 0.74%. Furthermore, an analysis of the data from each institution was performed to examine the relationship between the institution’s characteristics and error count. The results from a chi-square test indicated that there was an independent correlation between each institution and its error count. To confirm this correlation between error counts and the characteristics of each institution, a correlation analysis was conducted. The results, shown in a graph, revealed the relationship between factors that had high correlation coefficients and the error count. The findings suggest that the data quality was impacted by biases in the evaluation system, including the institution’s IT environment, infrastructure, and the number of collected samples. These results highlight the need to consider the scalability of research quality when evaluating clinical epidemiological information linked to human materials in future validation studies of data quality.

CTIVA: Censored time interval variable analysis

by Insoo Kim, Junhee Seok, Yoojoong Kim

Traditionally, datasets with multiple censored time-to-events have not been utilized in multivariate analysis because of their high level of complexity. In this paper, we propose the Censored Time Interval Analysis (CTIVA) method to address this issue. It estimates the joint probability distribution of actual event times in the censored dataset by implementing a statistical probability density estimation technique on the dataset. Based on the acquired event time, CTIVA investigates variables correlated with the interval time of events via statistical tests. The proposed method handles both categorical and continuous variables simultaneously—thus, it is suitable for application on real-world censored time-to-event datasets, which include both categorical and continuous variables. CTIVA outperforms traditional censored time-to-event data handling methods by 5% on simulation data. The average area under the curve (AUC) of the proposed method on the simulation dataset exceeds 0.9 under various conditions. Further, CTIVA yields novel results on National Sample Cohort Demo (NSCD) and proteasome inhibitor bortezomib dataset, a real-world censored time-to-event dataset of medical history of beneficiaries provided by the National Health Insurance Sharing Service (NHISS) and National Center for Biotechnology Information (NCBI). We believe that the development of CTIVA is a milestone in the investigation of variables correlated with interval time of events in presence of censoring.

Randomized clinical trial to compare the efficacy of self-expanding bare metal nitinol stent and balloon angioplasty alone for below-the-knee lesions following successful balloon angioplasty: 1-year clinical outcomes

by Jihun Ahn, HyeYon Yu, Seung-Woon Rha, Byoung Geol Choi, Dong Oh Kang, Cheol Ung Choi, Sangho Park, Jon Seo, Kichang Kim, Minung Kim, Yong Hoon Kim, Yong Seong Seo

This prospective, multicenter, randomized study aimed to compare the 1-year clinical outcomes after primary stenting with self-expanding bare metal nitinol stent (SENS) and plain old balloon angioplasty (POBA) in patients with critical limb ischemia (CLI) and below-the-knee (BTK) lesions. Overall, 119 patients with CLI and BTK lesions were randomized to POBA alone (POBA group, 61 patients) or primary stenting with SENS (stenting group, 58 patients) after achieving acceptable POBA results in target BTK lesions. Clinical outcomes including amputation and revascularization rates were prospectively compared for 1 year. After 1 year, similar incidence rates of individual clinical endpoints, including cardiac death (6.5% vs. 5.1%, p > 0.999), myocardial infarction (1.6% vs. 0.0%, p > 0.999), repeat revascularization (19.6% vs. 18.9%, p = 0.922), target lesion revascularization (13.1% vs. 17.2%, p = 0.530), and amputation (4.9% vs. 0.0%, p = 0.244), were observed. POBA appeared to have acceptable treatment outcomes compared with primary stenting with SENS after 1 year in CLI patients with BTK lesions undergoing percutaneous transluminal angioplasty (PTA).