BACKGROUND AND AIMS Irritable bowel syndrome (IBS) is associated with substantial costs to society. Extensive data on direct costs (healthcare consumption) and indirect costs (health-related productivity loss) are lacking. Hence, we examined the socioeconomic costs of IBS and assessed which patient characteristics are associated with higher costs. METHODS Cross-sectional data from three Rome-defined Dutch IBS patient cohorts (n=419) were collected. Bootstrapped mean direct and indirect costs were evaluated per IBS patient using validated questionnaires (i.e., medical cost questionnaire and productivity cost questionnaire, respectively). Multivariable regression analyses were performed to identify variables associated with higher costs. RESULTS Quarterly mean total costs per patient were €2.156 (95% CI €1793-2541, [$2.444]), consisting of €802 (€625-1010, [$909]) direct costs and €1.354 (€1072-1670, [$1535]) indirect costs. Direct costs consisted primarily of healthcare professional consultations, with costs related to gastrointestinal clinic visits accounting for 6% and costs related to mental healthcare visits for 20%. Higher direct costs were significantly associated with older age (p=0.007), unemployment (p=0.001), IBS subtypes other than constipation (p=0.033), lower disease-specific quality of life (p=0.027), and more severe depressive symptoms (p=0.001). Indirect costs consisted of absenteeism (45%), presenteeism (42%), and productivity loss related to unpaid labor (13%) and were significantly associated with the male sex (p=0.014) and more severe depressive symptoms (p=0.047). CONCLUSION Productivity loss is the main contributor to the socioeconomic burden of IBS. Direct costs were not predominantly related to gastrointestinal care, but rather to mental healthcare. Awareness of the nature of costs and contributing patient factors should lead to significant socioeconomic benefits for society.

BACKGROUND AND AIM Intestinal permeability (IP) plays an important role in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). We assessed site-specific (gastroduodenum, small intestine, colon and whole gut) IP in NAFLD patients and healthy controls (HC) and its association with the degree of hepatic steatosis, hepatic fibrosis and dietary composition in these NAFLD patients. METHODS In vivo site-specific IP was analysed with a validated multi-sugar test in NAFLD patients and HC. Furthermore, in NAFLD patients, hepatic steatosis (chemical shift MRI), hepatic fibrosis (transient elastography) and dietary composition (food frequency questionnaire) were assessed. RESULTS Fifty-two NAFLD patients and forty-six HC were included in this study. Small intestinal (P <0.001), colonic (P = 0.004) and whole gut (P <0.001) permeability were increased in NAFLD patients compared to HC. Furthermore, colonic permeability (P = 0.029) was significantly higher in NAFLD patients with clinically significant fibrosis compared to those without. Colonic permeability remained positively associated with the presence of clinically significant fibrosis (P = 0.017) after adjustment for age, sex and BMI. CONCLUSION Colonic permeability is increased in at least a subset of NAFLD patients compared to HC and is independently associated with clinically significant NAFLD fibrosis.

Summary: In allogeneic hematopoietic stem cell transplantation, donor αβ T cells attack recipient tissues, causing graft-vs-host disease (GVHD), a major cause of morbidity and mortality. A central question has been how GVHD is sustained despite T cell exhaustion from chronic antigen stimulation. The current model for GVHD holds that disease is maintained through the continued recruitment of alloreactive effectors from blood into affected tissues. Here we show, using multiple approaches including parabiosis of mice with GVHD, that GVHD is instead primarily maintained locally within diseased tissues. By tracking 1203 alloreactive T cell clones we fitted a mathematical model predicting that within each tissue a small number of progenitor T cells maintain a larger effector pool. Consistent with this, we identified a tissue-resident TCF-1+ subpopulation that preferentially engrafted, expanded, and differentiated into effectors upon adoptive transfer. These results suggest that therapies targeting affected tissues and progenitor T cells within them would be effective.

Computed tomography (CT) is a diagnostic imaging process that uses ionising radiation to obtain information about the interior anatomic structure of the human body. Considering that the medical use of ionising radiation implies exposing patients to radiation that may lead to unwanted stochastic effects and that those effects are less probable at lower doses, optimising imaging protocols is of great importance. In this paper, we used an assembled 3D-printed infant head phantom and matched its image quality parameters with those obtained for a commercially available adult head phantom using the imaging protocol dedicated for adult patients. In accordance with the results, an optimised scanning protocol was designed which resulted in dose reductions for paediatric patients while keeping image quality at an adequate level.

: The paper presents the chemical composition of the fruits of three apple cultivars (Jonagold Decosta, Red Idared and Gala Schnitzer Schniga) fertilized with three treatment: T 1 (control‒without fertilization); T 2 (300 kg/ha NPK (6:18:36) + 150 kg/ha N (calcium ammonium nitrate‒CAN)) and T 3 (foliar nutrition-mixture organic-mineral fertilizer commercially named ‘FitoFert Kristal’ (0.6%) (10:40:10) + ‘FitoFert Kristal’ (0.6%) (20:20:20) + ‘FoliFetril Ca’ (0.5%) (N:Ca) in Bosnia and Herzegovina during two years (2020‒2021). Significant differences of contents of soluble solids, total sugars, inverted sugars, sucrose, total phenolic content, content of flavonoids and antioxidant activity were found among cultivar/treatment combinations, cultivars, treatments and years. Differences in total acids content among treatments and years were not statistically significant, but significant differences among cultivars and cultivar/treatment combinations were found. The contents of soluble solids, total sugars and sucrose were the highest in fruits of cultivar Jonagold Decosta, while the highest contents of inverted sugars, total acids, total phenolics, flavonoids and antioxidant activity were found in fruits of Red Idared cultivar. The fertilization treatment T 2 significantly influenced the content of soluble solids, total sugars, inverted sugars, total acids, total phenolic, flavonoids and antioxidant activity in the apple fruits. According to the results obtained, we can say that fertilization treatment T 3 do not have much effect on bioactive ingredients, with the exception of the sucrose content. Among mineral elements, four were macroelements that were represented present in large amounts: potassium (K) (1266.15 mg kg –1 to 1652.89 mg kg –1 ), calcium (Ca) (122.76‒474.90 mg kg –1 ), phosphor (P) (86.14‒124.84 mg kg –1 ) and magnesium (Mg) (57.36‒70.68 mg kg –1 ). On the other hand, four microelements were determined: boron (B) (1.06‒14.25 mg kg –1 ); iron (Fe) (2.79‒4.62 mg kg –1 ); manganese (Mn) (0.27‒0.46 mg kg –1 ) and zinc (Zn) (0.15‒0.48 mg kg –1 ). Results showed that contents of macroelements and microelements have been strongly affected by cultivar/treatment combinations, cultivars, treatments and years.

Abstract Global brachial plexus injury (GBPI) mainly affects adults and causes severe life-changing consequences that lead to the deterioration of patients’ quality of life. Several surgical approaches have been described and reported in the literature to improve patients’ functional ability. A literature review is done on PubMed/MEDLINE and Embase using specific keywords to retrieve relevant articles assessing different surgical approaches for GBPI management. Inclusion and exclusion criteria were applied, and eligible articles were included in the review. The literature survey revealed that various surgical options had been used to manage GBPI patients. In this concise review, we discuss and compare the different surgical approaches related to GBPI and its outcome in terms of restoring elbow flexion and extension, shoulder abduction, and wrist and hand function. The primary surgical intervention relies mainly on transferring single or multiple nerves with/without nerve grafts to restore the function of the targeted muscle. Different techniques using a variety of nerve donors and recipients are compared to assess the functional outcomes of each option. Moreover, further options are addressed for delayed GBPI injuries or failed nerve transfer procedures, as in free functional muscle transfer techniques. In addition, information about brachial plexus injury cases faced in our center is presented along with our center’s approach to diagnosing and managing partial and GBPI cases.

Background and Objective Thymic epithelial tumors (TETs) are a rare group of neoplasms situated in the prevascular mediastinum. Due to their rarity and histological diversity, understanding their development is quite challenging, and their molecular profile is not well defined. Although advances in molecular profiling have improved our understanding of many solid cancers, TET remains poorly characterized. The human epidermal growth factor receptor 2 (HER2/ERBB2) has gained interest as a molecular target due to its role in oncogenesis and its therapeutic significance in various malignancies; however, its potential role in treating TET remains unclear. This review examines the expression patterns, gene amplification status, and clinical implications of HER2 in thymomas and thymic carcinomas, especially in the era of antibody-drug conjugates which target tumors with low HER2 expression. Methods PubMed, Embase and Web of Science research was conducted using the terms [HER2] OR [ERBB2] OR [ErbB2] OR [HER2/neu] OR [c-erB2] AND [thymic epithelial tumors], [HER2] OR [ERBB2] OR [ErbB2] OR [HER2/neu] OR [c-erB2] AND [thymoma], and [HER2] OR [ERBB2] OR [ErbB2] OR [HER2/neu] OR [c-erB2] AND [thymic carcinoma]. There were no restrictions on publication date. After analysis, nine articles met the research criteria. Key Content and Findings In one study, thymic carcinomas expressed HER2 frequently, with focal to strong membranous positivity in 8 of the 17 cases. In another, HER2 was expressed in 58.3% of cases with other members of the receptor family and signaling pathway ligands also demonstrating frequent expression. The immunohistochemical analysis revealed that the receptors epidermal growth factor receptor (EGFR) (33.3%), phosphorylated epidermal growth factor receptor (pEGFR) (33.3%), and human epidermal growth factor receptor 3 (HER3) (45.8%), along with the ligands transforming growth factor-α (TGF-α) (54.2%), amphiregulin (25.0%), and epiregulin (91.7%), were expressed in the tumor cells. Only one case showed HER2 gene amplification. In another study, HER2 expression was positive in only one case of thymic carcinoma (1/22), whereas there was no expression observed in any of the thymoma cases (0/22). In the other series, there were scarce or no cases with HER2 expression or gene amplification. Conclusions HER2 plays a still undefined role in TET, especially in thymic carcinoma. Although gene amplification is rare, protein expression is more frequent, suggesting potential for targeted therapy. Detailed molecular profiling and innovative research methods are essential to further explore the therapeutic potential of HER2 in these rare cancers.

BACKGROUND Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. METHODS WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. FINDINGS Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2-6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. INTERPRETATION In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. FUNDING European Society of Intensive Care Medicine, European Respiratory Society.

Objective: Romania began its COVID-19 immunization programme with approved vaccinations in three stages, as follows: The first step of vaccination is for health and social professionals, the second stage is for high-risk persons and the third stage is for the remainder of the general public. This study aims at assessment of knowledge, attitude and practice towards COVID-19 and vaccination against COVID-19 in the Romanian population during the third wave of the pandemic. Methods: This cross-sectional study was based on a Bosnian and Herzegovinian study on COVID-19 vaccination during the country’s third wave of COVID-19 pandemic. Results: Our study sample, dominantly female (629; 61.0%), with a bachelor’s degree (734; 71.2%), either single (539; 52.3%) or in a relationship (363; 35.2%), engaged in intellectual labour (910; 88.3%) and living in an urban environment (874; 84.8%) with a mean age of 25.07 ± 8.21 years, 294 (28.5%) people with COVID-19 symptoms and 86 (8.3%) were tested COVID-19 positive, had a mean knowledge score of 16.38 ± 4.0 with correct answer rates on questions ranging from 30.1% to 88.2%. Being single (odds ratio = 3.92, p = 0.029) or in a relationship (odds ratio = 3.79, p = 0.034), having a bachelor’s degree and higher (odds ratio = 1.61, p = 0.006) and being COVID-19 tested (odds ratio = 1.82, p < 0.001) were associated with higher knowledge test scores. Our sample had relatively optimistic attitudes towards final COVID-19 disease containment (712; 69.1%) and vaccination programmes (679; 65.9%). The majority of the sample followed socio-epidemiological measures and did not visit places of mass social gatherings (666; 64.1%) and wore masks (992; 95.7%) while being outside their home. In terms of vaccination rates, 382 (37.0%) of the individuals were presently immunized against COVID-19. Higher knowledge test scores (>15 points) (odds ratio = 1.66, p = 0.002) and positive attitudes of this study (odds ratio = 1.59, p = 0.001, odds ratio = 4.16, p < 0.001) were identified as independent predictors for vaccinating against COVID-19. Conclusion: Romanian citizens have had good knowledge, optimistic attitudes and appropriate practices towards COVID-19 vaccination during the third wave of COVID-19 outbreak in the country. Higher knowledge regarding the disease and vaccination against it not only increased attitudes towards the end of the pandemic, but also increased the willingness to be vaccinated and to avoid infection risk factors.

Abstract The use of multi-criteria decision-making (MCDM) methods to select the most appropriate one from a range of alternatives considering multiple criteria is a suitable methodology for making informed decisions. When constructing a decision or objective matrix (DOM) for MCDM procedure, either crisp numerical values or fuzzy linguistic terms can be used. A review of relevant literature indicates that decision experts often prefer to give linguistic terms (instead of crisp numerical values) based on their domain knowledge, to establish a fuzzy DOM. However, previous research articles have not adequately studied the selection between fuzzy and crisp DOM in MCDM, especially under the context of assessing the financial performance (FP) of listed firms – a notably complex decision-making problem. As such, the primary motivation of this study is to bridge this research gap through comparative analyses of fuzzy and crisp DOM in MCDM. Along this path, and in order to handle fuzzy DOM, this work also proposes two new fuzzy MCDM methods: fuzzy preference ranking on the basis of ideal-average distance (PROBID) and fuzzy sPROBID (simpler PROBID), extending the applicability of the original crisp PROBID and sPROBID methods. Moreover, for the first time in the literature, this work compares the FP rankings obtained using fuzzy MCDM methods with an objective benchmark we have identified, i.e., the real-life stock return (SR)-based ranking. The case study of ranking the FP of 32 listed firms demonstrates that the fuzzy MCDM methods produce higher correlation results with the SR-based ranking. The results also suggest that the proposed fuzzy sPROBID method with triangular fuzzy DOM performs the best for assessing the FP of firms in terms of Spearman’s rank correlation coefficient with the SR-based ranking. Overall, the contributions of this work are three-fold: first, it proposes two new fuzzy MCDM methods (i.e., fuzzy PROBID and fuzzy sPROBID); second, it advances the application of fuzzy MCDM methods in assessing and ranking the FP of listed firms to make rational investment decisions in the financial market; third, it studies the selection between fuzzy and crisp DOM through comparisons with an objective benchmark.

Background and Objectives: In the development of type 2 diabetes mellitus (T2DM) and its complications, genetic and environmental factors play important roles. Diabetic nephropathy (DN), one of the major microangiopathic chronic diabetic complications, is associated with an increased risk of major cardiovascular events and all-cause mortality. The present study was designed to investigate the possible modifying effect of glutathione transferase polymorphisms (GSTM1, GSTT1, GSTP1 rs1138272/rs1695, GSTO1 rs4925 and GSTO2 rs156697) in the susceptibility to T2DM and diabetic nephropathy. Materials and Methods: GSTM1 and GSTT1 deletion polymorphisms were determined by multiplex PCR, whereas GSTO1, GSTO2, and GSTP1 polymorphisms were determined by the real-time PCR in 160 T2DM patients and 248 age- and gender-matched controls. Advanced glycation end products (AGEs) were measured by ELISA. Results: Among six investigated GST polymorphisms, a significant association between the GST genotypes and susceptibility for development of diabetes mellitus was found for the GSTM1, GSTT1, GSTP1 (rs1138272) and GSTO1 polymorphisms. When the GST genotypes’ distribution in diabetes patients was assessed in the subgroups with and without diabetic nephropathy, a significant association was found only for the GSTO2 rs156697 polymorphism. Diabetic patients, carriers of the GSTM1 null, GSTT1 null and variant GSTO1*AA genotypes, had significantly increased levels of AGEs in comparison with carriers of the GSTM1 active, GSTT1 active and referent GSTO1*CC genotypes (p < 0.001, p < 0.001, p = 0.004, respectively). Conclusions: The present study supports the hypothesis that GST polymorphisms modulate the risk of diabetes and diabetic nephropathy and influence the AGEs concentration, suggesting the potential regulatory role of these enzymes in redox homeostasis disturbances.

The positive effects of green infrastructure in the urban environment are nowadays widely known and proven by research. Yet, greening, which serves to improve the indoor climate and people’s well-being, is integrated very limited in public facilities such as schools. Reasons for this are seen in a lack of knowledge and financing opportunities. A focus, among others, of the MehrGrüneSchulen research project is the interdisciplinary development of cost-effective greening solutions for schools. The designs were developed in close collaboration with students of a technical college (HTL) and a horticultural school. This study describes the development process and presents the results of the first implementations of greening systems at the HTL-building complex and at nine other schools in Austria.

The requirements for the efficient replacement of fossil fuel, combined with the growing energy crisis, places focus on hydrogen production. Efficient and cost-effective electrocatalysts are needed for H2 production, and novel strategies for their discovery must be developed. Here, we utilized Kinetic Monte Carlo (KMC) simulations to demonstrate that hydrogen evolution reaction (HER) can be boosted via hydrogen spillover to the support when the catalyst surface is largely covered by adsorbed hydrogen under operating conditions. Based on the insights from KMC, we synthesized a series of reduced graphene-oxide-supported catalysts and compared their activities towards HER in alkaline media with that of corresponding pure metals. For Ag, Au, and Zn, the support effect is negative, but for Pt, Pd, Fe, Co, and Ni, the presence of the support enhances HER activity. The HER volcano, constructed using calculated hydrogen binding energies and measured HER activities, shows a positive shift of the strong binding branch. This work demonstrates the possibilities of metal–support interface engineering for producing effective HER catalysts and provides general guidelines for choosing novel catalyst–support combinations for electrocatalytic hydrogen production.

The Angle-of-Arrival (AoA)-based approach is an appealing solution for unmanned aerial vehicle (UAV) positioning, and has received significant interest recently. In this article, we propose a novel framework for UAV three-dimensional (3-D) positioning, the core of which is to measure the two-dimensional (2-D) Angle-of-Departure (2D-AoD) and 2D-AoA via a bistatic multiple-input multiple-output (MIMO) radar. Unlike the existing positioning architectures, the MIMO radar is equipped with polarized array antennas. An estimator based on the parallel factor (PARAFAC) decomposition is developed. It first obtains the direction matrices via performing the PARAFAC decomposition of the array data. Thereafter, the rotational invariance characteristic is utilized to form a normalized polarization response vector, from which the 2D-AoD, 2D-AoA, and polarization status of the UAVs are achieved via incorporating the vector cross-product method and the least squares (LSs) technique. Finally, the 3-D positions of the UAVs are easily calculated via the location relationship between the 2D-AoD, 2D-AoA, and the coordinates of transmitting/receiving (Tx/Rx) array. The proposed framework is computationally friendly, and is capable of positioning anonymous UAV. Moreover, it is insensitive to the geometry of the Tx/Rx array, indicating that the proposed framework supports configurable Tx/Rx antennas. Simulation results are provided to verify our theoretical advantages.

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.