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The steep decline in the price of wind turbines and solar photovoltaics provides a possibility to decarbonize electricity deeply and affordably. This study uses the HOMER Pro energy modeling tool to model an optimized grid-connected renewable energy system for a community in southern Alberta, Canada. The study’s goal is to identify the best renewable energy technology combinations that can provide electricity at the lowest levelized cost of energy (LCOE) and has lower greenhouse gas emissions as compared to the electricity produced by traditional fossil fuel. Gleichen is a small town in southern Alberta that is close to numerous commercial wind and solar projects given the region’s high quality renewable resources. “Tri-brid” systems consisting of wind turbines, solar photovoltaics, and battery energy storage systems (BESS) are considered and compared based on electricity prices, net present cost, and greenhouse gas emissions savings. This tri-brid system is connected to the grid to sell excess generated electricity or buy electricity when there is less or no availability of solar and wind energy. The tri-brid energy system has an estimated LCOE of 0.0705 CAD/kWh, which is competitive with the price of electricity generated by natural gas and coal, which is 0.127 CAD/kWh.

The characteristics of powders on a bulk scale are heavily influenced by both the material properties and the size of their primary particles. Throughout the stages of storage and transportation in the powder processing industry, various forms of deformation and stress, such as pressure and shear, impact these materials. Recognizing the point at which a powder undergoes yielding becomes particularly significant in numerous applications. There are also times when the level of stress needed to maintain it must be understood. The measurement of powder yield and flow properties remains a challenge and is addressed in this study. As part of the European collaborative project, a number of shear experiments were performed using two shearing devices: the Schulze ring shearing device and the Anton Paar Powder Cell (APCC). These experiments have three purposes: (i) test reproducibility/consistency between two shear devices and test protocols; (ii) relate bulk behavior to microscopic particle properties, focusing on bulk density and thus the effect of cohesion between particles; and (iii) investigate the influence of the temperature of heated powders on the powder’s flow properties, which is important for industrial reactors. Interestingly, for samples with small particle sizes, bulk cohesion increases slightly, but bulk friction increases significantly because of particle interaction effects. The experimental data not only provide useful insight into the role of microscopically attractive van der Waals gravitational and/or compressive forces on the macroscopic flow behavior of bulk powders but also have industrial relevance. We also provide robust data of cohesive and attritional fine powder for silo design used for calibration and validation of silos, models, and computer simulations.

Patient-reported outcomes (PROs) offer a diverse array of potential applications within medical research and clinical practice. In comparative research, they can serve as tools for delineating the trajectories of health-related quality of life (HRQoL) across various cancer types. We undertook a secondary data analysis of a cohort of 1498 hospitalized cancer patients from 13 German cancer centers. We assessed the Physical and Mental Component Scores (PCS and MCS) of the 12-Item Short-Form Health Survey at baseline (t0), 6 (t1), and 12 months (t2), using multivariable generalized linear regression models. At baseline, the mean PCS and MCS values for all cancer patients were 37.1 and 44.3 points, respectively. We observed a significant improvement in PCS at t2 and in MCS at t1. The most substantial and significant improvements were noted among patients with gynecological cancers. We found a number of significant differences between cancer types at baseline, t1, and t2, with skin cancer patients performing best across all time points and lung cancer patients performing the worst. MCS trajectories showed less pronounced changes and differences between cancer types. Comparative analyses of HRQoL scores across different cancer types may serve as a valuable tool for enhancing health literacy, both among the general public and among cancer patients themselves.

Objective: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. Methods: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. Results: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. Discussion: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals.

Wide-bandgap semiconductors have been envisioned for power electronics applications because of their ability to operate at higher temperatures and higher applied voltages without breakdown. However, the presence of defects may cause device failure, necessitating a comprehensive understanding of material defects. This review provides a fingerprint of known defects in three envisioned semiconductors for power electronics: 4H-SiC, GaN, and β-Ga2O3. Via a detailed discussion of defects—the origins of electrically active charge traps—through their activation energies and capture cross-sections, we provide important insights into defect parameter distributions. This review not only serves as a reference but also offers a strategic roadmap for distinguishing between similar defects. Such knowledge is key for the development of more robust and efficient power electronic devices that can fully exploit the potential of wide-bandgap semiconductors.

Background: Dilated cardiomyopathy (DCM) involves myocardial remodeling, characterized by significant fibrosis and extracellular matrix expansion. These changes impair heart function, increasing the risk of heart failure and sudden cardiac death. This study investigates the prognostic value of circulating fibrosis biomarkers as a less invasive method in DCM patients. Methods: Plasma samples from 185 patients with confirmed DCM were analyzed to measure 13 circulating biomarkers using Luminex bead-based multiplex assays and ELISA. The prognostic value of these biomarkers was evaluated concerning heart failure-associated events and all-cause mortality. Results: Elevated MMP-2 levels (>1519.3 ng/mL) were linked to older age, higher diabetes prevalence, lower HDL, increased NT-proBNP and hs-TnT levels, and severe systolic dysfunction. High TIMP-1 levels (>124.9 ng/mL) correlated with elevated NT-proBNP, more atrial fibrillation, reduced exercise capacity, and larger right ventricles. Increased GDF-15 levels (>1213.9 ng/mL) were associated with older age, systemic inflammation, renal impairment, and poor exercise performance. Elevated OPN levels (>81.7 ng/mL) were linked to higher serum creatinine and NT-proBNP levels. Over a median follow-up of 32.4 months, higher levels of these biomarkers predicted worse outcomes, including increased risks of heart failure-related events and mortality. Conclusions: Circulating fibrosis biomarkers, particularly MMP-2, TIMP-1, GDF-15, and OPN, are valuable prognostic tools in DCM. They reflect the severity of myocardial remodeling and systemic disease burden, aiding in risk stratification and therapeutic intervention. Integrating these biomarkers into clinical practice could improve DCM management and patient prognosis.

This paper examines the integration of interactive 3D applications into the teaching process in mechanical engineering education. An innovative interactive 3D application has been developed as a teaching aid for engineering students. The main advantage is its easy availability through a web browser on mobile devices or desktop computers. It includes four explorable 3D gearbox models with assembly animations, linked technical information, and immersive virtual and augmented reality (AR) experiences. The benefits of using this application in the teaching process were monitored on a group of students at the end of the semester. Assessments conducted before and after the use of the interactive 3D application measured learning outcomes. Qualitative feedback from students was also collected. The results demonstrated significant improvements in engagement, spatial awareness, and understanding of gearbox principles compared to traditional methods. The versatility and accessibility of the application also facilitated self-directed learning, reducing the need for external resources. These findings indicate that interactive 3D tools have the potential to enhance student learning and engagement and to promote sustainable practices in engineering education. Future research could explore the scalability and applicability of these tools across different engineering disciplines and educational contexts.

This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.

Background: In this study focusing on colorectal carcinoma (CRC), we address the imperative task of predicting post-surgery treatment needs by identifying crucial tumor features within whole slide images of solid tumors, analogous to locating a needle in a histological haystack. We evaluate two approaches to address this challenge using a small CRC dataset. Methods: First, we explore a conventional tile-level training approach, testing various data augmentation methods to mitigate the memorization effect in a noisy label setting. Second, we examine a multi-instance learning (MIL) approach at the case level, adapting data augmentation techniques to prevent over-fitting in the limited data set context. Results: The tile-level approach proves ineffective due to the limited number of informative image tiles per case. Conversely, the MIL approach demonstrates success for the small dataset when coupled with post-feature vector creation data augmentation techniques. In this setting, the MIL model accurately predicts nodal status corresponding to expert-based budding scores for these cases. Conclusions: This study incorporates data augmentation techniques into a MIL approach, highlighting the effectiveness of the MIL method in detecting predictive factors such as tumor budding, despite the constraints of a limited dataset size.

Numerous intervention strategies have been developed to promote functional tissue repair following experimental spinal cord injury (SCI), including the bridging of lesion-induced cystic cavities with bioengineered scaffolds. Integration between such implanted scaffolds and the lesioned host spinal cord is critical for supporting regenerative growth, but only moderate-to-low degrees of success have been reported. Light and electron microscopy were employed to better characterise the fibroadhesive scarring process taking place after implantation of a longitudinally microstructured type-I collagen scaffold into unilateral mid-cervical resection injuries of the adult rat spinal cord. At long survival times (10 weeks post-surgery), sheets of tightly packed cells (of uniform morphology) could be seen lining the inner surface of the repaired dura mater of lesion-only control animals, as well as forming a barrier along the implant–host interface of the scaffold-implanted animals. The highly uniform ultrastructural features of these scarring cells and their anatomical continuity with the local, reactive spinal nerve roots strongly suggest their identity to be perineurial-like cells. This novel aspect of the cellular composition of reactive spinal cord tissue highlights the increasingly complex nature of fibroadhesive scarring involved in traumatic injury, and particularly in response to the implantation of bioengineered collagen scaffolds.

Pedestrian counting has attracted much interest of the academic and industry communities for its widespread application in many real-world scenarios. While many recent studies have focused on computer vision-based solutions for the problem, the deployment of cameras brings up concerns about privacy invasion. This paper proposes a novel indoor pedestrian counting approach, based on footstep-induced structural vibration signals with piezoelectric sensors. The approach is privacy-protecting because no audio or video data is acquired. Our approach analyzes the space-differential features from the vibration signals caused by pedestrian footsteps and outputs the number of pedestrians. The proposed approach supports multiple pedestrians walking together with signal mixture. Moreover, it makes no requirement about the number of groups of walking people in the detection area. The experimental results show that the averaged F1-score of our approach is over 0.98, which is better than the vibration signal-based state-of-the-art methods.

Extracellular vesicles (EVs), including small EVs (sEVs), are involved in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Yet, increased neuroinflammation can also be detected in the aging brain, and it is associated with increased glial activation. Changes in EV concentration are reported in aging tissues and senescence cells, suggesting a role of EVs in the process of aging. Here, we investigated the effect of peripheral sEVs from aged animals on neuroinflammation, specifically on glial activation. sEVs were isolated from the peripheral blood of young (3 months) and aged (24 months) C57BL/6J wildtype mice and injected into the peripheral blood from young animals via vein tail injections. The localization of EVs and the expression of selected genes involved in glial cell activation, including Gfap, Tgf-β, Cd68, and Iba1, were assessed in brain tissue 30 min, 4 h, and 24 h after injection. We found that sEVs from peripheral blood of aged mice but not from young mice altered gene expression in the brains of young animals. In particular, the expression of the specific astrocyte marker, Gfap, was significantly increased, indicating a strong response of this glial cell type. Our study shows that sEVs from aged mice can pass the blood-brain barrier (BBB) and induce glial cell activation.

The main objective of this study is to test the effect of thermal aquatic exercise on motor symptoms and quality of life in people with Parkinson’s Disease (PD). Fourteen participants with diagnosis of idiopathic PD completed the whole rehabilitation session and evaluation protocol (Hoehn and Yahr in OFF state: 2–3; Mini Mental State Examination >24; stable pharmacological treatment in the 3 months prior participating in the study). Cognitive and motor status, functional abilities and quality of life were assessed at baseline and after an intensive rehabilitation program in thermal water (12 sessions of 45 min in a 1.4 m depth pool at 32–36 ∘C). The Mini Balance Evaluation System Test (Mini-BESTest) and the PD Quality of Life Questionnaire (PDQ-39) were considered as main outcomes. Secondary assessment measures evaluated motor symptoms and quality of life and psychological well-being. Participants kept good cognitive and functional status after treatment. Balance of all the participants significantly improved (Mini-BESTest: p<0.01). The PDQ-39 significantly improved after rehabilitation (p=0.038), with significance being driven by dimensions strongly related to motor status. Thermal aquatic exercise may represent a promising rehabilitation tool to prevent the impact of motor symptoms on daily-life activities of people with PD. PDQ-39 improvement foreshows good effects of the intervention on quality of life and psychological well-being.

Organic field-effect transistors have been envisioned for advanced photodetectors because the organic semiconductors provide unique absorption characteristics, low-cost fabrication, or compatibility with flexible substrates. However, the response time of organic phototransistors still does not reach the required application level. Here, we report the photoresponse of copper phthalocyanine phototransistor in a steady state and under pulsed illumination. The detailed analysis based on the random walk among a field of traps was used to evaluate the dimensionality of electron transport in a device.

Background: Presynaptic forms of congenital myasthenic syndromes (CMS) due to pathogenic variants in SLC18A3 impairing the synthesis and recycling of acetylcholine (ACh) have recently been described. SLC18A3 encodes the vesicular ACh transporter (VAChT), modulating the active transport of ACh at the neuromuscular junction, and homozygous loss of VAChT leads to lethality. Methods: Exome sequencing (ES) was carried out to identify the molecular genetic cause of the disease in a 5-year-old male patient and histological, immunofluorescence as well as electron- and CARS-microscopic studies were performed to delineate the muscle pathology, which has so far only been studied in VAChT-deficient animal models. Results: ES unraveled compound heterozygous missense and nonsense variants (c.315G>A, p.Trp105* and c.1192G>C, p.Asp398His) in SLC18A3. Comparison with already-published cases suggests a more severe phenotype including impaired motor and cognitive development, possibly related to a more severe effect of the nonsense variant. Therapy with pyridostigmine was only partially effective while 3,4 diaminopyridine showed no effect. Microscopic investigation of the muscle biopsy revealed reduced fibre size and a significant accumulation of lipid droplets. Conclusions: We suggest that nonsense variants have a more detrimental impact on the clinical manifestation of SLC18A3-associated CMS. The impact of pathogenic SLC18A3 variants on muscle fibre integrity beyond the effect of denervation is suggested by the build-up of lipid aggregates. This in turn implicates the importance of proper VAChT-mediated synthesis and recycling of ACh for lipid homeostasis in muscle cells. This hypothesis is further supported by the pathological observations obtained in previously published VAChT-animal models.

Background: Approximately 71 million people are still in need of direct-acting antiviral agents (DAAs). To achieve the World Health Organization Hepatitis C elimination goals, insight into the prevalence and influence of resistance associated substitutions (RAS) is of importance. Collaboration is key since DAA failure is rare and real-life data are scattered. We have established a European collaboration, HepCare, to perform in-depth analysis regarding RAS prevalence, patterns, and multiclass occurrence. Methods: Data were extracted from the HepCare cohort of patients who previously failed DAA therapy. Geno—and subtypes were provided by submitters and mostly based on in-house assays. They were reassessed using the Comet HCV subtyping tool. We considered RAS to be relevant if they were associated with DAA failure in vivo previously reported in literature. Results: We analyzed 938 patients who failed DAA therapy from ten different European countries. There were 239 genotypes (GT) 1a, 380 GT1b, 19 GT2c, 205 GT3a, 14 GT4a, and 68 GT4d infections. Several unusual subtypes (n = 15) (GT1b/g/l, GT3b, GT4k/n/r/t) were present. RAS appeared in over 80% of failures and over a quarter had three or more RAS. Multiclass RAS varied over target region and genotype between 0–48%. RAS patterns such as the Q30R + L31M and Q30R + Y93H in GT1a, the L31V + Y93H and L31V + Y93H for GT1b, and A30K + L31M and A30K/V + Y93H for GT3a all occurred with a prevalence below 5%. Conclusion: RAS occur frequently after DAA failures and follow a specific genotype and drug related pattern. Interpretation of the influence of RAS on retreatment is challenging due to various patterns, patients’ characteristics, and previous treatment history. Moving towards HCV elimination, an ongoing resistance surveillance is essential to track the presence of RAS, RAS patterns and gather data for a re-treatment algorithm.

A series of bithienyl-terminated surfactants with various alkyl chain lengths (from C8 to C13) and phosphono or chlorodimethylsilyl anchoring groups were synthesized by palladium-catalyzed hydrophosphonation, or platinum-catalyzed hydrosilylation as a key step. Surfactants were tested in pentacene or α-sexithiophene-based organic field-effect transistors (OFETs) for the modification of the dielectric surface. The studied surfactants increased the effective mobility of the α-sexithiophene-based device by up to one order of magnitude. The length of alkyl chain showed to be significant for the pentacene-based device, as the effective mobility only increased in the case of dielectric modification with bithienylundecylphosphonic acid. AFM allowed a better understanding of the morphology of semiconductors on bare SiO2 and surfaces treated with bithienylundecylphosphonic acid.

The 2-phenoxybenzamide 1 from the Medicines for Malaria Venture Malaria Box Project has shown promising multi-stage activity against different strains of P. falciparum. It was successfully synthesized via a retrosynthetic approach. Subsequently, twenty-one new derivatives were prepared and tested for their in vitro activity against blood stages of the NF54 strain of P. falciparum. Several insights into structure-activity relationships were revealed. The antiplasmodial activity and cytotoxicity of compounds strongly depended on the substitution pattern of the anilino partial structure as well as on the size of substituents. The diaryl ether partial structure had further impacts on the activity. Additionally, several physicochemical and pharmacokinetic parameters were calculated (log P, log D7.4 and ligand efficiency) or determined experimentally (passive permeability and CYP3A4 inhibition). The tert-butyl-4-{4-[2-(4-fluorophenoxy)-3-(trifluoromethyl)benzamido]phenyl}piperazine-1-carboxylate possesses high antiplasmodial activity against P. falciparum NF54 (PfNF54 IC50 = 0.2690 µM) and very low cytotoxicity (L-6 cells IC50 = 124.0 µM) resulting in an excellent selectivity index of 460. Compared to the lead structure 1 the antiplasmodial activity was improved as well as the physicochemical and some pharmacokinetic parameters.

UAV-based photogrammetry has many applications today. Measuring of snow depth using Structure-from-Motion (SfM) techniques is one of them. Determining the depth of snow is very important for a wide range of scientific research activities. In the alpine environment, this information is crucial, especially in the sphere of risk management (snow avalanches). The main aim of this study is to test the applicability of fixed-wing UAV with RTK technology in real alpine conditions to determine snow depth. The territory in West Tatras as a part of Tatra Mountains (Western Carpathians) in the northern part of Slovakia was analyzed. The study area covers more than 1.2 km2 with an elevation of almost 900 m and it is characterized by frequent occurrence of snow avalanches. It was found that the use of different filtering modes (at the level point cloud generation) had no distinct (statistically significant) effect on the result. On the other hand, the significant influence of vegetation characteristics was confirmed. Determination of snow depth based on seasonal digital surface model subtraction can be affected by the process of vegetation compression. The results also point on the importance of RTK methods when mapping areas where it is not possible to place ground control points.

Reactive infectious mucosal eruptions (RIME) following Chlamydia pneumoniae infection is a rare and poorly understood clinical presentation that can pose a diagnostic challenge. We report the case of a previously healthy 21-year old male with a cough, fever, numerous penile and mouth ulcers, and severe conjunctivitis. Several differential diagnoses, including Herpes simplex infection, were considered before Chlamydia pneumoniae was established as the causative agent. The patient’s condition improved following treatment with clarithromycin and prednisolone tablets, and he had almost fully recovered at follow-up 10 days after discharge.

Purpose: To compare the changes in visual and ocular parameters in individuals with retinal drusen who were treated with two commercially available nutritional supplements. Methods: An open-label, single-center, randomized, parallel-treatment with an observational control group design was utilized. The treatment groups included individuals with fine retinal drusen sub-clinical age-related macular degeneration (AMD), while the control group consisted of ocular normal individuals. The treatment groups were randomly assigned to the micronized lipid-based carotenoid supplement, Lumega-Z (LM), or the PreserVision Age-Related Eye Disease Study 2 (AREDS-2) soft gel (PV). Visual performance was evaluated using the techniques of visual acuity, dark adaptation recovery and contrast sensitivity, at baseline, three months, and six months. Additionally, the macular pigment optical density (MPOD) was measured. The control group was not assigned any carotenoid supplement. The right eye and left eye results were analyzed separately. Results: Seventy-nine participants were recruited for this study, of which 68 qualified and 56 participants had useable reliable data. Of the individuals who completed this study, 25 participants belonged to the LM group, 16 belonged to the PV group, and 15 to the control group. The LM group demonstrated statistically significant improvements in contrast sensitivity function (CSF) in both eyes at six months (p < 0.001). The LM group displayed a positive linear trend with treatment time in CSF (p < 0.001), with benefits visible after just three months of supplementation. Although there was a trend showing improvement in CSF in the PV group, the change was not significant after a Bonferroni-corrected p-value of p < 0.00625. Visual acuity, dark adaptation recovery and MPOD did not significantly improve in either treatment groups. Conclusion: The LM group demonstrated greater and faster benefits in visual performance as measured by CSF when compared to the PV group. This trial has been registered at clinicaltrials.gov (NCT03946085).

Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. Two cohorts of patients with PCa who underwent radical prostatectomy (n = 40, n = 56) and benign prostate hyperplasia (BPH) controls (n = 8, n = 11) were profiled for SMPDL3B expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC; n = 131, n = 29 controls) and The Cancer Genome Atlas (TCGA; n = 497, n = 53 controls)) served for validation. SMPDL3B’s impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of SMPDL3B was seen in PCa compared to BPH (p < 0.001 each). A lower expression of SMPDL3B was associated with a shorter overall survival (OS) (p = 0.005) in long term follow-up. A SMPDL3B overexpression in PCa tissue was confirmed in the validation cohorts (p < 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival (p = 0.011) and progression-free interval (p < 0.001) were shorter. Knockdown of SMPDL3B impaired PC3 cell migration but not proliferation (p = 0.0081). In summary, SMPLD3B is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.

While there are numerous papers on microplastics (mps) being published every week, there is a need for improvement for the field to mature. The papers reporting numbers found in water bodies cannot be compared because there are no standard methods for collection and analysis. It is clear that using nets for sampling misses most of the microfibers, which are the most abundant form when whole water samples are analyzed, and that microscopic identification has a very high error rate compared to chemical analytical equipment which can also identify the polymers. It is clear that most animals studied eat mps; we should learn what attracts the animals to the mps and what proportion pass right through and are defecated vs those that move into the tissues. It is considered that mps are a vector for transfer of toxic chemicals into the food chain. Let us investigate to what degree what proportion of contaminants are removed in the digestive system vs. staying bound tightly to the mps. Experimental studies should also use environmentally relevant doses and the shapes and sizes of mps that are most abundant in the environment.

The contemporary academic environment in Canada has undergone reorganization based on neoliberal principles, and has increased attention focused on the importance of supporting interdisciplinary initiatives to address complex problems affecting global society. The purpose of our study was to examine the experience of people participating in a specific university-funded interdisciplinary research initiative. As there is a strong emphasis within this program on reporting on the outcomes of the funding that supports interdisciplinary collaboration, our aim was to explore how participation may shape one’s intellectual quality of life (iQoL) and how one’s iQoL could be conceptualized and understood. Using a pragmatic constructivist case study, focus group and individual interviews were undertaken with 30 participants involved with university-funded interdisciplinary research teams. Findings illustrate that their iQoL was shaped by their capacity to engage in and achieve what they viewed as their core work and its outcomes. Related sub-themes addressed the social and relational climate, institutional environment and structure, and expectations and resources. We argue that further development of iQoL as a unique construct is required to adequately measure the full range of people’s experiences in academia, particularly when aiming to address ‘wicked’ social and global problems within a predominantly neoliberal context.

With water scarcity representing an increasing threat to humans, the environment and the economy, companies are interested in exploring how their operations and supply chains affect water resources globally. To allow for systematically compiling the water footprint at the company level, the organizational water footprint method based on ISO 14046 and ISO/TS 14072 was developed. This paper presents the first complete organizational water scarcity footprint case study carried out for Neoperl GmbH, a German company that offers innovative solutions regarding drinking water for the plumbing industry. The cradle-to-gate assessment for one year includes, besides facility-based production activities, purchased materials, electricity and fuels, and supporting activities, such as company vehicles and infrastructure. Neoperl’s total freshwater consumption amounts to approximately 110,000 m3, 96% thereof being attributable to the supply chain, with freshwater consumption through purchased metals playing the predominant role. Metals (mainly stainless steel and brass) are major hotspots, also when considering the water scarcity-related local impacts resulting from freshwater consumption, which mainly affect China and Chile. These results can be used to improve the company’s supply chain water use in cooperation with internal and external stakeholders by means of, e.g., sustainable purchase strategies or eco-design options to substitute water intensive materials.

Luminous Blue Variables are massive evolved stars, here we introduce this outstanding class of objects. Described are the specific characteristics, the evolutionary state and what they are connected to other phases and types of massive stars. Our current knowledge of LBVs is limited by the fact that in comparison to other stellar classes and phases only a few “true” LBVs are known. This results from the lack of a unique, fast and always reliable identification scheme for LBVs. It literally takes time to get a true classification of a LBV. In addition the short duration of the LBV phase makes it even harder to catch and identify a star as LBV. We summarize here what is known so far, give an overview of the LBV population and the list of LBV host galaxies. LBV are clearly an important and still not fully understood phase in the live of (very) massive stars, especially due to the large and time variable mass loss during the LBV phase. We like to emphasize again the problem how to clearly identify LBV and that there are more than just one type of LBVs: The giant eruption LBVs or η Car analogs and the S Dor cycle LBVs.

Modern, mainly sustainability-driven trends, such as low-temperature washing or bleach-free liquid detergents, facilitate microbial survival of the laundry processes. Favourable growth conditions like humidity, warmth and sufficient nutrients also contribute to microbial colonization of washing machines. Such colonization might lead to negatively perceived staining, corrosion of washing machine parts and surfaces, as well as machine and laundry malodour. In this study, we characterized the bacterial community of 13 domestic washing machines at four different sampling sites (detergent drawer, door seal, sump and fibres collected from the washing solution) using 16S rRNA gene pyrosequencing and statistically analysed associations with environmental and user-dependent factors. Across 50 investigated samples, the bacterial community turned out to be significantly site-dependent with the highest alpha diversity found inside the detergent drawer, followed by sump, textile fibres isolated from the washing solution, and door seal. Surprisingly, out of all other investigated factors only the monthly number of wash cycles at temperatures ≥ 60 °C showed a significant influence on the community structure. A higher number of hot wash cycles per month increased microbial diversity, especially inside the detergent drawer. Potential reasons and the hygienic relevance of this finding need to be assessed in future studies.

Patient care frequently focuses on physical aspects of disease management, with variable attention given to spiritual needs. And yet, patients indicate that spiritual suffering adds to distress associated with illness. Spirituality, broadly defined as that which gives meaning and purpose to a person’s life and connectedness to the significant or sacred, often becomes a central issue for patients. Growing evidence demonstrates that spirituality is important in patient care. Yet healthcare professionals (HCPs) do not always feel prepared to engage with patients about spiritual issues. In this project, HCPs attended an educational session focused on using the FICA Spiritual History Tool to integrate spirituality into patient care. Later, they incorporated the tool when caring for patients participating in the study. This research (1) explored the value of including spiritual history taking in clinical practice; (2) identified facilitators and barriers to incorporating spirituality into person-centred care; and (3) determined ways in which HCPs can effectively utilize spiritual history taking. Data were collected using focus groups and chart reviews. Findings indicate positive impacts at organizational, clinical/unit, professional/personal and patient levels when HCPs include spirituality in patient care. Recommendations are offered.

Silica core-shell nanoparticles of about 60–120 nm with a closed outer layer of bismuth or molybdenum oxide of 1–10 nm were synthesized by an integrated chemical vapor synthesis/chemical vapor deposition process at atmospheric pressure. Film growth rates and activation energies were derived from transmission electron microscopy (TEM) images for a deposition process based on molybdenum hexacarbonyl and triphenyl bismuth as respective coating precursors. Respective activation energies of 123 ± 10 and 155 ± 10 kJ/mol are in good agreement with the literature and support a deposition mechanism based on surface-induced removal of the precursor ligands. Clean substrate surfaces are thus prerequisite for conformal coatings. Integrated aerosol processes are solvent-free and intrinsically clean. In contrast, commercial silica substrate particles were found to suffer from organic residues which hinder shell formation, and require an additional calcination step to clean the surface prior to coating. Dual layer core-shell structures with molybdenum oxide on bismuth oxide were synthesized with two coating reactors in series and showed similar film growth rates.

The use of sensor technologies is standard practice in the domain of precision farming. The variety of vendor-specific sensor systems, control units and processing software has led to increasing efforts in establishing interoperable sensor networks and standardized sensor data infrastructures. This study utilizes open source software and adapts the standards of the Open Geospatial Consortium to introduce a method for the realization of a sensor data infrastructure for precision farming applications. The infrastructure covers the control of sensor systems, the access to sensor data, the transmission of sensor data to web services and the standardized storage of sensor data in a sensor web-enabled server. It permits end users and computer systems to access the sensor data in a well-defined way and to build applications on top of the sensor web services. The infrastructure is scalable to large scenarios, where a multitude of sensor systems and sensor web services are involved. A real-world field trial was set-up to prove the applicability of the infrastructure.

Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon-α and ribavirin (pegIFN/RBV) treatment of HCV genotypes 1 and 3 infections. We conducted a candidate gene association study in a prospective cohort of 201 chronic HCV-infected individuals undergoing treatment with pegIFN/RBV. Differences between groups were compared in logistic regression adjusted for age, HCV viral load and interleukin 28B genotypes. Four single nucleotide polymorphisms (SNPs) located in the B-cell lymphoma 2-like 1 (BCL2L1) gene were significantly associated with SVR. SVR rates were significantly higher for carriers of the beneficial rs1484994 CC genotypes. In multivariate logistic regression, the rs1484994 SNP combined CC + TC genotypes were associated with a 3.4 higher odds ratio (OR) in SVR for the HCV genotype 3 (p = 0.02). The effect estimate was similar for genotype 1, but the association did not reach statistical significance. In conclusion, anti-apoptotic SNPs in the BCL2L1 gene were predictive of SVR to pegIFN/RBV treatment in HCV genotypes 1 and 3 infected individuals. These SNPs may be used in prediction of SVR, but further studies are needed.

Behavioral development occurs together with the development of the nervous system. Studies on mammals indicate that exposures to some chemicals during embryonic development at concentrations that do not produce anatomical malformations may nevertheless produce behavioral deficits later in life, an example of delayed effects. There have been reports of delayed effects in aquatic organisms. Delayed behavioral effects of mercury, chlorinated and other pesticides, polycyclic aromatic hydrocarbons (PAHs), and some synthetic hormones in the environment have been reported in fishes and invertebrates; in some cases behavioral effects are manifested years after the exposure. Another type of delayed behavioral effect results from exposure of mature females before fertilization (maternal exposure). Even when embryos and larvae are reared in clean water, offspring may manifest abnormal behaviors following maternal exposure. The reported behavioral changes are generally deleterious and compromise the fitness of the animal in its natural environment. Delayed effects and their impacts on fitness are not considered in standard short-term embryo bioassays, which will therefore underestimate neurotoxicity. The literature in the field is scattered and has not been reviewed. The objective of this paper is to review and synthesize what is known about delayed behavioral effects in aquatic biota.

Biphenyl neolignans such as honokiol and magnolol, which are the major active constituents of the Asian medicinal plant Magnolia officinalis, are known to exert a multitude of pharmacological and biological activities. Among these, cytotoxic and tumor growth inhibitory activity against various tumour cell lines are well-documented. To further elucidate the cytotoxic effects of honokiol derivatives, derivatizations were performed using tetrahydrohonokiol as a scaffold. The derivatizations comprised the introduction of functional groups, e.g., nitro and amino groups, as well as alkylation. This way, 18 derivatives, of which 13 were previously undescribed compounds, were evaluated against CCRF-CEM leukemia cells, U251 glioblastoma and HCT-116 colon cancer cells. The results revealed no significant cytotoxic effects in any of the three tested cell lines at a test concentration of 10 µM.

The emission properties of three 4-azafluorenone and five new α-carboline fluorophores in both solution and thin solid films were investigated. Fluorescence of the azafluorenone is clearly enhanced in thin solid films due to the presence of phenyl/biphenyl rotors, and these derivatives can be classified as green Aggregation-Induced Emission luminogens (AIEgens) with a non-emissive heteroaromatic core structure. Compared to azafluorenones, emission of α-carbolines is hypsochromically shifted to the blue region of the electromagnetic spectrum, and most of these derivatives exhibit strong violet-blue fluorescence in both solution and thin solid film layers. Further, the effective mobility and electroluminescence of new α-carbolines were investigated in prepared organic field-effect transistors and organic light-emitting diodes, respectively.

The Hepatitis C virus causes chronic infections in humans, which can develop to liver cirrhosis and hepatocellular carcinoma. The Bovine viral diarrhea virus is used as a surrogate model for antiviral assays for the HCV. From marine invertebrates and microorganisms isolated from them, extracts were prepared for assessment of their possible antiviral activity. Of the 128 tested, 2 were considered active and 1 was considered promising. The best result was obtained from the extracts produced from the Bacillus sp. isolated from the sponge Petromica citrina. The extracts 555 (500 µg/mL, SI>18) and 584 (150 µg/mL, SI 27) showed a percentage of protection of 98% against BVDV, and the extract 616, 90% of protection. All of them showed activity during the viral adsorption. Thus, various substances are active on these studied organisms and may lead to the development of drugs which ensure an alternative therapy for the treatment of hepatitis C.

In this study, we evaluate hydrogels based on oxidized hyaluronic acid, cross-linked with adipic acid dihydrazide, for their suitability as bioinks for 3D bioprinting. Aldehyde containing hyaluronic acid (AHA) is synthesized and cross-linked via Schiff Base chemistry with bifunctional adipic acid dihydrazide (ADH) to form a mechanically stable hydrogel with good printability. Mechanical and rheological properties of the printed and casted hydrogels are tunable depending on the concentrations of AHA and ADH cross-linkers.

Danburite is a calcium borosilicate that forms within the transition zones of metacarbonates and pegmatites as a late magmatic accessory mineral. We present here trace element contents obtained by femtosecond laser ablation-inductively coupled plasma (ICP)-mass spectrometry for danburite from Mexico, Tanzania, and Vietnam. The Tanzanian and Vietnamese samples show high concentrations of rare earth elements (∑REEs 1900 µg∙g−1 and 1100 µg∙g−1, respectively), whereas Mexican samples are depleted in REEs (

Infectious diseases are a global health burden and remain associated with high social and economic impact. Treatment of affected patients largely relies on antimicrobial agents that act by directly targeting microbial replication. Despite the utility of host specific therapies having been assessed in previous clinical trials, such as targeting the immune response via modulating the cytokine release in sepsis, results have largely been frustrating and did not lead to the introduction of new therapeutic tools. In this article, we will discuss current evidence arguing that, by applying the concept of hormesis, already approved pharmacological agents could be used therapeutically to increase survival of patients with infectious disease via improving disease tolerance, a defense mechanism that decreases the extent of infection-associated tissue damage without directly targeting pathogenic microorganisms.

The authors wish to add the following Acknowledgments and completed Table 1 to their paper published in Viruses [1], doi:10.3390/v5051219, website: http://www.mdpi.com/1999-4915/5/5/1219.

Microplastics have become a topic of considerable concern and intensive study over the past decade. They have been found everywhere in the oceans, including the deepest trenches and remotest parts of the Arctic. They are ingested by many animals and some are incorporated into tissues. There is considerable effort in studying what effects they have on marine life. It has become clear that when water samples are collected in ways that prevent most long thin particles from escaping through pores of a net, the most abundant type of microplastics found in water and sediments are microfibers (fibers with dimensions less than 5 mm). The major source of these pollutants is synthetic textiles, such as polyester or polyamides, which shed microfibers during their entire life cycle. Microfibers are released during textile manufacturing, everyday activities (e.g., washing, drying, wearing) and final disposal. The complexity of microfiber release mechanisms and of the factors involved make the identification and application of ways to reduce the inputs of microfibers very challenging. A comprehensive approach is strongly needed, taking into account solutions at a number of levels, such as re-engineering textiles to minimize shedding, applying washing machine filters, developing advanced wastewater treatment plants and improving the management of textile wastes. To harmonize and make mandatory the solutions identified, a variety of potential government policies and regulations is also needed.

Plastics, including microplastics, have generally been regarded as harmful to organisms because of their physical characteristics. There has recently been a call to understand and regard them as persistent, bioaccumulative, and toxic. This review elaborates on the reasons that microplastics in particular should be considered as “toxic pollutants”. This view is supported by research demonstrating that they contain toxic chemicals within their structure and also adsorb additional chemicals, including polychlorinated biphenyls (PCBs), pesticides, metals, and polycyclic aromatic hydrocarbons (PAHs), from the environment. Furthermore, these chemicals can be released into tissues of animals that consume microplastics and can be responsible for the harmful effects observed on biological processes such as development, physiology, gene expression, and behavior. Leachates, weathering, and biofilm play important roles in the interactions between microplastics and biota. Global policy efforts by the United Nations Environmental Assembly via the international legally binding treaty to address global plastic pollution should consider the designation of harmful plastics (e.g., microplastics) with associated hazardous chemicals as toxic pollutants.

Background: Sports-related concussion is a relevant risk of contact sports, with several million cases per year worldwide. Prompt identification is crucial to prevent complications and late effects but may be impeded by an overlap with dehydration-associated impairment of cognitive function. Researchers have extensively studied the effects of pronounced dehydration in endurance sports, especially in the heat. However, little is known about the effects of isolated and mild dehydration. Methods: Healthy recreational athletes underwent a standardized fluid deprivation test. Hypohydration was assessed by bioelectrical impedance analysis (BIA) and laboratory testing of electrolytes and retention parameters. Participants underwent cardiopulmonary exercise testing (CPET) with a cycle ramp protocol. Each participant served as their own control undergoing CPET in a hypohydrated [HYH] and a euhydrated [EUH] state. Effects were assessed using a shortened version of Sport Concussion Assessment Tool 3 (SCAT3). Results: Fluid deprivation caused a mild (2%) reduction in body water, resulting in a calculated body mass loss of 0.8% without alterations of electrolytes, serum-osmolality, or hematocrit. Athletes reported significantly more (1.8 ± 2.2 vs. 0.4 ± 0.7; p < 0.01) and more severe (4.4 ± 6.2 vs. 1.0 ± 1.9; p < 0.01) concussion-like symptoms in a hypohydrated state. Balance was worse in HYH by trend with a significant difference for tandem stance (1.1 ± 1.3 vs. 0.6 ± 1.1; p = 0.02). No relevant differences were presented for items of memory and concentration. Conclusions: Mild dehydration caused relevant alterations of concussion-like symptoms and balance in healthy recreational athletes in the absence of endurance exercise or heat. Further research is needed to clarify the real-life relevance of these findings and to strengthen the differential diagnosis of concussion.

The 4-substituted 3-amino-1,2,5-oxadiazole 1 from the Malaria Box Project of the Medicines for Malaria Venture foundation shows very promising selectivity and in vitro activity against Plasmodium falciparum. Within the first series of new compounds, various 3-acylamino analogs were prepared. This paper now focuses on the investigation of the importance of the aromatic substituent in ring position 4. A number of new structure–activity relationships were elaborated, showing that antiplasmodial activity and selectivity strongly depend on the substitution pattern of the 4-phenyl moiety. In addition, physicochemical parameters relevant for drug development were calculated (logP and ligand efficiency) or determined experimentally (CYP3A4-inhibition and aqueous solubility). N-[4-(3-ethoxy-4-methoxyphenyl)-1,2,5-oxadiazol-3-yl]-3-methylbenzamide 51 showed high in vitro activity against the chloroquine-sensitive strain NF54 of P. falciparum (PfNF54 IC50 = 0.034 µM), resulting in a very promising selectivity index of 1526.

Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in an alkaline medium. Their conversion to 5-substituted β-hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted β-aminoketones or a single δ-diketone. The new compounds were characterized using spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.

Wheat stripe rust disease (WRD) is extremely detrimental to wheat crop health, and it severely affects the crop yield, increasing the risk of food insecurity. Manual inspection by trained personnel is carried out to inspect the disease spread and extent of damage to wheat fields. However, this is quite inefficient, time-consuming, and laborious, owing to the large area of wheat plantations. Artificial intelligence (AI) and deep learning (DL) offer efficient and accurate solutions to such real-world problems. By analyzing large amounts of data, AI algorithms can identify patterns that are difficult for humans to detect, enabling early disease detection and prevention. However, deep learning models are data-driven, and scarcity of data related to specific crop diseases is one major hindrance in developing models. To overcome this limitation, in this work, we introduce an annotated real-world semantic segmentation dataset named the NUST Wheat Rust Disease (NWRD) dataset. Multileaf images from wheat fields under various illumination conditions with complex backgrounds were collected, preprocessed, and manually annotated to construct a segmentation dataset specific to wheat stripe rust disease. Classification of WRD into different types and categories is a task that has been solved in the literature; however, semantic segmentation of wheat crops to identify the specific areas of plants and leaves affected by the disease remains a challenge. For this reason, in this work, we target semantic segmentation of WRD to estimate the extent of disease spread in wheat fields. Sections of fields where the disease is prevalent need to be segmented to ensure that the sick plants are quarantined and remedial actions are taken. This will consequently limit the use of harmful fungicides only on the targeted disease area instead of the majority of wheat fields, promoting environmentally friendly and sustainable farming solutions. Owing to the complexity of the proposed NWRD segmentation dataset, in our experiments, promising results were obtained using the UNet semantic segmentation model and the proposed adaptive patching with feedback (APF) technique, which produced a precision of 0.506, recall of 0.624, and F1 score of 0.557 for the rust class.

Plasmodium falciparum (P. falciparum) and hepatitis B virus (HBV) co-infection is on the rise among pregnant women in northern Ghana. Mono-infection with either of these two pathogens results in unique metabolic alterations. Thus, we aimed to explicate the effects of this co-infection on the metabolome signatures of pregnant women, which would indicate the impacted metabolic pathways and provide useful prognostic or diagnostic markers. Using an MS/MS-based targeted metabolomic approach, we determined the serum metabolome in pregnant women with P. falciparum mono-infection, HBV mono-infection, P. falciparum, and HBV co-infection and in uninfected (control) women. We observed significantly decreased sphingolipid concentrations in subjects with P. falciparum mono-infection, whereas amino acids and phospholipids were decreased in subjects with HBV mono-infection. Co-infections were found to be characterized distinctively by reduced concentrations of phospholipids and hexoses (mostly glucose) as well as altered pathways that contribute to redox homeostasis. Overall, PC ae C40:1 was found to be a good discriminatory metabolite for the co-infection group. PC ae C40:1 can further be explored for use in the diagnosis and treatment of malaria and chronic hepatitis B co-morbidity as well as to distinguish co-infections from cases of mono-infections.

Background: Heat induces a thermoregulatory strain that impairs cardiopulmonary exercise capacity. The aim of the current study is to elucidate the effect of isolated dehydration on cardiopulmonary exercise capacity in a model of preparticipating hypohydration. Methods: Healthy recreational athletes underwent a standardised fluid deprivation test. Hypohydration was assessed by bioelectrical impedance analysis (BIA) and laboratory testing of electrolytes and retention parameters in the blood and urine. The participants underwent cardiopulmonary exercise testing (CPET) with a cycle ramp protocol. Each participant served as their own control undergoing CPET in a hypohydrated [HYH] and euhydrated [EUH] state. Results: Fluid deprivation caused a mild (2%) but significant reduction of body water (38.6 [36.6; 40.7] vs. 39.4 [37.4; 41.5] %; p < 0.01) and an increase of urine osmolality (767 [694; 839] vs. 537 [445; 629] mosm/kg; p < 0.01). Hypohydration was without alterations of electrolytes, serum osmolality or hematocrit. The oxygen uptake was significantly lower after hypohydration (−4.8%; p = 0.02 at ventilatory threshold1; −2.0%; p < 0.01 at maximum power), with a corresponding decrease of minute ventilation (−4% at ventilatory threshold1; p = 0.01, −3.3% at maximum power; p < 0.01). The power output was lower in hypohydration (−6.8%; p < 0.01 at ventilatory threshold1; −2.2%; p = 0.01 at maximum power). Conclusion: Isolated hypohydration causes impairment of workload as well as peak oxygen uptake in recreational athletes. Our findings might indicate an important role of hypohydration in the heat-induced reduction of exercise capacity.

The symbiosis between cnidarians and dinoflagellates underpins the success of reef-building corals in otherwise nutrient-poor habitats. Alterations to symbiotic state can perturb metabolic homeostasis and thus alter the release of biogenic volatile organic compounds (BVOCs). While BVOCs can play important roles in metabolic regulation and signalling, how the symbiotic state affects BVOC output remains unexplored. We therefore characterised the suite of BVOCs that comprise the volatilome of the sea anemone Exaiptasia diaphana (‘Aiptasia’) when aposymbiotic and in symbiosis with either its native dinoflagellate symbiont Breviolum minutum or the non-native symbiont Durusdinium trenchii. In parallel, the bacterial community structure in these different symbiotic states was fully characterised to resolve the holobiont microbiome. Based on rRNA analyses, 147 unique amplicon sequence variants (ASVs) were observed across symbiotic states. Furthermore, the microbiomes were distinct across the different symbiotic states: bacteria in the family Vibrionaceae were the most abundant in aposymbiotic anemones; those in the family Crocinitomicaceae were the most abundant in anemones symbiotic with D. trenchii; and anemones symbiotic with B. minutum had the highest proportion of low-abundance ASVs. Across these different holobionts, 142 BVOCs were detected and classified into 17 groups based on their chemical structure, with BVOCs containing multiple functional groups being the most abundant. Isoprene was detected in higher abundance when anemones hosted their native symbiont, and dimethyl sulphide was detected in higher abundance in the volatilome of both Aiptasia-Symbiodiniaceae combinations relative to aposymbiotic anemones. The volatilomes of aposymbiotic anemones and anemones symbiotic with B. minutum were distinct, while the volatilome of anemones symbiotic with D. trenchii overlapped both of the others. Collectively, our results are consistent with previous reports that D. trenchii produces a metabolically sub-optimal symbiosis with Aiptasia, and add to our understanding of how symbiotic cnidarians, including corals, may respond to climate change should they acquire novel dinoflagellate partners.

Patients with chronic hepatitis B (CHB) gradually develop T cell exhaustion, and the inhibitory receptor molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4), may play a role in this phenomenon. This systematic review investigates the role of CTLA-4 in the development of T cell exhaustion in CHB. A systematic literature search was conducted on PubMed and Embase on 31 March 2023 to identify relevant studies. Fifteen studies were included in this review. A majority of the studies investigating CD8+ T cells demonstrated increased expression of CTLA-4 in CHB patients, though one study found this only in HBeAg-positive patients. Three out of four studies investigating the expression of CTLA-4 on CD4+ T cells found upregulation of CTLA-4. Several studies showed constitutive expression of CLTA-4 on CD4+ regulatory T cells. CTLA-4 blockade resulted in heterogeneous responses for all T cell types, as it resulted in increased T cell proliferation and/or cytokine production in some studies, while other studies found this only when combining blockade of CTLA-4 with other inhibitory receptors. Although mounting evidence supports a role of CTLA-4 in T cell exhaustion, there is still insufficient documentation to describe the expression and exact role of CTLA-4 in T cell exhaustion in CHB.

This paper presents the results of research conducted to identify the factors that influence the decisions of company management to outsource accounting services. A transaction cost economics (TCE) model was used to analyse factors that influence high levels of outsourcing of accounting tasks in the case of Montenegro, where, based on our sample, 75.4% of companies enter outsourcing arrangements with bookkeeping agencies or with external accountants. With an adaptation of International Accounting Standards (IAS) and legal requirements for submission of standardised year-end reports, there is evident growth of bookkeeping and financial service providers on the market and an evident trend of companies entering accounting service outsourcing with those agencies. A survey was developed to investigate 12 variables that, according to the TCE model, influence outsourcing decisions. The selection of variables was based on previous research in the field using the TCE or Resource-Based View model (the most common models used for this analysis). In contrast, new variables were introduced that measure the effects of the introduction of IAS through legal reporting obligations in Montenegro. By developing the model this way, it became possible to predict 47% of the variance of the dependent variable and to identify the main factors (other than price) that influence the decision of managers to outsource accounting services.