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Abstract Kindler syndrome (KS) is a rare genodermatosis resulting from loss-of-function mutations in FERMT1, the gene that encodes Kindlin-1. KS patients have a high propensity to develop aggressive and metastatic cutaneous squamous cell carcinoma (cSCC). Here we show in non-KS-associated patients that elevation of FERMT1 expression is increased in actinic keratoses compared to normal skin, with a further increase in cSCC supporting a pro-tumorigenic role in this population. In contrast, we show that loss of Kindlin-1 leads to increased SCC tumor growth in vivo and in 3D spheroids, which was associated with the development of a hypoxic tumor environment and increased glycolysis. The metalloproteinase Mmp13 was upregulated in Kindlin-1-depleted tumors, and increased expression of MMP13 was responsible for driving increased invasion of the Kindlin-1-depleted SCC cells. These results provide evidence that Kindlin-1 loss in SCC can promote invasion through the upregulation of MMP13, and offer novel insights into how Kindlin-1 loss leads to the development of a hypoxic environment that is permissive for tumor growth.

Introduction There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS.Methods and analysis MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0–6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur.Ethics and dissemination The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numbers NCT03387670; ISRCTN82598726.

We report a continuous-wave Ti:sapphire laser with an output power of 1.03 W, achieved with two low-cost single-emitter diode pumps, both of blue wavelength (448 and 468 nm). Using a novel strategy of combining blue-wavelength pumping with a long, low-doping Ti:sapphire crystal, we maximise the available pump power while minimising deleterious effects associated with blue pump wavelengths, demonstrating Watt-level output powers.

Abstract The temperature dependent order parameter provides important information on the nature of magnetism. Using traditional methods to study this parameter in two-dimensional (2D) magnets remains difficult, however, particularly for insulating antiferromagnetic (AF) compounds. Here, we show that its temperature dependence in AF MPS3 (M(II) = Fe, Co, Ni) can be probed via the anisotropy in the resonance frequency of rectangular membranes, mediated by a combination of anisotropic magnetostriction and spontaneous staggered magnetization. Density functional calculations followed by a derived orbital-resolved magnetic exchange analysis confirm and unravel the microscopic origin of this magnetization-induced anisotropic strain. We further show that the temperature and thickness dependent order parameter allows to deduce the material’s critical exponents characterising magnetic order. Nanomechanical sensing of magnetic order thus provides a future platform to investigate 2D magnetism down to the single-layer limit.

The application of hydrophobic treatments as a means of protecting vulnerable stone heritage has been a topic of research for decades. The findings of previous research have shown that there are a number of factors that influence the efficiency of a treatment and that sometimes, if used incorrectly, such treatments can even accelerate stone weathering and decay. In this study, we revisit a hydrophobic treatment test area at Arbroath Abbey where the product was applied over 40 years ago, thus providing a rare opportunity to investigate the long-term efficiency of hydrophobic treatments. As well as assessing the condition of the treated area in situ by means of moisture analyses, lab-based accelerated salt weathering experiments are conducted to better understand the impact of silane-based treatments on sandstone durability. Moreover, the petrography and petrophysical properties of weathered sandstone (open porosity, capillary absorption, and vapour diffusion) before and after treatment are also characterised to provide a better understanding of how stone properties may influence the compatibility of the treatment. The field-based results show that the treated area has maintained a degree of hydrophobicity since its application over 40 years ago. Both field-based and lab-based analyses suggest that silane-based treatments can be used successfully in protecting sandstone when applied correctly, both in reducing the rate of decay and functioning over long periods of time. However, sandstone heterogeneity may mean that some individual stones are less compatible with the hydrophobic treatment tested than others. Further field-based analyses (including methods such as XRF and in situ vp) of the treated area is required in order to determine the state of conservation more accurately. These results highlight the complexity in selecting a suitable hydrophobic treatment, especially at built sites where the mineralogy and petrophysical properties of the stone may vary between blocks. However, such treatments may still be important to consider as many climates, including Scotland’s, are becoming progressively wetter, increasing the vulnerability of stone heritage to moisture ingress, accelerated decay, and eventual ruin.

Background and Aim: Inonotus obliquus (Ach. Ex. Pers), commonly known as Chaga, is a parasitic fungus that grows on birch trees. Indigenous North Americans and Northern Eurasians have used Chaga tea as a folk medicine for centuries, and there are currently significant interests in commercializing Chaga products, obtained either from conks (sclerotia) collected from nature or from laboratory cultured mycelia. The cultured mycelia's identity to date is based solely on chemical profiling and the morphologic characteristics; and genome identity are often overlooked and unreported in the literature. The aims of this study include: 1. To authenticate mycelium isolates derived from a Chaga sclerotium; 2. To determine Chaga sclerotium's bioactivities unreported previously. Experimental procedures: Identification of Chaga conk was carried out by chemical analyses, culture characteristics, and genome identity. The Chaga extracts’ bioactivities were evaluated via effects on cytokine and reactive oxygen species production on normal and cancer cell survival and proliferation. Results and Conclusion: The features of this mycelium isolate conformed to I. obliquus mycology, with > 99 % DNA sequence identity to the known GenBank Chaga Ribosomal Internal Spacer (ITS) sequence. Water extracts of Chaga were effective in protecting against oxidative stress in mouse neuroblastoma-spinal motor neuron NSC-34 cells and inhibited the proliferation of human brain glioblastoma DBTRG-05MG and pancreatic ductal adenocarcinoma PANC-1 cancer cell lines in vitro. In addition, the water extract potently stimulated inflammatory cytokines release from human blood cells, consistent with the biological response modifier features of mushroom beta- glucan polysaccharides.

Cells transmit mechanical force to the nucleus via the cytoskeleton. Here, the authors reveal a role for the actin regulator Mena in force transmission at the nuclear envelope, where it regulates nuclear architecture, chromatin organization and gene expression.

Abstract Two-dimensional magnetic materials with strong magnetostriction are attractive systems for realizing strain-tuning of the magnetization in spintronic and nanomagnetic devices. This requires an understanding of the magneto-mechanical coupling in these materials. In this work, we suspend thin Cr2Ge2Te6 layers and their heterostructures, creating ferromagnetic nanomechanical membrane resonators. We probe their mechanical and magnetic properties as a function of temperature and strain by observing magneto-elastic signatures in the temperature-dependent resonance frequency near the Curie temperature, T C. We compensate for the negative thermal expansion coefficient of Cr2Ge2Te6 by fabricating heterostructures with thin layers of WSe2 and antiferromagnetic FePS3, which have positive thermal expansion coefficients. Thus we demonstrate the possibility of probing multiple magnetic phase transitions in a single heterostructure. Finally, we demonstrate a strain-induced enhancement of T C in a suspended Cr2Ge2Te6-based heterostructure by 2.5 ± 0.6 K by applying a strain of 0.026% via electrostatic force.

The protocol described in the present article aims to validate the GLU test, a test of mid-pregnancy vaginal microbiome, for PTB risk prediction in pregnant First Nations women. Preterm birth (PTB; birth before 37 completed weeks gestation) is associated with a higher risk of adverse neonatal outcomes. First Nations communities are affected by increasing PTB rates, highest in remote communities, reaching 23%. Being able to predict women at high risk of PTB is one of the greatest challenges of our time. No reliable clinical predictors of PTB risk currently exist, beyond a previous history. Spontaneous PTB (sPTB) is highly associated with microbial infection. Recently, a Western Australian research team developed an innovative mid-pregnancy vaginal microbial DNA test, the ‘Gardnerella, Lactobacillus, Ureaplasma’ (GLU) test, capable of predicting up to 45% of sPTB cases. However, this test has only been validated in predominantly Caucasian pregnant women. The protocol described aims to validate the GLU test in pregnant First Nations women and where applicable, make modifications to this test to improve sensitivity and specificity within this population.

Glucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces tissue-specific glucocorticoid action and promotes angiogenesis in murine models of myocardial infarction. Angiogenesis is important in the growth of some solid tumours. This study used murine models of squamous cell carcinoma (SCC) and pancreatic ductal adenocarcinoma (PDAC) to test the hypothesis that 11β-HSD1 inhibition promotes angiogenesis and subsequent tumour growth. SCC or PDAC cells were injected into female FVB/N or C57BL6/J mice fed either standard diet, or diet containing the 11β-HSD1 inhibitor UE2316. SCC tumours grew more rapidly in UE2316-treated mice, reaching a larger (P

Background: : Given the specificity of bacteriophage attachment receptors, a single bacterial isolate is currently utilized to match to a bacteriophage therapeutic, thereby extrapolating activity to all bacteria in vivo. Consistently, the main bacteriophage attachment receptor for Staphylococcus aureus is teichoic acid, and it is known that this receptor has phenotypic variations in different in vivo environments. Consequently, the aim of this study was to determine whether bacteriophage activity is similar across all in vivo prosthetic joint infection environments. Methods: : Three patients with prosthetic joint infections who had S. aureus grow from arthrocentesis cultures and at least three deep tissue cultures were analyzed for growth inhibition with a library of 56 bacteriophages. Results: : Discordant bacteriophage activity was seen across the different in vivo environments. Furthermore, bacteriophages with the most robust lytic potential to the arthrocentesis isolates usually did not demonstrate activity corresponding to all the deep tissue clinical isolates. Conclusion: :Variations of bacteriophage activity can occur between the different in vivo clinical environments, which is likely secondary to different glycosylation patterns of teichoic acid. Consequently, if discordant activity is present, retreating with bacteriophages that have activity is likely needed for effective, reproducible outcomes.

Abstract Background Preterm birth accounts for approximately 11% of all livebirths globally. Due to improvements in perinatal care, more than 95% of these infants now survive into adulthood. Research has indicated a robust association between prematurity and increased cardiovascular risk factors and cardiovascular mortality. While the innate adverse effects of prematurity on these outcomes have been demonstrated, therapeutic strategies on the mitigation of these concerning developments are lacking. The primary objective of the NEOVASC clinical trial is therefore to investigate whether the administration of a prolonged exclusive human-milk diet in preterm infants is capable of alleviating the harmful effects of preterm birth on the early development of cardiovascular risk factors. Methods The NEOVASC study is a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial conducted in four Austrian tertiary neonatal care facilities. The purpose of the present trial is to investigate the effects of a prolonged exclusive human-milk-diet devoid of bovine-milk-based food components on cardiovascular and metabolic risk factors at 1, 2, and 5 years of corrected age. Primary outcomes include assessments of fasting blood glucose levels, blood pressure levels, and the distensibility of the descending aorta using validated echocardiographic protocols at 5 years of corrected age. The test group, which consists of 200 preterm infants, will therefore be compared to a control group of 100 term-born infants and a historical control group recruited previously. Discussion Given the emerging implications of an increased cardiovascular risk profile in the potentially growing population of preterm infants, further research on the mitigation of long-term morbidities in formerly preterm infants is urgently warranted. Further optimizing preterm infants’ nutrition by removing bovine-milk-based food components may therefore be an interesting approach worth pursuing. Trial registration ClinicalTrials.gov NCT04413994 . Registered on 4 June 2020.

Nonlinear dissipation is frequently observed in nanomechanical resonators, but its microscopic origin remains unclear. Here, nonlinear damping is found to be enhanced in graphene nanodrums close to internal resonance conditions, providing insights on the mechanisms at the basis of this phenomenon.

BackgroundDubai (United Arab Emirates; UAE) has a multi-national population which makes it exceptionally interesting study sample because of its unique demographic factors.ObjectiveTo stratify the risk factors for the multinational society of the UAE.MethodsA retrospective chart review of 560 patients sequentially admitted to inpatient care with laboratory confirmed COVID-19 was conducted. We studied patients’ demographics, clinical features, laboratory results, disease severity, and outcomes. The parameters were compared across different ethnic groups using tree-based estimators to rank the ethnicity-specific disease features. We trained ML classification algorithms to build a model of ethnic specificity of COVID-19 based on clinical presentation and laboratory findings on admission.ResultsOut of 560 patients, 43.6% were South Asians, 26.4% Middle Easterns, 16.8% East Asians, 10.7% Caucasians, and 2.5% are under others. UAE nationals represented half of the Middle Eastern patients, and 13% of the entire cohort. Hypertension was the most common comorbidity in COVID-19 patients. Subjective complaint of fever and cough were the chief presenting symptoms. Two-thirds of the patients had either a mild disease or were asymptomatic. Only 20% of the entire cohort needed oxygen therapy, and 12% needed ICU admission. Forty patients (~7%) needed invasive ventilation and fifteen patients died (2.7%). We observed differences in disease severity among different ethnic groups. Caucasian or East-Asian COVID-19 patients tended to have a more severe disease despite a lower risk profile. In contrast to this, Middle Eastern COVID-19 patients had a higher risk factor profile, but they did not differ markedly in disease severity from the other ethnic groups. There was no noticeable difference between the Middle Eastern subethnicities—Arabs and Africans—in disease severity (p = 0.81). However, there were disparities in the SOFA score, D-dimer (p = 0.015), fibrinogen (p = 0.007), and background diseases (hypertension, p = 0.003; diabetes and smoking, p = 0.045) between the subethnicities.ConclusionWe observed variations in disease severity among different ethnic groups. The high accuracy (average AUC = 0.9586) of the ethnicity classification model based on the laboratory and clinical findings suggests the presence of ethnic-specific disease features. Larger studies are needed to explore the role of ethnicity in COVID-19 disease features.

To solve the problems of low execution efficiency and insufficient security of traditional electronic payment mode, in this study, an improved mode of cross-border e-commerce payment based on fuzzy fractional-order ordinary differential equation and secure electronic transaction protocol is proposed. Firstly, the competition model of cross-border e-commerce payment platform is constructed using fuzzy fractional order ordinary differential equation. Based on the theory of Hopf bifurcation, the stability of the model is analyzed. Then, the cross-border e-commerce improved payment mode is built based on the secure electronic transaction protocol. Finally, the efficiency and security performance of the improved payment mode are compared with that of the traditional payment mode with face through simulation experiments. The results show that the improved mode takes less time in encryption and decryption than the traditional mode; the time spent on the security payment of the improved mode remains around 1.2 s, while that of the traditional mode is around 2.7 s; the improved mode security payment takes significantly less time than the traditional mode, which indicates that the payment mode proposed in this research based on fuzzy fractional order ordinary differential equation is not only more secure than the traditional payment mode, but also can effectively improve the payment speed of users and greatly enhance their shopping experience.

Electronics and magnetic phase transitions typically do not involve mechanical degrees of freedom directly, but their impact on thermodynamic properties affects the mechanical response of a material. Here the authors show that resonators made from 2D materials exhibit anomalies at phase transitions.

Abstract Background Cancer trials often incorporate intensive imaging with Magnetic Resonance Imaging (MRI) and Positron Emission Tomography with Computerised Tomography (PET/CT), which can be physically and mentally exhausting for patients. This questionnaire study aimed to determine the aspects of imaging that affect a patient’s decision to participate in clinical trials in order to inform the design of future trials that utilise imaging. This should achieve greater patient compliance and improve the patient experience. Method A detailed questionnaire assessing patient expectation and acceptability of imaging within clinical trials was developed in collaboration with two patient representatives. The questionnaire addressed the influence of scan type, length, frequency, scheduling, invasiveness and staff support on acceptability of imaging. It was applied to three patient groups. Group 1 consisted of patients newly recruited to studies with imaging, Group 2 consisted of previous participants in studies with imaging and Group 3 consisted of patients having imaging for clinical care. Results One hundred ninety six patients completed the questionnaires (Group 1:47; Group 2: 50 and Group 3: 99). The use of ionising radiation and number of scans required were identified as negative influences on decision to participate by 25% of Group 3 but only by 6% of Groups 1 and 2. Scan duration >30mins was perceived as a negative factor for decision to participate by all Groups (12–22%). Good communication provided by researchers in terms of discussing the study before and after reading study materials was a key factor in influencing decision to participate (> 50% in Groups 1 and 2 and > 20% in Group 3). Conclusion Factors relating to imaging procedures within clinical trials that affect participation have been identified with communication around study materials as the key determinant. These data will be used to influence the development of future research protocols. Modification of imaging requirements within clinical trials will improve patient tolerance and acceptability and is likely to raise recruitment.

An der Universitätsbibliothek der Freien Universität Berlin sind zwischen Mai 2019 und Mai 2021 im Rahmen eines umfassenden Change-Projekts weitreichende Veränderungen in der Organisation auf den Weg gebracht worden. Mit dem Ziel einer Ausrichtung an den Bedürfnissen der Nutzenden und einer Fokussierung auf die digitale Zukunft von wissenschaftlichen Bibliotheken wurde erstmalig eine Strategie formuliert. Außerdem ist die Organisation an verschiedenen Stellen umgestaltet worden, um die gegenwärtigen und zukünftigen Herausforderungen produktiv und zusammen mit den Angehörigen der Universität bearbeiten zu können. Dieser Beitrag erläutert den Verlauf des Projekts und seine wichtigsten Ergebnisse, beleuchtet einzelne Aspekte des Prozesses und wirft einen Blick auf die nächsten Schritte der Organisationsentwicklung.

BackgroundData on the epidemiological characteristics and clinical features of COVID-19 in patients of different ages and sex are limited. Existing studies have mainly focused on the pediatric and elderly population.ObjectiveAssess whether age and sex interact with other risk factors to influence the severity of SARS-CoV-2 infection.Material and MethodsThe study sample included all consecutive patients who satisfied the inclusion criteria and who were treated from 24 February to 1 July 2020 in Dubai Mediclinic Parkview (560 cases) and Al Ain Hospital (605 cases), United Arab Emirates. We compared disease severity estimated from the radiological findings among patients of different age groups and sex. To analyze factors associated with an increased risk of severe disease, we conducted uni- and multivariate regression analyses. Specifically, age, sex, laboratory findings, and personal risk factors were used to predict moderate and severe COVID-19 with conventional machine learning methods.ResultsNeed for O2 supplementation was positively correlated with age. Intensive care was required more often for men of all ages (p < 0.01). Males were more likely to have at least moderate disease severity (p = 0.0083). These findings were aligned with the results of biochemical findings and suggest a direct correlation between older age and male sex with a severe course of the disease. In young males (18–39 years), the percentage of the lung parenchyma covered with consolidation and the density characteristics of lesions were higher than those of other age groups; however, there was no marked sex difference in middle-aged (40–64 years) and older adults (≥65 years). From the univariate analysis, the risk of the non-mild COVID-19 was significantly higher (p < 0.05) in midlife adults and older adults compared to young adults. The multivariate analysis provided similar findings.ConclusionAge and sex were important predictors of disease severity in the set of data typically collected on admission. Sexual dissimilarities reduced with age. Age disparities were more pronounced if studied with the clinical markers of disease severity than with the radiological markers. The impact of sex on the clinical markers was more evident than that of age in our study.

Abstract Background Marzeptacog alfa (activated) (MarzAA), a novel recombinant activated human factor VII (FVIIa) variant, was developed to provide increased procoagulant activity, subcutaneous (SC) administration, and longer duration of action in people with hemophilia. Objectives To investigate if daily SC administration of MarzAA in subjects with inhibitors can provide effective prophylaxis. Methods This multicenter, open‐label phase 2 trial (NCT03407651) enrolled men with severe congenital hemophilia with an inhibitor. All subjects had a baseline annualized bleeding rate (ABR) of ≥12 events/year. Subjects received a single 18 μg/kg intravenous dose of MarzAA to measure 24‐hour pharmacokinetics (PK) and pharmacodynamics (PD), single 30 μg/kg SC dose to measure 48‐hour PK/PD, then daily SC 30 μg/kg MarzAA for 50 days. If spontaneous bleeding occurred, the dose was sequentially escalated to 60, 90, or 120 μg/kg, with 50 days at the final effective dose without spontaneous bleeding to proceed to a 30‐day follow‐up. The primary end point was reduction in ABR. Secondary end points were safety, tolerability, and antidrug antibody (ADA) formation. Results In the 11 subjects, the mean ABR significantly reduced from 19.8 to 1.6, and the mean proportion of days with bleeding significantly reduced from 12.3% to 0.8%. Of a total of 517 SC doses, six injection site reactions in two subjects were reported. No ADAs were detected. One fatal unrelated serious adverse event occurred: intracerebral hemorrhage due to untreated hypertension. Conclusions The data demonstrated that MarzAA was highly efficacious for prophylactic treatment in patients with inhibitors by significantly decreasing bleed frequency and duration of bleeding episodes.

Abstract Background Young people (YP; 12–24 years old) with rheumatic diseases face many challenges associated with chronic illness in addition to the physiological and psychosocial changes of adolescence. Timely access to developmentally appropriate multidisciplinary care is key to successfully managing rheumatic diseases, but gaps in the care of this vulnerable age group still exist. This study aimed to develop a benchmarking toolkit to enable comparative evaluation of YP rheumatology services in order to promote best practice and reduce variations in service delivery. Methods A staged and consultative method was used across a broad group of stakeholders in the UK (YP, parents/other carers, and healthcare professionals, HCPs) to develop this toolkit, with reference to pre-existing standards of YP-friendly healthcare. Eighty-seven YP (median age 19 years, range 12–24 years) and 26 rheumatology HCPs with 1–34 years of experience caring for YP have participated. Results Thirty quality criteria were identified, which were grouped into four main domains: assessment and treatment, information and involvement, accessibility and environment, and continuity of care. Two toolkit versions, one to be completed by HCPs and one to be completed by patients, were developed. These were further refined by relevant groups and face validity was confirmed. Conclusions A toolkit has been developed to systematically evaluate and benchmark YP rheumatology services, which is key in setting standards of care, identifying targets for improvement and facilitating research. Engagement from YP, clinical teams, and commissioners with this tool should facilitate investigation of variability in levels of care and drive quality improvement.

**Introduction**: Orofacial clefts have a wide range of severity and can create functional and aesthetic issues for the affected individuals as well as influence their social interactions and general happiness. The aim of this research was to investigate how parents/caregivers score functional and aesthetic aspects of their child’s cleft and their child’s social interactions and happiness. **Method**: Parents/caregivers attending the Christchurch Cleft Clinic in New Zealand between 2016 and 2019 were asked to complete a survey covering eight items—hearing, look of face, look of teeth, speech, teeth issues, food or liquid coming out of the nose, social interactions, general happiness and a free-text comment section. Items were scored using a visual analogue scale. Descriptive statistics were performed on the data and qualitative analysis of the free-text comments was conducted via thematic categorisation. The study was deemed an out-of-scope audit from the New Zealand Health and Disability Ethics Committee; locality approval was granted by the Canterbury District Health Board (RO# 19069) and consent was obtained from all participants. **Results**: A total of 226 completed surveys from 154 parents were assessed. Surveys that had any incomplete question (24) and/or had repeat submissions (72) were excluded, reducing the sample to 130 surveys. ‘Speech’, ‘look of the teeth’ and ‘teeth issues’ had the lowest (worst) mean scores. Negative functional issues relating to speech and fistulas were the most common free-text themes. **Conclusion**: Speech was a common concern for parents, emphasising the importance of speech language therapy as a key component in cleft treatment. Parental concerns regarding the look of their child’s teeth and teeth issues highlight the need for an interdisciplinary treatment approach. The inclusion of otolaryngology and psychology services to improve issues that arise from hearing, social and emotional challenges is also recommended.

Congenital diaphragmatic hernia (CDH) is a relatively common developmental defect with considerable mortality and morbidity. Formation of the diaphragm is a complex process that involves several cell types, each with different developmental origins. Owing to this complexity, the aetiology of CDH is not well understood. The pleuroperitoneal folds (PPFs) and the posthepatic mesenchymal plate (PHMP) are transient structures that are essential during diaphragm development. Using several mouse models, including lineage tracing, we demonstrate the heterogeneous nature of the cells that make up the PPFs. The conditional deletion of Wilms tumor 1 homolog (Wt1) in the non-muscle mesenchyme of the PPFs results in CDH. We show that the fusion of the PPFs and the PHMP to form a continuous band of tissue involves movements of cells from both sources. The PPFs of mutant mice fail to fuse with the PHMP and exhibit increased RALDH2 (also known as ALDH1A2) expression. However, no changes in the expression of genes (including Snai1, Snai2, Cdh1 and Vim) implicated in epithelial-to-mesenchymal transition are observed. Additionally, the mutant PPFs lack migrating myoblasts and muscle connective tissue fibroblasts (TCF4+/GATA4+), suggesting possible interactions between these cell types. Our study demonstrates the importance of the non-muscle mesenchyme in development of the diaphragm.

The article outlines the main activities of the first year of the project Wandel@FU-Bib, which focused on establishing a strategy for the libraries at Freie Universität Berlin, entitled “Creating spaces of knowledge”. The focus is on describing the process rather than the content. At the time of writing, the project had just passed its one year-anniversary and therefore its halfway point.

Abstract Background The Affordable Care Act (ACA) has improved healthcare access in the community health centers that have played a critical role in enrolling low income and minority patients. This study examined the ACA enrollment for one of the largest federally qualified community health centers in the country. Methods An exploratory sequential mixed method study was used as the main qualitative and quantitative approach for this study. Key stakeholders (n = 6) were interviewed as part of the qualitative component, and information about barriers and best practices were acquired. As part of the quantitative analysis, we examined cross-sectional data among 59,272 AltaMed enrollees in 2013–2015. We analyzed data on age, gender, language, ethnicity, and enrollment periods. The interviews were conducted first and followed by the data analysis. Results AltaMed was the top enroller of patients in ACA insurance plans in California (2013–14 and 2014–15) through the state exchange and Medicaid expansion. Using key stakeholder interviews, 5 main barriers were identified and 5 innovative solutions that allowed AltaMed to enroll people into the state exchange and Medicaid expansion. Barriers to enrollment included training, new workflows, and enrollment of Young Invincibles, and these enrollment barriers were overcome with community health workers. Conclusion Enrollment barriers were overcome through AltaMed’s community-based approach and long term community partnerships.

Im Einklang mit dem Diskurs über die digitale Transformation der akademischen Forschung und Lehre steigt der Bedarf an stärkerer Zusammenarbeit. Insbesondere bei drittmittelfinanzierten Forschungsprojekten können spezifische Kenntnisse über Digital Humanities und nicht-lateinische Schriften selten innerhalb der Organisation vermittelt werden und Projektwerkzeuge und -plattformen können oft nicht länger als die Dauer des Projekts gepflegt werden. Eine Lösung könnte in der Einbeziehung von Informationsinfrastruktureinrichtungen wie Bibliotheken oder Rechenzentren sein. Diese Institutionen sind jedoch in der Regel nicht in der Lage, alle Sprachen und Disziplinen zu unterstützen. Der Artikel zeigt praxisbezogene Beispiele für institutionsübergreifende Kollaboration und die Ansätze eines Expertennetzwerkes zu nicht-lateinischen Schriften in multilingualen Umgebungen auf.

From a social constructivist perspective, learning happens by way of engagement with other people and with objects in the environment, often through a process of play and exploration. The notion of tinkering illustrates this mode of creative play, which is relevant not only to youth learning but also to educators’ professional learning. In this study, we describe the experiences of a group of educators who participated in a professional learning program in the summer of 2020 that involved a series of activities for “tinkering at home.” Interviews focused on participants’ sense-making processes, the resources they sought out, and the facilitation choices they made if they included others in their tinkering. Thematic analysis revealed four characteristic features of the affective and relational flow of learning through tinkering: (1) generative openings, (2) multiple pathways for exploration, (3) impasse, and (4) resolution through social interaction. We discuss the implications of these themes for reflective pedagogical practice that is grounded in educators’ own experiential learning.

Functionalizing antimicrobial peptides with fluorescent groups is a useful strategy for imaging infection, but the tag can alter the performance of the probe. Here, the authors report a spacer-free method to directly functionalise an amino acid with a fluorogenic group and prepare peptide-based imaging agents for fungal infection.

The efficacy of pharmaceutical agents can be greatly improved through nanocarrier delivery. Encapsulation of pharmaceutical agents into a nanocarrier can enhance their bioavailability and biocompatibility, whilst also facilitating targeted drug delivery to specific locations within the body. However, detailed understanding of the in vivo activity of the nanocarrier-drug conjugate is required prior to regulatory approval as a safe and effective treatment strategy. A comprehensive understanding of how nanocarriers travel to, and interact with, the intended target is required in order to optimize the dosing strategy, reduce potential off-target effects, and unwanted toxic effects. Raman spectroscopy has received much interest as a mechanism for label-free, non-invasive imaging of nanocarrier modes of action in vivo. Advanced Raman imaging techniques, including coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS), are paving the way for rigorous evaluation of nanocarrier activity at the single-cell level. This review focuses on the development of Raman imaging techniques to study organic nanocarrier delivery in cells and tissues.

The patterns of skills in adults who have difficulty with reading may be different from those of children, and thus applying and interpreting methods of measurement may be complex. The goal of this study was to examine the relations among reading skills in this population, by modeling specific reading skills and method of measurement simultaneously using confirmatory factor analysis (CFA) models of hypothesized skills and methods. This study examines the relational structure between skills common reading assessments are measuring in this group, as well as the effect of the method of measurement on assessing reading skills in this group, focusing on the following questions: How do reading assessment methods (speed, battery) and skills (silent reading, contextual reading, phonic decoding) in a selection of measures of reading performance relate to each other in a sample of adults, and what are the implications for test selection and interpretation for this population? Results indicate that modeling reading in this population is complicated as some tests do not generalize fully to an overall reading factor, and the relation of specific reading skills and methods of measurement may be complex. The analysis of the structure of this study's selection of reading tests provides information about the relation between the tests themselves, and also about the performance of adult readers in these skill areas.

Strategic and Interactive Writing Instruction (SIWI) involves teaching cognitive writing strategies and apprenticing novices within collaborative writing communities. It is responsive to deaf students' diverse language experiences through embedded metalinguistic/linguistic components. A randomized controlled trial of SIWI was conducted with 15 teachers and 79 students in grades 3-5. Recount, information report, and persuasive genres were taught across three 9-week periods. Writing samples analyzed for writing traits, language clarity, and language complexity were collected prior to instruction for the genre, immediately following, and 9 weeks after withdrawal of instruction for the genre. Standardized writing measures and motivation surveys were collected at the beginning and end of the academic year. Genre-specific writing outcomes were statistically significant for recount and information report writing, with substantial effect sizes for treatment and maintenance. Standardized writing outcomes mirrored these results. All others variables demonstrated small to moderately large treatment effects, although not all statistically significant.

It is important to understand the nature of the effect that the COVID-19 pandemic had upon student learning, especially those at risk such as deaf students. The limited communication that many deaf students have at home may mean less support is available for learning remotely. Reading may be one of the areas where progress was diminished. We collected Measures of Academic Progress (MAP) scores in reading from deaf students in a residential school for the deaf in grades 3 to 12 every fall and spring from 2016 to 2021. A cohort-sequential approach yielded growth data (2570 observations), with 546 students measured up to 10 times each. As is typical of MAP reading achievement in grades 3 to 12, growth was steep in early grades, slowing in later grades. Students in the Alternative Curriculum performed lower and grew slower. Cohorts differed, with more recent cohorts typically having higher performance than older cohorts. Tenure had a substantial effect, suggesting that students who had been in the school for the deaf longer had higher performance compared to students who joined the school as older students. The pandemic appeared to have a strong, but diminishing effect in each semester, but this effect differed widely across demographic groups. This suggests that effects of the pandemic are neither clear nor simple for deaf students even within the same school. These findings have implications for understanding how the impact of pandemic may vary as a function of deaf students' educational experiences and other demographic factors.

This ethnographic study examines a girls-only summer maker program designed to empower girls who learned to use power tools to build their own designs. Drawing from theories of identity construction within figured worlds, the article shows how girls in the program authored themselves into roles that run counter to patriarchal notions of making and femininity. Illustrative examples show how girls played with gender presentation, produced gender-bending artifacts that became identity resources, and learned to collectively navigate traditionally male spaces. The article concludes with implications for the design of equitable maker learning environments.