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Abstract Background Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine protease which is essential for the desquamation of corneocytes and thus plays a pivotal role in maintaining skin homeostasis. In cancer, KLK7 overexpression was suggested to represent a route for metastasis through cleavage of cell junction and extracellular matrix proteins of cancer cells. Methods To comprehensively determine KLK7 protein expression in normal and neoplastic tissues, a tissue microarray containing 13,447 samples from 147 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results KLK7 positivity was found in 64 of 147 tumor categories, including 17 tumor categories with at least one strongly positive case. The highest rate of KLK7 positivity was found in squamous cell carcinomas from various sites of origin (positive in 18.1%-63.8%), ovarian and endometrium cancers (4.8%-56.2%), salivary gland tumors (4.8%-13.7%), bilio-pancreatic adenocarcinomas (20.0%-40.4%), and adenocarcinomas of the upper gastrointestinal tract (3.3%-12.5%). KLK7 positivity was linked to nodal metastasis (p = 0.0005), blood vessel infiltration (p = 0.0037), and lymph vessel infiltration (p

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum-sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use, whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic cross-linking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers—such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL), or the cell-free supernatants of planktonic or the flow-cell biofilm effluent of wild P. aeruginosa (PAO1)—the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and −80 °C and were ready for on-the-spot sensing without the need for recovery. The proof-of-concept, optical fiber-based, and whole-cell biosensor developed here demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules.

Similar to bulk metal forming, clinch joining is characterised by large plastic deformations and a variety of different 3D stress states, including severe compression. However, inherent to plastic forming is the nucleation and growth of defects, whose detrimental effects on the material behaviour can be described by continuum damage models and eventually lead to material failure. As the damage evolution strongly depends on the stress state, a stress-state-dependent model is utilised to correctly track the accumulation. To formulate and parameterise this model, besides classical experiments, so-called modified punch tests are also integrated herein to enhance the calibration of the failure model by capturing a larger range of stress states and metal-forming-specific loading conditions. Moreover, when highly ductile materials are considered, such as the dual-phase steel HCT590X and the aluminium alloy EN AW-6014 T4 investigated here, strong necking and localisation might occur prior to fracture. This can alter the stress state and affect the actual strain at failure. This influence is captured by coupling plasticity and damage to incorporate the damage-induced softening effect. Its relative importance is shown by conducting inverse parameter identifications to determine damage and failure parameters for both mentioned ductile metals based on up to 12 different experiments.

Stimulator of interferon genes protein (STING) activates the immune response in inflammatory cells. STING expression in cancer cells is less well characterized, but STING agonists are currently being evaluated as anticancer drugs. A tissue microarray containing 18,001 samples from 139 different tumor types was analyzed for STING by immunohistochemistry. STING-positive tumor cells were found in 130 (93.5%) of 139 tumor entities. The highest STING positivity rates occurred in squamous cell carcinomas (up to 96%); malignant mesothelioma (88.5%–95.7%); adenocarcinoma of the pancreas (94.9%), lung (90.3%), cervix (90.0%), colorectum (75.2%), and gallbladder (68.8%); and serous high-grade ovarian cancer (86.0%). High STING expression was linked to adverse phenotypes in breast cancer, clear cell renal cell carcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and papillary carcinoma of the thyroid (p < 0.05). In pTa urothelial carcinomas, STING expression was associated with low-grade carcinoma (p = 0.0002). Across all tumors, STING expression paralleled PD-L1 positivity of tumor and inflammatory cells (p < 0.0001 each) but was unrelated to the density of CD8+ lymphocytes. STING expression is variable across tumor types and may be related to aggressive tumor phenotype and PD-L1 positivity. The lack of relationship with tumor-infiltrating CD8+ lymphocytes argues against a significant IFN production by STING positive tumor cells.

EpCAM is expressed in many epithelial tumors and is used for the distinction of malignant mesotheliomas from adenocarcinomas and as a surrogate pan-epithelial marker. A tissue microarray containing 14,832 samples from 120 different tumor categories was analyzed by immunohistochemistry. EpCAM staining was compared with TROP2 and CKpan. EpCAM staining was detectable in 99 tumor categories. Among 78 epithelial tumor types, the EpCAM positivity rate was ≥90% in 60 categories—including adenocarcinomas, neuroendocrine neoplasms, and germ cell tumors. EpCAM staining was the lowest in hepatocellular carcinomas, adrenocortical tumors, renal cell neoplasms, and in poorly differentiated carcinomas. A comparison of EpCAM and CKpan staining identified a high concordance but EpCAM was higher in testicular seminomas and neuroendocrine neoplasms and CKpan in hepatocellular carcinomas, mesotheliomas, and poorly differentiated non-neuroendocrine tumors. A comparison of EpCAM and TROP2 revealed a higher rate of TROP2 positivity in squamous cell carcinomas and lower rates in many gastrointestinal adenocarcinomas, testicular germ cell tumors, neuroendocrine neoplasms, and renal cell tumors. These data confirm EpCAM as a surrogate epithelial marker for adenocarcinomas and its diagnostic utility for the distinction of malignant mesotheliomas. In comparison to CKpan and TROP2 antibodies, EpCAM staining is particularly common in seminomas and in neuroendocrine neoplasms.

BackgroundLifestyle-related diseases caused by inadequate diet and physical activity cause premature death, loss of healthy life years, and increased health care costs. Randomized controlled trial (RCT) studies indicate that preventive digital health interventions (P-DHIs) can be effective in preventing these health problems, but the results of these studies are mixed. Adoption studies have identified multiple factors related to individuals and the context in which they live that complicate the transfer of positive results from RCT studies to practical use. Implementation studies have revealed barriers to the large-scale implementation of mobile health (mHealth) solutions in general. Consequently, there is no clear path to delivering predictable outcomes from P-DHIs and achieving effectiveness when scaling up interventions to reduce health problems in society. ObjectiveThis research aimed to expand our understanding of how to increase the outcome predictability of P-DHIs by focusing on physical activity and diet behaviors and amplify our understanding of how to improve effectiveness in large-scale implementations. MethodsThe research objective was pursued through a multidisciplinary scoping review. This scoping review used the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) as a guide. A comprehensive search of Web of Science and PubMed limited to English-language journal articles published before January 2022 was conducted. Google Scholar was used for hand searches. Information systems theory was used to identify key constructs influencing outcomes of IT in general. Public health and mHealth literature were used to identify factors influencing the adoption of, outcomes from, and implementation of P-DHIs. Finally, the P-DHI investment model was developed based on information systems constructs and factors from the public health and mHealth literature. ResultsIn total, 203 articles met the eligibility criteria. The included studies used a variety of methodologies, including literature reviews, interviews, surveys, and RCT studies. The P-DHI investment model suggests which constructs and related factors should be emphasized to increase the predictability of P-DHI outcomes and improve the effectiveness of large-scale implementations. ConclusionsThe research suggests that outcome predictability could be improved by including descriptions of the constructs and factors in the P-DHI investment model when reporting from empirical studies. Doing so would increase our understanding of when and why P-DHIs succeed or fail. The effectiveness of large-scale implementations may be improved by using the P-DHI investment model to evaluate potential difficulties and possibilities in implementing P-DHIs to create better environments for their use before investing in them and when designing and implementing them. The cost-effectiveness of large-scale implementations is unknown; implementations are far more complicated than just downloading and using apps, and there is uncertainty accompanying implementations given the lack of coordinated control over the constructs and factors that influence the outcome.

Organizational ambidexterity describes firms' ability to pursue exploration and exploitation strategies simultaneously. It is, however, unclear if young SMEs should seek to develop organizations with this ability or if they are better off focusing on just one strategy. To shed light on this matter, this paper investigates the interaction between entrepreneurial orientation (EO) (organic organizing) and process improvement (mechanistic organizing) in relation to firm growth in young SMEs (small and medium-sized enterprises). We hypothesize that both types of strategies can produce growth for young SMEs but that, due to their incompatibility, young SMEs do not have the resources needed to successfully pursue them both. We test these hypotheses on a sample of 257 young Danish SMEs. Our results confirm that both EO and process improvement have a positive effect on firm growth. The results further show that while process improvement has a considerable positive effect in low EO firms, for high EO firms, this effect is minimal. Thus, high EO firms may waste important resources by putting too much effort into process improvement initiatives. [ABSTRACT FROM AUTHOR]

Similar to bulk metal forming, clinch joining is characterised by large plastic deformations and a variety of different 3D stress states, including severe compression. However, inherent to plastic forming is the nucleation and growth of defects, whose detrimental effects on the material behaviour can be described by continuum damage models and eventually lead to material failure. As the damage evolution strongly depends on the stress state, a stress-state-dependent model is utilised to correctly track the accumulation. To formulate and parameterise this model, besides classical experiments, so-called modified punch tests are also integrated herein to enhance the calibration of the failure model by capturing a larger range of stress states and metal-forming-specific loading conditions. Moreover, when highly ductile materials are considered, such as the dual-phase steel HCT590X and the aluminium alloy EN AW-6014 T4 investigated here, strong necking and localisation might occur prior to fracture. This can alter the stress state and affect the actual strain at failure. This influence is captured by coupling plasticity and damage to incorporate the damage-induced softening effect. Its relative importance is shown by conducting inverse parameter identifications to determine damage and failure parameters for both mentioned ductile metals based on up to 12 different experiments. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum-sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use, whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic cross-linking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers—such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL), or the cell-free supernatants of planktonic or the flow-cell biofilm effluent of wild P. aeruginosa (PAO1)—the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and −80 °C and were ready for on-the-spot sensing without the need for recovery. The proof-of-concept, optical fiber-based, and whole-cell biosensor developed here demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules. [ABSTRACT FROM AUTHOR]

Satellites enable the provision of global 5G coverage utilizing a customized protocol stack for direct access of 5G devices. This paper reports the results of a field trial based on an Open Source Software (OSS) 5G protocol stack modified for Satellite Communications. 5G New Radio (NR) functions have been adapted to support 3GPP Non-Terrestrial Networks (NTN) standardization for Release 17. Some of the currently discussed enhancements for 5G New Radio (NR) direct access for NTNs were evaluated in this study utilizing a geosynchronous satellite system. Non-Terrestrial Networks (NTN) devices and base station were software-defined solutions communicating via satellite through a standardized 5G NR waveform. The results show that Open Source Software (OSS) implementations running on general purpose platforms greatly support the research and standardization process for 5G-Beyond NTNs. New functions related to NTNs can be evaluated at an early stage over channel emulators or real world satellites to highlight the capabilities of space based 5G-Beyond networks. Therefore, OSS can be a starting point to turn the vision of 6G protocols on-board the satellite into reality.