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Abstract The cryo-EM structure of the human rhinovirus B14 determined in this study reveals 13-bp RNA duplexes symmetrically bound to regions around each of the 30 two-fold axes in the icosahedral viral capsid. The RNA duplexes (~12% of the ssRNA genome) define a quasi-dodecahedral cage that line a substantial part of the capsid interior surface. The RNA duplexes establish a complex network of non-covalent interactions with pockets in the capsid inner wall, including coulombic interactions with a cluster of basic amino acid residues that surround each RNA duplex. A direct comparison was made between the cryo-EM structure of RNA-filled virions and that of RNA-free (empty) capsids that resulted from genome release from a small fraction of viruses. The comparison reveals that some specific residues involved in capsid-duplex RNA interactions in the virion undergo remarkable conformational rearrangements upon RNA release from the capsid. RNA release is also associated with the asynchronous opening of channels at the 30 two-fold axes. The results provide further insights into the molecular mechanisms leading to assembly of rhinovirus particles and their genome uncoating during infection. They may also contribute to development of novel antiviral strategies aimed at interfering with viral capsid-genome interactions during the infectious cycle.

Abstract Background Insecticides are a crucial component of vector control. However, resistance constitute a threat on their efficacy and the gains obtained over the years through malaria vector control. In Gabon, little data on phenotypic insecticide resistance in Anopheles vectors are published, compromising the rational implementation of resistance management strategies. We assessed the susceptibility to pyrethroids, carbamates and organophosphates of Anopheles gambiae sensu lato (s.l.) and discuss the mechanisms involved in the pyrethroid resistance-phenotype. Methods A. gambiae s.l. larvae were collected from breeding sites in Lambaréné. Emerging adults were used in WHO tube assays at an insecticide concentration that defines resistance (diagnostic concentration). Subsequently, deltamethrin and permethrin were used at 5x and 10x diagnostic concentrations and after preexposure with the cytochrome p450 (and glutathione S-transferase) inhibitor piperonyl butoxide (PBO). A subset of mosquitoes was typed by molecular methods and screened using Taqman assays for mutations conferring target site resistance at the Voltage-gated sodium channel 1014 (Vgsc-1014) locus and the acetylcholinesterase (Ace-1) gene. Results All mosquitoes were A. gambiae sensu stricto (s.s.) and resistant to permethrin, deltamethrin and alphacypermethrin (mortality less than 98%). However, mosquitoes were susceptible to malathion but resistant to bendiocarb. The level of resistance was high for permethrin and at least moderate for deltamethrin. Pre-exposure to PBO significantly increased the mortality of resistant mosquitoes (P

Abstract People with severe asthma often lead sedentary lifestyles, which adversely affects overall health and asthma-specific outcomes. To inform future sedentary behaviour- interventions, this study aimed to explore perceptions of sedentary behaviour among people with severe asthma. Adults (≥ 18 years) with severe asthma (n = 21) participated in face-to-face interviews. Participants were asked open-ended questions about factors influencing their sitting behaviour. A thematic analysis was conducted on phrases and sentences relevant to sedentary behaviour. Participants were predominantly females (62%), with controlled asthma (median [Q1, Q3]: ACQ6 0.5 [0.2,1.8]) and receiving monoclonal antibody therapy (71%). Almost half of the participants were not meeting the physical activity guidelines (47%) and were sedentary (10.8 [9.7, 11.4] hours of sedentary behaviour per day). The analysis generated four main themes: (1) Sedentary behaviour often stems from habits and routines, (2) Asthma and associated health issues contribute to sedentary behaviour, (3) Participants’ responsibilities influence their activity levels, and; (4) Participants’ conscious balance between being physically active and sedentary. The results of this qualitative study offers insights into the perspectives of people with severe asthma regarding sedentary behaviour, highlighting the identification of strategies that can be implemented to improve sedentary behaviour in this population.

During our studies of the oxidation of gold(I) complexes of trialkylphosphane chalcogenides, general formula R1R2R3PEAuX, (R = tert-butyl or isopropyl, E = S or Se, X = Cl or Br) with PhICl2 or elemental bromine, we have isolated a set of seven mixed-valence by-products, the bis(trialkylphosphane chalcogenido)gold(I) tetrahalogenidoaurates(III) [(R1R2R3PE)2Au]+[AuX4]−. These correspond to the addition of one halogen atom per gold atom of the AuI precursor. Compound 1, bis(triisopropylphosphane sulfide)gold(I) tetrachloridoaurate(III), [Au(C9H21PS)2][AuCl4] or [(iPr3PS)2Au][AuCl4], crystallizes in space group P21/n with Z = 4; the gold(I) atoms of the two cations lie on twofold rotation axes, and the gold(III) atoms of the two anions lie on inversion centres. Compound 2, bis(tert-butyldiisopropylphosphane sulfide)gold(I) tetrachloridoaurate(III), [Au(C10H23PS)2][AuCl4] or [(tBuiPr2PS)2Au][AuCl4], crystallizes in space group P1 with Z = 4; the asymmetric unit contains two cations and two anions with no imposed symmetry. A least-squares fit of the two cations gave an r.m.s. deviation of 0.19 Å. Compound 3, bis(tri-tert-butylphosphane sulfide)gold(I) tetrachloridoaurate(III), [Au(C12H27PS)2][AuCl4] or [(tBu3PS)2Au][AuCl4], crystallizes in space group P1 with Z = 1; both gold atoms lie on inversion centres. Compound 4a, bis(tert-butyldiisopropylphosphane sulfide)gold(I) tetrabromidoaurate(III), [Au(C10H23PS)2][AuBr4] or [(tBuiPr2PS)2Au][AuBr4], crystallizes in space group P21/c with Z = 4; the cation lies on a general position, whereas the gold(III) atoms of the two anions lie on inversion centres. Compound 4b, bis(tert-butyldiisopropylphosphane selenide)gold(I) tetrabromidoaurate(III), [Au(C10H23PSe)2][AuBr4] or [(tBuiPr2PSe)2Au][AuBr4], is isotypic with 4a. Compound 5a, bis(tri-tert-butylphosphane sulfide)gold(I) tetrabromidoaurate(III), [Au(C12H27PS)2][AuBr4] or [(tBu3PS)2Au][AuBr4], is isotypic with compound 4a. Compound 5a, bis(tri-tert-butylphosphane sulfide)gold(I) tetrabromidoaurate(III), [Au(C12H27PS)2][AuBr4] or [(tBu3PS)2Au][AuBr4], crystallizes in space group P1 with Z = 1; both gold atoms lie on inversion centres. Compound 5b, bis(tri-tert-butylphosphane selenide)gold(I) tetrabromidoaurate(III), [Au(C12H27PSe)2][AuBr4] or [(tBu3PSe)2Au][AuBr4], is isotypic with 5a. All AuI atoms are linearly coordinated and all AuIII atoms exhibit a square-planar coordination environment. The ligands at the AuI atoms are antiperiplanar to each other across the S...S vectors. There are several short intramolecular H...Au and H...E contacts. Average bond lengths (Å) are: P—S = 2.0322, P—Se = 2.1933, S—Au = 2.2915, and Se—Au = 2.4037. The complex three-dimensional packing of 1 involves two short C—Hmethine...Cl contacts (and some slightly longer contacts). For 2, four C—Hmethine...Cl interactions combine to produce zigzag chains of residues parallel to the c axis. Additionally, an S...Cl contact is observed that might qualify as a ‘chalcogen bond’. The packing of 3 is three-dimensional, but can be broken down into two layer structures, each involving an S...Cl and an H...Cl contact. For the bromido derivatives 4a/b and 5a/b, loose associations of the anions form part of the packing patterns. For all four compounds, these combine with an E...Br contact to form layers parallel to the ab plane.

Abstract The warming of the Arctic had lead to a diverse range of impacts on local biota, including northward shifts of some species range. Here, we report past and present distribution and abundance of an Arctic zooplanktivorous seabird, the little auk Alle alle in West Greenland south of 74° N, and examine the changes in sea surface temperature (SST) and sea ice concentration (SIC) in the birds foraging areas in 1850–2007. We estimated the little auk population in the studied region to be 5,200 pairs in the 1930s, 6,000–6,500 pairs in the 1940-1970s and 70–80 pairs by the 2000s. We found that periods with increased SST and reduced SIC, especially in the last few decades, coincided with little auk population declines. Besides, years with little auk presence in breeding sites were characterized by either low SST and low to moderate SIC or higher SST but moderate to high SIC. Observed contraction of the breeding range and a decrease in abundance of the little auk may be attributed to more complex climate-driven changes in the marine ecosystem at finer spatial and temporal scales and/or cannot be easily detected given the coarseness of data used. It is possible that the population in this region has never been very numerous being subjected to local impacts such as disease, bycatch, predation, etc. The climate warming that is currently being observed, along with corresponding shifts in zooplankton communities, may lead to extirpation of the studied little auk populations.

Abstract Background Recent technological advances have resulted in low-cost GPS loggers that are small enough to be used on a range of seabirds, producing accurate location estimates (± 5 m) at sampling intervals as low as 1 s. However, tradeoffs between battery life and sampling frequency result in studies using GPS loggers on flying seabirds yielding locational data at a wide range of sampling intervals. Metrics derived from these data are known to be scale-sensitive, but quantification of these errors is rarely available. Very frequent sampling, coupled with limited movement, can result in measurement error, overestimating movement, but a much more pervasive problem results from sampling at long intervals, which grossly underestimates path lengths. Methods We use fine-scale (1 Hz) GPS data from a range of albatrosses and petrels to study the effect of sampling interval on metrics derived from the data. The GPS paths were sub-sampled at increasing intervals to show the effect on path length (i.e. ground speed), turning angles, total distance travelled, as well as inferred behavioural states. Results We show that distances (and per implication ground speeds) are overestimated (4% on average, but up to 20%) at the shortest sampling intervals (1–5 s) and underestimated at longer intervals. The latter bias is greater for more sinuous flights (underestimated by on average 40% when sampling > 1-min intervals) as opposed to straight flight (11%). Although sample sizes were modest, the effect of the bias seemingly varied with species, where species with more sinuous flight modes had larger bias. Sampling intervals also played a large role when inferring behavioural states from path length and turning angles. Conclusions Location estimates from low-cost GPS loggers are appropriate to study the large-scale movements of seabirds when using coarse sampling intervals, but actual flight distances are underestimated. When inferring behavioural states from path lengths and turning angles, moderate sampling intervals (10–30 min) may provide more stable models, but the accuracy of the inferred behavioural states will depend on the time period associated with specific behaviours. Sampling rates have to be considered when comparing behaviours derived using varying sampling intervals and the use of bias-informed analyses are encouraged.

The collection and preservation of biological material before DNA analysis is critical for inter alia biomedical research, medical diagnostics, forensics and biodiversity conservation. In this study, we evaluate an in-house formulated buffer called the Forensic DNA Laboratory-buffer (FDL-buffer) for preservation of biological material for long term at room temperature. Human saliva stored in the buffer for 8 years, human blood stored for 3 years and delicate animal tissues from the jellyfish Pelagia noctiluca comb jelly Beroe sp., stored for 4 and 6 years respectively consistently produced high-quality DNA. FDL-buffer exhibited compatibility with standard organic, salting out and spin-column extraction methods, making it versatile and applicable to a wide range of applications, including automation.

Abstract Organic solvents host the synthesis of high-value crystals used as pharmaceuticals and optical devices, among other applications. A knowledge gap persists on how replacing the hydrogen bonds and polar attraction that dominate aqueous environments with the weaker van der Waals forces affects the growth mechanism, including its defining feature, whether crystals grow classically or nonclassically. Here we demonstrate a rare dual growth mode of etioporphyrin I crystals, enabled by liquid precursors that associate with crystal surfaces to generate stacks of layers, which then grow laterally by incorporating solute molecules. Our findings reveal the precursors as mesoscopic solute-rich clusters, a unique phase favored by weak bonds such as those between organic solutes. The lateral spreading of the precursor-initiated stacks of layers crucially relies on abundant solute supply directly from the solution, bypassing diffusion along the crystal surface; the direct incorporation pathway may, again, be unique to organic solvents. Clusters that evolve to amorphous particles do not seamlessly integrate into crystal lattices. Crystals growing fast and mostly nonclassically at high supersaturations are not excessively strained. Our findings demonstrate that the weak interactions typical of organic systems promote nonclassical growth modes by supporting liquid precursors and enabling the spreading of multilayer stacks.

Abstract Live vaccines are ideal for inducing immunity but suffer from the need to attenuate their pathogenicity or replication to preclude the possibility of escape. Unnatural amino acids (UAAs) provide a strategy to engineer stringent auxotrophies, yielding conditionally replication incompetent live bacteria with excellent safety profiles. Here, we engineer Pseudomonas aeruginosa to maintain auxotrophy for the UAA p-benzoyl-l-phenylalanine (BzF) through its incorporation into the essential protein DnaN. In vivo evolution using an Escherichia coli-based two-hybrid selection system enabled engineering of a mutant DnaN homodimeric interface completely dependent on a BzF-specific interaction. This engineered strain, Pa Vaccine, exhibits undetectable escape frequency (

The compounds 2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyl N′-cyano-N-phenylcarbamimidothioate (C22H25N3O9S, 5a), 2′,3′,4′,6′-tetra-O-acetyl-β-D-galactopyranosyl N′-cyano-N-phenylcarbamimidothioate, (C22H25N3O9S, 5b), 2′,3′,4′,6′-tetra-O-acetyl-β-D-galactopyranosyl N′-cyano-N-methylcarbamimidothioate (C17H23N3O9S, 5c), and 2′,3′,4′,6′-tetra-O-acetyl-β-D-galactopyranosyl N′-cyano-N-p-tolylcarbamimidothioate (C23H27N3O9S, 5d) all crystallize in P212121 with Z = 4. For all four structures, the configuration across the central (formal) C=N(CN) double bond of the carbamimidothioate group is Z. The torsion angles C5—O1—C1—S (standard sugar numbering) are all close to 180°, confirming the β position of the substituent. Compound 5b involves an intramolecular hydrogen bond N—H...O1; in 5c this contact is the weaker branch of a three-centre interaction, whereas in 5a and 5d the H...O distances are much longer and do not represent significant interactions. The C—N bond lengths at the central carbon atom of the carbamimidothioate group are almost equal. All C—O—C=O torsion angles of the acetyl groups correspond to a synperiplanar geometry, but otherwise all four molecules display a high degree of conformational flexibility, with many widely differing torsion angles for equivalent groups. In the crystal packing, 5a, 5c and 5d form layer structures involving the classical hydrogen bond N—H...Ncyano and a variety of ‘weak’ hydrogen bonds C—H...O or C—H...S. The packing of 5b is almost featureless and involves a large number of borderline ‘weak’ hydrogen bonds. In an appendix, a potted history of wavelength preferences for structure determination is presented and it is recommended that, even for small organic crystals in non-centrosymmetric space groups, the use of Mo radiation should be considered.

The structures of seven gold(III) halide derivatives of general formula LAuX3 (L = methylpyridines or dimethylpyridines, X = Cl or Br) are presented: trichlorido(2-methylpyridine)gold(III), [AuCl3(C6H7N)], 1 (as two polymorphs 1a and 1b); tribromido(2-methylpyridine)gold(III), [AuBr3(C6H7N)], 2; tribromido(3-methylpyridine)gold(III), [AuBr3(C6H7N)], 3; tribromido(2,4-dimethylpyridine)gold(III), [AuBr3(C7H9N)], 4; trichlorido(3,5-dimethylpyridine)gold(III), [AuCl3(C7H9N)], 5; tribromido(3,5-dimethylpyridine)gold(III), [AuBr3(C7H9N)], 6, and trichlorido(2,6-dimethylpyridine)gold(III), [AuCl3(C7H9N)], 7. Additionally, the structure of 8, the 1:1 adduct of 2 and 6, [AuBr3(C6H7N)]·[AuBr3(C7H9N)], is included. All the structures crystallize solvent-free, and all have Z′ = 1 except for 5 and 7, which display crystallographic twofold rotation symmetry, and 4, which has Z′ = 2. 1a and 2 are isotypic. The coordination geometry at the gold(III) atoms is, as expected, square-planar. Four of the crystals (1a, 1b, 2 and 8) were non-merohedral twins, and these structures were refined using the ‘HKLF 5’ method. The largest interplanar angles between the pyridine ring and the coordination plane are observed for those structures with a 2-methyl substituent of the pyridine ring. The Au—N bonds are consistently longer trans to Br (average 2.059 Å) than trans to Cl (average 2.036 Å). In the crystal packing, a frequent feature is the offset-stacked and approximately rectangular dimeric moiety (Au—X)2, with antiparallel Au—X bonds linked by Au...X contacts at the vacant positions axial to the coordination plane. The dimers are connected by further secondary interactions (Au...X or X...X contacts, `weak' C—H...X hydrogen bonds) to form chain, double chain (`ladder') or layer structures, and in several cases linked again in the third dimension. Only 1b and 7 contain no offset dimers; these structures instead involve C—H...Cl hydrogen bonds combined with Cl...Cl contacts (1b) or Cl...π contacts (7). The packing patterns of seven further complexes LAuX3 involving simple pyridines (taken from the Cambridge Structural Database) are compared with those of 1–8.

Introduction. Vaccination could be the most effective means of preventing hemorrhagic fever with renal syndrome (HFRS), which is one of the leading zoonoses and a major cause of natural disease in humans. Therefore, research to develop an effective vaccine and the search for new non-toxic and effective adjuvants that can enhance and prolong the immune response, reduce the antigen concentration and reduce the frequency of dose administration is an urgent task. The aim of the study was to determine the dependence of the immunogenic activity of an experimental hantavirus vaccine based on Puumala virus (HV) on the antigen dose both in native form and in combination with carbohydrate adjuvants. Materials and methods. The immunoadjuvant effect of Ac3-LPS S. sonnei and S. flexneri 1B and emulsions of nanoemulsified squalene Sepivac SWE (SWE) as part of HV at the optimal and minimal doses was investigated by induction of neutralising antibodies after 3-fold immunisation (day 0, 14, 182) of guinea pigs (Cavia porcellus). Differences in the immunogenic activity of HV were assessed in the neutralisation reaction by 50% suppression of focal units in Vero E6 cell cultures. Results. A statistically significant increase in neutralising antibodies levels was observed after immunization both with HV at the optimal dose and for its combination with adjuvants. Ac3-LPS S. sonnei and SWE showed the most pronounced immunoadjuvant effect at concentrations of 50 and 100 μg/dose, respectively. The immunoadjuvant effect of the combination of the hantavirus vaccine with Ac3-LPS S. sonnei and SWE contributed to both an enhanced immune response and its duration. The tenfold reduction of the antigen dose in the presence of SWE allows optimization of the immune response to the vaccine. Conclusion. The results of this study show the prospects of using Ac3-LPS S. sonnei and Sepivac SWE in the vaccine for the prevention of HFRS.

Abstract A central concept of evolutionary biology, supported by broad scale allometric analyses, asserts that changing morphology should induce downstream changes in locomotor kinematics and energetics, and by inference selective fitness. However, if these mechanistic relationships exist at local intraspecific scales, where they could provide substrate for fundamental microevolutionary processes, is unknown. Here, analyses of selectively-bred duck breeds demonstrate that distinct body shapes incur kinematic shifts during walking, but these do not translate into differences in energetics. A combination of modular relationships between anatomical regions, and a trade-off between limb flexion and trunk pitching, are shown to homogenise potential functional differences between the breeds, accounting for this discrepancy between form and function. This complex interplay between morphology, motion and physiology indicates that understanding evolutionary links between the avian body plan and locomotor diversity requires studying locomotion as an integrated whole and not key anatomical innovations in isolation.

Abstract Despite great advancements in the treatment of chronic airway diseases, improvements in morbidity and mortality have stalled in recent years. Asthma and chronic obstructive pulmonary disease are complex and heterogeneous diseases that require tailored management based on individual patient characteristics and needs. The Treatable Traits (TTs) approach aims to personalise and improve patient care through the identification and targeting of clinically relevant and modifiable pulmonary, extra-pulmonary and behavioural traits. In this article, we outline the rationale for TTs-based management and provide practical guidance for its application in primary care. To aid implementation, seven potential ‘prime’ traits are proposed: airflow obstruction, eosinophilic inflammation, adherence, inhaler technique, smoking, low body mass index/obesity and anxiety and depression—selected for their prevalence, recognisability and feasibility of use. Some of the key questions among healthcare professionals, that may be roadblocks to widespread application of a TTs model of care, are also addressed.

Abstract Suspended drums made of 2D materials hold potential for sensing applications. However, the industrialization of these applications is hindered by significant device-to-device variations presumably caused by non-uniform stress distributions induced by the fabrication process. Here, we introduce a methodology to determine the stress distribution from their mechanical resonance frequencies and corresponding mode shapes as measured by a laser Doppler vibrometer (LDV). To avoid limitations posed by the optical resolution of the LDV, we leverage a manufacturing process to create ultra-large graphene drums with diameters of up to 1000 μm. We solve the inverse problem of a Föppl–von Kármán plate model by an iterative procedure to obtain the stress distribution within the drums from the experimental data. Our results show that the generally used uniform pre-tension assumption overestimates the pre-stress value, exceeding the averaged stress obtained by more than 47%. Moreover, it is found that the reconstructed stress distributions are bi-axial, which likely originates from the transfer process. The introduced methodology allows one to estimate the tension distribution in drum resonators from their mechanical response and thereby paves the way for linking the used fabrication processes to the resulting device performance.

Bis(2-methylpyridine)gold(I) dibromidoaurate(I), [Au(C6H7N)2][AuBr2], (1), crystallizes in space group C2/c with Z = 4. Both gold atoms lie on twofold axes and are connected by an aurophilic contact. A second aurophilic contact leads to infinite chains of alternating cations and anions parallel to the b axis, and the residues are further connected by a short H...Au contact and a borderline Br...Br contact. Bis(3-methylpyridine)gold(I) dibromidoaurate(I), [Au(C6H7N)2][AuBr2], (2), crystallizes in space group C2/m with Z = 2. Both gold atoms lie on special positions with symmetry 2/m and are connected by an aurophilic contact; all other atoms except for one methyl hydrogen lie in mirror planes. The extended structure is closely analogous to that of 1, although the structures are formally not isotypic. Bis(3,5-dimethylpyridine)gold(I) dichloridoaurate(I), [Au(C7H9N)2][AuCl2], (3) crystallizes in space group P\overline{1} with Z = 2. The cation lies on a general position, and there are two independent anions in which the gold atoms lie on inversion centres. The cation and one anion associate via three short H...Cl contacts to form a ribbon structure parallel to the b axis; aurophilic contacts link adjacent ribbons. Bis(3,5-dimethylpyridine)gold(I) dibromidoaurate(I), [Au(C7H9N)2][AuBr2], (4) is isotypic to 3. Attempts to make similar compounds involving 2-bromopyridine led instead to 2-bromopyridinium dibromidoaurate(I)–2-bromopyridine (1/1), (C5H5BrN)[AuBr2]·C5H4BrN, (5), which crystallizes in space group P\overline{1} with Z = 2; all atoms lie on general positions. The 2-bromopyridinium cation is linked to the 2-bromopyridine molecule by an N—H...N hydrogen bond. Two formula units aggregate to form inversion-symmetric dimers involving Br...Br, Au...Br and H...Br contacts.

Abstract Introduction Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. Methods In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. Results Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4–6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. Conclusions In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.

Frontal plane ankle motion is important for balance in walking but is seldom controlled in robotic prostheses. This article describes the design, control and performance of a semi-active two-degree-of-freedom robotic prosthetic ankle. The mechanism uses a non-backdrivable wedge cam system based on rotating inclined planes, allowing actuation only during swing phases for low power, light weight and compactness. We present details of the mechanism and its kinematic and mechatronic control, and a benchtop investigation of the system’s speed and accuracy in ankle angle control. The two-axis ankle achieves angular reorientation movements spanning ±10 deg in any direction in less than 0.9 s. It achieves a plantarflexion/dorsiflexion error of 0.35 ± 0.27 deg and an inversion/eversion error of 0.29 ± 0.25 deg. Backdriven motion during walking tests is negligible. Strengths of the design include self-locking behavior for low power and simple kinematic control. Two-axis ankle angle control could enable applications such as balance augmentation, turning assistance, and wearable perturbation training.

Abstract Lung cancer exhibits sex-biased molecular characteristics and epidemiological trends, suggesting a need for sex-specific approaches to understanding its etiology and treatment. DNA methylation alterations play critical roles in lung carcinogenesis and may serve as valuable biomarkers for precision medicine strategies. We employed the Infinium MethylationEPIC array to identify autosomal sex-related differentially methylated CpG sites (DM-CpGs) in lung epithelium of healthy individuals (32 females and 37 males) while controlling for age, BMI, and tobacco use. We correlated DM-CpGs with gene expression in lung epithelium and immune responses in bronchoalveolar lavage. We validated these DM-CpGs in lung tumors and adjacent normal tissue from The Cancer Genome Atlas (TCGA). Among 522 identified DM-CpGs, 61% were hypermethylated in females, predominantly located in promoter regions. These DM genes were implicated in cell-to-cell signaling, cellular function, transport, and lipid metabolism. Correlation analysis revealed sex-specific patterns between DM-CpGs and gene expression. Additionally, several DM-CpGs were correlated significantly with cytokines (IL-1β, IL-4, IL-12p70, and IFN-γ), macrophage, and lymphocyte counts. Also, some DM-CpGs were observed in TCGA lung adenocarcinoma, squamous cell carcinoma, and adjacent normal tissues. Our findings highlight sex-specific DNA methylation patterns in healthy lung epithelium and their associations with lung gene expression and lung immune biomarkers. These findings underscore the potential role of lung sex-related CpGs as epigenetic predispositions influencing sex disparities in lung cancer risk and outcomes, warranting further investigation for personalized lung cancer management strategies.

Abstract Background Difficulties with inhibitory control have been identified in eating disorders (EDs) and neurodevelopmental disorders (NDs; including attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder), and there appear to be parallels between the expression of these impairments. It is theorised that impairments in inhibitory control within NDs may represent a unique vulnerability for eating disorders (EDs), and this same mechanism may contribute to poorer treatment outcomes. This review seeks to determine the state of the literature concerning the role of inhibitory control in the overlap of EDs and neurodivergence. Method A scoping review was conducted to summarise extant research, and to identify gaps in the existing knowledge base. Scopus, Medline, PsycInfo, Embase, and ProQuest were systematically searched. Studies were included if the study measured traits of ADHD or autism, and symptoms of ED, and required participants to complete a performance task measure of inhibitory control. Where studies included a cohort with both an ND and ED, these results had to be reported separately from cohorts with a singular diagnosis. Studies were required to be published in English, within the last 10 years. Results No studies explored the relationship between autism and EDs using behavioural measures of inhibitory control. Four studies exploring the relationship between ADHD and EDs using behavioural measures of inhibitory control met selection criteria. These studies showed a multifaceted relationship between these conditions, with differences emerging between domains of inhibitory control. ADHD symptoms predicted poorer performance on measures of response inhibition in a non-clinical sample; this was not replicated in clinical samples, nor was there a significant association with EDs. Both ADHD and ED symptoms are associated with poor performance on attentional control measures; where these diagnoses were combined, performance was worse than for those with a singular diagnosis of ADHD. This was not replicated when compared to those with only ED diagnoses. Conclusion Impairments in attentional control may represent a unique vulnerability for the development of an ED and contribute to poor treatment outcomes. Further research is needed to explore the role of inhibitory control in EDs, ADHD and autism, including the use of both self-report and behavioural measures to capture the domains of inhibitory control.

Abstract The real-world measurement of minimum foot clearance (mFC) during the swing phase of gait is critical in efforts to understand and reduce the risk of trip-and-fall incidents in populations with gait impairments. Past research has focused on measuring clearance of a single point on a person’s foot, typically the toe—however, this may overestimate mFC and may even be the wrong region of the foot in cases of gait impairments or interventions. In this work, we present a novel method to reconstruct the swing-phase trajectory of an arbitrary number of points on a person’s shoe and estimate the instantaneous height and location of whole-foot mFC. This is achieved using a single foot-mounted inertial sensor and personalized shoe geometry scan, assuming a rigid-body IMU-shoe system. This combination allows collection and analysis using out-of-lab tests, potentially including clinical environments. Validation of single marker location using the proposed method vs. motion capture showed height errors with bias less than 0.05 mm, and 95% confidence interval of − 8.18 to + 8.09 mm. The method is demonstrated in an example data set comparing different interventions for foot drop, and it shows clear differences among no intervention, functional electrical stimulation, and ankle–foot orthosis conditions. This method offers researchers and clinicians a rich understanding of a person’s gait by providing objective 3D foot kinematics and allowing a unique opportunity to view the regions of the foot where minimum clearance occurs. This information can contribute to a more informed recommendation of specific interventions or assistive technology than is currently possible in standard clinical practice.

Abstract Introduction Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model. Methods Thirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume. Results In terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect. Conclusion Regeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.

Abstract Background Context (work environment) plays a crucial role in implementing evidence-based best practices within health care settings. Context is multi-faceted and its complex relationship with best practice use by care aides in long-term care (LTC) homes are understudied. This study used an innovative approach to investigate how context elements interrelate and influence best practice use by LTC care aides. Methods In this secondary analysis study, we combined coincidence analysis (a configurational comparative method) and qualitative analysis to examine data collected through the Translating Research in Elder Care (TREC) program. Coincidence analysis of clinical microsystem (care unit)-level data aggregated from a survey of 1,506 care aides across 36 Canadian LTC homes identified configurations (paths) of context elements linked consistently to care aides’ best practices use, measured with a scale of conceptual research use (CRU). Qualitative analysis of ethnographic case study data from 3 LTC homes (co-occurring with the survey) further informed interpretation of the configurations. Results Three paths led to very high CRU at the care unit level: very high leadership; frequent use of educational materials; or a combination of very high social capital (teamwork) and frequent communication between care aides and clinical educators or specialists. Conversely, 2 paths led to very low CRU, consisting of 3 context elements related to unfavorable conditions in relationships, resources, and formal learning opportunities. Our qualitative analysis provided insights into how specific context elements served as facilitators or barriers for best practices. This qualitative exploration was especially helpful in understanding 2 of the paths, illustrating the pivotal role of leadership and the function of teamwork in mitigating the negative impact of time constraints. Conclusions Our study deepens understanding of the complex interrelationships between context elements and their impact on the implementation of best practices in LTC homes. The findings underscore that there is no singular, universal bundle of context-related elements that enhance or hinder best practice use in LTC homes.

Abstract In the Southern Ocean, phytoplankton blooms are an annually recurring prominent feature that play a significant role in ocean CO2 uptake. Understanding the timing of the phytoplankton bloom is necessary to provide insights into the underlying physiological drivers, for the study of ecosystem dynamics and consequent patterns in downward carbon export. Previous studies have used chlorophyll (chl) and particulate organic carbon, from either satellites or biogeochemical‐Argo (BGC‐Argo) floats, to investigate bloom phenology, but provide inconsistent findings regarding bloom timing. Here, we compare bloom dynamics based on three diagnostics from 7114 BGC‐Argo float profiles, south of 60°S. Bloom onset consistently occurs earlier when calculated using chl than when based on phytoplankton carbon or nitrate uptake, and the decoupling increases with latitude. This suggests that phytoplankton synthesize increased chl to acclimate to low‐light conditions, before increasing their biomass. These results highlight the importance of considering phytoplankton physiology when choosing proxies for phytoplankton growth.