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Magnolia Cardona,1,2 Adem Sav,3 Zoe A Michaleff,1 Sarah T Thomas,2 Claudia C Dobler1,4 1Institute for Evidence Based Healthcare, Bond University, Robina, Queensland, Australia; 2Gold Coast Hospital and Health Service, Southport, Queensland, Australia; 3School of Public Health and Social Work, Queensland University of Technology, Brisbane, Queensland, Australia; 4The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, AustraliaCorrespondence: Magnolia Cardona, Institute for Evidence-Based Healthcare, Faculty of Health Sciences and Medicine Level 4, HSM Building 5, Bond University, Robina, Queensland, 4226, Australia, Tel +61 7 5595 0170, Email mcardona@bond.edu.auPurpose: To identify and rank areas of treatment burden in chronic heart failure (CHF), including solutions, that should be discussed during the clinical encounter from a patient, and doctors’ perspective.Patients and Methods: Patients with CHF and clinicians managing heart failure were invited. Nominal group technique sessions held either face to face or online in 2021– 2022, with individual identification of priorities and voting on ranking.Results: Four patient groups (N=22) and one doctor group (N=5) were held. For patients with heart failure, in descending order of priority Doctor-patient communication, Inefficiencies of the healthcare system, Healthcare access issues, Cost implications of treatment, Psychosocial impacts on patients and their families, and Impact of treatment work were the most important treatment burdens. Priorities independently identified by the doctors aligned with the patients’ but ranking differed. Patient solutions ranged from involvement of nurses or pharmacists to enhance understanding of discharge planning, through to linkage between health information systems, and maintaining strong family or social support networks. Doctors’ solutions covered timing medicines with activities of daily living, patient education on the importance of compliance, medication reviews to overcome clinical inertia, and routine clinical audits.Conclusion: The top treatment burden priorities for CHF patients were related to interaction with clinicians and health system inefficiencies, whereas doctors were generally aware of patients’ treatment burden but tended to focus on the complexity of the direct treatment work. Addressing the priority issues identified here can commence with clinicians becoming aware of the issues that matter to patients and proactively discussing feasible immediate and longer-term solutions during clinical encounters.Keywords: patient priorities, barriers, qualitative studies, older adults

Adem Sav,1 Sarah T Thomas,2 Magnolia Cardona,3,4 Zoe A Michaleff,4,5 Claudia C Dobler3,4,6 1School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; 2Gold Coast University Hospital, Southport, Queensland, Australia; 3Evidence-Based Practice Professorial Unit, Gold Coast Hospital, Southport, Queensland, Australia; 4Institute for Evidence Based Healthcare, Bond University, Gold Coast, Queensland, Australia; 5Northern NSW Local Health District, Lismore, New South Wales, Australia; 6The George Institute for Global Health, University of New South Wales, Kensington, New South Wales, AustraliaCorrespondence: Adem Sav, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia, Tel +61 7 3138 5795, Email adem.sav@qut.edu.auPurpose: Many people with chronic obstructive pulmonary disease (COPD) feel overburdened with the treatment and management of their illness. Although research has begun to shed light on how COPD patients experience treatment burden, most of what we know is limited to personal experiences of patients. The aim of this study is to identify and prioritise areas of treatment burden that should be discussed during the clinical encounter from the perspectives of COPD patients, carers, and respiratory physicians.Patients and Methods: Data were collected from participants using the nominal group technique. Five nominal group sessions were conducted in total (n = 31); three sessions with patients (n = 18), one with carers (n = 7) and another with respiratory physicians (pulmonologists or chest physicians) (n = 6). Each session was recorded and analyzed using thematic analysis.Results: Going beyond understanding patients’ and carers’ experiences of treatment burden, this study offers a practical viewpoint of what should be discussed in a clinical encounter. Each group of participants contextualized treatment burden issues for discussion from their own perspectives. There was strong agreement, however, across the groups that difficulties accessing healthcare, lack of education and information, and worry about COPD treatment and prognosis were the most important treatment burden priorities for discussion.Conclusion: Understanding and creating opportunities to discuss these issues in a clinical encounter is important in not only reducing treatment burden but also improving health outcomes and quality of life for COPD patients and their carers.Keywords: COPD, burden of treatment, treatment burden, nominal group technique

BACKGROUND: Training of health profession students in telehealth is important to ensure proper implementation for healthcare delivery. This prospective study aimed to analyze the effects of didactic and experiential learning on knowledge, confidence, and attitudes of telehealth among health profession students (Survey 1). The perceptions of a mixed model telehealth platform were also considered among these students and community clients (Survey 2). MATERIALS AND METHODS: A quasi-experimental repeated-measure study was conducted on 153 university health profession students in physician assistant, physical therapy, occupational therapy, and nursing (NR) across the 2020–2021 academic year. Survey 1 was administered to students pre/postdidactic telehealth training and at two sequential points within two semesters of telehealth experiential learning. Survey 2 was distributed among students and a pool of 19 community clients at 4 time points across the experience. Survey data were analyzed using R software. RESULTS: There was a significant improvement in telehealth knowledge, confidence, and attitudes among all student disciplines after the didactic module with marginal means ranging 3.313/5–4.318/5 for pretest to posttest 1. Improvement continued through experiential learning with marginal means ranging 4.170/5–4.369/5 in posttest 3. There was also a significant student and client approval of the telehealth platform with a student mean high of 3.962/5 ± 0.527 and client mean high of 4.727/5 ± 0.238. CONCLUSION: A didactic training module combined with experiential learning is effective for health profession students' improvement in perception, knowledge, and attitudes toward telehealth. Health profession students and community clients approve a mixed model telehealth platform.

Adults are skilled at using language to construct/negotiate identity and to signal affiliation with others, but little is known about how these abilities develop in children. Clearly, children mirror statistical patterns in their local environment (e.g., Canadian children using "zed" instead of "zee"), but do they flexibly adapt their linguistic choices on the fly in response to the choices of different peers? To address this question, we examined the effect of group membership on 7- to 9-year-olds' labeling of objects in a trivia game, exploring whether they were more likely to use a particular label (e.g., "sofa" vs. "couch") if members of their "team" also used that label. In a preregistered study, children (N = 72) were assigned to a team (red or green) and were asked during experimental trials to answer questions--which had multiple possible answers (e.g., "blackboard" or "chalkboard")--after hearing two teammates and two opponents respond to the same question. Results showed that children were significantly more likely to produce labels less commonly used by the community (i.e., dispreferred labels) when their teammates had produced those labels. Crucially, this effect was tied to group membership, and could not be explained by children simply repeating the most recently used label. These findings demonstrate how social processes (i.e., group membership) can guide linguistic variation in children.

Abstract Background Plasma levels of d-dimer are elevated in patients with thromboembolisms. Here we investigated the existence of interfering antibodies as a potential cause for elevated d-dimer levels. Case presentation A 42-year-old white Caucasian woman with a prior history of pulmonary embolism during her first pregnancy (treated with heparin therapy for 6 weeks postnatally) and hypothyroidism had a persistent elevated d-dimer without any clinical or ultrasound-based signs of thromboembolic conditions during her second pregnancy. We obtained informed consent and plasma was obtained from the patient. d-dimer levels were measured using two different assays. We also tested for the presence of rheumatoid factor, performed dilution series, and finally used an antibody depletion strategy. The two d-dimer assays performed similarly. Using our antibody depletion technique, we observed that ~ 1/3 of the increased plasma levels of d-dimer may be attributed to interfering antibodies. Conclusions Our results identify interfering antibodies as a potential contributor to an increased d-dimer in this patient. Our case highlights the potential of heterophilic interference for increased d-dimer and provides a procedure to determine this analytically.

Abstract Objectives The Ishikawa cell line is the most widely used model system for investigating implantation and endometrial cancer. Understanding the biology of this cell line is essential for developing effective interventional strategies. To gain a deeper understanding of its cellular protein profile, we extracted cellular proteins from Ishikawa cells and analyzed the peptides using mass spectrometry. Our goal was to create a proteomic resource specifically tailored for Ishikawa cells. This data set is of particular significance in the realm of targeted drug delivery. Liposomes are synthetic spherical vesicles composed of hydrophobic bilayer phospholipids and have received immense recognition as highly effective carriers for the delivery of pharmaceutical drugs and essential nutrients to the endometrium. Phosphatidylcholine and phosphatidylethanolamine are often combined to create functional liposomal systems. To discern any potential interfering effects originating from the liposome backbone, our investigation involved direct effects of phospholipid liposomes on endometrial epithelial cells. Data description The data set includes peptide spectra derived from the intracellular proteomes of Ishikawa endometrial cancer cell isolates and their phospholipid-treated counterparts. Representing a proteome-wide profile, this dataset aims to contribute to a broader understanding of the physiology of endometrial epithelial cells. Proteomic analysis identified key proteins involved in the intricate regulation of cellular metabolism, cell cycle progression, and signaling. Between-group analysis revealed no differentially expressed proteins after adjusting for multiple testing using the applied thresholds (p-value 1). Data are available via ProteomeXchange with identifier PXD050871.

Due to climate change, population increase, and the urban heat island effect (UHI), the demand for cooling energy, especially in urban areas, has increased and will further increase in the future. Technologies such as radiative cooling offer a sustainable and energy-free solution by using the wavelength ranges of the atmosphere that are transparent to electromagnetic radiation, the so-called atmospheric window (8–13 µm), to emit thermal radiation into the colder (3 K) outer space. Previous publications in the field of textile building cooling have focused on specific fiber structures and textile substrate materials as well as complex multi-layer constructions, which restrict the use for highly scaled outdoor applications. This paper describes the development of a novel substrate-independent coating with spectrally selective radiative properties. By adapting the coating parameters and combining low-emitting and solar-reflective particles, along with a matrix material emitting strongly in the mid-infrared range (MIR), substrate-independent cooling below ambient temperature is achieved. Moreover, the coating is designed to be easily applicable, with a low thickness, to ensure high flexibility and scalability, making it suitable for various applications such as membrane architecture, textile roofs, or tent construction. The results show a median daytime temperature reduction (7 a.m.–7 p.m.) of 2 °C below ambient temperature on a hot summer day.

Abstract To improve the prognosis of bladder and prostate cancer, highly specific and sensitive biomarkers are needed for early detection, prognosis prediction, and therapeutic stratification. Extracellular vesicles (EV) from plasma could fill this gap due to their potential to serve as cancer biomarkers. However, the enrichment of EV is a major challenge, because the highly abundant plasma proteins are interfering with analytical downstream applications like mass spectrometry (MS). Therefore, the purity requirements of the EV samples must be carefully considered when selecting or developing a suitable EV enrichment method. The aim of this study was to compare a self-designed EV enrichment method based on density cushion centrifugation (DCC) combined with size exclusion chromatography (SEC) and concentration (method 1) with the exoRNeasy midi kit from Qiagen (method 2) and with unprocessed plasma. Furthermore, the single steps of method 1 were evaluated for their effectiveness to enrich EV from plasma. The results showed that the EV samples enriched with method 1 contained the highest levels of EV and exosome markers with simultaneously low levels of highly abundant plasma proteins. In summary, the combination of DCC, SEC and concentration proved to be a promising approach to discover EV-based biomarkers from plasma of cancer patients.

Background: MRI fusion prostate biopsy has improved the detection of clinically significant prostate cancer (CSC). Continued refinements in predicting the pre-biopsy probability of CSC are essential for optimal patient counseling. We investigated potential factors related to improved cancer detection rates (CDR) of CSC in patients with PI-RADS ≥ 3 lesions. Methods: The pathology of 980 index lesions in 980 patients sampled by transrectal mpMRI-targeted prostate biopsy across four medical centers between 2017–2020 was reviewed. PI-RADS lesion distribution included 291 PI-RADS-5, 374 PI-RADS-4, and 315 PI-RADS-3. We compared CDR of index PI-RADS ≥ 3 lesions based on location (TZ) vs. (PZ), PSA density (PSAD), and history of prior negative conventional transrectal ultrasound-guided biopsy (TRUS). Results: Mean age, PSA, prostate volume, and level of prior negative TRUS biopsy were 66 years (43–90), 7.82 ng/dL (5.6–11.2), 54 cm3 (12–173), and 456/980 (46.5%), respectively. Higher PSAD, no prior history of negative TRUS biopsy, and PZ lesions were associated with higher CDR. Stratified CDR highlighted significant variance across subgroups. CDR for a PI-RADS-5 score, PZ lesion with PSAD ≥ 0.15, and prior negative biopsy was 77%. Conversely, the CDR rate for a PI-RADS-4 score, TZ lesion with PSAD < 0.15, and prior negative biopsy was significantly lower at 14%. Conclusions: For index PI-RADS ≥ 3 lesions, CDR varied significantly based on location, prior history of negative TRUS biopsy, and PSAD. Such considerations are critical when counseling on the merits and potential yield of prostate needle biopsy.

Abstract Introduction Ureterovascular fistula (UVF) is a rare but potentially life-threatening condition. Since its primary description by Moschkowitz in 1908, many case reports, studies and reviews have been written about this condition with the suggestive symptoms and risk factors repeatedly discussed. This study will be focusing on the different locations of 532 out of 605 fistulae published from 1908 up to 2022 besides eight new patients of our own. Material and methods A systematic review of the literature started using PubMed database searching for “ureteroarterial fistula”, “arteriovascular fistula” and “uretero vascular fistula” was performed yielding 122, 62 and 188 results respectively. Those studies and the cited literature in each study were examined to include studies, which did not appear in the primary search. A total of 605 patients in 315 publications were gathered. Only studies mentioning new patients, a clear indication of the location of the UVF, the presence/absence of urinary diversion (UD) as well as the type of UD if present were included. Ten duplicates as well as studies lacking information regarding the UVF and/or the UD (seven publications with 63 patients) were excluded, with 298 publications including 532 external patients remaining. Eight internal cases were included with a total of 540 cases. Results From the 540 included cases, 384 patients (71.1%) had no UD compared to 156 patients (28.9%) with UD. Due to the anatomical ureteral course, the common iliac artery (CIA) was the most common vascular component of UVF, irrespective of the presence or absence of UD. Any dispute to whether the crossing point is the common or the external iliac artery (EIA) was settled for the CIA. Further common vascular components besides CIA include the aorta, EIA, internal iliac artery (IIA) including its branches and vascular bypasses including the anastomosis sites. Other unusual arterial localizations were stated under the “others” category. Conclusion Identifying the location of the bleeding artery in UVF is critical and represents the most important step for successful management. We present the largest summary of described locations up to date including our own. Graphical Abstract

Abstract Terrestrial groundwater travels through subterranean estuaries before reaching the sea. Groundwater‐derived nutrients drive coastal water quality, primary production, and eutrophication. We determined how dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and dissolved organic nitrogen (DON) are transformed within subterranean estuaries and estimated submarine groundwater discharge (SGD) nutrient loads compiling > 10,000 groundwater samples from 216 sites worldwide. Nutrients exhibited complex, nonconservative behavior in subterranean estuaries. Fresh groundwater DIN and DIP are usually produced, and DON is consumed during transport. Median total SGD (saline and fresh) fluxes globally were 5.4, 2.6, and 0.18 Tmol yr−1 for DIN, DON, and DIP, respectively. Despite large natural variability, total SGD fluxes likely exceed global riverine nutrient export. Fresh SGD is a small source of new nutrients, but saline SGD is an important source of mostly recycled nutrients. Nutrients exported via SGD via subterranean estuaries are critical to coastal biogeochemistry and a significant nutrient source to the oceans.

Background and objective: With approval of novel systemic therapies within the past decade for metastatic hormone-sensitive (mHSPC) and castration-resistant (mCRPC) prostate cancer, patients may receive several therapy lines. However, the use of these treatments is under an ongoing change. We investigated contemporary treatment trends and progression-free (PFS) and overall (OS) survival of different therapy lines. Methods: Relying on our institutional tertiary-care database, we identified mHSPC and mCRPC patients. The main outcome consisted of treatment changes (estimated annual percentage change [EAPC]) within the past decade, as well as PFS and OS for different mHSPC and mCRPC treatment lines. Key findings and limitations: In 1098 metastatic patients, the median age was 70 yr with a median of two systemic therapy lines. For first-line mCRPC between 2013 and 2023, androgen deprivation monotherapy (ADT) monotherapy usage decreased significantly from 31% to 0% (EAPC −38.3%, p

The present work investigates the physicochemical stability of spray paints when irradiated with artificial solar light (at spectral range 300–800 nm). This research highlights the importance of understanding the materials used in street art and public murals, recognising them as a significant component of contemporary cultural heritage. By examining the stability and degradation of spray paints toward solar light exposure, the study aims to contribute to the preservation of contemporary murals, which reflect current social and cultural narratives. A physicochemical approach was employed for the study of spray paints’ physical and thermal properties, as well as the effect of specific photochemical ageing reactions/processes. The photochemical ageing results were compared with reference (unaged) samples. Specifically, a multi-technique approach was applied using stereo microscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle measurement, colorimetry, glossimetry, differential scanning calorimetry (DSC), UV-Vis spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and pyrolysis-GC/MS (Py-GC/MS). The photodegradation of the spray paints occurred from the first 144 h of solar light irradiation, resulting in changes in morphology, colour, gloss, roughness, and wettability. Regarding photochemical stability, ageing seems to affect the binders more than the synthetic organic pigments and the inorganic fillers. In particular, acrylic binders showed small chemical changes, whereas the alkyd, nitrocellulose, and styrene binders underwent severe chemical modification. The results suggest that simulated daylight irradiation prompts the migration of additives toward the surface of the spray paint films. In addition, the results of the analyses on the white spray paints in comparison with the coloured paints (from the same manufacturer) showed that there seems to be an active distinct photoageing mechanism involving titanium dioxide, but the whole issue needs further investigation.

Abstract Background Since the 1980s, soils in a 22-km2 area near Lake Neuchâtel in Switzerland have been recognized for their innate ability to suppress the black root rot plant disease caused by the fungal pathogen Thielaviopsis basicola. However, the efficacy of natural disease suppressive soils against insect pests has not been studied. Results We demonstrate that natural soil suppressiveness also protects plants from the leaf-feeding pest insect Oulema melanopus. Plants grown in the most suppressive soil have a reduced stress response to Oulema feeding, reflected by dampened levels of herbivore defense-related phytohormones and benzoxazinoids. Enhanced salicylate levels in insect-free plants indicate defense-priming operating in this soil. The rhizosphere microbiome of suppressive soils contained a higher proportion of plant-beneficial bacteria, coinciding with their microbiome networks being highly tolerant to the destabilizing impact of insect exposure observed in the rhizosphere of plants grown in the conducive soils. We suggest that presence of plant-beneficial bacteria in the suppressive soils along with priming, conferred plant resistance to the insect pest, manifesting also in the onset of insect microbiome dysbiosis by the displacement of the insect endosymbionts. Conclusions Our results show that an intricate soil–plant-insect feedback, relying on a stress tolerant microbiome network with the presence of plant-beneficial bacteria and plant priming, extends natural soil suppressiveness from soilborne diseases to insect pests. Video Abstract

Abstract Water clarity on the inshore Great Barrier Reef (GBR) is greatly influenced by terrestrial runoff of suspended particulate matter (SPM). Catchment sediment tracing studies often do not extend into the marine environment, preventing the analysis of preferential marine transport. This study employs novel collection and sediment tracing techniques to examine the transport of the terrigenous ‘mineral’ component of plume SPM within the GBR lagoon for two flood events. Utilising geochemical, radionuclide and clay mineral analysis, we trace terrigenous mineral sediments > 100 km from the river mouth. We show that the SPM geochemistry is highly influenced by particle-size fractionation, desorption, and dilution within the plume, rendering traditional tracing methods unviable. However, the ratios of rare earth elements (REE) to thorium (Th) provide stable tracers of mineral SPM transported across the catchment to marine continuum and allow the identification of discrete catchment sources for each flood event. Plume sediment radionuclides are also stable and consistent with sub-surface erosion sources.

In recent years, Artificial Intelligence has been used to assist healthcare professionals in detecting and diagnosing neurodegenerative diseases. In this study, we propose a methodology to analyze functional Magnetic Resonance Imaging signals and perform classification between Parkinson’s disease patients and healthy participants using Machine Learning algorithms. In addition, the proposed approach provides insights into the brain regions affected by the disease. The functional Magnetic Resonance Imaging from the PPMI and 1000-FCP datasets were pre-processed to extract time series from 200 brain regions per participant, resulting in 11,600 features. Causal Forest and Wrapper Feature Subset Selection algorithms were used for dimensionality reduction, resulting in a subset of features based on their heterogeneity and association with the disease. We utilized Logistic Regression and XGBoost algorithms to perform PD detection, achieving 97.6% accuracy, 97.5% F1 score, 97.9% precision, and 97.7%recall by analyzing sets with fewer than 300 features in a population including men and women. Finally, Multiple Correspondence Analysis was employed to visualize the relationships between brain regions and each group (women with Parkinson, female controls, men with Parkinson, male controls). Associations between the Unified Parkinson’s Disease Rating Scale questionnaire results and affected brain regions in different groups were also obtained to show another use case of the methodology. This work proposes a methodology to (1) classify patients and controls with Machine Learning and Causal Forest algorithm and (2) visualize associations between brain regions and groups, providing high-accuracy classification and enhanced interpretability of the correlation between specific brain regions and the disease across different groups.

Abstract The transient receptor potential canonical type 3 (TRPC3) channel plays a pivotal role in regulating neuronal excitability in the brain via its constitutive activity. The channel is intricately regulated by lipids and has previously been demonstrated to be positively modulated by PIP2. Using molecular dynamics simulations and patch clamp techniques, we reveal that PIP2 predominantly interacts with TRPC3 at the L3 lipid binding site, located at the intersection of pre-S1 and S1 helices. We demonstrate that PIP2 sensing involves a multistep mechanism that propagates from L3 to the pore domain via a salt bridge between the TRP helix and S4-S5 linker. Notably, we find that both stimulated and constitutive TRPC3 activity require PIP2. These structural insights into the function of TRPC3 are invaluable for understanding the role of the TRPC subfamily in health and disease, in particular for cardiovascular diseases, in which TRPC3 channels play a major role.

Abstract Background Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Abstract Background Understanding biodiversity patterns is a central topic in biogeography and ecology, and it is essential for conservation planning and policy development. Diversity estimates that consider the evolutionary relationships among species, such as phylogenetic diversity and phylogenetic endemicity indices, provide valuable insights into the functional diversity and evolutionary uniqueness of biological communities. These estimates are crucial for informed decision-making and effective global biodiversity management. However, the current methodologies used to generate these metrics encounter challenges in terms of efficiency, accuracy, and data integration. Results We introduce PhyloNext, a flexible and data-intensive computational pipeline designed for phylogenetic diversity and endemicity analysis. The pipeline integrates GBIF occurrence data and OpenTree phylogenies with the Biodiverse software. PhyloNext is free, open-source, and provided as Docker and Singularity containers for effortless setup. To enhance user accessibility, a user-friendly, web-based graphical user interface has been developed, facilitating easy and efficient navigation for exploring and executing the pipeline. PhyloNext streamlines the process of conducting phylogenetic diversity analyses, improving efficiency, accuracy, and reproducibility. The automated workflow allows for periodic reanalysis using updated input data, ensuring that conservation strategies remain relevant and informed by the latest available data. Conclusions PhyloNext provides researchers, conservationists, and policymakers with a powerful tool to facilitate a broader understanding of biodiversity patterns, supporting more effective conservation planning and policy development. This new pipeline simplifies the creation of reproducible and easily updatable phylogenetic diversity analyses. Additionally, it promotes increased interoperability and integration with other biodiversity databases and analytical tools.

We present a new class of tunable aryl alkyl ionic liquids (TAAILs) based on 1-aryl-4,5-dimethylimidazolium cations with electron-withdrawing and -donating substituents in different positions of the phenyl ring and the bis(trifluoromethylsulfonyl)imide (NTf2) anion. We investigated the effect of additional methyl groups in the backbone of the imidazolium core on the physical properties regarding viscosity, conductivity and electrochemical window. With an electrochemical window of up to 6.3 V, which is unprecedented for TAAILs with an NTf2 anion, this new class of TAAILs demonstrates the opportunities that arise from modifications in the backbone of the imidazolium cation.

Abstract Human Ebola virus (EBOV) outbreaks caused by persistent EBOV infection raises questions on the role of zoonotic spillover in filovirus epidemiology. To characterise filovirus zoonotic exposure, we collected cross-sectional serum samples from bushmeat hunters (n = 498) in Macenta Prefecture Guinea, adjacent to the index site of the 2013 EBOV-Makona spillover event. We identified distinct immune signatures (20/498, 4.0%) to multiple EBOV antigens (GP, NP, VP40) using stepwise ELISA and Western blot analysis and, live EBOV neutralisation (5/20; 25%). Using comparative serological data from PCR-confirmed survivors of the 2013-2016 EBOV outbreak, we demonstrated that most signatures (15/20) were not plausibly explained by prior EBOV-Makona exposure. Subsequent data-driven modelling of EBOV immunological outcomes to remote-sensing environmental data also revealed consistent associations with intact closed canopy forest. Together our findings suggest exposure to other closely related filoviruses prior to the 2013-2016 West Africa epidemic and highlight future surveillance priorities.

Abstract Previous research on the neural correlates of consciousness (NCC) in visual perception revealed an early event-related potential (ERP), the visual awareness negativity (VAN), to be associated with stimulus awareness. However, due to the use of brief stimulus presentations in previous studies, it remains unclear whether awareness-related negativities represent a transient onset-related response or correspond to the duration of a conscious percept. Studies are required that allow prolonged stimulus presentation under aware and unaware conditions. The present ERP study aimed to tackle this challenge by using a novel stimulation design. Male and female human participants (n = 62) performed a visual task while task-irrelevant line stimuli were presented in the background for either 500 or 1000 ms. The line stimuli sometimes contained a face, which needed so-called visual one-shot learning to be seen. Half of the participants were informed about the presence of the face, resulting in faces being perceived by the informed but not by the uninformed participants. Comparing ERPs between the informed and uninformed group revealed an enhanced negativity over occipitotemporal electrodes that persisted for the entire duration of stimulus presentation. Our results suggest that sustained visual awareness negativities (SVAN) are associated with the duration of stimulus presentation.

Abstract Background Countries in the Global South are currently facing momentous economic and social challenges, including major debt service problems. As in previous periods of global financial instability, a growing number of countries have turned to the International Monetary Fund (IMF) for financial assistance. The organization has a long track-record of advocating for extensive fiscal consolidation—commonly known as ‘austerity’—for its borrowers. However, in recent years, the IMF has announced major initiatives for ensuring that its loans support social spending, thus aiding countries in meeting their development targets and the Sustainable Development Goals. To assess this track record, we collected spending data on 21 loans signed in the 2020–2022 period, including from all their periodic reviews up to August 2023. Results We find that austerity measures remain a core part of the organization’s mandated policies for its borrowers: 15 of the 21 countries studied here experience a decrease in fiscal space over the course of their IMF programs. Against this fiscal backdrop, social spending floors have failed to live up to their promise. There is no streamlined definition of these floors, thus rendering their application haphazard and inconsistent. But even on their own terms, these floors lack ambition: they often do not foresee trajectories of meaningful social spending increases over time, and, when they do, many of these gains are eaten up by soaring inflation. In addition, a third of social spending floors are not implemented—a much lower implementation rate from that for austerity conditions, which the IMF prioritizes. In several instances, where floors are implemented, they are not meaningfully exceeded, thus—in practice—acting as social spending ceilings. Conclusions The IMF’s lending programs are still heavily focused on austerity, and its strategy on social spending has not represented the sea-change that the organization advertised. At best, social spending floors act as damage control for the painful budget cuts: they are instruments of social amelioration, underpinned by principles of targeted assistance for highly disadvantaged groups. Alternative approaches rooted in principles of universalism can be employed to build up durable and resilient social protection systems.

Abstract Background Komagataella phaffii (Pichia pastoris) has emerged as a common and robust biotechnological platform organism, to produce recombinant proteins and other bioproducts of commercial interest. Key advantage of K. phaffii is the secretion of recombinant proteins, coupled with a low host protein secretion. This facilitates downstream processing, resulting in high purity of the target protein. However, a significant but often overlooked aspect is the presence of an unknown polysaccharide impurity in the supernatant. Surprisingly, this impurity has received limited attention in the literature, and its presence and quantification are rarely addressed. Results This study aims to quantify this exopolysaccharide in high cell density recombinant protein production processes and identify its origin. In stirred tank fed-batch fermentations with a maximal cell dry weight of 155 g/L, the polysaccharide concentration in the supernatant can reach up to 8.7 g/L. This level is similar to the achievable target protein concentration. Importantly, the results demonstrate that exopolysaccharide production is independent of the substrate and the protein production process itself. Instead, it is directly correlated with biomass formation and proportional to cell dry weight. Cell lysis can confidently be ruled out as the source of this exopolysaccharide in the culture medium. Furthermore, the polysaccharide secretion can be linked to a mutation in the HOC1 gene, featured by all derivatives of strain NRRL Y-11430, leading to a characteristic thinner cell wall. Conclusions This research sheds light on a previously disregarded aspect of K. phaffii fermentations, emphasizing the importance of monitoring and addressing the exopolysaccharide impurity in biotechnological applications, independent of the recombinant protein produced.

The Paris Agreement's ambitious target of limiting the global temperature rise to 1.5°C remains elusive, with the world falling short of its climate commitments. The electricity sector, responsible for a substantial 39% of global carbon emissions, plays a pivotal role in curbing climate change. Transitioning to renewable energy sources is not just an environmental imperative but also a pressing economic challenge, especially for governments tasked with financing renewable projects. This study explores the economic dimensions of decarbonizing electricity grids, shedding light on the costs and benefits. This research quantifies the costs of current fossil fuel-based electricity production versus achieving net-zero emissions across ten Latin American countries by evaluating annual electricity generation costs and estimating the expenses of transitioning to renewables. We find that decarbonizing these countries’ electricity grids would lead to annual savings close to USD 21 billion annually, potentially contributing positively to their economies. The study also compares the energy policies for each of the ten Latin American nations included, evaluating the role of renewable-oriented policies in decarbonizing power generation. We also find that policies vary in effectiveness across countries, and have to be in line with geographical constraints and economic realities.

Much of the university spin-offs (USOs) literature either focuses on the influence of parent universities or the external environments on enterprise performance in economies with one aspect almost always neglected, that is, the role of USOs’ corporate governance. In this study, we examine the effects of USOs’ corporate governance structure which includes equity structure, board size and organizational form, on enterprise performance in a Chinese context, as well as the moderating effect of human capital on the relationship between board size and enterprise performance. This study takes 150 enterprises in 42 universities in Hubei Province as samples in 2017 using the weighted least square (WLS) method. The research finds evidence of positive relationships between equity structure and enterprise performance, as well as between board size and enterprise performance. However, a positive effect is not found between organizational form and enterprise performance, which shows a prominent negative effect. Moreover, human capital which is partially positive, influences the relationship between board size and enterprise performance. Therefore, these findings add some potentially noteworthy dimensions to the USOs literature that are especially important to USOs’ policy makers and other stakeholders.

Summary: Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design.

IntroductionBacterial infection and biofilm formation contribute to impaired healing in chronic diabetic wounds. Staphylococcus aureus and Pseudomonas aeruginosa are found in human diabetic wound biofilms. They may develop antibiotic resistance, increasing the urgency for alternative or complementary therapies. Diabetic wound healing may be improved with the use of biomedically engineered scaffolds, which can also serve as delivery systems for antibacterial compounds. Manuka honey is a potent antibacterial and wound care agent due to its high osmolarity, low pH, and constituents (such as methylglyoxal). Honey exhibits bacteriostatic and bactericidal effects, modulates the expression of biofilm forming genes, and restores antibiotic susceptibility in previously drug resistant pathogens.MethodsIn this study, we created a dermal regeneration template (DRT) composed of polycaprolactone-gelatin (PCL-gelatin) and Manuka honey to retain honey in the wound and also provide a scaffold for tissue regeneration.Results and discussionSoluble Manuka honey inhibited the planktonic and biofilm growth of both S. aureus (UWH3) and P. aeruginosa (PA14) co-cultures. Manuka honey embedded PCL-gelatin scaffolds did not exhibit bacteriostatic or bactericidal effects on cocultures of UHW3 and PA14; however, they promoted the expression of AgrA, a gene associated with dispersal of S. aureus biofilms.

BackgroundEmotions play an important role in the emergence, formation, and experience of dreams. The Central Image (CI) in a dream refers to the dream’s dominant or underlying emotion, and it is the best-remembered part of a dream. Bipolar disorders are characterized by strong emotions, particularly during manic and depressive episodes. In these patients, dreams and CIs may serve as a helpful diagnostic and therapeutic tool. This study aims to evaluate the feasibility of the CI Method and to check for differences concerning dreams and CI emotions between healthy controls and patients with bipolar disorder.MethodsOver a period of 3 weeks, 61 participants were asked to maintain a daily record of all dreams remembered. Dream reports were rated using the Central Image Method (CIM) by two independent, blinded raters. We assessed for interrater agreement on the CIM and for within and between group differences related to negative and positive CI emotions.ResultsMean agreement rates (weighted Cohen’s kappa) for the CI emotion ratings could be classified as very good: For primary CI emotion ratings, the mean weighted Cohen’s kappa was 0.99 (± 0.02), and for secondary CI emotions, it was 0.90 (± 0.17). Regarding the CI intensities, the mean agreement rate (Spearman’s correlation) was also strong. Evaluation of differences within the groups showed that there were more negative CI emotions than positive CI emotions in healthy controls and currently depressive patients; however, in the latter, the difference was statistically not significant. Analyses of differences between groups indicated that patients who were currently depressed recorded more negative CI emotions in dreams than those who were euthymic or healthy controls.DiscussionThe findings support the feasibility of the CIM. Our results might indicate different emotion regulation and defense mechanisms across bipolar disorder states, as reflected by the occurrence of negative and positive CI emotions.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Background: There is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark. Method: Nationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance. Results: 433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3–4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9–1.2), possible disease 1.0 (95%CI 0.8–1.2), and isolation 1.7 (95%CI 1.4–1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio [IRR] = 2.1, 95%CI 1.9–2.3, p

Spin coating stands out as the most employed thin-film deposition technique across a variety of scientific fields. Particularly in the past two decades, spin coaters have become increasingly popular due to the emergence of solution-processed semiconductors such as quantum dots and perovskites. However, acquiring commercial spin coaters from reputable suppliers remains a significant financial burden for many laboratories, particularly for smaller research or educational facilities. Prompted by the simple mechanical principles of the device, in this work, we present a 3D-printed analogue that can be printed and assembled in under 10 h and costs less than 5 euros per device. The operating principle is fully mechanical since the rotating motion is induced by gas flow. It does not require any additional components such as DC motors, motor drivers, circuitry or software and thus it can be fully operational off the grid. Additionally, the gas flow generates a purging effect that was found to be rather advantageous for film formation. To prove the effectiveness of this device, we have employed it to fabricate planar thin-film antimony sulfide (Sb2S3) solar cells. The optoelectronic characteristics of solar cells revealed noteworthy improvements, particularly in terms of repeatability, when compared to those fabricated with a commercial spin coater.

Resumé Artiklen undersøger, gennem et scoping review, hvilke gennemgående temaer der kan identificeres på tværs af internationale læreruddannelsers arbejde med undervisningsdifferentiering i et andenordensdidaktisk perspektiv. På baggrund af disse resultater diskuterer artiklen, hvordan man i en dansk læreruddannelseskontekst kan finde inspiration til at arbejde med undervisningsdifferentiering i et andenordendidaktisk perspektiv. Reviewet identificerer og præsenterer tre overordnede temaer, der præsenteres i en narrativ syntese: 1) Studiernes forståelser af undervisningsdifferentiering, 2) Andenordensdidaktiske perspektiver og 3) Diversitet. Artiklen diskuterer, hvorvidt og hvordan man i en dansk læreruddannelseskontekst kan adoptere den overordnede inspiration vedrørende undervisningsdifferentiering fra Carol Ann Tomlinson. Desuden diskuterer artiklen potentialet ved metakommentarer til studerende om differentieret undervisning som en central andenordensdidaktisk tilgang på læreruddannelsen. Slutteligt diskuterer artiklen, hvordan man som læreruddannelse kan forholde sig til diversitet og kommunikationen om diversitet mellem kollegaer, studerende og som uddannelsesinstitution. Abstract This article investigates, through a scoping review, which prominent themes that can be identified across international teacher education programs in their approach to differentiated instruction from a second-order didactic perspective. The article discusses how these findings can inspire the work on differentiated instruction from a second-order didactic perspective within the context of Danish teacher education. The review identifies and presents three overarching themes in a narrative synthesis: 1) The studies’ understandings of differentiated instruction, 2) Second-order didactic perspectives, and 3) Diversity. The article then discusses whether and how the overarching inspiration from Carol Ann Tomlinson on differentiated instruction can be adopted within the context of Danish teacher education. Additionally, the article discusses the potential of using metacommentary to students about differentiated instruction as a central second-order didactic approach. Finally, the article explores how teacher education can address diversity and communication about diversity among colleagues, students, and as an educational institution.

Abstract There is a biodiversity crisis, and to prevent extinctions the most important sites to be effectively conserved must be identified. Key Biodiversity Areas (KBAs) include sites of importance for species survival. Alliance for Zero Extinction (AZE) sites, a subset of KBAs, contain ≥95% of the population of highly threatened species. Currently, only 47 tree species have been identified using the AZE criteria. The Global Tree Assessment, assessing the extinction risk of the world's tree species, has enabled trees to be incorporated into KBA and AZE sites. Here we present a methodology to utilize data from the IUCN Red List to identify potential AZE species for trees. This 10‐part methodology identified 2909 tree species as potential AZE species across the world, representing at least 5% of described tree species. As further tree species are assessments are published on the IUCN Red List, this methodology will be important for identifying potential AZE species. The methodology can be applied and adapted to any taxa on the IUCN Red List. This analysis serves as a prioritization mechanism for identifying species in urgent need of conservation action to prevent extinctions. The species identified can feed into national KBA identification efforts.

BackgroundDigital health research plays a vital role in advancing equitable health care. The diversity of research teams is thereby instrumental in capturing societal challenges, increasing productivity, and reducing bias in algorithms. Despite its importance, the gender distribution within digital health authorship remains largely unexplored. ObjectiveThis study aimed to investigate the gender distribution among first and last authors in digital health research, thereby identifying predicting factors of female authorship. MethodsThis bibliometric analysis examined the gender distribution across 59,980 publications from 1999 to 2023, spanning 42 digital health journals indexed in the Web of Science. To identify strategies ensuring equality in research, a detailed comparison of gender representation in JMIR journals was conducted within the field, as well as against a matched sample. Two-tailed Welch 2-sample t tests, Wilcoxon rank sum tests, and chi-square tests were used to assess differences. In addition, odds ratios were calculated to identify predictors of female authorship. ResultsThe analysis revealed that 37% of first authors and 30% of last authors in digital health were female. JMIR journals demonstrated a higher representation, with 49% of first authors and 38% of last authors being female, yielding odds ratios of 1.96 (95% CI 1.90-2.03; P

Faces can acquire emotional meaning by learning to associate individuals with specific behaviors. Here, we investigated emotional evaluation and brain activations toward faces of persons who had given negative or positive evaluations to others. Furthermore, we investigated how emotional evaluations and brain activation generalize to perceptually similar faces. Valence ratings indicated learning and generalization effects for both positive and negative faces. Brain activation, measured with functional magnetic resonance imaging (fMRI), showed significantly increased activation in the fusiform gyrus (FG) to negatively associated faces but not positively associated ones. Remarkably, brain activation in FG to faces to which emotional meaning (negative and positive) was successfully generalized was decreased compared to neutral faces. This suggests that the emotional relevance of faces is not simply associated with increased brain activation in visual areas. While, at least for negative conditions, faces paired with negative feedback behavior are related to potentiated brain responses, the opposite is seen for perceptually very similar faces despite generalized emotional responses.