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Abstract Background Magnetic resonance imaging (MRI) is the imaging of choice for meniscal extrusion (ME). However, they may underappreciate the load-dependent changes of the meniscus. There is growing evidence that weight-bearing ultrasound (WB US) is more suitable, particularly in revealing occult extrusion. We therefore perform a systematic review and meta-analysis on the validity and reliability of US in diagnosing extrusion. Furthermore, we explored whether it detects differences in extrusion between loaded and unloaded positions and those with pathological (osteoarthritis and meniscal injury) and healthy knees. Methods The Cochrane Controlled Register of Trials, PubMed, Medline, and Embase were used to perform a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Data pertaining to intra- and interrater reliability of US in measuring meniscal extrusion (ME), its correlation with magnetic resonance imaging (MRI), and head-to-head comparison of potential factors to influence ME were included [loading versus unloading position; osteoarthritis (OA) or pathological menisci (PM) versus healthy knees; mild versus moderate–severe knee OA]. Pooled data were analyzed by random or fixed-effects models. Results A total of 31 studies were included. Intraclass correlation coefficients (ICC) for intra- and interrater reliability were minimum 0.94 and 0.91, respectively. The correlation between US and MRI was (r = 0.76). US detected ME to be greater in the loaded position in all knees (healthy, p

Statistics reveal that egg production has increased in recent decades. This growth suggests there is a global rise in available eggshell biomass due to the current underutilization of this bio-waste material. A number of different applications for waste eggshells (WEGs) are known, that include their use as an additive in human/animal food, soil amendment, cosmetics, catalyst, sorbent, and filler in polymer composites. In this article, worldwide egg production and leading countries are examined, in addition to a discussion of the various applications of eggshell biomass. Eggshells are a rich supplement of calcium carbonate; therefore, they can be added as a particulate filler to polymer composites. In turn, the addition of a lower-cost filler, such as eggshell or calcium carbonate, can reduce overall material fabrication costs. Polylactic acid (PLA) is currently a high-demand biopolymer, where the fabrication of PLA composites has gained increasing attention due to its eco-friendly properties. In this review, PLA composites that contain calcium carbonate or eggshells are emphasized, and the mechanical properties of the composites (e.g., tensile strength, flexural strength, tensile elastic modulus, flexural modulus, and elongation (%) at break) are investigated. The results from this review reveal that the addition of eggshell/calcium carbonate to PLA reduces the tensile and flexural strength of PLA composites, whereas an increase in the tensile and flexural modulus, and elongation (%) at break of composites are described herein.

Individuals who belong to a sexual minority are at greater risk of adverse health and social outcomes. These effects are observed during adolescence when many mental health problems, such as depression, first emerge. Here, we used a network analytic approach to better understand the role that sexual minority status plays in the association between depression, interpersonal difficulties and substance use in a large sample of mid-adolescents. In doing so, we used data from 8017 fourteen year olds from the UK’s Millennium Cohort Study, of which 490 self-identified as belonging to a sexual minority. We found that sexual minority status was highly central in the network and connected to multiple adverse outcomes, sometimes directly and sometimes indirectly. The largest single association was between sexual minority status and depression, and this link mediated multiple negative associations with being in a sexual minority. The shortest path to drinking, poor social support and closeness with parents and victimization occurred via depression. The shortest path to smoking and drug use occurred via conduct problems. We also identified three distinct profiles of adverse outcomes among those belonging to a sexual minority, highlighting the heterogeneous nature of this group.

Abstract Background The mechanosensory lateral line system is an important sensory modality in fishes, informing multiple behaviours related to survival including finding food and navigating in dark environments. Given its ecological importance, we may expect lateral line morphology to be under disruptive selection early in the ecological speciation process. Here we quantify the lateral line system morphology of two ecomorphs of the cichlid fish Astatotilapia calliptera in crater Lake Masoko that have diverged from common ancestry within the past 1,000 years. Results Based on geometric morphometric analyses of CT scans, we show that the zooplanktivorous benthic ecomorph that dominates the deeper waters of the lake has large cranial lateral line canal pores, relative to those of the nearshore invertebrate-feeding littoral ecomorph found in the shallower waters. In contrast, fluorescence imaging revealed no evidence for divergence between ecomorphs in the number of either superficial or canal neuromasts. We illustrate the magnitude of the variation we observe in Lake Masoko A. calliptera in the context of the neighbouring Lake Malawi mega-radiation that comprises over 700 species. Conclusions These results provide the first evidence of divergence in this often-overlooked sensory modality in the early stages of ecological speciation, suggesting that it may have a role in the broader adaptive radiation process.

FEBS Open Bio is committed to not only publishing sound science but also to supporting early‐career researchers and the scientific community as a whole. In this editorial, we look back at how the journal recognised and rewarded excellent research in 2023 and look forward to 2024.

Previous research highlights the potential of polyaniline-based biocomposites as unique adsorbents for humidity sensors. This study examines several preparative routes for creating polyaniline (PANI) and chitosan (CHT) composites: Type 1—in situ polymerization of aniline with CHT; Type 2—molecular association in acidic aqueous media; and a control, Type 3—physical mixing of PANI and CHT powders (without solvent). The study aims to differentiate the bonding nature (covalent vs. noncovalent) within these composites, which posits that noncovalent composites should exhibit similar physicochemical properties regardless of the preparative route. The results indicate that Type 1 composites display features consistent with covalent and hydrogen bonding, which result in reduced water swelling versus Type 2 and 3 composites. These findings align with spectral and thermogravimetric data, suggesting more compact structure for Type 1 materials. Dye adsorption studies corroborate the unique properties for Type 1 composites, and 1H NMR results confirm the role of covalent bonding for the in situ polymerized samples. The structural stability adopts the following trend: Type 1 (covalent and noncovalent) > Type 2 (possible trace covalent and mainly noncovalent) > Type 3 (noncovalent). Types 2 and 3 are anticipated to differ based on solvent-driven complex formation. This study provides greater understanding of structure-function relationships in PANI-biopolymer composites and highlights the role of CHT as a template that involves variable (non)covalent contributions with PANI, according to the mode of preparation. The formation of composites with tailored bonding modalities will contribute to the design of improved adsorbent materials for environmental remediation to versatile humidity sensor systems.

The use of plastic products or components in medical equipment and supplies results in challenges in terms of environmental sustainability and waste management for disposable, non-recyclable, and non-biodegradable materials. Medical plastic waste includes items ranging from syringes, tubing, intravenous (IV) bags, packaging, and more. Developing biodegradable replacements to petroleum-based plastics in medical equipment has not yet become an urgent priority, but it is an important endeavor. Examining alternatives involves several key themes, including material selection, testing, validation, and regulatory approval. To date, research includes studies on biodegradable polymers, composite materials, surface modifications, bacterial cellulose, three-dimensional (3D) printing with biodegradable materials, clinical trials and testing, collaboration with industry, regulatory considerations, sustainable packaging for medical devices, and life cycle analysis. The incorporation of bio-based and biodegradable plastics in the healthcare industry holds immense potential for reducing the environmental impact of medical plastic waste. The literature suggests that researchers and industry professionals are actively working towards finding sustainable alternatives that meet the stringent requirements of the medical industry. This paper reviews the efforts made so far to develop biodegradable and sustainable alternatives to plastic in medical equipment using a meta-analysis of resources, which include relevant papers published in English until June 2024. A total of 116 documents were found and screened by three reviewers for relevance. The literature reviewed indicated that various medical uses require plastics due to their unique properties, such as having strength and flexibility; being lightweight; and being able to prevent bacterial contamination. Among the alternatives, polycaprolactone (PCL), polylactic-co-glycolic acid (PLGA), starch-based acid, and polybutyric acid (PBS) have demonstrated favourable outcomes in terms of biocompatibility, safety, and efficacy. Additionally, a set of approaches to overcome these barriers and strategies is discussed alongside potential future solutions. This review aims to catalyze discussions and actions toward a more environmentally sustainable future in the medical industry by providing a comprehensive analysis of the current state, challenges, and prospects of this domain.

The availability of a sustainable technique for degumming lignocellulose fibers is a challenge for the fiber processing industry. Removal of non-cellulosic content from lignocellulose fibers is essential for improving their mechanical and chemical properties, which makes the fibers more suitable for various applications. Herein, a catalytic Fenton-based oxidation process was employed to isolate microcellulose fibers from raw flax fibers. Various complementary methods such as FT-IR/NMR spectroscopy and TGA were used to obtain insight into the thermal behavior of the treated fibers. The morphology of the fibers was studied using Scanning Electron Microscopy (SEM), whereas the surface chemical properties of the fibers was evaluated by a dye-based adsorption method, along with a potentiometric point-of-zero-charge method. To obtain fibers with suitable properties, such as uniform fiber diameter, several Fenton reaction parameters were optimized: pH (7), reaction time (15 h), iron sulfate (2 wt.%), and hydrogen peroxide (10 wt.%). The results indicate that, under the specified conditions, the average diameter of the raw fibers (12.3 ± 0.5 µm) was reduced by 58%, resulting in an average diameter of 5.2 ± 0.3 µm for the treated fibers. We demonstrate that the treated fibers had a lower dye adsorption capacity for methylene blue, consistent with the smoother surface features of the treated fibers over the raw flax fibers. Overall, this study contributes to utilization of the Fenton reaction an efficient oxidation technique for the production of lignocellulose fibers with improved physicochemical properties, such as reduced fiber diameter distribution, in contrast with traditional alkali-based chemical treatment.

Summary: Human pluripotent stem cell (hPSC)-derived tissues can be used to model diseases in cell types that are challenging to harvest and study at-scale, such as neutrophils. Neutrophil dysregulation, specifically neutrophil extracellular trap (NET) formation, plays a critical role in the prognosis and progression of multiple diseases, including COVID-19. While hPSCs can generate limitless neutrophils (iNeutrophils) to study these processes, current differentiation protocols generate heterogeneous cultures of granulocytes and precursors. Here, we describe a method to improve iNeutrophil differentiations through the deletion of GATA1. GATA1 knockout (KO) iNeutrophils are nearly identical to primary neutrophils in form and function. Unlike wild-type iNeutrophils, GATA1 KO iNeutrophils generate NETs in response to the physiologic stimulant lipopolysaccharide, suggesting they are a more accurate model when performing NET inhibitor screens. Furthermore, through deletion of CYBB, we demonstrate that GATA1 KO iNeutrophils are a powerful tool in determining involvement of a given protein in NET formation.

FEBS Open Bio is constantly evolving to best suit the needs of the scientific community. In this Editorial, we review the various new initiatives introduced in 2022 and look forward to the opportunities and challenges that lie ahead in 2023.

Reported here is a case of rapidly progressive metastatic castration-resistant prostate cancer treated with [ 177 Lu]Lu-PSMA-617 in the setting of severe renal impairment and impending ureteric obstruction. PSMA is expressed on renal tubular cells, raising the possibility of radiation-induced nephrotoxicity, and this level of renal impairment would typically exclude the patient from [ 177 Lu]Lu-PSMA-617 therapy. Multidisciplinary input, individualized dosimetry, and patient-specific dose reduction were used to ensure the cumulative dose to the kidneys remained within acceptable limits. He was initially planned for treatment with six cycles of [ 177 Lu]Lu-PSMA-617. However, he had an excellent response to therapy following four cycles of treatment and the last two cycles were omitted. He has been followed for 1-year posttherapy without evidence of disease recurrence. No acute or chronic nephrotoxicity was observed. This case report highlights the utility of [ 177 Lu]Lu-PSMA-617 therapy in severe renal impairment and provides evidence of relative safety in patients who would otherwise not be considered candidates for therapy.

Abstract Background Cluster algorithms are gaining in popularity in biomedical research due to their compelling ability to identify discrete subgroups in data, and their increasing accessibility in mainstream software. While guidelines exist for algorithm selection and outcome evaluation, there are no firmly established ways of computing a priori statistical power for cluster analysis. Here, we estimated power and classification accuracy for common analysis pipelines through simulation. We systematically varied subgroup size, number, separation (effect size), and covariance structure. We then subjected generated datasets to dimensionality reduction approaches (none, multi-dimensional scaling, or uniform manifold approximation and projection) and cluster algorithms (k-means, agglomerative hierarchical clustering with Ward or average linkage and Euclidean or cosine distance, HDBSCAN). Finally, we directly compared the statistical power of discrete (k-means), “fuzzy” (c-means), and finite mixture modelling approaches (which include latent class analysis and latent profile analysis). Results We found that clustering outcomes were driven by large effect sizes or the accumulation of many smaller effects across features, and were mostly unaffected by differences in covariance structure. Sufficient statistical power was achieved with relatively small samples (N = 20 per subgroup), provided cluster separation is large (Δ = 4). Finally, we demonstrated that fuzzy clustering can provide a more parsimonious and powerful alternative for identifying separable multivariate normal distributions, particularly those with slightly lower centroid separation (Δ = 3). Conclusions Traditional intuitions about statistical power only partially apply to cluster analysis: increasing the number of participants above a sufficient sample size did not improve power, but effect size was crucial. Notably, for the popular dimensionality reduction and clustering algorithms tested here, power was only satisfactory for relatively large effect sizes (clear separation between subgroups). Fuzzy clustering provided higher power in multivariate normal distributions. Overall, we recommend that researchers (1) only apply cluster analysis when large subgroup separation is expected, (2) aim for sample sizes of N = 20 to N = 30 per expected subgroup, (3) use multi-dimensional scaling to improve cluster separation, and (4) use fuzzy clustering or mixture modelling approaches that are more powerful and more parsimonious with partially overlapping multivariate normal distributions.

Abstract Aquatic invasive species, such as the signal crayfish (Pacifastacus leniusculus), present a major threat to freshwater ecosystems. However, these species can be challenging to detect in recently invaded habitats. Environmental DNA (eDNA)–based methods are highly sensitive and capable of detecting just a few copies of target DNA from non‐invasively collected samples. Therefore, they have considerable potential for broad‐scale use in mapping and monitoring the spread of invasive species. In this study, we aimed to increase our understanding of the current distribution of signal crayfish in a headwater stream system in the United Kingdom (tributaries of the River Wharfe, Addingham, Yorkshire). Environmental DNA sampling, assessment of water chemistry variables, and conventional crayfish hand‐searching were conducted across 19 study sites in five tributary streams. Using hand‐searching, we detected signal crayfish at 26% of the sites (5/19 study sites). However, using eDNA‐based methods, occupancy increased to 47% of study sites (9/19). Our sampling revealed previously unknown sites of crayfish occupancy, and using eDNA‐based methods, we were able to define the geographical extent of the invasion front in each headwater stream sampled. This study highlights that eDNA‐based methods are well‐suited for detecting newly established signal crayfish populations in recently invaded habitats, even when the invasive species is at low abundance and, therefore, might otherwise be under‐represented or undetected using conventional survey methods. Our study provides further evidence that headwater stream ecosystems are particularly vulnerable to signal crayfish invasion. However, their geomorphological features may make methods used to reduce or prevent invasive crayfish dispersal more effective than in other freshwater ecosystems.

Laszlo Nagy has been on the Editorial Board of FEBS Open Bio since the journal’s inception and is a passionate supporter of FEBS Press and other society journals. Currently, he is also an editor of FEBS Letters and The Journal of Clinical Investigation (JCI). He studied medicine at the University Medical School of Debrecen in Hungary, where he graduated with an M.D. and later Ph.D., and then moved to the United States to conduct postdoctoral research at the University of Texas–Houston and subsequently the Salk Institute in San Diego. Laszlo is a Professor of Medicine and Biological Chemistry at John Hopkins School of Medicine, where he is Co‐Director of the Institute for Fundamental Biomedical Research and Associate Director of the Center for Metabolic Origins of Disease, and Adjunct Professor at the University of Debrecen. Formerly, he was a Professor and Founding Director of the Genomic Control of Metabolism Program at the Sanford Burnham Prebys Medical Discovery Institute. He is also a member of the European Molecular Biology Organisation (EMBO), Academia Europaea, the Hungarian Academy of Sciences and The Henry Kunkel Society, and recipient of several awards, including the Boehringer Ingelheim Research Award, Cheryl Whitlock/Pathology Prize, a Wellcome Trust Senior Research Fellowship in Biomedical Sciences, and three Howard Hughes Medical Institute International Research Scholar Awards. In this fascinating interview, Laszlo Nagy shares the advice that changed his career trajectory, relates his views on scientific publishing, discusses new developments at The Johns Hopkins Center for Metabolic Origins of Disease, and outlines the prospects for future development of research and technology infrastructures in eastern Europe.

The Federation of European Biochemical Societies (FEBS) awarded FEBS Long‐Term Fellowships from 1979 until 2020, at which time the scheme was replaced with the FEBS Excellence Award. Over four decades, FEBS awarded a huge number of Long‐Term Fellowships, helping to support and promote the careers of excellent young researchers across Europe. To celebrate the exciting work performed by the FEBS Long‐Term Fellows, we present here a special ‘In the Limelight’ issue of FEBS Open Bio, containing four Mini‐reviews and four Research Protocols authored by the fellows themselves. The four Review articles provide timely updates on the respective research fields, while the Research Protocols describe how to perform challenging experimental methods in detail. We hope this issue will be a valuable resource for the community, and a celebration of the high‐quality work done by young scientists.

Abstract Background Anterior cruciate ligament (ACL) rupture is a very common knee injury in the sport active population. There is much debate on which treatment (operative or non-operative) is best for the individual patient. In order to give a more personalized recommendation we aim to evaluate the effectiveness and cost-effectiveness of a treatment algorithm for patients with a complete primary ACL rupture. Methods The ROTATE-trial is a multicenter, open-labeled cluster randomized controlled trial with superiority design. Randomization will take place on hospital level (n = 10). Patients must meet all the following criteria: aged 18 year or older, with a complete primary ACL rupture (confirmed by MRI and physical examination) and maximum of 6 weeks of non-operative treatment. Exclusion criteria consists of multi ligament trauma indicated for surgical intervention, presence of another disorder that affects the activity level of the lower limb, pregnancy, and insufficient command of the Dutch language. The intervention to be investigated will be an adjusted treatment decision strategy, including an advice from our treatment algorithm. Patient reported outcomes will be conducted at baseline, 3, 6, 12 and 24 months. Physical examination of the knee at baseline, 12 and 24 months. Primary outcome will be function of the knee measured by the International Knee Documentation Committee (IKDC) questionnaire. Secondary outcomes are, among others, the Tegner activity score, the Knee injury and Osteoarthritis Outcome Score (KOOS) and the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Healthcare use, productivity and satisfaction with ((non-)operative) care are also measured by means of questionnaires. In total 230 patients will be included, resulting in 23 patients per hospital. Discussion The ROTATE study aims to evaluate the effectiveness and cost-effectiveness of a treatment algorithm for patients with a complete primary ACL rupture compared to current used treatment strategy. Using a treatment algorithm might give the much-wanted personalized treatment recommendation. Trial registration This study is approved by the Medical Research Ethics Committee of Erasmus Medical Center in Rotterdam and prospectively registered at the Dutch Trial Registry on May 13th, 2020. Registration number: NL8637.

FEBS Open Bio continues to go from strength to strength, with 2021 perhaps marking its most exciting year. In this Editorial, the Editor‐in‐Chief Miguel A. De la Rosa looks back at all the new developments of 2021 and forecasts the outlook for 2022.

Skeletal muscles support the stability and mobility of the skeleton but differ in biomechanical properties and physiological functions. The intrinsic factors that regulate muscle-specific characteristics are poorly understood. To study these, we constructed a large atlas of RNA-seq profiles from six leg muscles and two locations from one muscle, using biopsies from 20 healthy young males. We identified differential expression patterns and cellular composition across the seven tissues using three bioinformatics approaches confirmed by large-scale newly developed quantitative immune-histology procedures. With all three procedures, the muscle samples clustered into three groups congruent with their anatomical location. Concomitant with genes marking oxidative metabolism, genes marking fast- or slow-twitch myofibers differed between the three groups. The groups of muscles with higher expression of slow-twitch genes were enriched in endothelial cells and showed higher capillary content. In addition, expression profiles of Homeobox (HOX) transcription factors differed between the three groups and were confirmed by spatial RNA hybridization. We created an open-source graphical interface to explore and visualize the leg muscle atlas (https://tabbassidaloii.shinyapps.io/muscleAtlasShinyApp/). Our study reveals the molecular specialization of human leg muscles, and provides a novel resource to study muscle-specific molecular features, which could be linked with (patho)physiological processes.

Aim: The triple network model of psychopathology posits that altered connectivity between the Salience (SN), Central Executive (CEN), and Default Mode Networks (DMN) may underlie neurodevelopmental conditions. However, this has yet to be tested in a transdiagnostic sample of young people. Method: We investigated this in 175 children (60 girls) that represent a heterogeneous population who are experiencing neurodevelopmental difficulties in cognition and behavior, and 60 comparison children (33 girls). Hyperactivity/impulsivity and inattention were assessed by parent-report. Resting-state functional Magnetic Resonance Imaging data were acquired and functional connectivity was calculated between independent network components and regions of interest. We then examined whether connectivity between the SN, CEN and DMN was dimensionally related to hyperactivity/impulsivity and inattention, whilst controlling for age, gender, and motion. Results: Hyperactivity/impulsivity was associated with increased functional connectivity between the SN, CEN, and DMN in at-risk children, whereas it was associated with decreased functional connectivity between the CEN and DMN in comparison children. These effects replicated in an adult parcellation of brain function and when using increasingly stringent exclusion criteria for in-scanner motion. Conclusion: Triple network connectivity characterizes transdiagnostic neurodevelopmental difficulties with hyperactivity/impulsivity. We suggest that this may arise from delayed network segregation, difficulties sustaining CEN activity to regulate behavior, and/or a heightened developmental mismatch between neural systems implicated in cognitive control relative to those implicated in reward/affect processing.

The lateral line system of fishes provides cues for collective behaviour, such as shoaling, but it remains unclear how anatomical lateral line variation leads to behavioural differences among species. Here we studied associations between lateral line morphology and collective behaviour using two morphologically divergent species and their second-generation hybrids. We identify collective behaviours associated with variation in canal and superficial lateral line morphology, with closer proximities to neighbouring fish associated with larger canal pore sizes and fewer superficial neuromasts. A mechanistic understanding of the observed associations was provided by hydrodynamic modelling of an artificial lateral line sensor, which showed that simulated canal-based neuromasts were less susceptible to saturation during unidirectional movement than simulated superficial neuromasts, while increasing the canal pore size of the simulated lateral line sensor elevated sensitivity to vortices shed by neighbouring fish. Our results propose a mechanism behind lateral line flow sensing during collective behaviour in fishes.

In celebration of the 10th anniversary of FEBS Open Bio, we spoke to some of the key figures of the journal’s genesis, development, and its future direction, and recount here their thoughts and experiences. Prof. Félix. Goñi discusses the role of the FEBS Publication Committee in the journal's beginnings, Dr Mary Purton relates her experiences as the journal's Executive Editor, Prof. László Fésüs explains how the journal developed during his tenure as Chair of the Publication Committee, and Prof. Johannes Buchner looks forward to the future of FEBS Press and academic publishing. Finally, Prof. John (Iain) Mowbray describes his “Friday afternoon thought” to start a new journal.

This month, FEBS Open Bio celebrates its 10th birthday. To celebrate the journal's first decade, we present this special anniversary issue, comprised of editorials, reviews, and research articles especially commissioned for the occasion. In this introductory editorial, we invite the reader to join us as we reminisce over the journal's past, celebrate its present, and look forward to its future.

In this study, an innovative composite was fabricated in which the matrix is partially derived from natural sources and the filler from undervalued eggshell waste material. The effect of coating eggshells and mineral limestone with 2 wt.% stearic acid on the mechanical properties of a bio-epoxy matrix was investigated. Eggshells and limestone (untreated and stearic acid-treated) fillers were added to the bio-epoxy matrix in quantities of 5, 10, and 20 wt.% loadings using a solution mixing technique. The CaCO3 content in eggshells was confirmed to be 88 wt.%, and the crystalline phase was found to be calcite. The stearic acid coating did not show any decrease in crystallinity of the fillers. Scanning electron microscopy (SEM) displayed changes in the fractured surfaces, which infers the fillers altered the bio-epoxy polymer. The mechanical property results showed enhancements in the composite tensile modulus and flexural modulus compared to the pure bio-epoxy, as expected. In contrast, despite the improvement in the tensile and flexural strengths of the stearic acid-treated fillers, the composite strength values were not higher than those of the unfilled bio-epoxy matrix. The energy absorbed by all composites in Charpy impact tests fell below that of the pure bio-epoxy and decreased with an increase in filler content for both untreated and stearic acid-treated fillers tested at 23 and −40 °C. Statistical analysis of the results was conducted using Statistical Analysis Software (SAS) with ranking based on Tukey’s method. The study identified that the addition of 5, 10, and 20 wt.% in a bio-epoxy matrix may be acceptable provided the end product requires lower tensile and flexural load requirements than those of the pure bio-epoxy. However, filler loadings below 5 wt.% would be a better choice.

The Mexico and Central American region has a history of mercury use that began at least two millennia before European colonisation in the 16th century. Archaeologists have reported extensive deposits of cinnabar (HgS) and other mercury materials in ancient human settlements across the region. However, there has been no consideration to date of the environmental legacy of this long history of anthropogenic mercury use. This review begins by synthesising our knowledge of the history and nature of anthropogenic mercury in ancient Mesoamerica based on archaeological data, with a particular focus on the Maya culture of lowland Guatemala, Belize, the Yucatan of Mexico, El Salvador, and Honduras. The Classic Period Maya used mercury for decorative and ceremonial (including funerary) purposes: Cinnabar (HgS) predominantly, but the archaeological record also shows rare finds of elemental mercury (Hg0) in important burial and religious contexts. In this review, we have located and summarised all published data sets collected from (or near) ancient Maya settlements that include environmental mercury measurements. Comparing mercury determinations from pre-Columbian Maya settlements located across the region confirms that seven sites from ten have reported at least one location with mercury concentrations that equal or exceed modern benchmarks for environmental toxicity. The locations with elevated mercury are typically former Maya occupation areas used in the Late Classic Period, situated within large urban settlements abandoned by c. 10th century CE. It is most likely that the mercury detected in buried contexts at Maya archaeological sites is associated with pre-Columbian mercury use, especially of cinnabar. In more complex contexts, where modern biological or specifically anthropogenic inputs are more probable, legacy mercury in the environment will have a more complex, and time transgressive input history. This review identifies current research gaps in our understanding of the long history of Maya mercury use and in the collection of robust total mercury datasets from the Maya world. We identify important areas for future research on the environmental persistence and legacy of mercury, including the need to interpret environment mercury data in the context of mercury exposure and human health at Maya archaeological sites.

Abstract Background Moderate-to-vigorous physical activity (MVPA) is proposed as key for cardiovascular diseases (CVD) prevention. At older ages, the role of sedentary behaviour (SB) and light intensity physical activity (LIPA) remains unclear. Evidence so far is based on studies examining movement behaviours as independent entities ignoring their co-dependency. This study examines the association between daily composition of objectively-assessed movement behaviours (MVPA, LIPA, SB) and incident CVD in older adults. Methods Whitehall II accelerometer sub-study participants free of CVD at baseline (N = 3319, 26.7% women, mean age = 68.9 years in 2012–2013) wore a wrist-accelerometer from which times in SB, LIPA, and MVPA during waking period were extracted over 7 days. Compositional Cox regression was used to estimate the hazard ratio (HR) for incident CVD for daily compositions of movement behaviours characterized by 10 (20 or 30) minutes greater duration in one movement behaviour accompanied by decrease in another behaviour, while keeping the third behaviour constant, compared to reference composition. Analyses were adjusted for sociodemographic, lifestyle, cardiometabolic risk factors and multimorbidity index. Results Of the 3319 participants, 299 had an incident CVD over a mean (SD) follow-up of 6.2 (1.3) years. Compared to daily movement behaviour composition with MVPA at recommended 21 min per day (150 min/week), composition with additional 10 min of MVPA and 10 min less SB was associated with smaller risk reduction – 8% (HR, 0.92; 95% CI, 0.87–0.99) – than the 14% increase in risk associated with a composition of similarly reduced time in MVPA and more time in SB (HR, 1.14; 95% CI, 1.02–1.27). For a given MVPA duration, the CVD risk did not differ as a function of LIPA and SB durations. Conclusions Among older adults, an increase in MVPA duration at the expense of time in either SB or LIPA was found associated with lower incidence of CVD. This study lends support to public health guidelines encouraging increase in MVPA or at least maintain MVPA at current duration.

The formation of large-scale brain networks represents crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. Here, the authors use generative network modelling to provide a computational framework for understanding neurodevelopmental diversity.

FEBS Open Bio and our fellow FEBS Press journals have a strong commitment to maintaining the integrity of the scientific literature. The life sciences, in particular, are suffering from an ongoing reproducibility crisis, and this may in part be fuelled by mistakes, manipulation or outright fabrication of the presented data. We were recently made aware of several articles published in FEBS Open Bio that appear to contain full or partial duplications of images from other published articles in a different scientific context. In most of these cases, the duplications were taken from previously published papers. After thorough investigation and subsequent discussion within FEBS Press and with Wiley's Integrity in Publishing Group, we have retracted most of these articles.

Background: Torus (buckle) fractures of the wrist are the most common fractures in children involving the distal radius and/or ulna. It is unclear if children require rigid immobilisation and follow-up or would recover equally as well by being discharged without any immobilisation or a bandage. Given the large number of these injuries, identifying the optimal treatment strategy could have important effects on the child, the number of days of school absence and NHS costs. Objectives: To establish whether or not treating children with a distal radius torus fracture with the offer of a soft bandage and immediate discharge (i.e. offer of a bandage) provides the same recovery, in terms of pain, function, complications, acceptability, school absence and resource use, as treatment with rigid immobilisation and follow-up as per usual practice (i.e. rigid immobilisation). Design: A pragmatic, multicentre, randomised controlled equivalence trial. Setting: Twenty-three UK emergency departments. Participants: A total of 965 children (aged 4–15 years) with a distal radius torus fracture were randomised from January 2019 to July 2020 using a secure, centralised, online-encrypted randomisation service. Exclusion criteria included presentation > 36 hours after injury, multiple injuries and an inability to complete follow-up. Interventions: A bandage was offered to 489 participants and applied to 458, and rigid immobilisation was carried out in 476 participants. Participants and clinicians were not blinded to the treatment allocation. Main outcome measures: The pain at 3 days post randomisation was measured using the Wong–Baker FACES Pain Rating Scale. Secondary outcomes were the patient-reported outcomes measurement system upper extremity limb score for children, health-related quality of life, complications, school absence, analgesia use and resource use collected up to 6 weeks post randomisation. Results: A total of 94% of participants provided primary outcome data. At 3 days, the primary outcome of pain was equivalent in both groups. With reference to the prespecified equivalence margin of 1.0, the adjusted difference in the intention-to-treat population was –0.10 (95% confidence interval –0.37 to 0.17) and the per-protocol population was –0.06 (95% confidence interval –0.34 to 0.21). There was equivalence of pain in both age subgroups (i.e. 4–7 years and 8–15 years). There was no difference in the rate of complications, with five complications (1.0%) in the offer of a bandage group and three complications (0.6%) in the rigid immobilisation group. There were no differences between treatment groups in functional recovery, quality of life or school absence at any point during the follow-up. Analgesia use was marginally higher at day 1 in the offer of a bandage group than it was in the rigid immobilisation group (83% vs. 78% of participants), but there was no difference at other time points. The offer of a bandage significantly reduced the cost of treatment and had a high probability of cost-effectiveness at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year. Limitations: Families had a strong pre-existing preference for the rigid immobilisation treatment. Given this, and the inability to blind families to the treatment allocation, observer bias was a concern. However, there was clear evidence of equivalence. Conclusions: The study findings support the offer of a bandage in children with a distal radius torus fracture. Future work: A clinical decision tool to determine which children require radiography is an important next step to prevent overtreatment of minor wrist fractures. There is also a need to rationalise interventions for other common childhood injuries (e.g. ‘toddler’s fractures’ of the tibia). Trial registration: This trial is registered as ISRCTN13955395 and UKCRN Portfolio 39678. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 33. See the NIHR Journals Library website for further project information.

Abstract Purpose The purpose of this study was to determine the effect of targeted eccentric calf muscle exercises compared to regular training on ankle dorsiflexion in healthy adolescent soccer players with a decreased ankle dorsiflexion. Methods Male adolescent players (aged 14–21 years) from two professional soccer clubs were evaluated with the Weight Bearing Dorsiflexion Lunge Test (WBDLT) at baseline and after 12 weeks of this prospective controlled study. One club served as the control group and the other as the intervention group. Players with decreased ankle dorsiflexion (WBDLT) ≤ 10 cm) performed stretching and eccentric calf muscle exercises three times per week next to regular training in the intervention group, and performed only regular training in the control group. Primary outcome was the between-group difference in change in WBDLT between baseline and 12 weeks. Results Of 107 eligible players, 47(44 %) had a decreased ankle dorsiflexion. The WBDLT (± standard deviation) increased in the intervention group from 7.1 (± 1.8) to 7.4 (± 2.4) cm (95 % Confidence Interval (CI)[-0.493 to 1.108], p = 0.381) and in the control group from 6.1 (± 2.4) to 8.2 (± 2.9) cm (95 % CI [1.313 to 2.659], p

Abstract Background The discovery that somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) has provided a foundation for in vitro human disease modelling, drug development and population genetics studies. Gene expression plays a critical role in complex disease risk and therapeutic response. However, while the genetic background of reprogrammed cell lines has been shown to strongly influence gene expression, the effect has not been evaluated at the level of individual cells which would provide significant resolution. By integrating single cell RNA-sequencing (scRNA-seq) and population genetics, we apply a framework in which to evaluate cell type-specific effects of genetic variation on gene expression. Results Here, we perform scRNA-seq on 64,018 fibroblasts from 79 donors and map expression quantitative trait loci (eQTLs) at the level of individual cell types. We demonstrate that the majority of eQTLs detected in fibroblasts are specific to an individual cell subtype. To address if the allelic effects on gene expression are maintained following cell reprogramming, we generate scRNA-seq data in 19,967 iPSCs from 31 reprogramed donor lines. We again identify highly cell type-specific eQTLs in iPSCs and show that the eQTLs in fibroblasts almost entirely disappear during reprogramming. Conclusions This work provides an atlas of how genetic variation influences gene expression across cell subtypes and provides evidence for patterns of genetic architecture that lead to cell type-specific eQTL effects.

The current research is focused on the mutual comparison (mechanical properties, response to humidity) of agro-waste composite materials. The purpose of this work is directed at the valorization of agro-waste biomass products and to investigate their mechanical stability for transport or other applications (in dry and wet states). Three different types of agro-waste (oat hull (Oh), torrefied wheat straw (S), and spent coffee grounds (SCG)) were blended with kaolinite (K) and chitosan (CHT) at variable weight ratios to yield ternary composites. Mechanical properties were represented by measuring hardness (in compression mode) and elastic modulus (under tension mode). Young’s (elastic) modulus was measured both for dried and hydrated samples. The pelletized materials were prepared in two forms: crosslinked (CL) with epichlorohydrin and non-crosslinked (NCL). The hardness of the Oh pellets was poor (75 N) and decreased by four times with greater agro-waste content, while crosslinking affected the hardness only slightly. S pellets had the highest level of hardness at 40% agro-waste content (160 N), with a concomitant decrease to 120 N upon crosslinking. SCG pellets had the least change in hardness for both CL and NCL specimens (105–120 N). The trends of Young’s modulus were similar to hardness. Hydration caused the elastic modulus to decrease ca. 100-fold. In general, S and SCG composites exhibit the greatest hardness and Young’s modulus compared to Oh composites (CL or NCL) in their dry state.

Abstract Background To assess diagnostic accuracy of quantitative double-echo in steady-state (qDESS) MRI for detecting synovitis in knee osteoarthritis (OA). Methods Patients with different degrees of radiographic knee OA were included prospectively. All underwent MRI with both qDESS and contrast-enhanced T1-weighted magnetic resonance imaging (CE-MRI). A linear combination of the two qDESS images can be used to create an image that displays contrast between synovium and the synovial fluid. Synovitis on both qDESS and CE-MRI was assessed semi-quantitatively, using a whole-knee synovitis sum score, indicating no/equivocal, mild, moderate, and severe synovitis. The correlation between sum scores of qDESS and CE-MRI (reference standard) was determined using Spearman’s rank correlation coefficient and intraclass correlation coefficient for absolute agreement. Receiver operating characteristic analysis was performed to assess the diagnostic performance of qDESS for detecting different degrees of synovitis, with CE-MRI as reference standard. Results In the 31 patients included, very strong correlation was found between synovitis sum scores on qDESS and CE-MRI (ρ = 0.96, p

Peptide receptor radionuclide therapy (PRRT) has been recently established as a treatment option for progressive gastro-entero-pancreatic neuroendocrine tumors (NETs) including four 200 mCi induction cycles. The purpose of this phase 2 trial is to expand use of PRRT to different types of NETs with the application of dose adjustment and evaluate value of maintenance therapy in patients who had disease control on induction therapy. Forty-seven PRRT naïve NET patients with different primary origin received 177Lu-DOTATATE induction therapy, ranging from 75 to 150 mCi per cycle, based on patients’ clinical status such as liver and renal function, extent of metastases, and previous therapies. Thirty-four patients underwent additional maintenance therapy (50–100 mCi per cycle) following induction course until they developed disease progression. The estimated median progression-free survival (PFS) was 36.1 months. The median PFS in our MNET subgroup was 47.7 months, which is markedly longer than NETTER-1 trial with median PFS of 28.4 months. The median PFS was significantly longer in patients who received PRRT as first-line treatment after disease progression on somatostatin analogs compared to patients who received other therapies first (p-value = 0.04). The total disease response rate (DRR) and disease control rate (DCR) was 32% and 85% based on RECIST 1.1 and 45% and 83% based on Choi criteria. This trial demonstrates longer PFS with the addition of low dose maintenance therapy to induction therapy compared to NETTER-1 trial that only included induction therapy. Also, we observed considerable efficacy of PRRT in various types of advanced NETs.

Abstract Purpose The aim of this study was to compare the biomechanics of a four-strand hamstring graft with a tripled semitendinosus graft, with and without adjustable extra-cortical button fixation, in a cadaveric model. Methods Four groups of 10 cadaveric hamstrings were tested: In group A, a tripled semitendinosus graft fixated with two adjustable extra-cortical buttons; in Group B, a four-strand semitendinosus and gracilis graft fixated with an adjustable extra-cortical button and a clamp; in group C, a tripled semitendinosus graft fixated to a steel hook and a clamp; in group D, a four-strand semitendinosus and gracilis graft fixated to a steel hook and a clamp. Each group was submitted to a cyclic loading test (1000 cycles between 50 and 250 Newton at a frequency of 0.5 hertz) and a load-to-failure test. Primary outcomes were ultimate failure load and stiffness. Secondary outcomes were graft elongation and graft diameter. Results There was no difference in ultimate failure load among groups. Group B achieved a median stiffness of 171 N/mm (interquartile range [IQR] 139–204) which was significantly higher than Group A (median 103 N/mm (74–119), p

Behavioural difficulties are seen as hallmarks of many neurodevelopmental conditions. Differences in functional brain organisation have been observed in these conditions, but little is known about how they are related to a child’s profile of behavioural difficulties. We investigated whether behavioural difficulties are associated with how the brain is functionally organised in an intentionally heterogeneous and transdiagnostic sample of 957 children aged 5–15. We used consensus community detection to derive data-driven profiles of behavioural difficulties and constructed functional connectomes from a subset of 238 children with resting-state functional Magnetic Resonance Imaging (fMRI) data. We identified three distinct profiles of behaviour that were characterised by principal difficulties with hot executive function, cool executive function, and learning. Global organisation of the functional connectome did not differ between the groups, but multivariate patterns of connectivity at the level of Intrinsic Connectivity Networks (ICNs), nodes, and hubs significantly predicted group membership in held-out data. Fronto-parietal connector hubs were under-connected in all groups relative to a comparison sample and children with hot vs cool executive function difficulties were distinguished by connectivity in ICNs associated with cognitive control, emotion processing, and social cognition. This demonstrates both general and specific neurodevelopmental risk factors in the functional connectome.

Research in asymmetric light transmission interfaces has been recently gaining traction. While traditionally considered for optical circuitry applications, there is a new interest to use these interfaces in luminescent solar concentrators. Previous studies have shown that applying them to the top surface of a concentrator could mitigate surface losses. This paper presents experimental results for proof-of-concept asymmetric light transmission interfaces that may have potential applications in luminescent solar concentrators. The interfaces and the underneath substrate were created in a single step from polydimethylsiloxane using silicon molds fabricated on wafers via anisotropic wet etching. The resulting structures were pyramidal in shape. Large surface areas of nanostructures repeating at 800 nm, 900 nm, and 1000 nm were tested for backward and forward transmission using a spectrometer. Results showed a 21%, 10%, and 0% average transmissivity difference between the forward and backward directions for each periodicity, respectively. The trends seen experimentally were confirmed numerically via COMSOL simulations.

Abstract Background De novo loss of function mutations in STXBP1 are a relatively common cause of epilepsy and intellectual disability (ID). However, little is known about the types and severities of behavioural features associated with this genetic diagnosis. Methods To address this, we collected systematic phenotyping data encompassing neurological, developmental, and behavioural characteristics. Participants were 14 individuals with STXBP1-associated neurodevelopmental disorder, ascertained from clinical genetics and neurology services UK-wide. Data was collected via standardised questionnaires administered to parents at home, supplemented by researcher observations. To isolate discriminating phenotypes, the STXBP1 group was compared to 33 individuals with pathogenic mutations in other ID-associated genes (ID group). To account for the potential impact of global cognitive impairment, a secondary comparison was made to an ability-matched subset of the ID group (low-ability ID group). Results The STXBP1 group demonstrated impairments across all assessed domains. In comparison to the ID group, the STXBP1 group had more severe global adaptive impairments, fine motor difficulties, and hyperactivity. In comparison to the low-ability ID group, severity of receptive language and social impairments discriminated the STXBP1 group. A striking feature of the STXBP1 group, with reference to both comparison groups, was preservation of social motivation. Conclusions De novo mutations in STXBP1 are associated with complex and variable neurodevelopmental impairments. Consistent features, which discriminate this disorder from other monogenic causes of ID, are severe language impairment and difficulties managing social interactions, despite strong social motivation. Future work could explore the physiological mechanisms linking motor, speech, and social development in this disorder. Understanding the developmental emergence of behavioural characteristics can help to focus clinical assessment and management after genetic diagnosis, with the long-term aim of improving outcomes for patients and families.

Summary: The mechanosensory lateral line system is used by fishes to sense hydrodynamic stimuli in their environment. It provides information about flow regimes, proximity to substrate, and the presence and identity of prey and predators and represents a means of receiving communication signals from other fish. Thus we may expect lateral line system structures to be under strong divergent selection during adaptive radiation. Here, we used X-ray micro-computed tomography scans to quantify variation in cranial lateral line canal morphology within the adaptive radiation of Lake Malawi cichlids. We report that cranial lateral line canal morphology is strongly correlated with diet and other aspects of craniofacial morphology, including the shape of oral jaws. These results indicate an adaptive role for the lateral line system in prey detection and suggest that diversification of this system has taken an important role in the spectacular evolution of Lake Malawi's cichlid fish diversity. : Ecology; Biological Sciences; Zoology; Animals; Evolutionary Biology Subject Areas: Ecology, Biological Sciences, Zoology, Animals, Evolutionary Biology

Abstract Shallow slip on the plate‐boundary fault during the 2004 Mw 9.2 Aceh‐Andaman Earthquake, offshore North Sumatra, has been linked to thick incoming sediments on the oceanic plate with advanced diagenetic and sediment property changes at the depths of plate boundary fault development. We couple age control, physical, and thermal property measurements from International Ocean Discovery Program (IODP) drilling with multichannel seismic reflection data to reconstruct the thermal structure and evolution of the incoming sediment column, up to the point of accretion/subduction. Lithospheric thermal rejuvenation around 58 Ma is required to explain anomalously high heat flux at IODP Site U1480, and heat flux within the trench is suppressed by very high sediment accumulation rates during the development of a thick trench wedge. Accumulation of up to ∼4.5 km of thick Nicobar Fan and trench wedge sediments produces temperatures >150°C within the basal sediments where the décollement develops, resulting in total pre‐subduction diagenetic dehydration of basal sediments. The smectite‐illite transformation within these basal sediments produces sufficient fluid to explain a polarity reversal on a pre‐décollement reflector. We suggest that the boundary between basal‐pelagic and siliciclastic‐fan sediments has trapped fluid over the last ∼1 Myr, as a result of primary lithological properties, diagenetic fluid release, and cementation, controlling décollement formation at this weakened level. Pre‐subduction dehydration of large portions of the accreted sediment column strengthens the décollement beneath the prism, extending co‐seismic velocity‐weakening behavior close to the trench, which may occur at other subduction zones with similar sediment compositions, thicknesses, and/or temperatures.

Previous studies have identified localized associations between childhood environment – namely their socio-economic status (SES) – and particular neural structures. The primary aim of the current study was to test whether associations between SES and brain structure are widespread or limited to specific neural pathways. We employed advances in whole-brain structural connectomics to address this. Diffusion tensor imaging was used to construct whole-brain connectomes in 113 6−12 year olds. We then applied an adapted multi-block partial-least squares (PLS) regression to explore how connectome organisation is associated with childhood SES (parental income, education levels, and neighbourhood deprivation). The Fractional Anisotropy (FA) connectome was significantly associated with childhood SES and this effect was widespread. We then pursued a secondary aim, and demonstrated that the connectome mediated the relationship between SES and cognitive ability (matrix reasoning and vocabulary). However, the connectome did not significantly mediate SES relationships with academic ability (maths and reading) or internalising and externalising behavior. This multivariate approach is important for advancing our theoretical understanding of how brain development may be shaped by childhood environment, and the role that it plays in predicting key outcomes. We also discuss the limitations with this new methodological approach.

Central venous catheters are widely used in haemodialysis therapy, having to respect design requirements for appropriate performance. These are placed within the right atrium (RA); however, there is no prior computational study assessing different catheter designs while mimicking their native environment. Here, a computational fluid dynamics model of the RA, based on realistic geometry and transient physiological boundary conditions, was developed and validated. Symmetric, split and step catheter designs were virtually placed in the RA and their performance was evaluated by: assessing their interaction with the RA haemodynamic environment through prediction of flow vorticity and wall shear stress (WSS) magnitudes (1); and quantifying recirculation and tip shear stress (2). Haemodynamic predictions from our RA model showed good agreement with the literature. Catheter placement in the RA increased average vorticity, which could indicate alterations of normal blood flow, and altered WSS magnitudes and distribution, which could indicate changes in tissue mechanical properties. All designs had recirculation and elevated shear stress values, which can induce platelet activation and subsequently thrombosis. The symmetric design, however, had the lowest associated values (best performance), while step design catheters working in reverse mode were associated with worsened performance. Different tip placements also impacted on catheter performance. Our findings suggest that using a realistically anatomical RA model to study catheter performance and interaction with the haemodynamic environment is crucial, and that care needs to be given to correct tip placement within the RA for improved recirculation percentages and diminished shear stress values.

Coronary bifurcations are prone to atherosclerotic plaque growth, experiencing regions of reduced wall shear stress (WSS) and increased platelet adhesion. This study compares effects across different rheological approaches on hemodynamics, combined with a shear stress exposure history model of platelets within a stenosed porcine bifurcation. Simulations used both single/multiphase blood models to determine which approach best predicts phenomena associated with atherosclerosis and atherothrombosis. A novel Lagrangian platelet tracking model was used to evaluate residence time and shear history of platelets indicating likely regions of thrombus formation. Results show a decrease in area of regions with pathologically low time-averaged WSS with the use of multiphase models, particularly in a stenotic bifurcation. Significant non-Newtonian effects were observed due to low-shear and varying hematocrit levels found on the outer walls of the bifurcation and distal to the stenosis. Platelet residence time increased 11% in the stenosed artery, with exposure times to low-shear sufficient for red blood cell aggregation (>1.5 s). increasing the risk of thrombosis. This shows stenotic artery hemodynamics are inherently non-Newtonian and multiphase, with variations in hematocrit (0.163–0.617) and elevated vorticity distal to stenosis (+15%) impairing the function of the endothelium via reduced time-averaged WSS regions, rheological properties and platelet activation/adhesion.

Hemodialysis catheters are used to support blood filtration, yet there are multiple fundamentally different approaches to catheter tip design with no clear optimal solution. Side-holes have been shown to increase flow rates and decrease recirculation but have been associated with clotting/increased infection rates. This study investigates the impact of changing the shape, size and number of side-holes on a simple symmetric tip catheter by evaluating the velocity, shear stress and shear rate of inflowing blood. A platelet model is used to examine the residence time and shear history of inflowing platelets. The results show that side-holes improve the theoretical performance of the catheters, reducing the maximum velocity and shear stress occurring at the tip compared to non-side-hole catheters. Increasing the side-hole area improved performance up to a point, past which not all inflow through the hole was captured, and instead a small fraction slowly 'washed-out' through the remainder of the tip resulting in greater residence times and increasing the likelihood of platelet adhesion. An oval shaped hole presents a lower chance of external fibrin formation compared to a circular hole, although this would also be influenced by the catheter material surface topology which is dependent on the manufacturing process. Overall, whilst side-holes may be associated with increased clotting and infection, this can be reduced when side-hole geometry is correctly implemented though; a sufficient area for body diameter (minimising residence time) and utilising angle-cut, oval shaped holes (reducing shear stress and chances of fibrin formation partially occluding holes).

Abstract Background Changes in bone mineral density have been implicated with the onset of osteoarthritis, but its role in inducing failure of articular cartilage mechanically is unclear. This study aimed to determine the effect of substrate density, as the underlying bone, on the surface damage of cartilage-off-bone, at frequencies associated with gait, and above. Methods Bovine articular cartilage samples were tested off-bone to assess induced damage with an indenter under a compressive sinusoidal load range of 5–50 N at frequencies of 1, 10 and 50 Hz, corresponding to normal and above normal gait respectively, for up to 10,000 cycles. Cartilage samples were tested on four underlying substrates with densities of 0.1556, 0.3222, 0.5667 and 0.6000 g/cm3. India ink was applied to identify damage as cracks, measured across their length using ImageJ software. Linear regression was performed to identify if statistical significance existed between substrate density, and surface damage of articular cartilage-off-bone, at all three frequencies investigated (p 0.05) in surface damage with an increase in substrate density, at which the maximum mean crack length were 3.01 ± 3.41 mm and 5.65 ± 6.54 mm, respectively. Crack formation at all frequencies tended to form at the periphery of the cartilage specimen, with multiple straight-line cracking observed at 10 Hz, in comparison to single straight-line configurations produced at 1 and 50 Hz. Conclusions The effect of substrate density on the surface damage of articular cartilage-off-bone is multi-factorial, with an above-normal gait frequency. At 1 Hz cartilage damage is not associated with substrate density, however at 10 Hz, it is. This study has implications on the effects of the factors that contribute to the onset of osteoarthritis.

Summary: We assessed the pluripotency of human induced pluripotent stem cells (iPSCs) maintained on an automated platform using StemFlex and TeSR-E8 media. Analysis of transcriptome of single cells revealed similar expression of core pluripotency genes, as well as genes associated with naive and primed states of pluripotency. Analysis of individual cells from four samples consisting of two different iPSC lines each grown in the two culture media revealed a shared subpopulation structure with three main subpopulations different in pluripotency states. By implementing a machine learning approach, we estimated that most cells within each subpopulation are very similar between all four samples. The single-cell RNA sequencing analysis of iPSC lines grown in both media reports the molecular signature in StemFlex medium and how it compares to that observed in the TeSR-E8 medium. : Stem Cells Research; Transcriptomics; Automation Subject Areas: Stem Cells Research, Transcriptomics, Automation

Purpose: To report a case of necrotic uveal melanoma presenting as orbital cellulitis with an intraocular hemorrhage. Observations: A 61 year-old non-verbal male presented with a two-week history of right eyelid swelling and erythema unresponsive to antibiotics. In addition to these signs of orbital cellulitis, he presented with an opaque media precluding fundus visualization. He was later found to have a collar-button shaped mass consistent with uveal melanoma on B scan ultrasonography during an exam under anesthesia. The patient underwent enucleation with histopathology confirming a necrotic uveal melanoma. Conclusion and Importance: This case demonstrates how necrotic uveal melanoma can present as orbital cellulitis and the importance of keeping the diagnosis on the differential. Keywords: Orbital cellulitis, Necrotic uveal melanoma

Acoustic emission (AE) testing detects the onset and progression of mechanical flaws. AE as a diagnostic tool is gaining traction for providing a tribological assessment of human joints and orthopaedic implants. There is potential for using AE as a tool for diagnosing joint pathologies such as osteoarthritis and implant failure, but the signal analysis must differentiate between wear mechanisms—a challenging problem! In this study, we use supervised learning to classify AE signals from adhesive and abrasive wear under controlled joint conditions. Uncorrelated AE features were derived using principal component analysis and classified using three methods, logistic regression, k-nearest neighbours (KNN), and back propagation (BP) neural network. The BP network performed best, with a classification accuracy of 98%, representing an exciting development for the clustering and supervised classification of AE signals as a bio-tribological diagnostic tool.

The development of polyaniline (PANI)/biomaterial composites as humidity sensor materials represents an emerging area of advanced materials with promising applications. The increasing attention to biopolymer materials as desiccants for humidity sensor components can be explained by their sustainability and propensity to absorb water. This review represents a literature survey, covering the last decade, which is focused on the interrelationship between the core properties and moisture responsiveness of multicomponent polymer/biomaterial composites. This contribution provides an overview of humidity-sensing materials and the corresponding sensors that emphasize the resistive (impedance) type of PANI devices. The key physicochemical properties that affect moisture sensitivity include the following: swelling, water vapor adsorption capacity, porosity, electrical conductivity, and enthalpies of adsorption and vaporization. Some key features of humidity-sensing materials involve the response time, recovery time, and hysteresis error. This work presents a discussion on various types of humidity-responsive composite materials that contain PANI and biopolymers, such as cellulose, chitosan and structurally related systems, along with a brief overview of carbonaceous and ceramic materials. The effect of additive components, such as polyvinyl alcohol (PVA), for film fabrication and their adsorption properties are also discussed. The mechanisms of hydration and proton transfer, as well as the relationship with conductivity is discussed. The literature survey on hydration reveals that the textural properties (surface area and pore structure) of a material, along with the hydrophile–lipophile balance (HLB) play a crucial role. The role of HLB is important in PANI/biopolymer materials for understanding hydration phenomena and hydrophobic effects. Fundamental aspects of hydration studies that are relevant to humidity sensor materials are reviewed. The experimental design of humidity sensor materials is described, and their relevant physicochemical characterization methods are covered, along with some perspectives on future directions in research on PANI-based humidity sensors.