Explore the vast range of titles available.

In organizational research, growing attention has been given to the dynamic nature of workplace relationships and how such dynamic processes shape key behavioural outcomes. Experience sampling methodology (ESM) brings more opportunity than any other research option to examine such fluctuations and relevant causal relationships. ESM can be described as a quantitative method which allows individuals to assess discrete evaluative states on multiple events by combining three distinct elements; person, variables and occasion. Despite its increasing prevalence and popularity, however, there has been only a few attempts to investigate the most appropriate design, measurement and analysis choices for experience sampling data. Even though ESM has been utilized in organizational research for some time, systematic investigations regarding how these issues have been addressed and how the method has been applied to specific organizational topics are limited. This study provides a systematic and critical assessment of the use of ESM in current organizational research (2010‑2020) by reviewing a random sample of 50 ESM studies indexed in ISI Web of Science with the aim of identifying the current state of practice. The selected studies were analysed based on several methodological aspects including the type of ESM protocol applied, sample characteristics, data sources, specified interval and total duration of data collection, structure and properties of designated measures, analytic strategy, and the research model to be tested. Findings show that organization studies vary considerably based on how they design and implement ESM. Moreover, despite the availability of good practices, many studies fail to attain recommended standards about sample size, data collection procedures, data characteristics and measurement quality. As such, this paper offers several insights regarding how time‑based within‑person frameworks can be improved in future studies to account for dynamic organizational phenomena.

Cervical cancer has recently become one of the most prevalent cancers among women throughout the world. Traditional cancer therapies generate side effects due to off-target toxicity. Thus, novel cancer medications coupled with suitable drug delivery systems are required to improve cancer therapies. Melittin peptide has a high affinity to disrupt cancer cells. In this study, we designed targeted and redox-responsive Melittin conjugates for cervical cancer and then tested them in vitro. Folic acid and squamous cell carcinoma-specific peptide (CKQNLAEG) were used as targeting agents to design various conjugates. Our findings indicate that both anticancer conjugates were effective against different cancer cell lines, including MCF-7, C33A, and HeLa. Moreover, these conjugates were found to have antioxidant and antibacterial effects as well as reduced hemolytic activity. The CM–Target (N-terminus cysteine modified-Melittin–targeting peptide-functionalized conjugate) has become more stable and acted specifically against squamous cell carcinoma, whereas folic acid (FA)–containing conjugates acted efficiently against all cancer types studied, especially for breast cancer. According to our results, these anticancer conjugates may be possible anticancer drug candidates that have fewer adverse effects.

Recent reports on antibiotic resistance have highlighted the need to reduce the impact of this global health issue through urgent prevention and control. The World Health Organization currently considers antibiotic resistance as one of the most dangerous threats to global health. Therefore, Antimicrobial peptides (AMPs) are promising for the development of novel antibiotic molecules due to their high antimicrobial effects, non-inducing antimicrobial resistance (AMR) properties, and broad spectrum. Hence, in this study, we developed novel antimicrobial peptide/polymer conjugates to reduce the adverse effects of TN6 (RLLRLLLRLLR) peptide. We demonstrate how our constructs function in vitro in terms of antimicrobial activity, hemolytic activity, cytotoxicity, and protease resistance. Our findings show that our molecules are effective against different types of microorganisms such as Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , methicillin-resistant S. aureus , vancomycin-resistant Enteroccus faecium , and Candida albicans , which are known to be pathogenic and antibiotic-resistant. Our constructs generally showed low cytotoxicity relative to the peptide in HaCaT and 3T3 cells. Especially these structures are very successful in terms of hemotoxicity. In the bacteremia model with S. aureus , the naked peptide (TN6) was hemotoxic even at 1 µg/mL, while the hemotoxicity of the conjugates was considerably lower than the peptide. Remarkably in this model, the hemolytic activity of PepC-PEG-pepC conjugate decreased 15-fold from 2.36 to 31.12 µg/mL compared to the bacteria-free 60-min treatment. This is proof that in the case of bacteremia and sepsis, the conjugates specifically direct to bacterial cell membranes rather than red blood cells. In addition, the PepC-PEG-pepC conjugate is resistant to plasma proteases. Moreover, morphological and intracellular damage of the peptide/conjugates to Escherichia coli are demonstrated in SEM and TEM images. These results suggest our molecules can be considered potential next-generation broad-spectrum antibiotic molecule/drug candidates that might be used in clinical cases such as bacteremia and sepsis.

In this study, the in vitro photodynamic therapy (PDT) activity of two zinc phthalocyanines (ZnPc1 and ZnPc2) was systematically examined in human umbilical vein endothelial cells, focusing on PDT-induced cytotoxicity, reactive oxygen species (ROS) generation, and inhibition of angiogenic processes. Both the ZnPcs demonstrated minimal cytotoxicity in the absence of light, confirming their safety as photosensitizers. ZnPc-PDT led to significant cell death via apoptosis. ZnPc1 exhibited enhanced ROS generation, particularly at elevated concentrations. Furthermore, ZnPc1-mediated PDT showed more pronounced inhibition of endothelial cell migration, invasion, and capillary-like tube formation than ZnPc2. Wound-healing assays revealed a substantial delay in human umbilical vein endothelial cell (HUVEC) migration following ZnPc1-PDT, which also displayed a more significant inhibition of VEGF-induced directional migration and invasion. Endothelial tube formation was more effectively disrupted by ZnPc1-PDT, even at lower concentrations, compared to ZnPc2. Collectively, these findings highlight the superior cytotoxic and anti-angiogenic properties of ZnPc1 compared with ZnPc2, highlighting its potential as a highly effective photosensitizer for photodynamic therapy. The ability of ZnPc1 to simultaneously target tumor cells and disrupt angiogenesis establishes it as a potent candidate for integrated cancer therapies that combine both antitumor and antiangiogenic strategies, offering a more effective approach to combat cancer progression.

In this study, the PDT activities of 2,9(10),16(17),23(24)-tetrakis(2-dimethylammoniumethoxy) phthalocyaninatozinc(II) tetraiodide (ZnPc1) and 1,8(11),15(18),22(25)-tetrakis(2-trimethylaminoethoxy)phthalocyaninatozinc(II)tetraiodide (ZnPc2) compounds were investigated in 2D monolayer cultures and 3D spheroids of three human cancer cell lines: human submaxillary salivary gland epidermoid carcinoma (A253), human colon colorectal adenocarcinoma (HT29), and human pharynx squamous carcinoma (FaDu) cells. The results indicate that both molecules are non-toxic in the absence of light, which is a crucial feature of an effective photosensitizer. Upon exposure to light, ZnPc1 exhibited significant cytotoxicity in all three cell lines, particularly in FaDu cells, in both 2D monolayer cultures and 3D spheroids, whereas ZnPc2 showed moderate efficacy compared to ZnPc1. PDT using both phthalocyanine (Pc) molecules resulted in substantial reactive oxygen species (ROS) production. Delayed ROS production is higher than that of immediate ROS, indicating their ability to stimulate ROS production over an extended period and retain an oxidative stress response in the cells rather than immediately after PDT. Among these molecules, ZnPc1 induced both immediate and delayed ROS production more efficiently than ZnPc2. Furthermore, singlet oxygen yields of ZnPc1 were higher than ZnPc2, which is consistent with the cytotoxicity results. These findings confirmed that PDT induces an ROS-mediated cytotoxic response. The mechanisms of cellular death triggered by PDT were evaluated, and the results revealed that apoptosis was the predominant process. These findings underscore the potential of ZnPc1 as a potent photosensitizer in PDT while also highlighting the differences between 2D and 3D culture models in evaluating PDT efficacy. While the 2D system enables simplified cytotoxicity evaluation, the 3D spheroid model better replicates physiologically relevant environment and treatment resistance. This comparison underscores necessity of integrating 3D models in PDT studies for more predictive in vivo insights.

The EGFR pathway is activated by ligand binding, and EGFR overexpression is linked to malignancies like colorectal and head and neck cancer. This pathway is targeted by monoclonal antibodies such as Cetuximab; however, drug resistance can arise, frequently because of EGFR gene alterations like mutation, particularly in domain III, which inhibits Cetuximab binding. EGFR and MEGFR (R497K mutated EGFR) plasmids were transfected into Chinese hamster ovary (CHO) cells, which do not express EGFR. Real-time PCR was performed using probes that were specifically developed for the R497K mutation. Furthermore, Cetuximab binding to EGFR and MEGFR was examined using molecular modeling. According to molecular modeling, the R497K mutation modifies the domain III structure, which lowers the binding affinity of Cetuximab. Curiously, Cetuximab also showed binding to MEGFR’s domain IV. Real-time PCR showed that the probes specifically identified MEGFR in transfected CHO cells. The R497K mutation may result in treatment resistance by decreasing Cetuximab binding or increasing competitive ligand binding. Therefore, for individualized treatment, it is essential to find EGFR mutations in patient tumor samples. The R497K mutation may be successfully detected by the designed oligonucleotide probes, allowing for the early identification of potential resistance and directing the development of suitable treatment strategies.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine associated with TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), which play important roles in several inflammatory diseases. There is a growing interest in developing alternative molecules that can be used as TNF blockers. In this study, we focused on TNF-α-, TNFR1-, and TNFR2-mimicking peptides to inhibit TNF-α receptor binding in various ways. Six peptides (OB1, OB2, OB5, OB6, OB7, and OB8) were developed to bind TNFR1, TNFR2, and TNF-α. OB1 and OB2 bound to TNF-α with lower Kd values of 300 and 46.7 nM, respectively, compared to previously published sequences. These synthetic peptides directly and indirectly inhibited TNF-α in vitro without cytotoxicity to L929 cells, and OB1 significantly inhibited apoptosis in the presence of hTNF-α. Peptides developed in this study may prove to be useful for therapeutic inhibition of TNF-α.

Background/Objectives: The stress testing of biotherapeutic products is a critical component of drug development, enabling the assessment of stability, biosimilarity, and degradation pathways. Subjecting biosimilar monoclonal antibodies to controlled stress conditions yields essential insights into their structural and functional integrity, informing formulation optimization and mitigating risks before clinical trials. In this study, biosimilar products were comprehensively characterized and compared with originator products under forced degradation. The aim was to expose the products to different stress conditions such as oxidative, pH, thermal, freeze/thaw, and agitation. The products were then tested at defined time points using validated analytical methods. Methods: This study employed size-exclusion chromatography to detect aggregated forms. Isoelectric focusing characterized protein charge variants (e.g., acidic/basic isoforms) from post-translational modifications, while capillary electrophoresis quantified product-related impurities (aggregates and fragments). In addition, a complement assay was used to determine the efficacy and potency under specific stress conditions. Results: Our findings showed that biosimilar and originator products exhibited similar degradation profiles. The biosimilar monoclonal antibody was found to be analytically similar to the originator product in terms of critical parameters related to efficacy and safety under various stress conditions such as aggregation profile, biological activity, and charge variant distribution. Conclusions: Forced degradation studies facilitated the comprehensive and well-validated characterization of the structure and biological activity of biosimilar monoclonal antibody products.

Introduction: Focused Assessment with Sonography for Trauma (FAST) has attracted attention for its use in the detection of intra-abdominal pathology for pediatric patients. However, computed tomography (CT) remains the gold standard for the assessment of blunt torso trauma. The study examines the effectiveness of FAST both in the detection of intra-abdominal pathology in pediatric patients (<19 years) with blunt torso trauma and in the determination of the need for CT for further examination. Methods: The study was designed as a retrospective observational investigation of diagnostic value. The pediatric patients who were admitted to the Emergency Department with blunt torso trauma between January 2013 and October 2016 were included in the study. The sample of the study comprised 255 patients who met the inclusion criteria. The primary outcome was the effectiveness of FAST in the detection of intra-abdominal pathology and the determination of the need for CT. The secondary outcome was to identify the agreement between CT and FAST for intra-abdominal injuries. The Chi-square test and Fisher's exact test were used for comparisons. A logistic regression model was developed to determine the variables that independently affect the agreement between FAST and CT. Results: FAST was determined to have low sensitivity (20.3%) despite its high specificity (87%). However; FAST had a good negative likelihood ratio. There was a poor agreement between CT and FAST in terms of the presence of both intra-abdominal and intrathoracic injuries in pediatric patients with blunt trunk trauma. The error rate of FAST increased by five-fold, especially in the presence of concomitant thorax trauma. However, FAST had a good negative likelihood ratio. Conclusion: FAST should not be regarded as an equivalent tool to CT for pediatric patients with blunt torso trauma. It is, instead, a noteworthy complementary tool that is a negative predictor.

Polymer coatings as thin films stand out as a commonly used strategy to modify biosensor surfaces for improving detection performance; however, nonspecific biomolecule interactions and the limited degree of ligand conjugation on the surface have necessitated the development of innovative methods for surface modification. To this end, methacrylated tethered telechelic polyethylene glycol (PEG-diMA) chains of three different molecular weights (2, 6, and 10 kDa) were synthesized herein and used for obtaining thiolated nanoparticles (NPs) upon adding excess amounts of a tetra-thiol crosslinker. Characterized according to their size, surface charge, morphology, and thiol amounts, these nanoparticles were immobilized on gold surfaces that mimicked gold-coated mass sensor platforms. The PEG-based nanoparticles, prepared especially by PEG6K-diMA polymers, were shown to result in the preparation of a monolayer and smooth coating of 80–120 nm thickness. Cysteine-modified NTS(8–13) peptide (RRPYIL) was conjugated to thiolated NP with reversible disulfide bonds and it was demonstrated that its cleavage with a reducing agent such as dithiothreitol (DTT) restores the NP-immobilized gold surface for at least two cycles. Together with its binding studies to NTSR2 antibodies, it was revealed that the peptide-conjugated NP-modified gold surface could be employed as a model for a reusable sensor surface for the detection of biomarkers of same or different types.