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Present and future climatic trends are expected to markedly alter water fluxes and stores in the hydrologic cycle. In addition, water demand continues to grow due to increased human use and a growing population. Sustainably managing water resources requires a thorough understanding of water storage and flow in natural, agricultural, and urban ecosystems. Measurements of stable isotopes of water (hydrogen and oxygen) in the water cycle (atmosphere, soils, plants, surface water, and groundwater) can provide information on the transport pathways, sourcing, dynamics, ages, and storage pools of water that is difficult to obtain with other techniques. However, the potential of these techniques for practical questions has not been fully exploited yet. Here, we outline the benefits and limitations of potential applications of stable isotope methods useful to water managers, farmers, and other stakeholders. We also describe several case studies demonstrating how stable isotopes of water can support water management decision-making. Finally, we propose a workflow that guides users through a sequence of decisions required to apply stable isotope methods to examples of water management issues. We call for ongoing dialogue and a stronger connection between water management stakeholders and water stable isotope practitioners to identify the most pressing issues and develop best-practice guidelines to apply these techniques.

BACKGROUND & AIMS: Lacticaseibacillus rhamnosus GG (LGG) is the worlds most consumed probiotic but its mechanism of action on intestinal permeability and differentiation along with its interactions with an essential source of signaling metabolites, dietary tryptophan (trp), are unclear. METHODS: Untargeted metabolomic and transcriptomic analyses were performed in LGG monocolonized germ-free mice fed trp-free or -sufficient diets. LGG-derived metabolites were profiled in vitro under anaerobic and aerobic conditions. Multiomic correlations using a newly developed algorithm discovered novel metabolites tightly linked to tight junction and cell differentiation genes whose abundances were regulated by LGG and dietary trp. Barrier-modulation by these metabolites were functionally tested in Caco2 cells, mouse enteroids, and dextran sulfate sodium experimental colitis. The contribution of these metabolites to barrier protection is delineated at specific tight junction proteins and enterocyte-promoting factors with gain and loss of function approaches. RESULTS: LGG, strictly with dietary trp, promotes the enterocyte program and expression of tight junction genes, particularly Ocln. Functional evaluations of fecal and serum metabolites synergistically stimulated by LGG and trp revealed a novel vitamin B3 metabolism pathway, with methylnicotinamide (MNA) unexpectedly being the most robust barrier-protective metabolite in vitro and in vivo. Reduced serum MNA is significantly associated with increased disease activity in patients with inflammatory bowel disease. Exogenous MNA enhances gut barrier in homeostasis and robustly promotes colonic healing in dextran sulfate sodium colitis. MNA is sufficient to promote intestinal epithelial Ocln and RNF43, a master inhibitor of Wnt. Blocking trp or vitamin B3 absorption abolishes barrier recovery in vivo. CONCLUSIONS: Our study uncovers a novel LGG-regulated dietary trp-dependent production of MNA that protects the gut barrier against colitis.

Over the course of fifty years, Gianni Vattimo was a friend, teacher, and adversary for me. I must resist the temptation to speak here of my own memories of him in order to provide readers of this brief essay with what I think is destined to endure after Vattimo’s death, the essence of which can be found in the collection of his writings entitled Scritti filosofici e politici (Philosophical and Political Writings).

Abstract Background Cancer navigation programs aim to support, educate, and empower patients and families, addressing barriers to diagnostics, treatment, and care. Navigators engage with people to ensure timely access to services and resources. While promising for older people with cancer, these programs are scarce in Europe, and research on their effectiveness and implementation is limited. We describe the protocol of the EU NAVIGATE randomized controlled trial, aimed to evaluate (1) effectiveness and cost-effectiveness of NavCare-EU, an intervention that aims to support older people with cancer throughout their illness trajectory, spanning the continuum of supportive, palliative, and end-of-life care, and (2) the intervention’s implementation processes and feasibility of its integration into different health care systems in Europe, contextual barriers and facilitators for effective and sustainable implementation, and mechanisms involved in reaching the outcomes. Methods We will conduct a multisite pragmatic fast-track randomized controlled trial with embedded convergent mixed-method process evaluation in Belgium, Ireland, Italy, Netherlands, Poland, and Portugal. The study targets people with cancer and declining health, 70 years or older, and their close family caregivers. The trial compares the NavCare-EU intervention plus standard care with standard care alone. We will perform a baseline measurement prior to randomization and follow-up measurements at 12 weeks, 24 weeks, and 48 weeks in intervention and control group, and an additional measurement at 72 weeks in the control group. Primary outcomes, measured at 24 weeks are (1) the older person’s global health status/quality of life, a 2-item subscale from EORTC-QLQ-C30 (revised) measuring health-related quality of life, (2) level of social support measured with Medical Outcomes Study Social Support Survey (MOS-SSS scale). The study will include at least 246 older persons with completed global health status/quality of life at 24 weeks. Discussion The EU NAVIGATE trial will cross-nationally test the effectiveness and cost-effectiveness of a navigation intervention for older people with cancer and their family caregivers, and its implementation in different health care systems in Europe. As continuity and access to health, social, and community care is a priority for patients and caregivers, the trial is timely and critically needed. Trial registration Clinicaltrials.gov: identifier NCT06110312 (2023/10/31).

This paper presents a statistical analysis of air temperature data from 32 stations in Italy and the UK up to 2000 m above sea level from 2002 to 2021. The data came from both highland and lowland areas in order to evaluate the differences due to both location and elevation. The analysis focused on detecting trends at annual and monthly timescales, employing ordinary least-squares (OLS), robust S-estimator regression, and Mann–Kendall (MK) and Sen's slope methods. Hierarchical clustering (HCA) using dynamic time warping (DTW) was then applied to the monthly data to analyze the intra-annual pattern similarity of trends within and across the groups. Two different regions of Europe were chosen because of the different climate and temperature trends – namely, the northern UK (smaller trends) and the northwest Italian Alps (larger trends). The main novelty of the work is to show that stations with similar locations and altitudes have similar monthly slopes by quantifying them using DTW and clustering. These results reveal the nonrandomness of different trends throughout the year and between different parts of Europe, with a modest influence of altitude in wintertime. The findings revealed that group average trends were close to the National Oceanic and Atmospheric Administration (NOAA) values for the areas in Italy and the UK, confirming the validity of analyzing a small number of stations. More interestingly, intra-annual patterns were detected commonly at the stations of each of the groups and are clearly different between them. Confirming the different climates, most highland and lowland stations in Italy exhibit statistically significant positive trends, while in the UK, both highland and lowland stations show statistically nonsignificant negative trends. Hierarchical clustering in combination with DTW showed consistent similarity between monthly patterns of means and trends within the group of stations and inconsistent similarity between patterns across groups. The use of the 12 distance correlation matrices (dcor) (one for each month) also contributes to what is the main result of the paper, which is to clearly show the different temporal patterns in relation to location and (in some months) altitude. The anomalous behaviors detected at 3 of the 32 stations, namely Valpelline, Fossano, and Aonoch Mòr, can be attributed, respectively, to the facts that Valpelline is the lowest-elevation station in its group; Fossano is the southernmost of the Italian stations, with some sublittoral influence; and Aonoch Mòr has a large number of missing values. In conclusion, these results improve our understanding of temperature spatio-temporal dynamics in two very different regions of Europe and emphasize the importance of consistent analysis of data to assess the ongoing effects of climate change. The intra-annual time patterns of temperature trends could also be compared with climate model results.

Abstract Individuals with rare skeletal disorders like Multiple Osteochondromas and Ollier Disease often experience physical and psychological burdens. Adventure therapy, with activities like sailing in outdoor settings, promotes personal growth and psychological well-being, potentially improving health-related quality of life (HRQoL). This study aimed to evaluate the impact of a sailing program on health-related quality of life and participant satisfaction in individuals with Multiple Osteochondromas and Ollier Disease. A quasi-experimental one-group pre-post design was employed, with HRQoL assessed using the EQ-5D® instrument and participant satisfaction measured via a feedback survey. Data were collected before and after the five-day sailing program conducted in the Mediterranean Sea in 2022 and 2023, involving participants diagnosed with Multiple Osteochondromas and Ollier Disease. Statistical analyses were performed using the Wilcoxon signed-rank test and McNemar’s test for paired data. A significance level of p

Abstract Embedding of cell-surface receptors into a membrane defines their dynamics but also complicates experimental characterization of their signaling complexes. The hepatocyte growth factor receptor MET is a receptor tyrosine kinase involved in cellular processes such as proliferation, migration, and survival. It is also targeted by the pathogen Listeria monocytogenes, whose invasion protein, internalin B (InlB), binds to MET, forming a signaling dimer that triggers pathogen internalization. Here we use an integrative structural biology approach, combining molecular dynamics simulations and single-molecule Förster resonance energy transfer (smFRET) in cells, to investigate the early stages of MET activation. Our simulations show that InlB binding stabilizes MET in a conformation that promotes dimer formation. smFRET reveals that the in situ dimer structure closely resembles one of two previously published crystal structures, though with key differences. This study refines our understanding of MET activation and provides a methodological framework for studying other plasma membrane receptors.

Abstract Multiplexed local charge storage, close to quantum processors at cryogenic temperatures could generate a multitude of control signals, for electronics or qubits, in an efficient manner. Such cryogenic electronics require generating quasi-static control signals with small area footprint, low noise, high stability, low power dissipation and, ideally, in a multiplexed fashion to reduce the number of input/outputs. In this work, we integrate capacitors with cryogenic high-electron mobility transistor (HEMT) arrays and demonstrate quasi-static bias generation using gate pulses controlled in time and frequency domains. Multi-channel bias generation is also demonstrated. Operation at 4 K exhibits improved bias signal variability and greatly reduced subthreshold swing, reaching values of ~6 mV/decade. Due to the very low threshold voltage of 80 mV at 4 K and the steep subthreshold swing, these circuits can provide an advantage over the silicon-based complementary metal-oxide-semiconductor equivalents by allowing operation at significantly reduced drive bias in the low output voltage regime

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.

We report a case of persistent disseminated mpox evolving over >6 months in an HIV/hepatitis B virus co-infected patient in France who had

This review discusses available evidence on the mechanisms of action of bacterial lysates, and the clinical effects of their sublingual administration. Bacterial lysates act through many immunological effects, including dendritic cell activation, modification of circulating lymphocyte subsets and antibody production. The production of salivary IgA was repeatedly shown to be induced by the sublingual administration of a prototype bacterial lysate containing soluble and corpuscular antigens. Bacterial lysates are a useful tool for the prevention of recurrent respiratory tract infections. Sublingual administration should be the preferred option.

IntroductionWalking ability is essential for maintaining functional independence, but it can be impaired by conditions like hemiplegia resulting from a stroke event. In post-stroke populations, accurately assessing gait anomalies is crucial for rehabilitation to promote functional recovery, and to prevent falls or injuries.MethodsThe aim of this study is to evaluate gait-related parameters using a solution based on a single RGB-D camera, specifically Microsoft Azure Kinect DK (MAK), on a short walkway in both healthy (n= 27) and post-stroke individuals with hemiplegia (n= 20). The spatio-temporal and center of mass (CoM) parameters estimated by this approach were compared with those obtained from a gold standard motion capture (MoCap) system for instrumented 3D gait analysis.ResultsThe overall findings demonstrated high levels of accuracy (> 93%), and strong correlations (r > 0.9) between the parameters estimated by the two systems for both healthy and hemiplegic gait. In particular, some spatio-temporal parameters showed excellent agreement in both groups, while CoM displacements exhibited slightly lower correlation values in healthy individuals.DiscussionThe results of the study suggest that a solution based on a single optical sensor could serve as an effective intermediate tool for gait analysis, not only in clinical settings or controlled environments but also in those contexts where gold standard systems are not feasible.

Background Central nervous system (CNS)-active polypharmacy is frequent and potentially harmful in older patients. Data on its burden outside the USA and European countries remain limited. Aims To estimate the period prevalence of and factors associated with out-of-hospital CNS-active polypharmacy in older adults. Method We used data from a cohort of out-patients aged ≥60 years affiliated to the Hospital Italiano de Buenos Aires’ health maintenance organisation on 1 January 2021. A CNS-active polypharmacy event was defined as the concurrent exposure to ≥3 CNS-active medications (i.e. antidepressants, anti-epileptics, antipsychotics, benzodiazepines, Z-drugs and opioids) through filled out-of-hospital prescriptions. We calculated the period prevalence of CNS-active polypharmacy for 2021. We identified factors associated with CNS-active polypharmacy using a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals (CI). Results We included 63 857 patients. Pre-existing mental health diagnoses included anxiety (21%), depressive (14%) and sleep (11%) disorders. CNS-active polypharmacy occurred in 4535 patients, for a period prevalence of 7.1% (95% CI: 6.9–7.3%). The combination of an antidepressant, an antipsychotic and a benzodiazepine accounted for 21% of the CNS-active polypharmacy events. Frontotemporal dementia (odds ratio: 14.67; 95% CI: 4.47–48.20), schizophrenia (odds ratio: 7.93; 95% CI: 4.64–13.56), bipolar disorder (odds ratio: 7.20; 95% CI: 5.45–9.50) and depressive disorder (odds ratio: 3.50; 95% CI: 3.26–3.75) were associated with CNS-active polypharmacy. Conclusions One in 14 adults aged 60 years and older presented out-of-hospital CNS-active polypharmacy. Future studies should evaluate measures to reduce CNS-active medication use in this population.

Background: Navigation interventions could support, educate and empower older people with cancer and/or their family caregivers by addressing barriers and ensuring timely access to needed services and resources throughout the continuum of supportive, palliative and end-of-life care. Objectives: European Union (EU) NAVIGATE is an interdisciplinary and cross-country Horizon Europe-funded project (2022–2027) aiming to evaluate the effectiveness, cost-effectiveness and implementation of a navigation intervention for older people with cancer and their family caregivers in Europe. EU NAVIGATE aims to advance the evidence on cancer patient navigation in Europe. Design: Adaptation, implementation and evaluation of a navigation intervention with an international pragmatic randomized controlled trial (RCT) and embedded mixed-method process evaluation at its core. A logic model guides dissemination and impact-generating strategies. EU NAVIGATE involves six experienced EU academic partners; one EU national cancer league with their affiliated academic partner; three EU dissemination partners; and a Canadian partner. Methods: We adapted the Canadian Navigation: Connecting, Advocating, Resourcing, and Engaging (Nav-CARE © ) volunteer programme to healthcare contexts in Belgium, Ireland, Italy, the Netherlands, Poland and Portugal following the new ADAPT guidance. Nav-CARE was developed over the past 15 years and supports people with declining health and their families to improve their quality of life and well-being, foster empowerment and facilitate timely and equitable access to healthcare and social services. In EU NAVIGATE, the navigation intervention is being provided by trained and mentored social workers in Poland and by trained and mentored volunteers in the other five countries. Via a pragmatic RCT with process evaluation, we implement and evaluate the navigation intervention to study its impact on older people with cancer and their family caregivers. We also aim to understand its cost-effectiveness, how to optimally implement it in different countries, and its differential effects in patient subgroups. We will also map existing cancer navigation interventions in Europe, the United States and Canada to position EU NAVIGATE within the field of navigation interventions worldwide. Conclusion: EU NAVIGATE aims to deliver high-quality evidence on a navigation intervention for older people with cancer in Europe and to develop practice and policy recommendations for sustainable implementation of navigation interventions in Europe and beyond.

Building on the dynamic capability perspective, this study investigates effective digitalization and digital transformation strategies in the tech industry by highlighting the relevance of the digital divide among developed and developing economies. Further, the study identifies the key challenges, opportunities, and strategies for digitalization and digital transformation. The study embraced a qualitative approach for in-depth exploration of the phenomenon through a comparative study of two countries, i.e., Hong Kong and Pakistan. Data was collected using interviews and analyzed using content analysis to identify recurring patterns and critical insights for meaningful interpretations to address the study objective. We proposed a framework for effective digitalization and digital transformation in the tech industry from the perspective of developed and developing economies. The strategies identified in this research are categorized in technopreneurship and improved human resource practices to address the challenges faced by both developed and developing countries. The study findings contribute to a deeper understanding of the digital transformation phenomenon in the wake of changing workforce dynamics and technological disruptions, as well as the digital divide between developed and developing countries. Further, the study will help policymakers devise and implement resilient strategies in the tech industry, to help reduce the digital divide.

This research focused on the detailed analytical characterization of the poultry litter-derived biochar followed by its conversion into electrodes for supercapacitor application. Biochar was prepared from poultry waste by pyrolysis at 600 °C for 3 hours and activated it by mixing with potassium hydroxide and re-pyrolyzed at the same temperature for 1 hour. Both the biochar and activated biochar were analyzed using Scanning Electron Microscopy (SEM), Infrared spectroscopy (IR), Time of Flight – Secondary Ion Mass Spectroscopy (ToF-SIMS), and X-ray Photoelectron Spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) analyses. SEM analyses suggested that the biochar’s surface became more porous and homogeneous after activation with potassium hydroxide. The specific surface area of biochar increased by more than 200 folds to 814 m2g−1 after KOH-activation confirmed from BET analysis. IR indicated the activated biochar contained sulfur- and phosphorous-functional groups but few or no oxygen-functional groups. The decrease in oxides of nitrogen, sulfur, and phosphorous was also observed in ToF-SIMS analysis. In spite of the decrease of oxides, the surface oxygen concentration (at%) increased from 42.3% to 46.6% after activation and was assumed to be present as C-O corroborated by XPS. The specific capacitance of activated biochar calculated from galvanostatic charge-discharge is 152 F/g attributed to its hierarchical porosity, heteroatoms presence, and hydrophilicity. This research is expected to contribute towards the sustainable management of agricultural wastes.