Search

Allisandra K Rha,1 Anne S Maguire,1,2 Douglas R Martin1,2 1Scott-Ritchey Research Center, Auburn University, Auburn, AL, 36849, USA; 2Department of Anatomy, Physiology, and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, 36849, USACorrespondence: Douglas R MartinScott-Ritchey Research Center, Auburn University, 1265 H.C. Morgan Drive, Auburn, AL, 36849, USATel +1 334 844 5951Email martidr@auburn.eduAbstract: The lysosomal storage disorder, GM1 gangliosidosis (GM1), is a neurodegenerative condition resulting from deficiency of the enzyme β-galactosidase (β-gal). Mutation of the GLB1 gene, which codes for β-gal, prevents cleavage of the terminal β-1,4-linked galactose residue from GM1 ganglioside. Subsequent accumulation of GM1 ganglioside and other substrates in the lysosome impairs cell physiology and precipitates dysfunction of the nervous system. Beyond palliative and supportive care, no FDA-approved treatments exist for GM1 patients. Researchers are critically evaluating the efficacy of substrate reduction therapy, pharmacological chaperones, enzyme replacement therapy, stem cell transplantation, and gene therapy for GM1. A Phase I/II clinical trial for GM1 children is ongoing to evaluate the safety and efficacy of adeno-associated virus-mediated GLB1 delivery by intravenous injection, providing patients and families with hope for the future.Keywords: GM1 gangliosidosis, gene therapy, biomarkers, chaperone, GLB1, LSD

Cheryl A Lawson,1,2 Douglas R Martin2,3 1Department of Pathobiology, 2Scott-Ritchey Research Center, 3Department of Anatomy, Physiology and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL, USA Abstract: GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. Keywords: GM2 gangliosidosis, Tay–Sachs disease, Sandhoff disease, lysosomal storage disorder, sphingolipidosis, brain disease

Abstract Background The COVID-19 pandemic necessitated the rapid availability of evidence to respond in a timely manner to the needs of practice settings and decision-makers in health and social services. Now that the pandemic is over, it is time to put in place actions to improve the capacity of systems to meet knowledge needs in a situation of crisis. The main objective of this project was thus to develop an action plan for the rapid syntheses of evidence in times of health crisis in Quebec (Canada). Methods We conducted a three-phase collaborative research project. First, we carried out a survey with producers and users of rapid evidence syntheses (n = 40) and a group interview with three patient partners to prioritize courses of action. In parallel, we performed a systematic mapping of the literature to identify rapid evidence synthesis initiatives developed during the pandemic. The results of these two phases were used in a third phase, in which we organized a deliberative workshop with 26 producers and users of rapid evidence syntheses to identifying strategies to operationalize priorities. The data collected at each phase were compared to identify common courses of action and integrated to develop an action plan. Results A total of 14 specific actions structured into four main axes were identified over the three phases. In axis 1, actions on raising awareness of the importance of evidence-informed decision-making among stakeholders in the health and social services network are presented. Axis 2 includes actions to promote optimal collaboration of key stakeholders in the production of rapid evidence synthesis to support decision-making. Actions advocating the use of a variety of rapid evidence synthesis methodologies known to be effective in supporting decision-making are presented in axis 3. Finally, axis 4 is about actions on the use of effective knowledge translation strategies to promote the use of rapid evidence synthesis products to support decision-making. Conclusions This project led to the development of a collective action plan aimed at preparing the Quebec ecosystem and other similar jurisdictions to meet knowledge needs more effectively in times of health emergency. The implementation of this plan and its evaluation will enable us to continue to fine-tune it.

The role and competencies of the chief learning officer (CLO) have been evolving, demonstrating a need to identify them from research-based evidence. In this qualitative study based on the interviews of 12 chief learning officers, we address the different roles performed by CLOs and the essential professional competencies needed for them to perform the role of a CLO, as contextualized in organizations in the United States. We developed a Chief Learning Officer Competency Model that includes 6 competency domains, 13 roles, and 31 competencies for CLOs. The findings have implications for current CLOs and professionals aspiring to serve as CLOs. The results also have implications for education and leadership graduate and professional development programs that support learning and development and business professionals with the knowledge and skills needed to grow and function as a CLO. [ABSTRACT FROM AUTHOR]

Abstract Background In critically ill patients, deep sedation and mechanical ventilation suppress the brain-diaphragm-lung axis and are associated with cognitive issues in survivors. Methods This exploratory crossover design study investigates whether phrenic nerve stimulation can enhance brain activity and connectivity in six deeply sedated, mechanically ventilated patients with acute respiratory distress syndrome. Results Our findings indicate that adding phrenic stimulation on top of invasive mechanical ventilation in deeply sedated, critically ill, moderate acute respiratory distress syndrome patients increases cortical activity, connectivity, and synchronization in the frontal-temporal-parietal cortices. Conclusions Adding phrenic stimulation on top of invasive mechanical ventilation in deeply sedated, critically ill, moderate acute respiratory distress syndrome patients increases cortical activity, connectivity, and synchronization. The observed changes resemble those during diaphragmatic breathing in awake humans. These results suggest that phrenic nerve stimulation has the potential to restore the brain-diaphragm-lung crosstalk when it has been shut down or impaired by mechanical ventilation and sedation. Further research should evaluate the clinical significance of these results.

Abstract Coordination compounds of lanthanides are indispensable in biomedical applications as MRI contrast agents and radiotherapeutics. However, since the introduction of the chelator DOTA four decades ago, there has been only limited progress on improving their thermodynamic stability and kinetic inertness, which are essential for safe in vivo use. Here, we present ClickZip, an innovative synthetic strategy employing a coordination-templated formation of a 1 ,5-triazole bridge that improves kinetic inertness up to a million-fold relative to DOTA, expanding utility of lanthanide chelates beyond traditional uses. Acting as unique mass tags, the ClickZip chelates can be released from (biological) samples by acidic hydrolysis, chromatographically distinguished from interfering lanthanide species, and sensitively detected by mass spectrometry. Lanthanides enclosed in ClickZip chelates are chemically almost indistinguishable, providing a more versatile alternative to chemically identical isotopic labels for multiplexed analysis. The bioanalytical potential is demonstrated on tagged cell-penetrating peptides in vitro, and anti-obesity prolactin-releasing peptides in vivo.

Abstract Background Social anxiety disorder (SAD) is one of the most prevalent anxiety disorders in Canada. Viable therapy options for the treatment of SAD include CBT being delivered virtually. In Australia, an innovative internet-delivered cognitive-behavioral therapy (iCBT) program for social anxiety has been developed, implemented, and demonstrated as effective. To make available high-quality and real-time evidence in response to the crucial need to access psychological services to meet population mental health needs, we propose to conduct a Canadian adaptation of the iCBT Shyness Program and to examine the program’s effectiveness, and implementation in two Canadian provinces (Quebec and Ontario). Methods The overall study design is a hybrid effectiveness-implementation study of a quasi-experimental parallel group trial. Prior to implementing the iCBT Shyness Program, it will undergo an initial adaptation to the Canadian context and focus groups will be conducted with key actor groups to discuss the adaptations to the graphics, narration of the lessons, and this to better reflect varying socio-cultural context among Canadian French- and English-speaking populations. We will evaluate the effectiveness of the program in three parallel pathways reflecting real-world pathways: (1) self-refer to the intervention; (2) recommended by a health professional without guidance; and (3) recommended by a health professional, with low-intensity guidance. Data collection will be carried out at baseline, at the beginning of each lesson, 12-week and 6-month follow-up. Outcomes measured will include anxiety and depressive symptoms, psychological distress, disability, as well as health service utilization and satisfaction. Semi-structured interviews will then be conducted with study participants and health care providers to explore facilitating factors and barriers to the implementation of the iCBT adapted program. Discussion This study will provide evidence on the effectiveness, barriers and facilitating factors to implementing a low-intensity iCBT in the Canadian context for SAD, which will bridge an important care gap for undeserved populations in Canada with SAD. Findings will inform the eventual scaling up of the program in community-based primary care across Canada. This would improve equity of the health care system by helping a large number of Canadians to timely access to mental health services. Trial registration clinicaltrials.gov NCT06403995. Prospectively registered on 05/03/2024.

Sleep cycles are defined as episodes of non-rapid eye movement (non-REM) sleep followed by an episode of REM sleep. Fractal or aperiodic neural activity is a well-established marker of arousal and sleep stages measured using electroencephalography. We introduce a new concept of ‘fractal cycles’ of sleep, defined as a time interval during which time series of fractal activity descend to their local minimum and ascend to the next local maximum. We assess correlations between fractal and classical (i.e. non-REM – REM) sleep cycle durations and study cycles with skipped REM sleep. The sample comprised 205 healthy adults, 21 children and adolescents and 111 patients with depression. We found that fractal and classical cycle durations (89±34 vs 90±25 min) correlated positively (r=0.5, p

Objectives: Evidence suggests that renal function increasingly deteriorates in patients with apparently treatment-resistant hypertension (ATRH) in comparison with those who have non-resistant arterial hypertension (NAH). We aimed to assess the long-term decline in renal function between these patient groups and identify specific risk factors contributing to the progression of renal dysfunction. Methods: Data for 265 patients with ATRH and NAH in a hypertension excellence centre were retrospectively evaluated. Demographic characteristics, co-morbidities, laboratory findings, secondary causes of hypertension, medication and exposure to contrast agents were assessed. To address differences between groups, adjustment with linear mixed-effect models was used. Results: Data from the first 4 years of follow-up were evaluated. After adjustment for age and diabetes, which were identified as independent risk factors for renal dysfunction progression in the study cohort, the mean decrease in estimated glomerular filtration rate per year was steeper with ATRH than with NAH (−1.49 vs. −0.65 mL/min/1.73 m2 per year; difference in slope, 0.83 mL/min/1.73 m2 per year; 95% confidence interval [CI]: 0.25–1.41, p = 0.005). In subgroup analyses, without Holm–Bonferroni correction, the prescription of MRA indicated a faster decline in renal function in ATRH. Following correction, no specific therapeutic risk factor was associated with faster progression of renal dysfunction. Conclusions: Renal function declines twice as fast with ATRH compared with NAH, independently of age and diabetes. Larger studies are needed to reveal risk factors for renal dysfunction in patients with hypertension.

Abstract Background With recent advancements in the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), healthcare specialists may face challenges making treatment and management decisions based on latest evidence for the optimal care of patients with these conditions. This study aimed to identify specific knowledge, skills, and confidence gaps impacting the treatment of CLL and MCL, to inform future educational activities. Methods Hematologists and hemato-oncologists (HCPs, n = 224) from France (academic settings), Germany, and the United States (academic and community settings) responded to a 15-minute quantitative needs assessment survey that measured perceived knowledge, skills, and confidence levels regarding different aspects of treatment and management of CLL and MCL patients, as well as clinical case questions. Descriptive statistics (cross tabulations) and Chi-square tests were conducted. Results Four areas of educational need were identified: (1) sub-optimal knowledge of treatment guidelines; (2) sub-optimal knowledge of molecular testing to inform CLL/MCL treatment decisions; (3) sub-optimal skills when making treatment decisions according to patient profile (co-morbidities, molecular testing results); and (4) challenges balancing the risk of toxicities with benefits of treatment. Over one-third of the respondents reported skill gaps when selecting suitable treatment options and prescribing therapies and reported a lack in confidence to initiate and manage treatment. Larger gaps in knowledge of guidelines and skills in patient assessment were identified in MCL, compared to CLL. Conclusions This study suggests the need for continuing medical education specifically to improve knowledge of treatment guidelines, and to assist clinicians in developing skills and confidence when faced with clinical decision-making scenarios of patients with specific comorbidities and/or molecular test results, for example, through case-based learning activities.

Abstract Shaping Metal–Organic Frameworks (MOFs) poses a significant challenge for their widespread application on a large scale. In particular, a precise control over crystal orientation and arrangement on substrates are expected to provide exiting opportunities for novel materials with customized characteristics and enhanced performance in catalysis, gas storage, sensing, optics and electronics. Here we demonstrated for the first time that microwave irradiation can induce well controlled epitaxial growth of urchin-like MIL-53(Al) crystals via the hydrothermal conversion of Atomic Layer Deposition alumina layers on SiC foams. The resulting large, ordered crystals feature specific size, homogeneity, dispersion, and quantity that strongly correlate with the nature of the ceramic support and its ability to absorb microwaves. Furthermore, the supported MIL-53(Al) urchins were considered as templates for generating nanostructured alumina fibers on SiC foams, providing attractive catalyst carriers with high specific surface areas.

Abstract Background Morphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF. Methods In this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support. Results Twenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 – 43] mm in the Morphine group vs. 40 [36 – 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 – 30] vs. 35 [30 – 44], p=0.044) and four hours later (18 [10 – 29] vs. 50 [30 – 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046) Conclusion In this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate. Trial registration The protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022.

ABSTRACT Multi-infection of plants by viruses is very common and can change drastically infection parameters such as virus accumulation, distribution, and vector transmission. Sugar beet is an important crop that is frequently co-infected by the polerovirus beet chlorosis virus (BChV) and the closterovirus beet yellows virus (BYV), both vectored by the green peach aphid (Myzus persicae). These phloem-limited viruses are acquired while aphids ingest phloem sap from infected plants. Here we found that co-infection decreased transmission of BChV by ~50% but had no impact on BYV transmission. The drastic reduction of BChV transmission was due to neither lower accumulation of BChV in co-infected plants nor reduced phloem sap ingestion by aphids from these plants. Using the signal amplification by exchange reaction fluorescent in situ hybridization technique on plants, we observed that 40% of the infected phloem cells were co-infected and that co-infection caused redistribution of BYV in these cells. The BYV accumulation pattern changed from distinct intracellular spherical inclusions in mono-infected cells to a diffuse form in co-infected cells. There, BYV co-localized with BChV throughout the cytoplasm, indicative of virus-virus interactions. We propose that BYV-BChV interactions could restrict BChV access to the sieve tubes and reduce its accessibility for aphids and present a model of how co-infection could alter BChV intracellular movement and/or phloem loading and reduce BChV transmission.IMPORTANCEMixed viral infections in plants are understudied yet can have significant influences on disease dynamics and virus transmission. We investigated how co-infection with two unrelated viruses, BChV and BYV, affects aphid transmission of the viruses in sugar beet plants. We show that co-infection reduced BChV transmission by about 50% without affecting BYV transmission, despite similar virus accumulation rates in co-infected and mono-infected plants. Follow-up experiments examined the localization and intracellular distribution of the viruses, leading to the discovery that co-infection caused a redistribution of BYV in the phloem vessels and altered its repartition pattern within plant cells, suggesting virus-virus interactions. In conclusion, the interplay between BChV and BYV affects the transmission of BChV but not BYV, possibly through direct or indirect virus-virus interactions at the cellular level. Understanding these interactions could be crucial for managing virus propagation in crops and preventing yield losses.

Background: This is a novel rat study using native peptide therapy, focused on reversing quadriceps muscle-to-bone detachment to reattachment and stable gastric pentadecapeptide BPC 157 per-oral therapy for shared muscle healing and function restoration. Methods: Pharmacotherapy recovering various muscle, tendon, ligament, and bone lesions, and severed junctions (i.e., myotendinous junction), per-oral in particular (BPC 157/kg/day 10 µg, 10 ng), provides muscle-to-bone reattachment after quadriceps muscle detachment, both complete (rectus muscle) and partial (vastus muscles). Results: Immediately post-injury, and at 1, 2, 3, 5, 7, 14, 21, 28, 60, and 90 days post-injury, quadriceps muscle-to-bone detachment showed definitive healing failure (impaired walking and permanent knee flexure). Contrarily, macro/microscopic, ultrasonic, magnetic resonance, biomechanical, and functional assessments revealed that BPC 157 therapy recovering effects for all time points were consistent. All parameters of the walking pattern fully improved, and soon after detachment and therapy application, muscle approached the bone, leaving a minimal gap (on ultrasonic assessment), and leg contracture was annihilated. The healing process occurs immediately after detachment from both sides: the muscle and the bone. The reattachment fibers from the ends of the muscle could be traced into the new bone formed at the surface (note, at day 3 post-detachment, increased mesenchymal cells occurred with periosteum reactivation). Consequently, at 3 months, the form was stable, and the balance between the muscle and bone was the following: well-organized bone, newly formed as more cortical bone providing a narrower bone marrow space, and the muscle and mature fibers were oriented parallel to the bone axis and were in close contact with bone. Conclusions: Therefore, to achieve quadriceps muscle-to-bone reattachment, the BPC 157 therapy reversing course acts from the beginning, resolving an otherwise insurmountable deleterious course.

This study explores Zeolitic Imidazolate Frameworks (ZIFs) as promising materials for adsorbing alcohol vapors, one of the main contributors to air quality deterioration and adverse health effects. Indeed, this sub-class of Metal–Organic Frameworks (MOFs) offers a promising alternative to conventional adsorbents like zeolites and activated carbons for air purification. Specifically, this investigation focuses on ZIF-8_Br, a brominated version of ZIF-8_CH3, to evaluate its ability to capture aliphatic alcohols at lower partial pressures. The adsorption properties have been investigated using both experimental and computational methods combining Density Functional Theory and Grand Canonical Monte Carlo simulations. The Ideal Adsorbed Solution Theory (IAST) has been used to assess the material selectivity in the presence of binary equimolar alcohol mixtures. Compared to ZIF-8_CH3, the brominated analog has been shown to feature a higher affinity for alcohols, a property that could be advantageously exploited in environmental remediation or in the development of membranes for alcohol vapor sensors.

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Educational Data Mining and learning analytics have gained significant prominence in recent years, garnering attention from researchers worldwide. This is primarily due to their potential to improve decision-making processes within higher education. This study utilizes Educational Data Mining to suggest a clustering-based approach for classifying students based on their academic performance, specifically focusing on their interactions within Learning Management Systems in blended learning settings. Log data from the Learning Management System Moodle platform was analyzed to determine if valuable insights could be derived from student activities without the need for personal or invasive data. Given the large dataset, Principal Component Analysis and Uniform Manifold Approximation and Projection were employed for dimensionality reduction. Three unsupervised learning models—BIRCH, DBSCAN, and GMM—were then applied to identify distinct student clusters. The results from the comparison revealed that the BIRCH algorithm was the most effective in accurately categorizing students based on their activities. Further analysis of identified clusters revealed a strong correlation between student engagement and academic outcomes, with two high-risk clusters demonstrating the highest dropout rates. To better understand the reasons behind the found clusters, the course duration was subsequently divided into intervals, and standard machine learning methods were applied to predict at-risk students over time, confirming that early identification of at-risk students using clustering is feasible. This study demonstrates the efficacy of non-invasive data collection and unsupervised learning models in predicting student success, emphasizing the importance of temporal and content-specific analysis. The proposed approach leverages clustering algorithms to enhance the understanding of student behavior by identifying patterns and grouping students with similar learning and engagement profiles. This supports the development of targeted interventions that are tailored to specific student needs, ultimately improving retention and success.

Abstract Drug repositioning is a faster and more affordable solution than traditional drug discovery approaches. From this perspective, computational drug repositioning using knowledge graphs is a very promising direction. Knowledge graphs constructed from drug data and information can be used to generate hypotheses (molecule/drug - target links) through link prediction using machine learning algorithms. However, it remains rare to have a holistically constructed knowledge graph using the broadest possible features and drug characteristics, which is freely available to the community. The OREGANO knowledge graph aims at filling this gap. The purpose of this paper is to present the OREGANO knowledge graph, which includes natural compounds related data. The graph was developed from scratch by retrieving data directly from the knowledge sources to be integrated. We therefore designed the expected graph model and proposed a method for merging nodes between the different knowledge sources, and finally, the data were cleaned. The knowledge graph, as well as the source codes for the ETL process, are openly available on the GitHub of the OREGANO project ( https://gitub.u-bordeaux.fr/erias/oregano ).

Abstract Side effects of mechanical ventilation, such as ventilator-induced diaphragmatic dysfunction (VIDD) and ventilator-induced lung injury (VILI), occur frequently in critically ill patients. Phrenic nerve stimulation (PNS) has been a valuable tool for diagnosing VIDD by assessing respiratory muscle strength in response to magnetic PNS. The detection of pathophysiologically reduced respiratory muscle strength is correlated with weaning failure, longer mechanical ventilation time, and mortality. Non-invasive electromagnetic PNS designed for diagnostic use is a reference technique that allows clinicians to measure transdiaphragm pressure as a surrogate parameter for diaphragm strength and functionality. This helps to identify diaphragm-related issues that may impact weaning readiness and respiratory support requirements, although lack of lung volume measurement poses a challenge to interpretation. In recent years, therapeutic PNS has been demonstrated as feasible and safe in lung-healthy and critically ill patients. Effects on critically ill patients’ VIDD or diaphragm atrophy outcomes are the subject of ongoing research. The currently investigated application forms are diverse and vary from invasive to non-invasive and from electrical to (electro)magnetic PNS, with most data available for electrical stimulation. Increased inspiratory muscle strength and improved diaphragm activity (e.g., excursion, thickening fraction, and thickness) indicate the potential of the technique for beneficial effects on clinical outcomes as it has been successfully used in spinal cord injured patients. Concerning the potential for electrophrenic respiration, the data obtained with non-invasive electromagnetic PNS suggest that the induced diaphragmatic contractions result in airway pressure swings and tidal volumes remaining within the thresholds of lung-protective mechanical ventilation. PNS holds significant promise as a therapeutic intervention in the critical care setting, with potential applications for ameliorating VIDD and the ability for diaphragm training in a safe lung-protective spectrum, thereby possibly reducing the risk of VILI indirectly. Outcomes of such diaphragm training have not been sufficiently explored to date but offer the perspective for enhanced patient care and reducing weaning failure. Future research might focus on using PNS in combination with invasive and non-invasive assisted ventilation with automatic synchronisation and the modulation of PNS with spontaneous breathing efforts. Explorative approaches may investigate the feasibility of long-term electrophrenic ventilation as an alternative to positive pressure-based ventilation.

The simultaneous consideration of a numerical model and of different observations can be achieved using data-assimilation methods. In this contribution, the ensemble Kalman filter (EnKF) is applied to obtain the system-state development and also an estimation of unknown model parameters. An extension of the Kalman filter used is presented for the case of uncertain model parameters, which should not or cannot be estimated due to a lack of necessary measurements. It is shown that incorrectly assumed probability density functions for present uncertainties adversely affect the model parameter to be estimated. Therefore, the problem is embedded in a multilayered uncertainty space consisting of the stochastic space, the interval space, and the fuzzy space. Then, we propose classifying all present uncertainties into aleatory and epistemic ones. Aleatorically uncertain parameters can be used directly within the EnKF without an increase in computational costs and without the necessity of additional methods for the output evaluation. Epistemically uncertain parameters cannot be integrated into the classical EnKF procedure, so a multilayered uncertainty space is defined, leading to inevitable higher computational costs. Various possibilities for uncertainty quantification based on probability and possibility theory are shown, and the influence on the results is analyzed in an academic example. Here, uncertainties in the initial conditions are of less importance compared to uncertainties in system parameters that continuously influence the system state and the model parameter estimation. Finally, the proposed extension using a multilayered uncertainty space is applied on a multi-degree-of-freedom (MDOF) laboratory structure: a beam made of stainless steel with synthetic data or real measured data of vertical accelerations. Young’s modulus as a model parameter can be estimated in a reasonable range, independently of the measurement data generation.

Abstract The coexistence of the charge-density wave (CDW) and superconducting phases and their tunability under external pressure remains one of the key points in understanding the electronic structure of AV3Sb5 (A = K, Rb, Cs) kagome metals. Here, we employ synchrotron-based infrared spectroscopy assisted by density-functional calculations to study the pressure evolution of the electronic structure at room temperature up to 17 GPa experimentally. The optical spectrum of CsV3Sb5 is characterized by the presence of localized carriers seen as a broad peak at finite frequencies in addition to the conventional metallic Drude response. The non-monotonic pressure dependence of this low-energy peak reflects the re-entrant behavior of superconductivity and may be interpreted in terms of electron-phonon coupling, varying with the growth and shrinkage of the Fermi surface under pressure. Moreover, drastic modifications in the low-energy interband absorptions are observed upon the suppression of CDW. These changes are related to the upward shift of the Sb2 p x + p y band that eliminates part of the Fermi surface around the M-point, whereas band saddle points do not move significantly. These observations shed new light on the mixed electronic and lattice origin of the CDW in CsV3Sb5.

Abstract Background Venovenous extracorporeal membrane oxygenation (VV ECMO) is frequently associated with deep sedation and neuromuscular blockades, that may lead to diaphragm dysfunction. However, the prevalence, risk factors, and evolution of diaphragm dysfunction in patients with VV ECMO are unknown. We hypothesized that the prevalence of diaphragm dysfunction is high and that diaphragm activity influences diaphragm function changes. Methods Patients with acute respiratory distress syndrome (ARDS) requiring VV ECMO were included in two centers. Diaphragm function was serially assessed by measuring the tracheal pressure in response to phrenic nerve stimulation (Ptr,stim) from ECMO initiation (Day 1) until ECMO weaning. Diaphragm activity was estimated from the percentage of spontaneous breathing ventilation and by measuring the diaphragm thickening fraction (TFdi) with ultrasound. Results Sixty-three patients were included after a median of 4 days (3–6) of invasive mechanical ventilation. Diaphragm dysfunction, defined by Ptr, stim ≤ 11 cmH2O, was present in 39 patients (62%) on Day 1 of ECMO. Diaphragm function did not change over the study period and was not influenced by the percentage of spontaneous breathing ventilation or the TFdi during the 1 week. Among the 63 patients enrolled in the study, 24 (38%) were still alive at the end of the study period (60 days). Conclusions Sixty-two percent of patients undergoing ECMO for ARDS related to SARS CoV-2 infection had a diaphragm dysfunction on Day 1 of ECMO initiation. Diaphragm function remains stable over time and was not associated with the percentage of time with spontaneous breathing. ClinicalTrials.gov Identifier NCT04613752 (date of registration February 15, 2021).

Abstract Background This study hypothesized that patients with extubation failure exhibit a loss of lung aeration and heterogeneity in air distribution, which could be monitored by chest EIT and lung ultrasound. Patients at risk of extubation failure were included after a successful spontaneous breathing trial. Lung ultrasound [with calculation of lung ultrasound score (LUS)] and chest EIT [with calculation of the global inhomogeneity index, frontback center of ventilation (CoV), regional ventilation delay (RVD) and surface available for ventilation] were performed before extubation during pressure support ventilation (H0) and two hours after extubation during spontaneous breathing (H2). EIT was then repeated 6 h (H6) after extubation. EIT derived indices and LUS were compared between patients successfully extubated and patients with extubation failure. Results 40 patients were included, of whom 12 (30%) failed extubation. Before extubation, when compared with patients with successful extubation, patients who failed extubation had a higher LUS (19 vs 10, p = 0.003) and a smaller surface available for ventilation (352 vs 406 pixels, p = 0.042). After extubation, GI index and LUS were higher in the extubation failure group, whereas the surface available for ventilation was lower. The RVD and the CoV were not different between groups. Conclusion Before extubation, a loss of lung aeration was observed in patients who developed extubation failure afterwards. After extubation, this loss of lung aeration persisted and was associated with regional lung ventilation heterogeneity. Trial registration Clinical trials, NCT04180410, Registered 27 November 2019—prospectively registered, https://clinicaltrials.gov/ct2/show/NCT04180410 .

Climate change is one of the largest threats for biodiversity as changing climatic conditions often make existing habitat sites less suitable. This poses new challenges for species conservation, in particular in agricultural landscapes, where climate change may also induce modifications in agricultural land use. To conserve species in agricultural landscapes, agri-environment schemes (AES) which compensate farmers for implementing conservation measures are commonly used. However, current research on the cost-effective design of AES largely ignores necessary adaptations of conservation measures given climate change. We develop a climate-ecological-economic (CEE) model to examine how the cost-effective design of AES has to be modified under climate change. We apply the model to the conservation of eight meadow bird species in Northern Germany and determine the cost-effective conservation measures under recent and future climatic conditions. We find that the timing of conservation measures in the AES needs to be changed in the RCP8.5 scenario given the species’ phenological adaptations and the impact of extreme events (inundations) on costs. The novelty of the research lies in the development of a CEE model which considers both spatial and temporal changes in costs and benefits to develop recommendations for the cost-effective design of AES under climate change.

Abstract Background This study focused on the impact of therapeutic alliance on therapy dropout in a naturalistic sample of patients with borderline pathology receiving dialectical behavior therapy (DBT) in a residential setting. We assumed that low therapeutic alliance shortly after admission would be associated with elevated dropout. Methods 44 participants with borderline pathology (≥ 3 DSM-5 borderline personality disorder criteria) in a residential DBT program completed a quality assurance questionnaire set assessing demographic information, pretreatment psychopathology and therapeutic alliance during the first seven days of their residential stay. Predictors of dropout were investigated using binary logistic regression analyses. Results The dropout rate was 34.1% (n = 15). In binary logistic regression analyses with variables covering demographic and clinical characteristics, comorbidities and childhood trauma history, only the therapeutic alliance significantly predicted dropout (z = -2.371, p = .018). Conclusions This study supports the importance of therapy process variables, here the therapeutic alliance at the beginning of treatment, as predictors of therapy dropout in borderline pathology. If this finding is replicated, it shows the potential importance of monitoring the therapeutic relationship throughout the therapeutic process. ClinicalTrials.gov Identifier: NCT05289583, retrospectively registered on March 11, 2022.

Abstract Background Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress, fatigue and sleep disturbances, which are associated with reduced quality of life (QoL) and increased societal costs. Only limited psychosocial treatment options are available. As Mindfulness-Based Cognitive Therapy (MBCT) has demonstrated to improve psychological distress, QoL and sleep in other populations, MBCT might also be effective in patients with IBD. Methods The MindIBD study is a prospective, multicentre, randomised controlled trial comparing MBCT plus Treatment As Usual (TAU) versus TAU alone in a targeted number of 136 IBD patients in remission, aged 16 years and older with at least mild psychological distress (Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Primary outcome is reduction of psychological distress post-intervention, measured by the HADS. In addition, the effect of MBCT on sleep quality (including actigraphy and electroencephalography recordings), fatigue, disease activity, perceived disease control, QoL and positive mental health will be examined. Assessments will be conducted at baseline and at 3, 6, 9 and 12 months follow-up. Cost-effectiveness will be determined and a process evaluation will be conducted. Discussion This study will provide valuable insight into the clinical effect of MBCT on psychological distress, sleep quality, fatigue and QoL in IBD patients and into the cost-effectiveness. If effective, MBCT can be a valuable addition to the available psychosocial interventions for patients with IBD. Moreover, findings from this study may also be applicable in patients with other chronic conditions. Trial registration ClinicalTrials.gov: NCT04646785, registered on 30/11/2020.

We have investigated the magnetic ground state properties of the quantum spin trimer compound strontium hydroxy copper chloride SrCu(OH)_{3}Cl using bulk magnetization, specific heat measurements, nuclear magnetic resonance (NMR), and electron spin resonance (ESR) spectroscopy. SrCu(OH)_{3}Cl consists of layers with isolated Cu^{2+} triangles and hence provides an opportunity to understand the magnetic ground state of an isolated system of S = 1/2 arranged on an equilateral triangle. Although magnetization measurements do not exhibit a phase transition to a long-range ordered state down to T = 2 K, they reveal the characteristic behavior of isolated trimers with an exchange of J=154 K. The Curie-Weiss behavior changes around 50–80 K, as is also seen in the NMR spin-lattice relaxation rate. In zero magnetic field, our specific heat data establish a second-order phase transition to an antiferromagnetic ground state below T= 1.2 K. We have drawn a magnetic field-temperature (H-T) phase diagram based on the specific heat measurements. The ESR data show divergence of the linewidth at lower temperatures, which precedes the phase transition to an antiferromagnetic long-range ordered state with unconventional critical exponents. The temperature variation of the g-factor further confirms the antiferromagnetic phase transition and reflects the underlying magnetocrystalline anisotropy of the compound.

Metal–Organic Frameworks (MOFs) are particularly attractive sorbents with great potential for the removal of toxic dye pollutants from industrial wastewaters. The uniform dispersion of MOF particles on suitable substrates then represents a key condition to improve their processability and provide good accessibility to the active sites. In this work, we investigate the efficiency of a natural bacterial cellulose material derived from Kombucha (KBC) as an active functional support for growing and anchoring MOF particles with UiO-66 structures. An original hierarchical microstructure was obtained for the as-developed Kombucha cellulose/UiO-66 (KBC-UiO) composite material, with small MOF crystals (~100 nm) covering the cellulose fibers. Promising adsorption properties were demonstrated for anionic organic dyes such as fluorescein or bromophenol blue in water at pH 5 and pH 7 (more than 90% and 50% removal efficiency, respectively, after 10 min in static conditions). This performance was attributed to both the high accessibility and uniform dispersion of the MOF nanocrystals on the KBC fibers together with the synergistic effects involving the attractive adsorbing properties of UiO-66 and the surface chemistry of KBC. The results of this study provide a simple and generic approach for the design of bio-sourced adsorbents and filters for pollutants abatement and wastewater treatment.

Introduction Lucid dreaming opens the possibility to rehearse sport skills within a dream while sleeping (Peters et al. 2023; Stumbrys et al. 2016). But so far, no induction techniques have been developed to induce reliable lucid dreams. One potential technique is to apply external stimulation while a person is sleeping in order to send a hint into the dream which might enhance lucidity in the ongoing dream. Several studies have tested dream incorporation rates (DIR) with different stimuli and different results (Schredl, 2018), but none with a larger sample size and a within-design. Furthermore, in this study we wanted to explore body related stimulations to evoke in future studies lucid dreams. Methods 10-Channel polysomnography and three different bodily stimulation methods were combined during three consecutive test nights with each night using one stimulation method (plus adaptation night). The three stimulation methods consisted of electrical forearm muscle stimulation (EMS), galvanic vestibular stimulation (GVS), and haptic vibration stimulation (HS). During REM sleep, one of the three stimuli was presented or a sham condition was applied in a counterbalanced order. The stimuli were followed by REM awakenings, resulting in corresponding verbal dream reports. With the help of those reports, the translation from a physical arm movement, vestibular sensation and vibration into the dream environment was investigated using dream content analysis. Movement of the dream arm, balance related activity and tactile or somatosensory sensations targeted the dream incorporations of EMS, GVS and HS respectively. Results Movement of the arm was present in 23.2%, 8.1% and 23.5% of EMS, GVS and HS dreams respectively. Balance-related activity was present in 6.1%, 7.9% and 5.8% of EMS, GVS and HS dreams respectively. Finally, tactile and somatosensory sensations were present in 13.6%, 0% and 6.3% of the EMS, GVS and HS dreams respectively. After correcting for sham condition, tactile and somatosensory sensations on the EMS dreams seem to be the strongest incorporation effect upon stimulation. Discussion/Conclusion We tested dream incorporation of three different stimulation methods using a within-design on a larger sample size, a method that has never been attempted before. GVS appears unsuccessful in altering dream content, but this might be confounded due to challenges in methodology. EMS evokes the most dream incorporation in the scale of tactile and somatosensory dream content followed by HS. The investigation of the incorporation of external kinesthetic stimulation into dream content represents a fundamental contribution to various scientific fields and could foster future research on lucid dream induction, enabling the further exploration of sport practice in a sleep state. References Peters, E., Golembiewski, S., Erlacher, D., & Dresler, M. (2023). Extending mental practice to sleep: Enhancing motor skills through lucid dreaming. Medical Hypotheses, 174, Article 111066. https://doi.org/10.1016/j.mehy.2023.111066 Schredl, M. (2018). Researching Dreams: The Fundamentals. Springer International. https://doi.org/10.1007/978-3-319-95453-0 Stumbrys, T., Erlacher, D., & Schredl, M. (2016). Effectiveness of motor practice in lucid dreams: A comparison with physical and mental practice. Journal of Sports Sciences, 34(1), 27–34. https://doi.org/10.1080/02640414.2015.1030342

Abstract Objective Clinical practice guidelines (CPGs) are evidence‐based tools well‐suited to translate the latest research evidence into recommendations for routine clinical care. Given the rapid expansion of psychosocial oncology research, they represent a key opportunity for informing the treatment decisions of overburdened clinicians, standardizing service delivery, and improving patient‐reported outcomes. Yet, there is little consensus on how clinicians can most effectively access these tools and little to no information on the current availability and scope of CPGs for the range of psychosocial symptoms and concerns experienced by patients with cancer. Method Our environmental scan consisted of an academic and gray literature designed to identify currently available CPGs addressing a range of cancer‐related psychosocial symptoms. Results Findings revealed a total of 23 existing psychosocial oncology CPGs that met full eligibility criteria. The gray literature search was found to be more effective at identifying CPGs (n = 22) compared to the academic search (n = 9). Conclusion Several concerns arose from the systematic search. The limited publication of CPGs in peer‐reviewed journals may make clinicians and stakeholders more hesitant to implement CPGs due to uncertainties about the methodological rigor of the development process. Further, many existing CPGs are outdated or failed to be updated according to guideline recommendations, meaning that the recommendations may fall short of their purpose to translate up‐to‐date research findings. Future directions Future research should seek to systematically assess the quality of existing psychosocial oncology CPGs and shed light on the current state of implementation and adherence in clinical practice in order to better inform guideline developers on the current needs of the psychosocial oncology community.

We present a genome assembly from an individual female Thereva unica (a stiletto fly; Arthropoda; Insecta; Diptera; Therevidae). The genome sequence is 910.1 megabases in span. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 17.66 kilobases in length.

As it is a commentary we do not have a usual abstract Today’s energy systems are critically dependent on water for hydropower and thermoelectric power generation, which relies on a large amount of cooling water. However, even with increasing climatic pressures and growing concerns surrounding energy security, the availability of high-quality integrated water data sets remains poor (1, 2). This is surprising considering broad climate impacts on energy systems worldwide. Numerous regions experienced water-related power generation issues throughout the 2010 s, including coal generation during the 2015 Polish drought, repeated curtailment of French nuclear plants, and hydropower curtailment in the US, Romania, China, Ghana, and Brazil, among others (3). The 2022 heat waves saw broad water-energy issues across the EU, with France altering regulatory requirements to keep nuclear plants running (resulting in higher water temperatures) (4) and hydroelectric curtailment across several countries. There is clear evidence of impacts on energy security today (5) and how this issue is poised to become more acute into the 21st century (6, 7).

Coordination incentives like the agglomeration bonus have been proposed to induce the spatial agglomeration of biodiversity conservation efforts and counter the loss and fragmentation of species habitats. Most theoretical and empirical analyses of the agglomeration bonus make unrealistic assumptions about the spatial structure of landholdings. This paper presents a spatially explicit agent-based simulation model to explore how the spatial structure of landholdings affects the performance of the agglomeration bonus. It turns out that if the number of land parcels per landowner is large and their land is spatially cohesive, a higher proportion and agglomeration of conserved land parcels can be achieved for the given budget, implying a higher level of cost-effectiveness. This also has implications for the cost-effective design of coordination incentives. The observed effects are especially high if the conservation costs vary strongly in space.

We introduce Dreamento (Dream engineering toolbox), an open-source Python package for dream engineering using sleep electroencephalography (EEG) wearables. Dreamento main functions are (1) recording, real-time monitoring, analysis, and sensory stimulation, and (2) offline post-processing of the resulting data, both in a graphical user interface. In real-time, Dreamento is capable of (1) data visualization, scaling, and navigation, (2) power-spectrum analysis, (3) automatic sleep scoring, (4) sensory stimulation (visual, auditory, tactile), (5) establishing text-to-speech communication, and (6) managing annotations of automatic and manual events. The offline functions aid in post-processing the acquired data with features to reformat the wearable data and integrate it with non-wearable recorded modalities such as electromyography (EMG). Dreamento was primarily developed for (lucid) dreaming studies. Nevertheless, its applications can be extended to other areas of sleep research such as closed-loop auditory stimulation and targeted memory reactivation to enhance memory consolidation during sleep.

Abstract Background In patients on mechanical ventilation, positive end-expiratory pressure (PEEP) can decrease cardiac output through a decrease in cardiac preload and/or an increase in right ventricular afterload. Increase in central blood volume by fluid administration or passive leg raising (PLR) may reverse these phenomena through an increase in cardiac preload and/or a reopening of closed lung microvessels. We hypothesized that a transient decrease in PEEP (PEEP-test) may be used as a test to detect volume responsiveness. Methods Mechanically ventilated patients with PEEP ≥ 10 cmH2O (“high level”) and without spontaneous breathing were prospectively included. Volume responsiveness was assessed by a positive PLR-test, defined as an increase in pulse-contour-derived cardiac index (CI) during PLR ≥ 10%. The PEEP-test consisted in reducing PEEP from the high level to 5 cmH2O for one minute. Pulse-contour-derived CI (PiCCO2) was monitored during PLR and the PEEP-test. Results We enrolled 64 patients among whom 31 were volume responsive. The median increase in CI during PLR was 14% (11–16%). The median PEEP at baseline was 12 (10–15) cmH2O and the PEEP-test resulted in a median decrease in PEEP of 7 (5–10) cmH2O, without difference between volume responsive and unresponsive patients. Among volume responsive patients, the PEEP-test induced a significant increase in CI of 16% (12–20%) (from 2.4 ± 0.7 to 2.9 ± 0.9 L/min/m2, p 8.6% during the PEEP-test with a sensitivity of 96.8% (95% confidence interval (95%CI): 83.3–99.9%) and a specificity of 84.9% (95%CI 68.1–94.9%). The area under the receiver operating characteristic curve of the PEEP-test for detecting volume responsiveness was 0.94 (95%CI 0.85–0.98) (p 8.6% during a PEEP-test, which consists in reducing PEEP to 5 cmH2O, reliably detects volume responsiveness in mechanically ventilated patients with a PEEP ≥ 10 cmH2O. Trial registration ClinicalTrial.gov (NCT 04,023,786). Registered July 18, 2019. Ethics Committee approval CPP Est III (N° 2018-A01599-46).