Recombinant immune complexes as vaccines against infectious diseases.

New vaccine technologies are needed to combat many existing infections and prepare better for those that may emerge in the future. The conventional technologies that rely on protein-based vaccines are still severely restricted by the sparsity and poor accessibility of available adjuvants. One possible solution to this problem is to enhance antigen immunogenicity by a more natural means by complexing it with antibodies in the form of immune complexes (ICs). However, natural ICs are impractical as vaccines, and significant research efforts have been made to generate them in recombinant form, with plant bioengineering being at the forefront of these efforts. Here, we describe the challenges and progress made to date to make recombinant IC vaccines applicable to humans.

Effectiveness of simulation-based interventions on empathy enhancement among nursing students: a systematic literature review and meta-analysis.

BACKGROUND: This study aimed to secure and analyze evidence regarding the enhancement of nursing students' empathy through simulation-based interventions. It comprehensively analyzed self-reported emotions and reactions as primary outcomes, along with the results reported by nursing students who experienced simulation-based interventions, including empathy. METHODS: This systematic literature review and meta-analysis investigated the effects of simulation-based interventions on enhancing empathy among nursing students. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for the systematic review and meta-analysis. The following details were considered: population, nursing students; intervention, simulation-based interventions targeting empathy enhancement; comparators, control groups without intervention or those undergoing general non-simulation-based classes; and outcomes, self-reported empathy. RESULTS: In the systematic review of 28 studies, it was found that the use of simulation-based interventions among nursing students led to an increase in empathy, albeit with a small effect size. This was demonstrated through a pooled, random-effects meta-analysis, yielding an effect size (Hedge's g) of 0.35 (95% CI: 0.14, 0.57, p = 0.001). The results of meta-regression and subgroup analysis significantly increased in empathy for studies published after 2019 (Hedge's g = 0.52, 95% CI: 0.31 to 0.73, p < 0.001), quasi-experimental research design (Hedge's g = 0.51, 95% CI: 0.27 to 0.74, p < 0.001), more than 60 participants (Hedge's g = 0.31, 95% CI: 0.02 to 0.59, p = 0.034), and simulation-based interventions in nursing education (Hedge's g = 0.43, 95% CI: 0.22 to 0.65, p < 0.001). CONCLUSIONS: Considering factors such as variations in sample size, research approaches, and the effects of independent studies on empathy, this systematic literature review and meta-analysis suggests that simulation-based education can significantly improve nursing students' overall empathy skills.

Enhancing nursing competency through virtual reality simulation among nursing students: a systematic review and meta-analysis.

Aim: Studies on the effectiveness of virtual reality (VR) in nursing education have explored its impact on learning outcomes, emotional immersion and engagement, learner self-confidence, and satisfaction, generally showing positive aspects. However, there is a need for a systematic review to examine the specific influence of VR-based education on nursing students' practical competency. Method: According to the PRISMA 2020 guidelines, 22 studies were selected based on inclusion criteria from 579 articles, published from January 1, 2018, to March 31, 2024, across nine major databases including PubMed and EMbase. The target population comprised nursing students, and the intervention focused on VR-based simulations aimed at enhancing competency, compared to control groups receiving either no intervention or conventional non-virtual simulation. The primary outcome, nursing competency, was analyzed using MIX 2.0 Pro (Ver. 2.0.1.6, BiostatXL, 2017) to calculate pooled effect sizes. Result: The pooled effect size for nursing competency was determined to be large, with Hedge's g = 0.88 (95% CI, 0.47 to 1.29). Meta-regression analysis identified several factors associated with an increase in nursing competency. These included studies published after 2022, approval of an IRB, absence of funding, randomized controlled trials (RCTs), interventions reported as shorter than 4 weeks or not reported, sessions fewer than 4 or not reported, session duration under 1 h or not reported, and observational measurement methods. Additional factors enhancing nursing competency were the inclusion of a pre-briefing before simulations, the absence of a debriefing afterward, and the exclusion of other activities during the simulation. Conclusion: By combining the results of the included studies, the systematic review and meta-analysis accounted for variations in sample size, study methodology, and independent intervention effects, providing an overall evaluation of the effectiveness of simulation-based education in improving nursing students' competency. Limitation: The selection criteria for the studies analyzed, which included only those published in English or Korean and reported precise means, standard deviations, and sample sizes, could lead to selection bias and limit the generalization of our study results. Systematic review registration: PROSPERO International Prospective Register of Systematic Reviews: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023446348.

Effectiveness of a Patient Safety Incident Disclosure Education Program: A Quasi-Experimental Study.

BACKGROUND: The accurate disclosure of patient safety incidents is necessary to minimize patient safety incidents and medical disputes. As prospective healthcare providers, nursing students need to possess the ability to disclose patient safety incidents. PURPOSE: This study was designed to investigate the effect of a patient safety incident disclosure education program for undergraduate nursing students on participants' knowledge and perception of disclosure of these incidents, attitudes toward patient safety, and self-efficacy regarding disclosure of these incidents. METHODS: A quasi-experimental study with a nonequivalent pretest-posttest design was conducted on fourth-year undergraduate nursing students recruited between September 6 and October 22, 2021, through convenience sampling from two universities in South Korea. The experimental group (n = 25) received the education program. The control group (n = 25) received educational materials on the disclosure of patient safety incidents only. Knowledge and perceptions of patient safety incident disclosure, attitudes toward patient safety, and self-efficacy regarding incident disclosure were measured. Data were analyzed using descriptive analysis, t test, χ2 test, Fisher's exact test, Mann-Whitney U test, Wilcoxon signed-rank test, and ranked analysis of covariance. RESULTS: Posttest results revealed knowledge (p < .001), perceptions (p = .031), and self-efficacy (p < .001) with regard to the disclosure of patient safety incidents were all significantly higher in the experimental group than in the control group. Posttest attitudes toward patient safety were not significantly different between the two groups (p = .908). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The patient safety incident disclosure education program effectively enhances the knowledge, perception, and self-efficacy of nursing students with regard to safety incidents. The findings may be used to improve training and educational programs in nursing colleges and hospitals to improve the knowledge, perception, and self-efficacy of nursing students with regard to disclosing patient safety incidents in clinical settings.

Overview and Discussion of the Competition on Legal Information, Extraction/Entailment (COLIEE) 2023.

We summarize the 10th Competition on Legal Information Extraction and Entailment. In this tenth edition, the competition included four tasks on case law and statute law. The case law component includes an information retrieval task (Task 1), and the confirmation of an entailment relation between an existing case and a selected unseen case (Task 2). The statute law component includes an information retrieval task (Task 3), and an entailment/question-answering task based on retrieved civil code statutes (Task 4). Participation was open to any group based on any approach. Ten different teams participated in the case law competition tasks, most of them in more than one task. We received results from 8 teams for Task 1 (22 runs) and seven teams for Task 2 (18 runs). On the statute law task, there were 9 different teams participating, most in more than one task. 6 teams submitted a total of 16 runs for Task 3, and 9 teams submitted a total of 26 runs for Task 4. We describe the variety of approaches, our official evaluation, and analysis of our data and submission results.

Legal Information Retrieval and Entailment Using Transformer-based Approaches.

The challenge of information overload in the legal domain increases every day. The COLIEE competition has created four challenge tasks that are intended to encourage the development of systems and methods to alleviate some of that pressure: a case law retrieval (Task 1) and entailment (Task 2), and a statute law retrieval (Task 3) and entailment (Task 4). Here we describe our methods for Task 1 and Task 4. In Task 1, we used a sentence-transformer model to create a numeric representation for each case paragraph. We then created a histogram of the similarities between a query case and a candidate case. The histogram is used to build a binary classifier that decides whether a candidate case should be noticed or not. In Task 4, our approach relies on fine-tuning a pre-trained DeBERTa large language model (LLM) trained on SNLI and MultiNLI datasets. Our method for Task 4 was ranked third among eight participating teams in the COLIEE 2023 competition. For Task 4, We also compared the performance of the DeBERTa model with those of a knowledge distillation model and ensemble methods including Random Forest and Voting.

Progression-directed therapy in patients with oligoprogressive castration-resistant prostate cancer.

PURPOSE: Oligoprogressive lesions are observed in a subset of patients who progress to castration-resistant prostate cancer (CRPC), while other lesions remain controlled by systemic therapy. This study evaluates the impact of progression-directed therapy (PDT) on these oligoprogressive lesions. MATERIALS AND METHODS: This retrospective study included 40 patients diagnosed with oligoprogressive CRPC. PDT was performed for treating all progressive sites using radiotherapy. Fifteen patients received PDT using radiotherapy for all progressive sites (PDT group) while 25 had additional first-line systemic treatments (non-PDT group). In PDT group, 7 patients underwent PDT and unchanged systemic therapy (PDT-A group) and 8 patients underwent PDT with additional new line of systemic therapy on CRPC (PDT-B group). The Kaplan-Meier method was used to assess treatment outcomes. RESULTS: The prostate specific antigen (PSA) nadir was significantly lower in PDT group compare to non-PDT group (p=0.007). A 50% PSA decline and complete PSA decline were observed in 13 patients (86.7%) and 10 patients (66.7%) of PDT group and in 18 patients (72.0%) and 11 patients (44.0%) of non-PDT group, respectively. The PSA-progression free survival of PDT-B group was significantly longer than non-PDT group. The median time to failure of first-line systemic therapy on CRPC was 30.2 months in patients in PDT group and 14.9 months in non-PDT group (p=0.014). PDT-B group showed a significantly longer time to progression than non-PDT group (p=0.025). Minimal PDT-related adverse events were observed. CONCLUSIONS: PDT can delay progression of disease and enhance treatment efficacy with acceptable tolerability in oligoprogressive CRPC.

Systematic identification of a synthetic lethal interaction in brain-metastatic lung adenocarcinoma.

Metastatic lung adenocarcinoma (LuAC) presents a significant clinical challenge due to the short latency and the lack of efficient treatment options. Therefore, identification of molecular vulnerabilities in metastatic LuAC holds great importance in the development of therapeutic drugs against this disease. In this study, we performed a genome-wide siRNA screening using poorly and highly brain-metastatic LuAC cell lines. Using this approach, we discovered that compared to poorly metastatic LuAC (LuAC-Par) cells, brain-metastatic LuAC (LuAC-BrM) cells exhibited a significantly higher vulnerability to c-FLIP (an inhibitor of caspase-8)-depletion-induced apoptosis. Furthermore, in vivo studies demonstrated that c-FLIP knockdown specifically inhibited growth of LuAC-BrM, but not the LuAC-Par, tumors, suggesting the addiction of LuAC-BrM to the function of c-FLIP for their survival. Our in vitro and in vivo analyses also demonstrated that LuAC-BrM is more sensitive to c-FLIP-depletion due to ER stress-induced activation of the c-JUN and subsequent induction of stress genes including ATF4 and DDIT3. Finally, we found that c-JUN not only sensitized LuAC-BrM to c-FLIP-depletion-induced cell death but also promoted brain metastasis in vivo, providing strong evidence for c-JUN's function as a double-edged sword in LuAC-BrM. Collectively, our findings not only reveal a novel link between c-JUN, brain metastasis, and c-FLIP addiction in LuAC-BrM but also present an opportunity for potential therapeutic intervention.

Whole Process of Standardization of Diffusion-Weighted Imaging: Phantom Validation and Clinical Application According to the QIBA Profile.

Background: To use the apparent diffusion coefficient (ADC) as reliable biomarkers, validation of MRI equipment performance and clinical acquisition protocols should be performed prior to application in patients. This study aims to validate various MRI equipment and clinical brain protocols for diffusion weighted imaging (DWI) using commercial phantom, and confirm the validated protocols in patients' images. Methods: The performance of four different scanners and clinical brain protocols were validated using a Quantitative Imaging Biomarker Alliance (QIBA) diffusion phantom and cloud-based analysis tool. We evaluated the performance metrics regarding accuracy and repeatability of ADC measurement using QIBA profile. The validated clinical brain protocols were applied to 17 patients, and image quality and repeatability of ADC were assessed. Results: The MRI equipment performance of all four MRI scanners demonstrated high accuracy in ADC measurement (ADC bias, -2.3% to -0.4%), excellent linear correlation to the reference ADC value (slope, 0.9 to 1.0; R2, 0.999-1.000), and high short-term repeatability [within-subject-coefficient-of-variation (wCV), 0% to 0.3%]. The clinical protocols were also validated by fulfilling QIBA claims with high accuracy (ADC bias, -3.1% to -0.7%) and robust repeatability (wCV, 0% to 0.1%). Brain DWI acquired using the validated clinical protocols showed ideal image quality (mean score ≥ 2.9) and good repeatability (wCV, 1.8-2.2). Conclusions: The whole process of standardization of DWI demonstrated the robustness of ADC with high accuracy and repeatability across diverse MRI equipment and clinical protocols in accordance with the QIBA claims.

Live attenuated smallpox vaccine candidate (KVAC103) efficiently induces protective immune responses in mice.

Smallpox, caused by the variola virus belonging to the genus Orthopoxvirus, is an acute contagious disease that killed 300 million people in the 20th century. Since it was declared to be eradicated and the national immunization program against it was stopped, the variola virus has become a prospective bio-weapon. It is necessary to develop a safe vaccine that protects people from terrorism using this biological weapon and that can be administered to immunocompromised people. Our previous study reported on the development of an attenuated smallpox vaccine (KVAC103). This study evaluated cellular and humoral immune responses to various doses, frequencies, and routes of administration of the KVAC103 strain, compared to CJ-50300 vaccine, and its protective ability against the wild-type vaccinia virus Western Reserve (VACV-WR) strain was evaluated. The binding and neutralizing-antibody titers increased in a concentration-dependent manner in the second inoculation, which increased the neutralizing-antibody titer compared to those after the single injection. In contrast, the T-cell immune response (interferon-gamma positive cells) increased after the second inoculation compared to that of CJ-50300 after the first inoculation. Neutralizing-antibody titers and antigen-specific IgG levels were comparable in all groups administered KVAC103 intramuscularly, subcutaneously, and intradermally. In a protective immunity test using the VACV-WR strain, all mice vaccinated with CJ-50300 or KVAC103 showed 100% survival. KVAC103 could be a potent smallpox vaccine that efficiently induces humoral and cellular immune responses to protect mice against the VACV-WR strain.

Marked enhancement of the immunogenicity of plant-expressed IgG-Fc fusion proteins by inclusion of cholera toxin non-toxic B subunit within the single polypeptide.

Immunoglobulin G (IgG)-based fusion proteins have been widely exploited as a potential vaccine delivery platform but in the absence of exogenous adjuvants, the lack of robust immunity remains an obstacle. Here, we report on a key modification that overcomes that obstacle. Thus, we constructed an IgG-Fc vaccine platform for dengue, termed D-PCF, which in addition to a dengue antigen incorporates the cholera toxin non-toxic B subunit (CTB) as a molecular adjuvant, with all three proteins expressed as a single polypeptide. Following expression in Nicotiana benthamiana plants, the D-PCF assembled as polymeric structures of similar size to human IgM, a process driven by the pentamerization of CTB. A marked improvement of functional properties in vitro and immunogenicity in vivo over a previous iteration of the Fc-fusion protein without CTB [1] was demonstrated. These include enhanced antigen presenting cell binding, internalization and activation, complement activation, epithelial cell interactions and ganglioside binding, as well as more efficient polymerization within the expression host. Following immunization of mice with D-PCF by a combination of systemic and mucosal (intranasal) routes, we observed robust systemic and mucosal immune responses, as well as systemic T cell responses, significantly higher than those induced by a related Fc-fusion protein but without CTB. The induced antibodies could bind to the domain III of the dengue virus envelope protein from all four dengue serotypes. Finally, we also demonstrated feasibility of aerosolization of D-PCF as a prerequisite for vaccine delivery by the respiratory route.

Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional study.

PURPOSE: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. METHODS AND MATERIALS: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. RESULTS: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. CONCLUSION: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Mucosal and systemic immune responses after a single intranasal dose of nanoparticle and spore-based subunit vaccines in mice with pre-existing lung mycobacterial immunity.

Tuberculosis (TB) is a major global health threat that claims more than one million lives annually. With a quarter of the global population harbouring latent TB, post-exposure vaccination aimed at high-risk populations that could develop active TB disease would be of great public health benefit. Mucosal vaccination is an attractive approach for a predominantly lung disease like TB because it elicits both local and systemic immunity. However, the immunological consequence of mucosal immunisation in the presence of existing lung immunity remains largely unexplored. Using a mycobacterial pre-exposure mouse model, we assessed whether pre-existing mucosal and systemic immune responses can be boosted and/or qualitatively altered by intranasal administration of spore- and nanoparticle-based subunit vaccines. Analysis of lung T cell responses revealed an increasing trend in the frequency of important CD4 and CD8 T cell subsets, and T effector memory cells with a Th1 cytokine (IFNγ and TNFα) signature among immunised mice. Additionally, significantly greater antigen specific Th1, Th17 and IL-10 responses, and antigen-induced T cell proliferation were seen from the spleens of immunised mice. Measurement of antigen-specific IgG and IgA from blood and bronchoalveolar lavage fluid also revealed enhanced systemic and local humoral immune responses among immunised animals. Lastly, peripheral blood mononuclear cells (PBMCs) obtained from the TB-endemic country of Mozambique show that individuals with LTBI showed significantly greater CD4 T cell reactivity to the vaccine candidate as compared to healthy controls. These results support further testing of Spore-FP1 and Nano-FP1 as post-exposure TB vaccines.

Radiologic Progression of Interstitial Lung Abnormalities following Surgical Resection in Patients with Lung Cancer.

In this study, we aimed to assess the prevalence of interstitial lung abnormalities (ILAs) and investigate the rates and risk factors associated with radiologic ILA progression among patients with lung cancer following surgical resection. Patients who underwent surgical resection for lung cancer at our institution from January 2015 to December 2020 were retrospectively evaluated and grouped according to their ILA status as having no ILAs, equivocal ILAs, or ILAs. Progression was determined by simultaneously reviewing the baseline and corresponding follow-up computed tomography (CT) scans. Among 346 patients (median age: 67 (interquartile range: 60-74) years, 204 (59.0%) men), 22 (6.4%) had equivocal ILAs, and 33 (9.5%) had ILAs detected upon baseline CT. Notably, six patients (6/291; 2.1%) without ILAs upon baseline CT later developed ILAs, and 50% (11/22) of those with equivocal ILAs exhibited progression. Furthermore, 75.8% (25/33) of patients with ILAs upon baseline CT exhibited ILA progression (76.9% and 71.4% with fibrotic and non-fibrotic ILAs, respectively). Multivariate analysis revealed that ILA status was a significant risk factor for ILA progression. ILAs and equivocal ILAs were associated with radiologic ILA progression after surgical resection in patients with lung cancer. Hence, early ILA detection can significantly affect clinical outcomes.

Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer.

Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.

Synergistic Effects of Metformin and Trastuzumab on HER2 Positive Gastroesophageal Adenocarcinoma Cells In Vitro and In Vivo.

The incidence of HER2 amplification in advanced gastroesophageal adenocarcinoma (GC) reportedly ranges between 10% and 20%, depending on the population studied and the geographical region. Trastuzumab (Tmab) is the standard treatment for GCs with HER2 amplification. Metformin, a widely used antidiabetic drug, is an activator of AMP kinase that can affect the mTOR signaling pathway. The following GC cells were evaluated: HER2+ NCI-N87, YCC-19, YCC-38, OE19, OE33, and HER2- AGS. The effects of Tmab and metformin on these cell lines were assessed as single agents and in combination using cell viability assays, Western blotting, and xenograft models. Metformin induced phosphorylation of AMP kinase in all tested GC cells and dephosphorylation of mTOR in Tmab-sensitive GC cells. We observed that treatment with Tmab in combination with metformin induced a significant decrease in the number of colonies formed on soft agar by N87, YCC-19, YCC-38, and OE19 cells (88%, 95%, 73%, and 98%, respectively), in comparison to the number formed by control cells or cells in the single-treatment groups. No growth inhibition was detected in OE33 cells treated with Tmab alone. Combination with metformin resulted in decreased phosphorylation of HER2 and its downstream targets, AKT and ERK, in Tmab-sensitive HER2+ cells. Phospho-receptor tyrosine kinase (RTK) arrays were used to profile the phospho-proteome, which demonstrated a synergistic decrease in phosphorylation of EGFR, HER2, and HER3. Furthermore, the combination of Tmab and metformin exhibited enhanced antitumor effects in a xenograft model. Collectively, these data suggest that Tmab and metformin act synergistically in HER2+ GC cells. Since metformin is widely used and relatively non-toxic, its addition to the therapeutic regimen along with Tmab could enhance the clinical efficacy in patients with HER2+ GC.

Serological analysis reveals differential antibody responses between TB patients and latently infected individuals from the TB endemic country of Mozambique.

Serological antibody profiling of tuberculosis (TB) patients and household contacts with latent TB infection (LTBI) could identify risk indicators of disease progression, and potentially also serve as an easily accessible diagnostic tool to discriminate between these two stages of Mycobacterium tuberculosis (Mtb) infection. Yet, despite significant efforts over many decades, neither application has yet fully materialised, and this is at least in part due to inconsistent and varying antibody profiles from different TB endemic regions. In this study, we conducted a retrospective exploratory analysis of serum antibodies in a cohort of active TB patients (ATB) and their interferon-gamma release assay (IGRA) positive household contacts (LTBI), as well as healthy controls (HC) from Mozambique, a country with a high TB burden from the Sub-Saharan region. Using several Mtb antigens as well as crude preparations of culture filtrate proteins (CFP) from Mtb and Bacille Calmette Guérin (BCG), we report that the most discriminatory response for TB and LTBI was observed for serum IgA antibodies to the MPT64 antigen, followed by IgG antibodies to Ag85B and CFP, with ATB patients having significantly higher levels than LTBI or BCG-vaccinated healthy controls. Conversely, sera from LTBI individuals had higher levels of IgG antibodies to the HBHA antigen than ATB. While our sample size (n = 21 for ATB, 18 for LTBI and 17 for HC) was too small to fully evaluate the diagnostic potential of these differing serological profiles, our study however preliminarily indicated high level of sensitivity (95%) and specificity (97%) of an ELISA MPT64-IgA test for discriminating TB from LTBI and healthy controls, supporting the notion that it alone, or possibly in combination with other antigens such as Ag85B or CFP could lead to development of an easily accessible diagnostic tool for TB.

Establishment and characterization of BMC-PDC-019: a novel patient-derived cell line of EGFR-mutant pulmonary adenocarcinoma transformed into small-cell lung cancer.

Transformed small-cell lung cancer (tSCLC) from EGFR-mutant adenocarcinoma is a rare and aggressive form of lung cancer that can occur when the tumor develops resistance to EGFR targeted therapy and the cancer cells acquire additional genomic alterations that cause them to transform into SCLC. Treatment for tSCLC has not been established yet, and chemotherapy regimens for de novo SCLC are mostly recommended. However, these treatments showed disappointing outcome, and novel anti-cancer agents and immunological approaches are currently being developed. The patient-derived cell line is a critical tool for pre-clinical and translational research, but cell line models for tSCLC are not publicly available from cell banks. The aim of this study was to establish and characterize a novel cell line for tSCLC. Using a lymph-node biopsy tissue from a 58-year-old female patient, whose tumor was EGFR-mutant lung adenocarcinoma progressed on afatinib, we successfully established a cell line, named BMC-PDC-019. The tumor sample and cell line showed a typical expression of SCLC markers, such as CD56 and synaptophysin. The population doubling-time of BMC-PDC-019 cells was 48 h. We examined a range of proliferation-inhibiting effects of anti-cancer drugs currently used for de novo SCLC, using BMC-PDC-019 cells. We concluded that BMC-PDC-019 would be a useful tool for pre-clinical and translational research.

Factors Affecting the Sexual Behavior of Korean University Students.

Recent incidents in Room n, sexual harassment by social leaders, and the #MeToo movement showed Korea's immature and distorted sexual culture. This cross-sectional descriptive study investigated the factors affecting the sexual behavior of Korean university students. The participants comprised 258 university students from S and C. The data collection period was from 29 November 2021 to 3 December 2021, and an online survey was conducted on sexual behavior, sexual attitudes, and subject characteristics. The collected data were analyzed using PASW Statistics 25.0. The average age of the participants was 21.38 ± 1.62 years old; the average age when they first watched a pornographic video on YouTube was 14.25 ± 2.55 years old. Sexual behavior was statistically significantly higher for men over 21 and under 14 when they first watched a pornographic video. As the age of the subjects increased, the younger the age of viewing pornographic videos and the thumbnail viewing path of the pornographic videos affected sexual behavior, with an explanatory power of 11.0% (F = 6.27, p < 0.001). Higher sexual attitudes in the communion and permissiveness domains showed greater influence on sexual behavior; the explanatory power was 24.0% (F = 10.02, p < 0.001). Korean university students must be educated on sex early to develop correct sexual attitudes and engage in correct and responsible sexual behaviors in their youth.