Recent publications
In this study, nickel and cobalt nanoparticles were successfully synthesized through the simple reduction of nickel and cobalt salts using polyvinyl alcohol (PVA) and sodium borohydride as a reducing agent. These nanoparticles were then loaded onto the surface of supportive TiO2 particles to prepare and assess single and double-metal-doped TiO2 photocatalysts, such as Co-TiO2, Ni-TiO2, and Ni, Co-TiO2 using a simple reduction method. These photocatalysts were utilized for the first time for the removal of methyl red (MR) and methyl blue (MB) dyes from aqueous systems. The doping of cobalt and nickel transition metals was employed to decrease the band gap of the titanium dioxide catalyst. The prepared particles underwent analysis via SEM, TEM, FT-IR, XRD, TGA, and EDX. Several important factors, such as the initial solution pH, the concentration of MR and MB dyes, temperature, and catalyst dosage were investigated. The results revealed that Ni, Co-TiO2 NPs exhibited the highest photocatalytic degradation efficiency toward MR (approximately 98.5%) and MB (approximately 88.9%) compared to Co-TiO2 and Ni-TiO2 under optimal conditions (i.e. initial solution pH ~ 3, [MR] = 2, [MB] = 1, [PMS] = 1 mM, catalyst dosage ~ 0.2 g/L, and temperature ~ 298 K). The XRD peak at a 38° 2θ angle indicates the presence of cobalt, which increases with the concentration of cobalt. Moreover, all reactions occurred in an aqueous medium, and the photocatalysts remained stable during the reaction, allowing for their repeated use. Furthermore, they are environmentally friendly and have promising applications in the treatment of organic wastewater.
Boron-hydrogen compounds are of increasing importance as electrolytes in solid state batteries, for hydrogen storage and possibly as high temperature super conductors. Solvent based methods are of increasing importance to...
Aims
The objective of this study was to examine the effects of empagliflozin on endothelium‐dependent and endothelium‐independent vasodilatation and systemic hemodynamic parameters and to assess the role of the nitric oxide (NO) system in patients with type 2 diabetes (T2DM).
Materials and Methods
In this double‐blind, placebo‐controlled cross over trial, patients with T2DM were treated with either empagliflozin 10 mg or matching placebo for 4 weeks. Following a 2‐week washout, participants were crossed over to 4 weeks of the opposite treatment. Forearm blood flow (FBF) was measured after each treatment period using venous occlusion plethysmography. Acetylcholine and sodium nitroprusside (SNP) were infused into the brachial artery to assess endothelium‐dependent and endothelium‐independent vasodilatory function, respectively. Total peripheral resistance, 24‐h blood pressure (BP) and biochemical markers of NO activity were measured as well.
Results
Sixteen participants completed the trial. The mean age was 68 ± 8 years, and 69% were male. The SNP response increased by 21% (geometric mean ratio 1.21, 95% CI: 1.09; 1.33) during treatment with empagliflozin compared to placebo ( p ≤ 0.001), but not during acetylcholine infusion ( p = 0.290). Empagliflozin decreased 24‐h systolic BP by 5 mmHg (95% CI: −9; −1 mmHg) ( p = 0.015), diastolic BP by 2 mmHg (95% CI: −5; 0 mmHg) ( p = 0.029) and systemic vascular resistance by 48 dyn×s/m ⁵ (95% CI: −94; −1 dyn×s/m ⁵ ) ( p = 0.044). Furthermore, empagliflozin reduced plasma levels of nitrite and urinary levels of NOx.
Conclusions
Empagliflozin improves endothelium‐independent vasodilation, reduces vascular resistance and lowers 24‐h BP in patients with T2DM, whereas no change in endothelial‐dependent vasodilation was observed.
Trial registration
EU Clinical Trials Register number: 2019‐004303‐12 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004303-12/DK ).
Poor sleep quality is well recognised in both post‐traumatic stress disorder (PTSD) and pain conditions. Comorbid chronic pain is prevalent in populations with PTSD and is believed to maintain symptoms of PTSD and increase the complexity of the condition. Ongoing diminished sleep quality may serve to maintain pain and PTSD symptoms, and thus affect the efficacy of first‐line PTSD treatment. This study examined the mechanisms underlying the PTSD–pain relationship over time by investigating if perceived sleep quality mediates the relationship between PTSD symptom severity and levels of pain interference. Furthermore, we considered whether the interrelation between these three variables could in fact be linked in an alternative model where the causality was reversed, with pain interference mediating the relation between PTSD severity and perceived sleep quality. Relationships among our variables were assessed within a path analysis framework, conducted and controlled for covariates using structural equation modelling and mediation analysis. The analysis of our hypothesised model revealed that improvement in perceived sleep quality was a significant partial mediator of the association between reduction in PTSD severity and pain interference. Approximately 28% of the effect of PTSD severity on pain interference was mediated by improvement in perceived sleep quality. Evaluation of our alternative model revealed a non‐significant mediation effect. Sleep thus represents a modifiable mechanism that contributes to the mutual maintenance of PTSD and pain. The study is the first to investigate these relationships in trauma‐affected refugees and thus contributes new knowledge and clinical implications for the treatment of poor sleep quality and pain symptomatology in trauma‐affected refugees.
Genome-wide association study (GWAS) is a powerful tool for identifying marker-trait associations that can accelerate breeding progress. Yet, its power is typically constrained in newly established breeding programs where large phenotypic and genotypic datasets have not yet accumulated. Expanding the dataset by inclusion of data from well-established breeding programs with many years of phenotyping and genotyping can potentially address this problem. In this study we performed single- and multi-population GWAS on heading date and lodging in four barley breeding populations with varying combinations of row-type and growth habit. Focusing on a recently established 6-rowed winter (6RW) barley population, single-population GWAS hardly resulted in any significant associations. Nevertheless, the combination of the 6RW target population with other populations in multi-population GWAS detected four and five robust candidate quantitative trait loci for heading date and lodging, respectively. Of these, three remained undetected when analysing the combined populations individually. Further, multi-population GWAS detected markers capturing a larger proportion of genetic variance in 6RW. For multi-population GWAS, we compared the findings of a univariate model (MP1) with a multivariate model (MP2). While both models surpassed single-population GWAS in power, MP2 offered a significant advantage by having more realistic assumptions while pointing towards robust marker-trait associations across populations. Additionally, comparisons of GWAS findings for MP2 and single-population GWAS allowed identification of population-specific loci. In conclusion, our study presents a promising approach to kick-start genomics-based breeding in newly established breeding populations.
Hyperammonaemic encephalopathy in the absence of liver failure is a major diagnostic challenge. A rare cause is as a complication to previous gastric bypass surgery, a condition reported to be associated with high mortality. In this case report, we present the exhaustive diagnostic work-up and clinical reversal of deep and recurrent hyperammonaemic encephalopathy in a patient with previous gastric bypass surgery. As a key finding, the patient exhibited an extreme reduction of the in vivo capacity for urea synthesis, which was reverted by long-standing correction of severe protein and micronutrient malnourishment (Functional Hepatic Nitrogen Clearance; 2.9 to 25.5 L/h). In addition, we observed reduced levels of fasting plasma amino acids (α-amino nitrogen; 2.7 to 3.6 mmol/L) and glucagon (0.3 to 2.6 pmol/L) before clinical improvement, which may contribute to the non-functioning urea synthesis. These observations elucidate the underlying pathophysiology of hyperammonaemia as a complication of gastric bypass and highlight a potential mechanism – non-functioning urea cycle as a result of protein malnourishment and hepatic glucagon resistance.
Objective
To develop an accurate method for converting dose-area product (DAP) to patient dose for dental cone-beam computed tomography (CBCT) using deep learning.
Methods
24,384 CBCT exposures of an adult phantom were simulated with PCXMC 2.0, using permutations of tube voltage, filtration, source-isocenter distance, beam width/height and isocenter position. Equivalent organ doses as well as DAP values were recorded. Next, using the aforementioned scan parameters as inputs, neural networks (NN) were trained using Keras for estimating the equivalent dose per DAP for each organ. Two methods were explored for positional input features: (1) ‘Coordinate’ mode, which uses the (continuous) XYZ-coordinates of the isocenter, and (2) ‘AP/JAW’ mode, which uses the (categorical) anteroposterior and craniocaudal position. Each network was trained, validated and tested using a 3/1/1 data split. Effective dose (ED) was calculated from the combination of NN outputs using ICRP 103 tissue weighting factors. The performance of the resulting NN models for estimating ED/DAP was compared with that of a multiple linear regression (MLR) model as well as direct conversion coefficients (CC).
Results
The mean absolute error (MAE) for organ dose/DAP on the test data ranged from 0.18% (bone surface) to 2.90% (oesophagus) in ‘Coordinate’ mode and from 2.74% (red bone-marrow) to 14.13% (brain) in ‘AP/JAW’ mode. The MAE for ED was 0.23% and 4.30%, respectively, for the two modes, vs. 5.70% for the MLR model and 20.19%-32.67% for the CCs.
Conclusion
NNs allow for an accurate estimation of patient dose based on DAP in dental CBCT.
Objective
Occipital Nerve Stimulation (ONS) is increasingly used to treat a range of chronic, refractory headache conditions, most notably chronic cluster headache (CCH).
Despite this, there is still no consensus on the optimal implantation technique. Clinical reports and reviews in the field have reported remarkably high complication rates of which several can be directly related to the surgical approach.
We here describe a comprehensive and detailed surgical approach used at Aarhus University Hospital, Denmark, aiming to improve paresthesia coverage and minimize complications.
Methods
The implantation procedure described here is performed with a sleep‐awake anesthetic regimen in a lateral position using anatomical landmarks and perioperative testing based on patient feedback. A single lead is subcutaneously implanted from behind the ear and across the back of the head, and the implantable pulse generator (IPG) is placed below the right clavicle.
Results
From March 2018 to June 2024, 45 CCH patients were implanted using this approach and followed up for a total of 86.3 patient years. A total of 22 adverse events (AEs) occurred in 17 patients, with nine AEs requiring revision surgery. Notably, no instances of lead migration, lead breakage, or muscle/neck stiffness were observed. Temporary occipital dysesthesia was the most frequent non‐surgical AE, resolving spontaneously within weeks. The rate of serious adverse events (SAEs) was one per 9.6 patient years. Six patients had the ONS system explanted due to lack of efficacy.
Conclusions
The surgical approach described here in detail offers several advantages, with a favorable complication profile, satisfactory paresthesia coverage, and good perioperative patient comfort. Advances in the surgical technique are vital to both patients and healthcare providers, and we believe this approach is a valuable contribution toward improved patient outcomes and procedural efficiency.
Copper is an essential micronutrient and yet is highly toxic to cells at elevated concentrations. P1B‐ATPase proteins are critical for this regulation, providing active extrusion across cellular membranes. One unique molecular adaptation of P1B‐ATPases compared to other P‐type ATPases is the presence of metal‐binding domains (MBDs) at the cytosolic termini, which however are poorly characterized with an elusive mechanistic role. Here we present the MBD architecture in metal‐free and metal‐bound forms of the archetype Cu⁺‐specific P1B‐ATPase LpCopA, determined using NMR. The MBD is composed of a flexible tail and a structured core with a metal ion binding site defined by three sulfur atoms, one of which is pertinent to the so‐called CXXC motif. Furthermore, we demonstrate that the MBD rather than being involved in ion delivery likely serves a regulatory role, which is dependent on the classical P‐type ATPase E1‐E2 transport mechanism. Specifically, the flexible tail appears responsible for autoinhibition while the metal‐binding core is used for copper sensing. This model is validated by a conformation‐sensitive and MBD‐targeting nanobody that can structurally and functionally replace the flexible tail. We propose that autoinhibition of Cu⁺‐ATPases occurs at low copper conditions via MBD‐mediated interference with the soluble domains of the ATPase core and that metal transport is enabled when copper levels rise, through metal‐induced dissociation of the MBD. This allows P1B‐ATPase ‘vacuum cleaners’ to tune their own activity, balancing the levels of critical micronutrients in the cells.
Marine soft sediments play crucial roles in global biogeochemical cycles and biodiversity. Yet, with organisms often hidden in the sediment, they pose challenges for effective monitoring and management. This study introduces a novel approach utilizing sediment microtopography as a proxy for ecosystem functioning and biodiversity. Combining field sampling, benthic chamber incubations, and advanced Structure‐from‐Motion photogrammetry techniques, we investigated the relationships between microtopographic features and various ecological parameters across diverse subtidal habitats. Our findings reveal strong associations between sediment microtopography and environmental variables, benthic fluxes, biodiversity metrics, and community functional traits, with microtopography consistently explaining more than 50% of the variance in the data. This research demonstrates the potential of sediment microtopography as a cost‐effective and scalable tool for assessing soft‐sediment ecosystem dynamics and informing conservation strategies. By providing insights into the links between habitat structure and ecological processes, this study advances our understanding of marine benthic ecology and opens new possibilities for habitat assessment applications worldwide.
An inclusive clinical trial ecosystem is essential to obtain scientific results that can be generalized to a broad patient population. When possible, all efforts should be made to remove geographic, demographic, cultural and ethnic barriers for enrolment in clinical trials. However, to do this effectively, we need more knowledge about factors influencing clinical trial participation and practical frameworks to enhance diversity in clinical trials.
Commentary on: Jones et al. Inequalities in geographic barriers and patient representation in lymphoma clinical trials across England. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19907.
Children’s agential behaviours in the archaeological record have often been overlooked. Despite efforts to centre children in the past through ‘an archaeology of childhood’, there remains a fundamental challenge of rigorously distinguishing children’s behaviours from those of adults. In Upper Palaeolithic art, this has been addressed through the analysis of anatomical measurements of traces produced by hands and figures, demonstrating that children were often engaging in artistic behaviours. However, the dependency on anatomical measurements limits the cases for Upper Palaeolithic children’s art. We here integrate developmental psychological research on children’s drawings into a framework within which children’s art in the Upper Palaeolithic record can be identified, without needing to rely on anatomical measurements. This work emphasises the intangible dimensions of narrative and play inherent within modern children’s art making behaviours as a starting point for understanding children as artists in the Upper Palaeolithic. Focusing on a case study of the Panel of the Masks from Las Monedas cave (Cantabria, Spain), this approach is demonstrated to have significant potential in both detecting children’s art and appreciating the playful nature of its making. We further propose ways that this approach can be employed to identify additional cases of children’s art in the Upper Palaeolithic record through specific methods that facilitate in-depth analysis of the properties of possible cases of children’s art.
Multiple myeloma (MM) is a haematological malignancy with abnormal proliferation of plasma cells in the bone marrow (BM), and MM patients with highly proliferative plasma cells have reduced overall survival. Circular RNAs (circRNAs) are endogenous, non‐coding molecules that are promising biomarkers in cancer. Here, we present the largest study of circRNAs in MM to date and explore the prognostic potential of circRNAs and the link between proliferation and circRNA expression in MM. We performed deep total RNA sequencing (RNA‐seq) on two cohorts: one cohort consisting of 45 whole BM MM patient samples and 13 healthy controls (HCs), and another cohort consisting of 43 CD138‐purified plasma cell MM patient samples. We found that circRNAs are globally upregulated in the whole BM of MM patients compared to HCs. In whole BM, low proliferation and high circRNA levels were associated with a poor prognosis, while in purified plasma cells, low proliferation and high circRNA levels were associated with a favourable prognosis. Individual circRNAs from purified plasma cells were found to be significantly associated with MM patient outcomes and provide additional prognostic value to the proliferative indexes. Together, our findings emphasise the potential of circRNAs as prognostic biomarkers in MM.
The tusk of the male narwhal is a prolonged canine tooth, reaching a size of up to 3 m in length. The tusk erupts through the young narwhal’s upper left lip and, over time, develops into an elongated structure composed of dentine growth layers with an outer coating of cementum. In this study, we utilized bomb radiocarbon (¹⁴C) to estimate the ages of three narwhal tusks, which allowed us to validate the assumption that one growth layer is deposited annually in narwhal tusks. We used radiocarbon values from samples collected from the annual growth layers along the lengths of the erupted tusks and from the tip and base of embedded teeth, together with published radiocarbon data from three North Atlantic whale species, for the purpose of building a model of the incorporation of bomb radiocarbon in marine mammal tissues. The results obtained contribute significantly to our understanding of narwhal growth and longevity, enhancing our comprehension of isotope flow in the Arctic marine environment and their incorporation into the living tissue of a marine top predator. The bomb radiocarbon model can serve as a valuable reference chronology for dating museum or field specimens of narwhals and other North Atlantic marine animals.
The Smithian–Spathian boundary interval is characterised by a positive carbon isotopic excursion in both δ¹³Ccarb and δ¹³Corg, concurrent with a major marine ecosystem reorganisation and the resurgence of microbialite facies. While these δ¹³C records have been traditionally interpreted as capturing global carbon cycle behaviour, recent studies have suggested that at least some excursions in early Triassic δ¹³C values may incorporate influences from authigenic or early diagenetic processes. To examine the mechanistic drivers of Smithian–Spathian boundary geochemistry, the carbonate geochemistry of a core from Georgetown, Idaho (USA), was analysed using a coupled δ44/40Ca, δ²⁶Mg and trace‐metal framework. While the δ¹³C record in the Georgetown core is broadly similar to other Smithian–Spathian boundary sections, portions of the record coincide with substantial shifts in δ44/40Ca, δ²⁶Mg and trace‐metal compositions that cannot feasibly be interpreted as primary. Furthermore, these geochemical variations correspond with lithology: The δ¹³C record is modulated by variations in the extent of dolomitisation, and the diagenetic styles recognised here coincide with individual lithostratigraphic units. A primary shift in local sea water δ¹³C values is inferred from the most geochemically unaltered strata, from ca 3‰ in the middle Smithian to ca 5‰ in the early Spathian, although the timing and pathway through which this occurs cannot be readily identified nor extrapolated globally. Therefore, the Georgetown core may not directly record exogenic carbon cycle evolution, showing that there is a need for the careful reconsideration of the Smithian–Spathian boundary—and more broadly, Early Triassic—geochemical records to examine potential local and diagenetic influences on sedimentary geochemistry.
Introduction/Aims
MScanFit motor unit number estimation (MUNE) is the most recent MUNE method which has shown promising results in extremity muscles, but it has not been applied to bulbar muscles. Bulbar muscles are particularly important in the diagnosis of amyotrophic lateral sclerosis (ALS). This study aimed to investigate the feasibility and reliability of MScanFit MUNE in the accessory nerve and trapezius muscles.
Methods
A total of twenty healthy participants were examined twice within 1–2 weeks. We extracted the MScanFit MUNE and size parameter, and compound muscle action potential (CMAP) amplitude values. The reliability of these parameters was assessed using the intra‐rater coefficient of variation (CoV), intraclass correlation coefficient (ICC), and Bland–Altman plots. We also correlated MUNE values with CMAP amplitudes using correlation coefficients.
Results
Mean MUNE values (Day 1 = 132.1 and Day 2 = 137.4), CMAP amplitudes (Day 1 = 9.71 mV and Day 2 = 10.10 mV) and size parameters did not differ between the two sessions ( p > 0.05). CoV showed excellent reliability for MUNE values, size parameters, and CMAP amplitudes (CoV < 7%) whereas ICCs showed moderate reliability for MUNE values (ICC = 0.619), poor to moderate reliability for size parameters (between 0.393 and 0.689), and good reliability for CMAP amplitude (ICC = 0.864) There was no correlation between MUNE values and CMAP amplitudes.
Discussion
MScanFit MUNE is applicable and mostly reliable in the trapezius muscle. Further studies in patients are needed to investigate the sensitivity of MScanFit in this muscle in detecting motor unit loss, particularly in ALS.
The oceans play a pivotal role in mitigating climate change by sequestering approximately 25% of annually emitted carbon dioxide (CO2). High‐latitude oceans, especially the Arctic continental shelves, emerge as crucial CO2 sinks due to their cold, low saline, and highly productive ecosystems. However, these heterogeneous regions remain inadequately understood, hindering accurate assessments of their carbon dynamics. This study investigates variation in pCO2 levels during peak ice sheet melt, in the Greenland coastal ocean and estimates rates of air‐sea exchange across 6° of latitude. The East and West coast of Greenland displayed distinct regions with unique controlling factors. Though, both coasts represent CO2 sinks in summer. Geographical variation in pCO2 and air‐sea exchange was linked intricately to freshwater export from the Greenland ice sheet and levels of primary production in these ecosystems. Air‐sea exchange of CO2 ranged from 0.23 to −64 mmol m⁻² day⁻¹. However, we found that flux estimation faces substantial uncertainties (up to 672%) due to wind product averaging and gas exchange formula selection. Upscaling only heightens this uncertainty leading to wide ranging estimates of Greenland coastal CO2 uptake between −16 and −26 Tg C year⁻¹ (This study, Dai et al., 2022, https://doi.org/10.1146/annurev‐earth‐032320‐090746; Laruelle et al., 2014, https://doi.org/10.1002/2014gb004832). Obtaining a reliable assessment of air‐sea CO2 exchange necessitates data collection across seasons, and, even more so, refinement of the gas transfer velocity estimations in the Arctic coastal zone.
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