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Field production of common beans benefit from root microbial associations, although they are generally considered to be weaker nitrogen fixers than other legumes. Therefore, the number of nodules on the roots of 64 accessions of the European common bean (Phaseolus vulgaris L.) and the relationship between the number of nodules per accession and other plant characteristics (growth type, earliness, seed yield, and total nitrogen content in seeds) were studied. The results indicated that growth type and earliness influenced the number of nodules per accession (the contributions of principal component analysis were 34.9% for Dim1 and 29.8% for Dim2). The average number of nodules per accession with indeterminate growth type was almost five times higher (20.1) than for accessions with determinate growth type (4.4). Common bean accessions with regular growth cycle length had the highest number of nodules (21.9). In contrast, nodulation efficiency, measured as seed yield per plant and total nitrogen content in seeds, were not correlated with the number of nodules per accession (correlation analysis, r

Aims To analyse the measurement properties of the Spanish version of the COPM (Canadian Occupational Performance Measure) in older adult rehabilitation inpatients.Method A sample of 172 users from 17 inpatient care facilities for older adults (47% nursing homes) participated in a quantitative prospective study. We examined validity by correlating the COPM with the Barthel Index (BI), the Lawton Instrumental Activities of Daily Living scale (IADL), the EuroQol-five domains-three level questionnaire (EQ-5D-3L), and the Client-Centred Rehabilitation Questionnaire (CCRQ) and by examining associations with demographic variables. Reliability was evaluated through test-retest and responsiveness through differences in change scores in two types of care facilities.Results Participants prioritised 637 occupational performance problems, mainly in the area of self-care (70.5%). The COPM scale scores were significantly correlated with BI, IADL, EQ-5D-3L (except the pain dimension), and CCRQ (except the family involvement and continuity dimensions). COPM scores did not show statistically significant differences concerning educational level. Regarding reliability, high test-retest correlations were obtained (>.80). Nursing home users showed less responsiveness to rehabilitation than other users (change score < 2 vs. > 2 points).Conclusion and significance The Spanish COPM provides satisfactory measurement properties as a client-centred instrument in older adult rehabilitation inpatient.

Aim The latest guidelines from ACC/AHA define hypertension at systolic blood pressure (SBP) 130-139 mmHg or diastolic blood pressure (DBP) 80-89 mmHg in contrast to guidelines from ESC/ESH defining hypertension at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg. The aim was to determine whether the ACC/AHA definition of hypertension identifies persons at elevated risk for future cardiovascular outcome.Methods In a Danish prospective cardiovascular study, 19,721 white men and women aged 20-98 years were examined up to five occasions between 1976 and 2015. The population was followed until December 2018. The ACC/AHA definition of the BP levels were applied: Normal: SBP

AbstractThe Canary Islands are a Spanish archipelago of volcanic origin in the Atlantic Ocean near the Saharan coast. The extensive intricacy and multitude of variables inherent in the Canary Islands winemaking tradition have posed a substantial challenge, preventing comprehensive research on the main factors contributing to the character of local wine, thus, far. This challenge arises from a convergence of factors including the presence of 14 different grape varieties, and radically different climatic, soil and geographic conditions. This investigation sought to start unraveling this complexity by discerning the impacts of various geographical (specifically, island-related) and management factors (namely, organic vs. conventional practices) on soils and wines within the Canary Islands. Additional variables, such as wine type (red and white) and island of origin, were explored and correlated with the chosen management system. Pairs of organic and conventional wine and soil samples, possessing similar characteristics, were systematically collected from each of the seven wine-producing islands in the Canary archipelago. An examination of elemental composition, oenological attributes and fertility parameters was conducted, followed by comprehensive statistical analysis. Among the variables examined, only the island of origin emerged as statistically significant within the sample. Concerning soil fertility, organic samples exhibited elevated levels of organic matter compared to their conventional counterparts. No notable disparities were observed between the two production methods in terms of soil metal composition and other fertility parameters. However, it is noteworthy that four soil samples surpassed the legally permissible limits for Nickel (Ni) and Mercury (Hg), with three of these instances originating from Lanzarote.

BackgroundHealth care workers (HCWs) are often impacted by distressing situations during patient care and can experience the second victim phenomenon (SVP). Addressing an adequate response, training, and increasing awareness of the SVP can increase HCWs’ well-being and ultimately improve the quality of care and patient safety. ObjectiveThis study aims to describe and evaluate a multimodal training organized by the European Researchers’ Network Working on Second Victims to increase knowledge and overall awareness of SVP and second victim programs. MethodsWe implemented a multimodal training program, following an iterative approach based on a continuous quality improvement process, to enhance the methodology and materials of the training program over the duration of 2 years. We conducted web-based surveys and group interviews to evaluate the scope and design of the training, self-directed learning materials, and face-to-face activities. ResultsOut of 42 accepted candidates, 38 (90%) participants attended the 2 editions of the Training School program. In the second edition, the level of participants’ satisfaction increased, particularly when adjusting the allocated time for the case studies’ discussion (P

Plasma cytokine levels were quantified among 30 persons with HIV (PWH) identified as elite controllers (15 transient controllers [studied a median of 1.38 years before losing viral control] and 15 persistent controllers). Thirty antiretroviral therapy (ART)-naive PWH, 30 ART-treated PWH with undetectable viremia, and 30 HIV-uninfected controls also were studied. Higher levels of cytokines were recognized among PWH than among controls, with EC displaying the highest levels. Elevated levels of IP-10 and MIG were identified among transient controllers as predictors of the loss of viral control. These findings offer feasible biomarkers for predicting virologic outcome and loss of control in EC.

Abstract Lipid bi‐layered particles known as membrane vesicles (MVs), produced by Gram‐positive bacteria are a communication tool throughout the entire bacterial growth. However, the MVs characteristics may vary across all stages of maternal culture growth, leading to inconsistencies in MVs research. This, in turn, hinders their employment as nanocarriers, vaccines and other medical applications. In this study, we aimed to comprehensively characterize MVs derived from Lacticaseibacillus rhamnosus CCM7091 isolated at different growth stages: early exponential (6 h, MV6), late exponential (12 h, MV12) and late stationary phase (48 h, MV48). We observed significant differences in protein content between MV6 and MV48 (data are available via ProteomeXchange with identifier PXD041580), likely contributing to their different immunomodulatory capacities. In vitro analysis demonstrated that MV48 uptake rate by epithelial Caco‐2 cells is significantly higher and they stimulate an immune response in murine macrophages RAW 264.7 (elevated production of TNFα, IL‐6, IL‐10, NO). This correlated with increased expression of lipoteichoic acid (LTA) and enhanced TLR2 signalling in MV48, suggesting that LTA contributes to the immunomodulation. In conclusion, we showed that Lacticaseibacillus rhamnosus CCM7091‐derived MVs from the late stationary phase boost the immune response the most effectively, which pre‐destines them for therapeutical application as nanocarriers.

Objective To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit.Design Individual participant data meta-analysis.Data sources Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset.Eligibility criteria for selecting studies Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model.Results The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, −18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R2) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of −22.3 g (Allen cohort), −33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (−154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making.Conclusions The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required.Trial registration PROSPERO CRD42019135045

Summary: The immune system has emerged as an important target of thyroid hormones (THs); however, the role of TH in T cells has so far remained elusive. In this study, we assessed the effect of TH receptor α (TRα) signaling on activation and function of T cells. Our findings show that lack of canonical TRα action not only increased the frequency of regulatory T cells (Treg) but propelled an activated and migratory Treg phenotype and nuclear factor κB (NF-κB) activation in Treg. Conversely, canonical TRα action reduced activation of the NF-κB pathway previously shown to play a pivotal role in Treg differentiation and function. Taken together, our findings demonstrate that TRα impacts T cell differentiation and phenotype. Given the well-known interaction of inflammation, immune responses, and TH axis in e.g., severe illness, altered TH-TRα signaling may have an important role in regulating T cell responses during disease.

Johann Baptist Joseph Maximilian Reger is best known for his organ compositions. He favored the genres of the Baroque. He treated and developed the genres of chorale prelude, fugue and fantasia in his own individual way. He was inspired by his friend and performer Karl Straube (1873-1950), organist of the St. Thomas Church in Leipzig, who provided him with inspiration and ideas for his compositions. The present study focuses on the chorale fantasias pertaining to the composer’s group of works for organ. These compositions by Reger are considered to be seminal works of organ literature. They were composed in a short period between 1898 and 1900. Reger designed the registration of the organ works for the disposition of German late Romantic organs, which are characterized by a faithful imitation of an orchestral sound. Formally, they follow the structure of the Baroque chorale variation and chorale partita. The titles of the chorale fantasias echo the opening lines of the sacred hymns they are based on. The melodies date from the 16th and 17th centuries and belong to the hymn repertoire of German Lutheran congregations. Some of them can also be found in the Hungarian Reformed congregational hymnal.

BackgroundEquity-deserving groups (EDGs) have increased emergency department (ED) use, and often report negative ED care. Past studies have largely been qualitative and suffer from methodological bias and lack of comparison groups, thereby limiting their identification of interventions to ensure equitable care among equity-deserving populations. This study sought to better understand ED care experiences among EDGs in our local setting.Materials and methodsWe conducted a community-engaged, mixed-methods cross-sectional study using sensemaking methodology at the Kingston Health Sciences Centre's ED and Urgent Care Centre (Ontario, Canada), as well as at community partner organizations. From June-August 2021, eligible participants were invited to complete a survey about an ED care experience within the previous 24 months. Multiple-choice questions collected demographic/ED visit information including self-identification with up to three EDGs (Indigenous; having a disability; experiencing mental health concerns; persons who use substances (PWUS); 2SLGBTQ+; people who experience homelessness (PWEH); a visible minority; or having experienced violence). We evaluated differences in overall ED care experiences by EDG self-identification using chi-squared tests. Quantitative analysis of survey questions disaggregated by EDG status, and a thematic analysis of participant experiences are presented.ResultsOverall, 1,973 unique participants completed the survey (949 controls and 994 EDGs) sharing 2,114 ED care experiences in total. Participants who identified as PWUS, having mental health concerns, 2SLGBTQ+, PWEH, or having a disability, reported more negative overall experiences (p < 0.001). Compared with controls, each of the eight EDGs were statistically more likely to report feelings of judgement/disrespect, that there was too little attention paid to their needs (p < 0.001), and that it was more important to be treated with kindness/respect than to receive the best possible care (p < 0.001). Thematic analysis supported quantitative findings and identified four themes: stigma/judgement, poor staff communication, lack of compassionate care, and patients feeling unsupported.DiscussionNegative ED care experiences were pervasive among EDGs including feelings of judgement/stigma and a perception that a better understanding of personal situation/identity/culture was needed to improve care. Qualitative findings identified the following future interventions: universal trauma-informed care, improved care for addiction/substance use, and improved access to mental health care resources.

Gegen die in der Literatur zu Blockchainanwendungen verbreitete These, diese erforderten kein nutzerseitiges Vertrauen oder generierten ein neuartiges „vertrauenloses Vertrauen“, wird in diesem Beitrag zunächst gezeigt, dass auch in der Nutzung von Blockchainanwendungen Vertrauensbeziehungen eine Rolle spielen. Es wird dafür argumentiert, Vertrauen im Rahmen von Blockchainanwendungen als ‚Institutionenvertrauen‘ zu verstehen. Das klassische bilaterale interpersonale Vertrauensverständnis von Vertrauenssubjekt und Vertrauensobjekt bleibt dabei strukturell erhalten, die Zuschreibung von Vertrauenswürdigkeit durch das Vertrauenssubjekt erfolgt in einem default-and-challenge Modell. Dabei zeigt sich bereits aus begrifflichen Gründen: Je ‚sicherer‘ das System, desto weniger bedarf es nutzerseitigen Vertrauens. Vertrauen setzt Vulnerabilität voraus. Diese ist mit Blick auf Blockchainanwendungen bei den meisten Nutzer:innen in hohem Maße vorhanden.

Introduction Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child’s neurodevelopment and behaviour development, overall health and mortality.Methods and analysis This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of

Immunocompromised children are at risk of developing severe COVID-19 infection. We conducted a pilot prospective study to evaluate the impact of cancer treatment and stem cell transplantation on immunogenicity of two doses of BNT162b2 vaccine in pediatric patients.Humoral, B- and T-cell responses to the BNT162b2 vaccine were assessed before, after the first and the second dose in patients aged 5–12 years (n = 35) and in a group of healthy donors (HD, n = 12). Patients were divided in three groups: solid tumors (ST, n = 11), hematological malignancies (HM, n = 14) and Hematopoietic Stem Cell Transplantation (HSCT) recipients (n = 10). After two vaccine doses, the seroconversion rate was 79.3 % (72.7 % in ST, 66.7 % in HM and 100 % in HSCT). The antibodies production was not associated to the presence of memory B and T-cells. Memory B-cells were measurable in 45.5 % ST, 66.6 % HSCT and in 22.0 % HM. The specific T-cell response was observed in most ST (81.8 %) and HSCT (85.7 %) patients and at lesser extent in those with HM (55.5 %). The combination of all immunological parameters (antibodies, memory B and T cells) showed that a significant fraction of HM (33.3 %) and ST (18.2 %) patients completely failed to respond to vaccination. Although able to produce antibodies, 11.1 % of HM and 27.3 % of ST had no B- and T-cell memory. HSCT subgroup showed the best immune function, with 80 % complete response and optimal T-cell function.Combination of anti-RBD antibody, and specific memory B- and T-cell responses represents a reliable read-out of vaccine immune efficacy in frail patients.

BackgroundThe periodontal ligament (PDL) experiences considerable mechanical stresses between teeth and bone, vital for tissue adaptation, especially in orthodontic tooth movement (OTM). While recent research emphasizes the role of innate lymphoid cells (ILCs) in regulating sterile inflammation, their involvement in periodontal tissues during OTM remains largely unexplored.MethodsIn this study, PDL tissues from orthodontic patients (n = 8) were examined using flow cytometry to detect ILC subtypes. Transwell co-culture systems were used to expose PDL cells to mechanical strain, followed by measuring migration and ratios of sorted ILC subtypes. Statistical analyses were conducted using paired Student’s t-test, Kruskal-Wallis test, Dunn’s post-test and one-way/two-way ANOVA with Tukey’s post-test (p≤ 0.05; **, p≤ 0.01; ***, p≤ 0.001).ResultsOur findings demonstrate a significant increase in CD127+ CD161+ ILC frequencies in PDL tissues during OTM, indicating ILC involvement in sterile inflammation induced by orthodontic forces. Co-culture assays show directed migration of ILC subsets towards PDL cells and substantial proliferation and expansion of ILCs.ConclusionsThis study is the first to comprehensively investigate the role of ILCs in sterile inflammation during OTM, revealing their presence and distribution within PDL tissues’ innate immune response in vivo, and exploring their migratory and proliferative behavior in vitro. The results suggest a crosstalk between ILCs and PDL cells, potentially influencing the inflammatory response and tissue remodeling processes associated with OTM.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a leading cause of chronic liver disease, has increased worldwide along with the epidemics of obesity and related dysmetabolic conditions characterized by impaired glucose metabolism and insulin signaling, such as type 2 diabetes mellitus (T2D). MASLD can be defined as an excessive accumulation of lipid droplets in hepatocytes that occurs when the hepatic lipid metabolism is totally surpassed. This metabolic lipid inflexibility constitutes a central node in the pathogenesis of MASLD and is frequently linked to the overproduction of lipotoxic species, increased cellular stress, and mitochondrial dysfunction. A compelling body of evidence suggests that the accumulation of lipid species derived from sphingolipid metabolism, such as ceramides, contributes significantly to the structural and functional tissue damage observed in more severe grades of MASLD by triggering inflammatory and fibrogenic mechanisms. In this context, MASLD can further progress to metabolic dysfunction-associated steatohepatitis (MASH), which represents the advanced form of MASLD, and hepatic fibrosis. In this review, we discuss the role of sphingolipid species as drivers of MASH and the mechanisms involved in the disease. In addition, given the absence of approved therapies and the limited options for treating MASH, we discuss the feasibility of therapeutic strategies to protect against MASH and other severe manifestations by modulating sphingolipid metabolism.

Bloch points in magnetic materials are attractive entities in view of magnetic information transport. Here, Bloch point configuration has been investigated and experimentally determined in a magnetic trilayer (Gd12Co88/Nd17Co83/Gd24Co76) with carefully adjusted composition within the ferrimagnetic GdxCo1-x alloys in order to engineer saturation magnetization, exchange length, and interlayer couplings (ferromagnetic vs antiferromagnetic). X-ray vector magnetic tomography has allowed us to determine experimentally Bloch point polarity (related to topological charge) and Bloch point helicity γ (determined by magnetostatic energy). At the bottom layer (close to the ferromagnetic interface), Bloch points adopt a standard circulating configuration with helicity γ close to π/2. Within the top layer (with much lower saturation magnetization), Bloch points nucleate within a Neel-like exchange spring domain wall created by the antiferromagnetic coupling and adopt an uncommon hyperbolic configuration, characterized by much larger helicity angles. Our results indicate a path for Bloch point engineering in future applications adjusting material parameters and domain wall characteristics.

Zebrafish larvae are a model organism increasingly used in the study of the effect of neuroactive chemicals on vertebrate sleep/wake cycles. Sleep disturbances have a negative impact on mood, cognition and overall health. Here we present a protocol to assess over 24 h sleep/wake cycles in zebrafish larvae subjected to 12 h light/dark periods in 48-well plates, using video-tracking technologies. The protocol can be used to determine if the exposure to environmental pollutants or drugs can lead to sleep disturbances. The results on the effect of the tire rubber-derived 6PPD-quinone on zebrafish sleep/wake cycles presented here demonstrate the suitability of using this protocol in fish neurotoxicity studies. This protocol provides a new relevant tool to be used in the pharmacology and toxicology fields.

Tengkawang oil that hasn’t through purification process contains free fatty acid that can affect its quality, where this essence is the polluter that must be removed because it can caused a rancid. The removal of free fatty acid content on Tengkawang oil was done through adsorption process utilizing palm fronds adsorbent by using its cellulose content. Palm fronds went through dilegnification process using 10% of NaOH, then adsorption process was conducted with adsorbent concentration variety 5, 10, 15, 20 and 25%. Adsorbent characterized by utilizing FTIR and SAA, from FTIR result shows that palm fronds contain berlignocellulose function cluster, after delignification the C=C lignin compound function cluster still can be found on FTIR result and after adsorption O-H cluster went through intensity decrement which shows that cellulose content and hydroxyl (-OH) cluster reacted with adsorbat. Furthermore, there’s absorption on C-H function cluster that indicates the existence of free fatty acid compound and other polluter that adsorbed by palm fronds adsorbent. The characteristic of palm fronds adsorbent after delignification process was conducted shows the pore size is on micropore range with surface area of 6.480 m2/g, pore volume of 0.01138 cc/g and pore radius of 12.4 Å. The result of the research shows decreasing percentage of free fatty acid, capacity value and adsorption effectiveness of Tengkawang oil that the highest is on adsorbent concentration as much as 25% with decreasing percentage of free fatty acid as much as 4.68%, adsorption capacity as much as 207.19 mg/g and adsorption effectiveness as much as 36.28%. Keywords: adsorption; delignification; free fatty acid; tengkawang oil

Bahan ajar yang baik memiliki kriteria tertentu atau standar tertentu seperti tentang relevansinya dengan kurikulum yang sedang berlaku. Pendekatan STEM menawarkan kesempatan kepada guru untuk memperkenalkan siswa pada berbagai konsep untuk mengajarkan materi pengajaran yang dapat diintegrasikan ke dalam ilmu alam termasuk kimia. Penelitian ini bertujuan untuk mendeskripsikan penyajian aspek-aspek STEM pada bahan ajar kimia SMA kelas XI pada materi laju reaksi. Metode pada penelitian ini adalah metode deskriptif kualitatif dengan pendekatan analisisisi. Sumber data berasal dari bahan ajar kimia SMA kelas XI yang paling banyak digunakan di Kota Pematangsiatar sejumlah tiga buku. Teknik pengambilan objek penelitian menggunakan teknik purposive sampling. Pengumpulan data dilakukan menganalisis materi berdasarkan indikator STEM. Uji validitas instrumen menggunakan formula Gregory sedangkan uji validitas data menggunakan triangulasi data. Hasil penelitian menunjukkan bahwa presentase kemunculan kutipan pada setiap buku yaitu pada buku A memiliki aspek Science 30 %, Technology 40 %, dan Mathematic 30 %. Pada buku B aspek Science 19,05 %, Technology 42,86 %, Engineering 9,52 % dan Mathematic 28, 57 %. Pada buku C yaitu aspek Science sebesar 25 %, Technology 25 %, Engineering 18,75 % dan Mathematic 31,25 %. Berdasarkan total kemunculan indicator aspek STEM, maka urutan bahan ajar yang memenuhi aspek STEM adalah Buku B > Buku C > Buku A, sehingga buku B memiliki jumlah kemunculan kutipan aspek STEM paling banyak.

Abstract Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation of Piezo1 (Piezo1 Col2a1Cre ), but not of Piezo2, developed a near absence of trabecular bone below the chondrogenic growth plate postnatally. Moreover, all Piezo1 Col2a1Cre animals displayed multiple fractures of rib bones at 7 days of age, which were located close to the growth plates. While skeletal growth was only mildly affected in these mice, OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age. Likewise, when OA was induced by anterior cruciate ligament transection, only the chondrocyte inactivation of Piezo1, not of Piezo2, resulted in attenuated articular cartilage degeneration. Importantly, osteophyte formation and maturation were also reduced in Piezo1 Col2a1Cre mice. We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes. Finally, we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes. Collectively, our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes, but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

Abstract Antibiotic resistance in staphylococcal strains and its impact on public health and agriculture are global problems. The development of new anti-staphylococcal agents is an effective strategy for addressing the increasing incidence of bacterial resistance. In this study, ethanolic extracts of Cannabis sativa L. made from plant parts harvested during the whole vegetation cycle under various nutritional treatments were assessed for in vitro anti-staphylococcal effects. The results showed that all the cannabis extracts tested exhibited a certain degree of growth inhibition against bacterial strains of Staphylococcus aureus, including antibiotic-resistant and antibiotic-sensitive forms. The highest antibacterial activity of the extracts was observed from the 5th to the 13th week of plant growth across all the nutritional treatments tested, with minimum inhibitory concentrations ranging from 32 to 64 µg/mL. Using HPLC, Δ9-tetrahydrocannabinolic acid (THCA) was identified as the most abundant cannabinoid in the ethanolic extracts. A homolog of THCA, tetrahydrocannabivarinic acid (THCVA), reduced bacterial growth by 74%. These findings suggest that the cannabis extracts tested in this study can be used for the development of new anti-staphylococcal compounds with improved efficacy.

Abstract Background It is estimated that since 2014, approximately 7.3 million Venezuelan migrants/refugees have left the country. Although both male and female migrants/refugees are vulnerable, female migrants/refugees are more likely to face discrimination, emotional, physical, and sexual violence. Currently there is a lack of literature that explores the experiences of pregnant Venezuelan migrants/refugees. Our aim is to better understand the experience of this vulnerable population to inform programming. Methods In the parent study, Spryng.io’s sensemaking tool was used to gain insight into the gendered migration experiences of Venezuelan women/girls. A total of 9339 micronarratives were collected from 9116 unique participants in Peru, Ecuador and Brazil from January to April 2022. For the purpose of this analysis, two independent reviewers screened 817 micronarratives which were identified by the participant as being about someone who was pregnant, ultimately including 231 as part of the thematic analysis. This was an exploratory study and an open thematic analysis of the narratives was performed. Results The mean age and standard deviation of our population was 25.77 ± 6.73. The majority of women in the sample already had at least 1 child (62%), were married at the time of migration (53%) and identified as low socio-economic status (59%). The qualitative analysis revealed the following main themes among pregnant Venezuelan migrants/refugees: xenophobia in the forms of racial slurs and hostile treatment from health-care workers while accessing pregnancy care; sexual, physical, and verbal violence experienced during migration; lack of shelter, resources and financial support; and travelling with the hopes of a better future. Conclusion Pregnant Venezuelan migrants/refugees are a vulnerable population that encounter complex gender-based and societal issues that are rarely sufficiently reported. The findings of this study can inform governments, non-governmental organizations, and international organizations to improve support systems for pregnant migrants/refugees. Based on the results of our study we recommend addressing xenophobia in health-care centres and the lack of shelter and food in host countries at various levels, creating support spaces for pregnant women who experience trauma or violence, and connecting women with reliable employment opportunities and maternal healthcare.

Izhodišča: Na podlagi prehranske obravnave in postavljene diagnoze motnja prehranjenosti ali s prehranjenostjo povezane motnje lahko oblikujemo posamezniku prilagojeni načrt prehranskih ukrepov. Ta je nujen, da vzdržujemo ali izboljšamo posameznikovo prehranjenost, pripravijo in izvajajo pa ga bolnik, njegovi bližnji in večstrokovna skupina, ki deluje v okviru različnih organizacijskih oblik ukvarjanja s klinično prehrano. Metode: Skupina 42 slovenskih strokovnjakov iz 19 slovenskih zdravstvenih ustanov je oblikovala eksplicitni terminološki dogovor. Osnovnim pojmom s področja prehranske oskrbe in organizacijskih oblik klinične prehrane smo določili slovenski termin in ustrezno terminološko definicijo, pri čemer smo izhajali tako iz strokovne literature področja kot iz jezikoslovne literature. Temelj oblikovanja terminologije so terminološke smernice Evropskega združenja za klinično prehrano in presnovo. Rezultati: V prispevku predstavljamo slovenske termine in terminološke definicije načrta prehranskih ukrepov, prehranske podpore in prehranske terapije. Opredelili smo tudi prehransko okolje, diete, paliativno prehrano in oblike hrane ter hranjenja v klinični prehrani. Opisali smo tudi možnosti za organizacijo prehranske oskrbe v zdravstvenih in negovalnih ustanovah. Zaključek: Poenoteno razumevanje osnovnih pojmov s področja prehranske terapije, prehranske podpore in organizacijskih oblik klinične prehrane je nujno za uspešno sporazumevanje med strokovnjaki, poenoteno poučevanje in razvoj ter vključitev organizacijskih oblik klinične prehrane v zdravstveni sistem.

Abstract Analyzing seismic data in a timely manner is essential for potential eruption forecasting and early warning in volcanology. Here, we demonstrate that unsupervised machine learning methods can automatically uncover hidden details from the continuous seismic signals recorded during Iceland’s 2021 Geldingadalir eruption. By pinpointing the eruption’s primary phases, including periods of unrest, ongoing lava extrusion, and varying lava fountaining intensities, we can effectively chart its temporal progress. We detect a volcanic tremor sequence three days before the eruption, which may signify impending eruptive activities. Moreover, the discerned seismicity patterns and their temporal changes offer insights into the shift from vigorous outflows to lava fountaining. Based on the extracted patterns of seismicity and their temporal variations we propose an explanation for this transition. We hypothesize that the emergence of episodic tremors in the seismic data in early May could be related to an increase in the discharge rate in late April.

To mitigate dangerous climate change, a drastic reduction of CO2 emissions is needed by 2030. Buildings contribute significantly to emissions, with the use phase of existing buildings being responsible for the majority of energy consumption. In addition, environmental problems associated with the production of raw materials, construction, and the end of life of buildings are serious concerns that require urgent solutions. Life cycle assessment (LCA) and the EU-recommended Environmental Footprint (EF) are widely accepted tools to measure environmental impacts throughout a product life cycle. However, assessing the environmental performance of wooden buildings remains a challenge. This study presents a benchmark for an average new European wooden building fulfilling the European nearly Zero Energy Building (nZEB) requirement. The benchmark utilizes the recommended EU EF impact categories with normalization and weighting, allowing for easy and quick comparisons. The results communicate the average environmental impact per square meter of floor area over one year. This benchmark is a suitable comparison point for new wooden building designs and is used as an effective tool for architects and designers during the initial planning stages of wooden buildings. By using this benchmark, the environmental performance of the building can be improved, and the communication and interpretation of LCA results can be facilitated for customers and other relevant stakeholders.

The increase in childhood obesity is one of the biggest public health problems of the 21st century. Among the contributing dietary factors is the high consumption of sugar-sweetened beverages (SSB) and sweetened fruit juices (SFJ). On the other hand, regular consumption of milk and dairy products has decreased in many countries over the years, although research has shown an inverse association between dairy consumption and obesity. The aim of this study was to determine the effects of a dietary intervention within a multidisciplinary structured programme on reducing the consumption of SSB and SFJ and simultaneously increasing the consumption of milk and diary products in obese children/adolescents. The study included 100 participants of both sexes who had been diagnosed with obesity and participated in a five-day multidisciplinary structured programme focused on dietary intrevention. Standard anthropometric measurements and a validated questionnaire were used during the study. The mean age of the participants was 12.61±1.90 years, body mass index (BMI) was 98.38±1.26 percentiles; mean consumption of SSB was 1.68 ± 2.89 dL; SFJ was 3.72±5.09 dL and milk and dairy products was 3.10±2.35 dL per day at the start of the intervention. After the five-day programme, patients were reeducated once a month for the first six months, then every two months for up to 24 months. After 24 months, a significant decrease in SSB and SFJ intake (p

Studies suggest that central venous catheter bloodstream infections (BSIs) increased during the COVID-19 pandemic. We investigated catheter-related BSIs in Switzerland and found peripheral venous catheter (PVC) BSI incidence increased during 2021–2022 compared with 2020. These findings should raise awareness of PVC-associated BSIs and prompt inclusion of PVC BSIs in surveillance systems.

Abstract Non-invasive prenatal tests for the detection of fetal aneuploidies are predominantly based on the analysis of cell-free DNA (cfDNA) from the plasma of pregnant women by next-generation sequencing. The development of alternative tests for routine genetic laboratories is therefore desirable. Multiplex digital droplet PCR was used to detect 16 amplicons from chromosome 21 and 16 amplicons from chromosome 18 as the reference. Two fluorescently labeled lock nucleic acid probes were used for the detection of reaction products. The required accuracy was achieved by examining 12 chips from each patient using Stilla technology. The plasma cfDNA of 26 pregnant women with euploid pregnancies and 16 plasma samples from pregnancies with trisomy 21 were analyzed to determine the cutoff value for sample classification. The test was validated in a blind study on 30 plasma samples from pregnant patients with a risk for trisomy 21 ranging from 1:4 to 1:801. The results were in complete agreement with the results of the invasive diagnostic procedure (sensitivity, specificity, PPV, and NPV of 100%). Low cost, and speed of analysis make it a potential screening method for implementation into the clinical workflow to support the combined biochemical and ultrasound results indicating a high risk for trisomy 21.

Introduction: Selected anthropometric indicators, such as anthropometric measurements, indices, or ratios could be reliable predictors of future cardiometabolic risk in primary prevention, especially in young adults. Aim: This study aimed to establish cardiometabolic risk status in young Eastern Slovak adults according to anthropometric indicators. Material and methods: Indicators used in this study, such as heart rate, blood pressure, five anthropometric measurements, as well as a total of 23 anthropometric indices and ratios were selected based on the available literature. These indicators were analyzed in 162 young adult participants of both sexes with a mean age of 20.78±2.22 years. The analyzed indices and ratios were calculated by routine anthropometry and were correlated with blood pressure and heart rate in the whole research group as well as among subgroups divided according to sex, obesity and hypertension status. Results: Our results showed frequently higher values of input characteristics in males (71.88%), and statistically significant differences between sexes in 81.25% of the characteristics. The values of systolic blood pressure were above the norm in all males, and they also dominated in the obesity group. Correlation analyses conducted on all participants and in subgroups indicated a positive statistical significance in several indicators. The vast majority of the anthropometric indicators were significantly correlated with physiological indicators in almost all subgroups. Only A body shape index (ABSI) correlation coefficients did not show a significant correlation with physiological indicators in all analyzed subgroups. The correlations tended to be stronger among subgroup exhibiting potential to obesity. All analyzed indices and ratios were significantly correlated (p ≤ 0.05), predominantly with blood pressure components rather than heart rate, especially in participants with the potential for disease complications than in participants without them. Conclusion: The analyzed indicators are noninvasive and useful although they may be at different levels of association and clinical significance for various conditions. Thus some of the indicators may be standardly used in the early diagnostic process for monitoring cardiovascular health and risk stratification of patients.

Izhodišča: Pomembno vlogo pri prehranski obravnavi imata tako presejanje prehranske ogroženosti kot prehranski pregled, na podlagi katerega lahko postavimo diagnozo motnje prehranjenosti ali s prehranjenostjo povezane motnje. Ocena posameznikovega prehranskega stanja, ki jo pridobimo s prehransko obravnavo, je namreč ključna za načrtovanje učinkovite prehranske oskrbe. Za razvoj področja je pomembno, da so vsi termini, ki se uporabljajo pri kliničnem delu, usklajeni. Taki terminološki dokumenti v mednarodnem prostoru že obstajajo, smiselni pa so tudi za slovenščino in naše okolje. Metode: Prispevek temelji na eksplicitnem terminološkem dogovoru skupine 42 relevantnih slovenskih strokovnjakov iz 19 slovenskih ustanov. Osnova oblikovanja terminoloških smernic je terminološki dokument Evropskega združenja za klinično prehrano in presnovo, pri čemer so bili upoštevani tudi novejši izsledki klinične prehrane. Rezultati: Predstavljeni so slovenski termini in terminološke definicije s področja klinične prehrane. Opredeljeni so osnovni pojmi s področja prehranske obravnave, ki je praviloma del medicinske obravnave. Predstavljena sta pojma prehranska ogroženost in presejanje prehranske ogroženosti, ob čemer so navedeni tudi različni presejalni testi za presejanje prehranskih motenj in s prehranjenostjo povezanih stanj. Podrobno so opredeljeni tudi prehranski pregled in njegovi sestavni deli. Zaključki: Tako presejanje prehranske ogroženosti kot prehranski pregled sta bistvena za diagnostično obravnavo v okviru klinične prehrane, poenoteno razumevanje terminologije pa omogoča primerno prepoznavo patoloških stanj pri bolnikih in pripravo ustreznega načrta prehranskih ukrepov.

Abstract The Northwest Tailings Containment Area at the inactive Giant Mine (Canada) contains a complex mixture of arsenic-containing substances, including flotation tailings (84.8 wt%; with 0.4 wt% residual S), roaster calcine wastes (14.4 wt% Fe oxides), and arsenic trioxide (0.8 wt%) derived from an electrostatic precipitator as well as As-containing water (21.3 ± 4.1 mg L−1 As) derived from the underground mine workings. In the vadose zone the tailings pore water has a pH of 7.6 and contains elevated metal(loid)s (2.37 ± 5.90 mg L−1 As); mineral oxidizers account for 2.5% of total 16S rRNA reads in solid samples. In the underlying saturated tailings, dissolved Fe and As concentrations increase with depth (up to 72 and 20 mg L−1, respectively), and the mean relative abundance of Fe(III)-reducers is 0.54% of total reads. The potential for As mobilization via both reductive and oxidative (bio)processes should be considered in Giant Mine remediation activities. The current remediation plan includes installation of an engineered cover that incorporates a geosynthetic barrier layer.

This study evaluated the effect of different feed pushing-up frequencies on the behavior, dry matter intake and milk production of dairy cows in the first lactation. In each monitoring, 32 - 37 dairy cows of Czech spotted cattle at the peak of lactation were represented. After the feed was delivered to cows, the feed was pushed-up 2, 3, 4, 5, or 6 times in 5 different frequencies within 12 hours. Each frequency was monitored for 1 month in four repetitions. The behavior of dairy cows during feeding was monitored for 15 minutes after the feed delivery and after each food pushing-up. We evaluated how often the dairy cows came to the feeding table, how they used mixed ration and milk production. The frequency of feed pushing-ups has shown an effect on the dairy cow's milk yield. As a result of the 2, 3, 4, 5 and 6 feed pushing-up frequencies, the average milk production per cow per day was 24.52; 25.84; 25.48; 25.78; 26.03 kg. Also feed conversion increased with the frequency of feed pushing-ups to 1.22; 1.29; 1.25; 1.30 aand nd 1.30 kg of milk from 1 kg of received dry matter. TMR dry matter utilization increased by 1% on average.

Abstract There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p

Abstract Background People who use substances (PWUS) encounter significant barriers to accessing care for their complex health needs. As a result, emergency departments (EDs) often become the first point of healthcare access for many PWUS and are a crucial setting for the study of health inequities. This study aimed to understand the ED healthcare experiences of PWUS with the intent of informing ways of improving the delivery of equitable care. Methods This qualitative study was part of a larger cross-sectional, mixed-methods study that examined ED experiences among diverse underserved and equity-deserving groups (EDGs) within Kingston, Ontario, Canada. Participants shared and self-interpreted a story about a memorable ED or UCC visit within the preceding 24 months. Data from participants who self-identified as having substance use experiences was analyzed through inductive thematic analysis. Results Of the 1973 unique participants who completed the survey, 246 participants self-identified as PWUS and were included in the analysis. Most participants were

While brewer’s yeast (Saccharomyces cerevisiae), a rich source of proteins and B vitamins, is commonly used as an animal feed supplement, its use in aquaculture has been limited. Here, we assess its impact on 192 individuals of common carp (Cyprinus carpio) production and haematological and biochemical parameters from blood plasma using a control group fed commercial feed with 20% soybean meal and three test groups fed commercial feed with (i) 17.50% soybean + 2.50% brewer’s yeast (group B-2.5), (ii) 15% soybean + 5% yeast (group B-5) and (iii) 10% soybean and 10% yeast (group B-10). At the end of the experiment, all fish were weighed and measured and subsequently blood samples were taken from eight fish in each tank. There was a significant increase in total length (3%) and weight (5.37%) in group B-5. While fish muscle nitrogenous matter and protein efficiency ratio increased slowly across experimental groups, Fulton’s and Clark’s condition factors changed minimally (range 2.73–2.89%). Apparent net protein utilisation increased to 17.63% in B-10, suggesting that increasing yeast levels result in improved nitrogen utilisation. All fish muscle fat levels were within optimal range (4.16–4.68%) and, while there was a significant increase in erythrocytes in B-5 (up 0.40 T.L−1), haemoglobin levels increased only slightly in B-5 and B-10 (average 4.50 g.L−1) and B-10 had the lowest number of leukocytes (6.8 G.L−1). No significant changes were recorded in blood plasma biochemical parameters. Our results suggest that a 5% brewer’s yeast feed supplement represents a useful protein source for carp aquaculture.

(1) Background: Analyses of retrieved inserts allow for a better understanding of TKA failure mechanisms and the detection of factors that cause increased wear. The purpose of this implant retrieval study was to identify whether insert volumetric wear significantly differs among groups of common causes of total knee arthroplasty failure, whether there is a characteristic wear distribution pattern for a common cause of failure, and whether nominal insert size and component size ratio (femur-to-insert) influence linear and volumetric wear rates. (2) Methods: We digitally reconstructed 59 retrieved single-model cruciate-retaining inserts and computed their articular load-bearing surface wear utilizing an optical scanner and computer-aided design models as references. After comprehensively reviewing all cases, each was categorized into one or more of the following groups: prosthetic joint infection, osteolysis, clinical loosening of the component, joint malalignment or component malposition, instability, and other isolated causes. The associations between volumetric wear and causes of failure were estimated using a multiple linear regression model adjusted for time in situ. Insert linear penetration wear maps from the respective groups of failure were further processed and merged to create a single average binary image, highlighting a potential wear distribution pattern. The differences in wear rates according to nominal insert size (small vs. medium vs. large) and component size ratio (≤1 vs. >1) were tested using the Kruskal–Wallis test and the Mann–Whitney test, respectively. (3) Results: Patients with identified osteolysis alone and those also with clinical loosening of the component had significantly higher volumetric wear when compared to those without both causes (p = 0.016 and p = 0.009, respectively). All other causes were not significantly associated with volumetric wear. The instability group differentiated from the others with a combined peripheral antero-posterior wear distribution. Linear and volumetric wear rates showed no significant differences when compared by nominal insert size (small vs. medium vs. large, p = 0.563 and p = 0.747, respectively) or by component (femoral-to-insert) size ratio (≤1 vs. >1, p = 0.885 and p = 0.055, respectively). (4) Conclusions: The study found increased volumetric wear in cases of osteolysis alone, with greater wear when combined with clinical loosening compared to other groups. The instability group demonstrated a characteristic peripheral anterior and posterior wear pattern. Insert size and component size ratio seem not to influence wear rates.

Rapid technological advancements in recent years have opened the door to innovative solutions in the field of telecommunications and wireless systems; thus, new materials and manufacturing methods have been explored to satisfy this demand. This paper aims to explore the application of low-cost, commercially available 3D-printed ceramic/polymer composite filaments to design dielectric resonators (DRs) and check their suitability for use in high-frequency applications. Three-dimensional printing was used to fabricate the three-dimensional dielectric resonant prototypes. The filaments were characterized in terms of their thermal and mechanical properties and quality of printability. Additionally, the filaments’ dielectric properties were analyzed, and the prototypes were designed and simulated for a target frequency of ~2.45 GHz. Afterward, the DRs were successfully manufactured using the 3D printing technique, and no post-processing techniques were used in this study. A simple and efficient feeding method was used to finalize the devices, while the printed DRs’ reflection coefficient (S11) was measured. Results on prototype size, manufacture ease, printability, cost per volume, and bandwidth (BW) were used to evaluate the materials’ suitability for high-frequency applications. This research presents an easy and low-cost manufacturing process for DRs, opening a wide range of new applications and revolutionizing the manufacturing of 3D-printed high-frequency devices.

Beyond the human-related conception, Urban Science is a broad concept that includes and concerns various interconnected issues linked to Natural, Engineering, Human, Social, and Computational Sciences. Natural Science is represented by issues linked to GeoScience and BioScience. GeoScience issues concern (i) the physical-environmental aspects linked to (a) design, planning, and expansion of the urban environment; (b) urban management interventions; (c) prevention and (d) mitigation of natural and human-induced risks; (e) defense against natural and human-induced risks and (ii) cultural aspects linked to (a) educational purposes and (b) promoting, enhancing, and disseminating scientific as well as territorial and environmental knowledge and awareness. Geoscience is represented also by Street Geology, a silent geology mainly present in historical centers of urban areas, but not only, and that can be used as an educational tool, an opportunity for broader discussions on geological-environmental and socio-cultural issues. Look, see, understand, and take awareness are four steps that give voice to street geology. This paper highlights some aspects of GeoScience in two different urban areas, located in Southern Italy, represented by (a) the Longobard Walls of Benevento (BN) and (b) the 1794 Vesuvius’ lava flow in Torre del Greco (NA).

Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins such as collagen I to promote cell adhesion. While studies have demonstrated the significant benefits of culturing cells on collagen I, its effects on the HepG2 cell line after exposure to palmitate (PA) have not been investigated. Therefore, this study aimed to assess the effects of PA-induced lipotoxicity in HepG2 cultured in the absence or presence of collagen I. HepG2 cultured in the absence or presence of collagen I was exposed to PA, followed by analyses that assessed cell proliferation, viability, adhesion, cell death, mitochondrial respiration, reactive oxygen species production, gene and protein expression, and triacylglycerol accumulation. Culturing HepG2 on collagen I was associated with increased cell proliferation, adhesion, and expression of integrin receptors, and improved cellular spreading compared to culturing them in the absence of collagen I. However, PA-induced lipotoxicity was greater in collagen I-cultured HepG2 than in those cultured in the absence of collagen I and was associated with increased α2β1 receptors. In summary, the present study demonstrated for the first time that collagen I-cultured HepG2 exhibited exacerbated cell death following exposure to PA through integrin-mediated death. The findings from this study may serve as a caution to those using 2D models or 3D scaffold-based models of HepG2 in the presence of collagen I.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Background Significant progress in the field of cystic fibrosis (CF) has substantially extended the life expectancy of patients with CF (pwCF). Consequently, the population of adult pwCF has outnumbered paediatric patients in most developed countries. Ageing is a new factor that can contribute to disease complexity and can require adaptation of CF units. Therefore, the necessity for standardised, specialised and multidisciplinary care is imperative. Concerns arise regarding the adequacy of current healthcare, therapeutic and educational offerings. Methods To address these concerns, a multinational survey was conducted to assess the current state of care in specialised multidisciplinary adult and paediatric CF units and identify areas for improvement. Responses were collected from 44 centres providing regular care to CF patients. Results The survey unveiled considerable disparities in the availability of critical resources, including diagnostic access, supplementary testing, treatment modalities, transplant and transition programmes, and healthcare professionals’ training. Conclusion This study underscores the urgent need to standardise care across these centres in order to minimise disparities in terms of available resources and training with a particular emphasis on adult pwCF who are becoming more numerous and showing different needs with ageing. The changing landscape of CF in adulthood will require constant monitoring to ensure proper adaptation of the current model of care.

This editorial of JASC explores the notion of awareness-based approach to collective action for social change as embodying a "Third Option". Such an approach is characterized by transcending binary thinking and advocating for new ontological and epistemological paradigms that challenge conventional dualities, promoting relationality, interdependence, and inclusivity. This editorial advocates for approaches that honor the relational essence of existence, fostering genuine connections that acknowledge and transcend differences. Emphasizing the importance of ethical engagement and the integration of Indigenous wisdom, this issue calls for a holistic reimagining of our systems, grounded in humility and relational accountability. The editorial concludes by affirming the potential of collective action, inspired by place and purpose, to create just, sustainable, and life-affirming futures.

In the context of polycrisis and systemic collapse, the primary challenge we face is a widely shared sense of collective depression—a lack of agency in regard to the bigger picture. What does it take to serve evolutionary transformation in the face of systemic collapse? In our view, it takes a form of knowing which extends beyond the current constructs of first-, second- and third-person knowing around which much of our current learning, knowledge, and leadership systems are organized. In this paper, we suggest fourth-person knowing as a distinct epistemology at the intersection of the other three, and we draw on our action research to illuminate five phenomena that point to and distinguish fourth-person knowing: (1) knowing that comes through me but is not of me; (2) knowing that shows up in my individual experience as a decentering of perception; (3) a heightened sense of potential, of possibilities that previously were experienced as unattainable now appear to be in reach; (4) sensing your own agency in helping the ‘universe’ (the larger field) to evolve; and (5) significant long term impact in terms of practical results. It is our hope that by articulating fourth person knowing we can provide an epistemic basis upon which research and inquiry methodologies can be built, complementing first-, second- and third-person forms of inquiry, methodologies based on deep sensing and presencing that support individuals and collectives to recognize, connect with and manifest what is theirs to do in the wider context of this moment and the incipient patterns of emergence and movement making.

Este estudio pretende desvelar uno de los códigos secretos más utilizados por Carlos V en las cartas escritas en francés y enviadas al embajador Simon Renard entre 1549 y 1554. Nos centraremos en particular en una carta cifrada enviada en 1554 y conservada en la Bibliothèque municipale de Besançon. De este modo, veremos cómo se utilizó este lenguaje cifrado para tratar la cuestión del matrimonio entre María Tudor y Felipe de España. Esta carta nos permitirá ilustrar el tipo de contenido susceptible de ser cifrado. A continuación, explicaremos el funcionamiento de dicha cifra y veremos cómo se codificó la lengua francesa para salvaguardar los secretos del imperio.

BackgroundIn early infected or severe coronavirus disease 2019 (COVID-19) patients, circulating NK cells are consistently reduced, despite being highly activated or exhausted. The aim of this paper was to establish whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (SP) may directly trigger NK cells and through which receptor(s).MethodsSP-stimulated human NK cells have been evaluated for the expression of activation markers, cytokine release, and cytotoxic activity, as well as for gene expression profiles and NF-kB phosphorylation, and they have been silenced with specific small interfering RNAs.ResultsSPs from the Wuhan strain and other variants of concern (VOCs) directly bind and stimulate purified NK cells by increasing activation marker expression, cytokine release, and cytolytic activity, prevalently in the CD56brightNK cell subset. VOC-SPs differ in their ability to activate NK cells, G614, and Delta-Plus strains providing the strongest activity in the majority of donors. While VOC-SPs do not trigger ACE2, which is not expressed on NK cells, or other activating receptors, they directly and variably bind to both Toll-like receptor 2 (TLR2) and TLR4. Moreover, SP-driven NK cell functions are inhibited upon masking such receptors or silencing the relative genes. Lastly, VOC-SPs upregulate CD56dimNK cell functions in COVID-19 recovered, but not in non-infected, individuals.ConclusionsTLR2 and TLR4 are novel activating receptors for SP in NK cells, suggesting a new role of these cells in orchestrating the pathophysiology of SARS-CoV-2 infection. The pathogenic relevance of this finding is highlighted by the fact that free SP providing NK cell activation is frequently detected in a SARS-CoV-2 inflamed environment and in plasma of infected and long-COVID‐19 subjects.

Within the islets of Langerhans, beta cells orchestrate synchronized insulin secretion, a pivotal aspect of metabolic homeostasis. Despite the inherent heterogeneity and multimodal activity of individual cells, intercellular coupling acts as a homogenizing force, enabling coordinated responses through the propagation of intercellular waves. Disruptions in this coordination are implicated in irregular insulin secretion, a hallmark of diabetes. Recently, innovative approaches, such as integrating multicellular calcium imaging with network analysis, have emerged for a quantitative assessment of the cellular activity in islets. However, different groups use distinct experimental preparations, microscopic techniques, apply different methods to process the measured signals and use various methods to derive functional connectivity patterns. This makes comparisons between findings and their integration into a bigger picture difficult and has led to disputes in functional connectivity interpretations. To address these issues, we present here a systematic analysis of how different approaches influence the network representation of islet activity. Our findings show that the choice of methods used to construct networks is not crucial, although care is needed when combining data from different islets. Conversely, the conclusions drawn from network analysis can be heavily affected by the pre-processing of the time series, the type of the oscillatory component in the signals, and by the experimental preparation. Our tutorial-like investigation aims to resolve interpretational issues, reconcile conflicting views, advance functional implications, and encourage researchers to adopt connectivity analysis. As we conclude, we outline challenges for future research, emphasizing the broader applicability of our conclusions to other tissues exhibiting complex multicellular dynamics.