X-ray detection of a nova in the fireball phase.

Novae are caused by runaway thermonuclear burning in the hydrogen-rich envelopes of accreting white dwarfs, which leads to a rapid expansion of the envelope and the ejection of most of its mass1,2. Theory has predicted the existence of a 'fireball' phase following directly on from the runaway fusion, which should be observable as a short, bright and soft X-ray flash before the nova becomes visible in the optical3-5. Here we report observations of a bright and soft X-ray flash associated with the classical Galactic nova YZ Reticuli 11 h before its 9 mag optical brightening. No X-ray source was detected 4 h before and after the event, constraining the duration of the flash to shorter than 8 h. In agreement with theoretical predictions4,6-8, the source's spectral shape is consistent with a black-body of 3.27+0.11-0.33 × 105 K (28.2+0.9-2.8 eV), or a white dwarf atmosphere, radiating at the Eddington luminosity, with a photosphere that is only slightly larger than a typical white dwarf.

Multi-scale systems genomics analysis predicts pathways, cell types, and drug targets involved in normative variation in peri-adolescent human cognition.

An open challenge in human genetics is to better understand the systems-level impact of genotype variation on developmental cognition. To characterize the genetic underpinnings of peri-adolescent cognition, we performed genotype-phenotype and systems analysis for binarized accuracy in nine cognitive tasks from the Philadelphia Neurodevelopmental Cohort (~2,200 individuals of European continental ancestry aged 8-21 years). We report a region of genome-wide significance within the 3' end of the Fibulin-1 gene (P = 4.6 × 10-8), associated with accuracy in nonverbal reasoning, a heritable form of complex reasoning ability. Diffusion tensor imaging data from a subset of these participants identified a significant association of white matter fractional anisotropy with FBLN1 genotypes (P < 0.025); poor performers show an increase in the C and A allele for rs77601382 and rs5765534, respectively, which is associated with increased fractional anisotropy. Integration of published human brain-specific 'omic maps, including single-cell transcriptomes of the developing human brain, shows that FBLN1 demonstrates greatest expression in the fetal brain, as a marker of intermediate progenitor cells, demonstrates negligible expression in the adolescent and adult human brain, and demonstrates increased expression in the brain in schizophrenia. Collectively these findings warrant further study of this gene and genetic locus in cognition, neurodevelopment, and disease. Separately, genotype-pathway analysis identified an enrichment of variants associated with working memory accuracy in pathways related to development and to autonomic nervous system dysfunction. Top-ranking pathway genes include those genetically associated with diseases with working memory deficits, such as schizophrenia and Parkinson's disease. This work advances the "molecules-to-behavior" view of cognition and provides a framework for using systems-level organization of data for other biomedical domains.

Single-cell RNA sequencing defines disease-specific differences between chronic nodular prurigo and atopic dermatitis.

BACKGROUND: Chronic nodular prurigo (CNPG) is an inflammatory skin disease that is maintained by a chronic itch-scratch cycle likely rooted in neuroimmunological dysregulation. This condition may be associated with atopy in some patients, and there are now promising therapeutic results from blocking type 2 cytokines such as IL-4, IL-13, and IL-31. OBJECTIVES: This study aimed to improve the understanding of pathomechanisms underlying CNPG as well as molecular relationships between CNPG and atopic dermatitis (AD). METHODS: We profiled skin lesions from patients with CNPG in comparison with AD and healthy control individuals using single-cell RNA sequencing combined with T-cell receptor sequencing. RESULTS: We found type 2 immune skewing in both CNPG and AD, as evidenced by CD4+ helper T cells expressing IL13. However, only AD harbored an additional, oligoclonally expanded CD8A+IL9R+IL13+ cytotoxic T-cell population, and immune activation pathways were highly upregulated in AD, but less so in CNPG. Conversely, CNPG showed signatures of extracellular matrix organization, collagen synthesis, and fibrosis, including a unique population of CXCL14-IL24+ secretory papillary fibroblasts. Besides known itch mediators such as IL31 and oncostatin M, we also detected increased levels of neuromedin B in fibroblasts of CNPG lesions compared with AD and HC, with neuromedin B receptors detectable on some nerve endings. CONCLUSIONS: These data show that CNPG does not harbor the strong disease-specific immune activation pathways that are typically found in AD but is rather characterized by upregulated stromal remodeling mechanisms that might have a direct impact on itch fibers.

Population-based physical activity promotion with a focus on health equity: a review of reviews.

BACKGROUND: The extent to which people are physically active is dependent upon social gradients. Numerous studies have shown that especially people with social disadvantages do not meet the physical activity (PA) recommendations. A promising strategy to alleviate this issue are approaches that promote PA in the general population. In addition, several researchers have raised concerns that population-based health interventions may increase health inequities. The aim of the current review of reviews was therefore to identify successful population-based PA promotion approaches with a particular focus on health equity. METHODS: Six electronic databases were examined for systematic reviews on population-based PA promotion for the period 2015 to 2021. A reference list and grey literature search were also conducted. Two independent reviewers used inclusion/exclusion criteria to screen titles and abstracts of the potentially relevant literature and conducted a quality assessment for each identified review. All included reviews of population-based approaches for PA promotion with a focus on disadvantaged populations and/or health equity were narratively summarized. RESULTS: Our search resulted in 4,411 hits. After a systematic review process, six reviews met the inclusion criteria and were included after they were all rated as high quality. We identified that mass-media campaigns, point-of-decision prompts, environmental approaches, policy approaches, and community-based multi-component approaches can promote PA in the general population. Across populations with social disadvantages mass-media campaigns, point-of-decision prompts and policy approaches are likely to be effective as long as they are tailored. Regarding environmental approaches, the results are inconsistent. None of the reviews on community-based multi-component approaches provided evidence on health equity. CONCLUSION: There are several effective approaches to promote PA in the general population but evidence regarding health equity is still sparse. Future studies should therefore pay more attention to this missing focus. Furthermore, there is a lack of evidence regarding the type of tailoring and the long-term impact of population-based approaches to PA promotion. However, this requires appropriate funding programmes, complex study designs and evaluation methods.

Multi-level stakeholders' perspectives on implementation and scaling up community-based health promotion in Germany.

Community-based health promotion has the potential to address existing health inequities, although such approaches are scarcely scaled up. For a successful scale up, various stakeholders at different levels and sectors need to be involved. The article's aims are to assess what kind of external support communities need for implementation and to identify facilitators and barriers for scaling up community-based health promotion. Two national digital workshops were conducted in Germany with stakeholders at the community level (n = 161) and with stakeholders at the federal and state levels (n = 84). Protocols were compiled and coded using qualitative content analysis. During the first workshop, we revealed 11 themes for external support needs ('Strategic approach', 'Define & compare indicators', 'International human resource', 'Tools & Aids', 'External conduction of the assessment', 'Involvement of people in difficult life situations', 'Overview of actors', 'Moderation', 'Obtain funding', 'Quality assurance/evaluation' and 'External support'). Eleven facilitators and barriers were identified for scaling up ('Assessment and evaluation', 'Intersectoral collaboration and partnerships', 'Communication', 'Characteristics of the program', 'Political and legal conditions', 'Political support', 'Local coordinator', 'Resources', 'Participation', 'Strategic planning/methods' and 'Intermediary organization'). The identified results provide practice-based evidence on support needed for scaling up, facilitators that promote scaling up and barriers that might hinder scaling up community-based health promotion in Germany. In a next step, this practice-based evidence needs to be systematically integrated with scientific-based evidence on key components for scaling up such approaches for the development of an effective scaling-up concept.

The major aim of this article is to describe how German stakeholders at different levels (local, federal and state) from various sectors (e.g. health, social or sports) were involved to develop a scaling-up concept for a community-based health promotion approach with a focus on health equity in the field of physical activity promotion. Different actors from science, policy and practice discussed facilitators and barriers for the scale up and what external support communities need to implement a community-based health promotion approach, with a focus on people in difficult life situations (e.g. individuals with social disadvantages). We identified 14 different kind of support needs and 11 facilitators and barriers for scaling up community-based health promotion approaches in the field of physical activity promotion. Various actors emphasized the need for improved collaboration and partnerships across several sectors as well as changes in current political and legal conditions. Furthermore, the role and some characteristics of an external organization to support a successful scaling-up process were also discussed among actors.

Diagnostic difficulties in pediatric annular dermatoses.

The polymorphic presentation of annular dermatoses in the pediatric population renders them a diagnostic challenge to the clinician. They include various distinct disease entities that can be vaguely categorized according to the age of onset. Herein, we report on a young girl with clinical characteristics of Wells' syndrome, while histological findings favored the diagnosis of annular erythema of infancy (AEI). Although morphological and histological similarities do exist, AEI and eosinophilic annular erythema (EAE) of childhood are considered as distinct entities in the literature. Wells' syndrome (WS) is an eosinophilic dermatosis and histologically characterized by eosinophilic dermal infiltration with the hallmark feature of "flame figures." Based on this case, we discuss and review the differential diagnoses of annular dermatoses in children.

Comparison of Permethrin-Based Treatment Strategies against Scabies in Infants and Young Children.

OBJECTIVE: To optimize the permethrin-based therapies for scabies infestations in infants and young children, the efficacies of 3 different regimens were evaluated. STUDY DESIGN: The retrospective analysis encompassed 85 infants and children aged <4 years with scabies. The children had received either topical permethrin 5% on the entire body on days 1/8, on days 1/8/15, on days 1/8/15 plus interim applications restricted to hands and feet on days 2/3/4//9/10/11, or alternative treatments. RESULTS: The intensified regimen, consisting of full-body permethrin applied on days 1/8/15 and hands/feet on days 2/3/4//9/10/11, resulted in cure of scabies in 73.5% of the cases. The cure rates were significantly greater compared with full-body permethrin given on days 1/8, which led to eradication in 44%, and were greater compared with the clearance in children who had received full-body permethrin on days 1/8/15 (53.8%) or alternative treatments (60%). For patients in whom permethrin had previously been applied, the intensified regimen resulted in eradication of scabies in 71.4% of the cases, compared with 30% and 55.6% after full-body permethrin on days 1/8 and 1/8/15, respectively. CONCLUSIONS: The intensified regimen of full-body permethrin plus interim applications on hands/feet, which aims at reducing the number of mites present on the frequently heavily infested palmoplantar sites in addition to the standard entire body application, appears efficacious in curing scabies in young children.

Dermatoscopy of Neoplastic Skin Lesions: Recent Advances, Updates, and Revisions.

OPINION STATEMENT: Dermatoscopy (dermoscopy) improves the diagnosis of benign and malignant cutaneous neoplasms in comparison with examination with the unaided eye and should be used routinely for all pigmented and non-pigmented cutaneous neoplasms. It is especially useful for the early stage of melanoma when melanoma-specific criteria are invisible to the unaided eye. Preselection by the unaided eye is therefore not recommended. The increased availability of polarized dermatoscopes, and the extended use of dermatoscopy in non-pigmented lesions led to the discovery of new criteria, and we recommend that lesions should be examined with polarized and non-polarized dermatoscopy. The "chaos and clues algorithm" is a good starting point for beginners because it is easy to use, accurate, and it works for all types of pigmented lesions not only for those melanocytic. Physicians, who use dermatoscopy routinely, should be aware of new clues for acral melanomas, nail matrix melanomas, melanoma in situ, and nodular melanoma. Dermatoscopy should also be used to distinguish between different subtypes of basal cell carcinoma and to discriminate highly from poorly differentiated squamous cell carcinomas to optimize therapy and management of non-melanoma skin cancer. One of the most exciting areas of research is the use of dermatoscopic images for machine learning and automated diagnosis. Convolutional neural networks trained with dermatoscopic images are able to diagnose pigmented lesions with the same accuracy as human experts. We humans should not be afraid of this new and exciting development because it will most likely lead to a peaceful and fruitful coexistence of human experts and decision support systems.

Microwave Chip-Based Beam Splitter for Low-Energy Guided Electrons.

We present a novel beam splitter for low-energy electrons using a micro-structured guiding potential created above the surface of a planar microwave chip. Beam splitting arises from smoothly transforming the transverse guiding potential for an electron beam from a single-well harmonic confinement into a double well, thereby generating two separated output beams with 5 mm lateral spacing. Efficient beam splitting is observed for electron kinetic energies up to 3 eV, in excellent agreement with particle tracking simulations. We discuss prospects of this novel beam splitter approach for electron-based quantum matter-wave optics experiments.

Diagnostic test accuracy in longitudinal study settings: theoretical approaches with use cases from clinical practice.

OBJECTIVES: In this study, we evaluate how to estimate diagnostic test accuracy (DTA) correctly in the presence of longitudinal patient data (ie, repeated test applications per patient). STUDY DESIGN AND SETTING: We used a nonparametric approach to estimate the sensitivity and specificity of three tests for different target conditions with varying characteristics (ie, episode length and disease-free intervals between episodes): 1) systemic inflammatory response syndrome (n = 36), 2) depression (n = 33), and 3) epilepsy (n = 30). DTA was estimated on the levels 'time', 'block', and 'patient-time' for each diagnosis, representing different research questions. The estimation was conducted for the time units per minute, per hour, and per day. RESULTS: A comparison of DTA per and across use cases showed variations in the estimates, which resulted from the used level, the time unit, the resulting number of observations per patient, and the diagnosis-specific characteristics. Intra- and inter-use-case comparisons showed that the time-level had the highest DTA, particularly the larger the time unit, and that the patient-time-level approximated 50% sensitivity and specificity. CONCLUSION: Researchers need to predefine their choices (ie, estimation levels and time units) based on their individual research aims, estimands, and diagnosis-specific characteristics of the target outcomes to make sure that unbiased and clinically relevant measures are communicated. In cases of uncertainty, researchers could report the DTA of the test using more than one estimation level and/or time unit.

The Limitations and Potentials of Evaluating Economic Aspects of Community-Based Health Promotion: A Critical Review.

Community-based health promotion (CBHP) interventions are promising approaches to address public health problems; however, their economic evaluation presents unique challenges. This review aims to explore the opportunities and limitations of evaluating economic aspects of CBHP, focusing on the assessment of intervention costs and outcomes, and the consideration of political-level changes and health equity. A systematic search of the PubMed, Web of Science and PsycInfo databases identified 24 CBHP interventions, the majority of which targeted disadvantaged communities. Only five interventions included a detailed cost/resource assessment. Outcomes at the operational level were mainly quantitative, related to sociodemographics and environment or health status, while outcomes at the political level were often qualitative, related to public policy, capacity building or networks/collaboration. The study highlights the limitations of traditional health economic evaluation methods in capturing the complexity of CBHP interventions. It proposes the use of cost-consequence analysis (CCA) as a more comprehensive approach, offering a flexible and multifaceted assessment of costs and outcomes. However, challenges remain in the measurement and valuation of outcomes, equity considerations, intersectoral costs and attribution of effects. While CCA is a promising starting point, further research and methodological advancements are needed to refine its application and improve decision making in CBHP.

Monitoring the Morphological Changes of Skeleton-PtCo Electrocatalyst during PEMFC Start-Up/Shut-Down probed by in†situ WAXS and SAXS.

Advanced in situ analyses are indispensable for comprehending the catalyst aging mechanisms of Pt-based PEM fuel cell cathode materials, particularly during accelerated stress tests (ASTs). In this study, a combination of in situ small-angle and wide-angle X-ray scattering (SAXS & WAXS) techniques were employed to establish correlations between structural parameters (crystal phase, quantity, and size) of a highly active skeleton-PtCo (sk-PtCo) catalyst and their degradation cycles within the potential range of the start-up/shut-down (SUSD) conditions. Despite the complex case of the sk-PtCo catalyst comprising two distinct fcc alloy phases, our complementary techniques enabled in situ monitoring of structural changes in each crystal phase in detail. Remarkably, the in situ WAXS measurements uncover two primary catalyst aging processes, namely the cobalt depletion (regime I) followed by the crystallite growth via Ostwald ripening and/or particle coalescence (regime II). Additionally, in situ SAXS data reveal a continuous size growth over the AST. The Pt-enriched shell thickening based on the Co depletion within the first 100 SUSD cycles and particle growth induced by additional potential cycles were also collaborated by ex situ STEM-EELS. Overall, our work shows a comprehensive aging model for the sk-PtCo catalyst probed by complementary in situ WAXS and SAXS techniques.

Gas-Phase Characterization of Redox-Active Manganese Complexes.

Manganese complexes exhibit a rich redox chemistry, usually accompanied by structural reorganization during the redox processes often followed by ligand dissociation or association. The push-pull ligand 2,6-diguanidylpyridine (dgpy) stabilizes manganese in the oxidation states +II, +III, and + IV in the complexes [Mn(dgpy)2]n+ (n = 2-4) without change in the coordination sphere in the condensed phase [Heinze et al., Inorganic Chemistry, 2022, 61, 14616]. In the condensed phase, the manganese(IV) complex is a very strong oxidant. In the present work, we investigate the stability and redox activity of the MnIV complex and its counterion (PF6-) adducts in the gas phase, using two modified 3D Paul ion trap mass spectrometers. Six different cationic species of the type [Mnx(dgpy)2(PF6)y]n+ (x = II, III, IV, y = 0-3, n = 1-3) could be observed for the three oxidation states MnIV, MnIII, and MnII, of which one observed complex also contains a reduced dgpy ligand. MnII species showed the highest relative stability in collision induced dissociation and UV/vis photo dissociation experiments. The lowest stability is observed in the presence of one or more counterions, which correlates to a lower total charge n+. Gas phase UV/vis spectra show similar features as the condensed phase spectra only differing in relative band intensities. The strongly oxidizing MnIV complex reacts with triethylamine (NEt3) in the gas phase to give MnIII, while MnIII species show little reactivity toward NEt3.

Scrutinizing the human TEX genes in the context of human male infertility.

BACKGROUND: Infertility affects around 15% of all couples worldwide and is increasingly linked to variants in genes specifically expressed in the testis. Well-established causes of male infertility include pathogenic variants in the genes TEX11, TEX14, and TEX15, while few studies have recently reported variants in TEX13B, TEX13C, FAM9A (TEX39A), and FAM9B (TEX39B). OBJECTIVES: We aimed at screening for novel potential candidate genes among the human TEX ("testis expressed") genes as well as verifying previously described disease associations in this set of genes. MATERIALS AND METHODS: To this end, we screened the exome sequencing data of 1305 men, including 1056 crypto- and azoospermic individuals, and determined cell-specific expression by analyzing testis-specific single-cell RNA sequencing data for genes with identified variants. To investigate the overarching role in male fertility, we generated testis-specific knockdown (KD) models of all 10 orthologous TEX genes in Drosophila melanogaster. RESULTS: We detected rare potential disease-causing variants in TEX10, TEX13A, TEX13B, TEX13C, TEX13D, ZFAND3 (TEX27), TEX33, FAM9A (TEX39A), and FAM9B (TEX39B), in 28 infertile men, of which 15 men carried variants in TEX10, TEX27, and TEX33. The KD of TEX2, TEX9, TEX10, TEX13, ZFAND3 (TEX27), TEX28, TEX30, NFX1 (TEX42), TEX261, and UTP4 (TEX292) in Drosophila resulted in normal fertility. DISCUSSION: Based on our findings, the autosomal dominant predicted genes TEX10 and ZFAND3 (TEX27) and the autosomal recessive predicted gene TEX33, which all three are conceivably required for germ cell maturation, were identified as novel potential candidate genes for human non-obstructive azoospermia. We additionally identified hemizygous loss-of-function (LoF) variants in TEX13B, TEX13C, and FAM9A (TEX39A) as unlikely monogenic culprits of male infertility as LoF variants were also found in control men. CONCLUSION: Our findings concerning the X-linked genes TEX13B, TEX13C, and FAM9A (TEX39A) contradict previous reports and will decrease false-positive reports in genetic diagnostics of azoospermic men.

Cognitive function in SMA patients with 2 or 3 SMN2 copies treated with SMN-modifying or gene addition therapy during the first year of life.

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease, causing progressive muscle weakness due to loss of lower motoneurons. Since 2017, three therapies, two modifying gene transcription and one adding the defective gene, have been approved with comparable efficacy on motor outcome. Data on cognitive outcomes of treated SMA type 1 patients is limited. The aim of this study was to evaluate cognitive function in symptomatic and presymptomatic SMA type 1 patients with two or three SMN2 copies who received SMN-modifying or gene-addition therapy in the first year of life. METHODS: Cognitive testing was performed in 20 patients, including 19 symptomatic SMA type 1 patients with up to three SMN2 copies and 1 pre-symptomatically treated patient. Children were tested using Bayley Scales of Infant Development (BSID-III) at the age of 2 or 3 years or the Wechsler Preschool and Primary Scale of Intelligence (WPSII-IV) at the of age of 5 years. RESULTS: 11/20 patients showed subnormal cognitive development. Boys had significantly lower cognitive scores. Patients requiring assisted ventilation or feeding support were more likely to have cognitive deficits. Achieving more motor milestones was associated with a better cognitive outcome. CONCLUSION: Treated patients with SMA type 1 have heterogeneous cognitive function with 55 % of patients showing deficits. Risk factors for cognitive impairment in our cohort were male gender and need for assisted ventilation or feeding support. Therefore, cognitive assessment should be included in the standard of care to allow early identification of deficits and potential therapeutic interventions.

Natural genetic variation quantitatively regulates heart rate and dimension.

The polygenic contribution to heart development and function along the health-disease continuum remains unresolved. To gain insight into the genetic basis of quantitative cardiac phenotypes, we utilize highly inbred Japanese rice fish models, Oryzias latipes, and Oryzias sakaizumii. Employing automated quantification of embryonic heart rates as core metric, we profiled phenotype variability across five inbred strains. We observed maximal phenotypic contrast between individuals of the HO5 and the HdrR strain. HO5 showed elevated heart rates associated with embryonic ventricular hypoplasia and impaired adult cardiac function. This contrast served as the basis for genome-wide mapping. In a segregation population of 1192 HO5 x HdrR F2 embryos, we mapped 59 loci (173 genes) associated with heart rate. Experimental validation of the top 12 candidate genes in loss-of-function models revealed their causal and distinct impact on heart rate, development, ventricle size, and arrhythmia. Our study uncovers new diagnostic and therapeutic targets for developmental and electrophysiological cardiac diseases and provides a novel scalable approach to investigate the intricate genetic architecture of the vertebrate heart.

Comparison of humans versus mobile phone-powered artificial intelligence for the diagnosis and management of pigmented skin cancer in secondary care: a multicentre, prospective, diagnostic, clinical trial.

BACKGROUND: Diagnosis of skin cancer requires medical expertise, which is scarce. Mobile phone-powered artificial intelligence (AI) could aid diagnosis, but it is unclear how this technology performs in a clinical scenario. Our primary aim was to test in the clinic whether there was equivalence between AI algorithms and clinicians for the diagnosis and management of pigmented skin lesions. METHODS: In this multicentre, prospective, diagnostic, clinical trial, we included specialist and novice clinicians and patients from two tertiary referral centres in Australia and Austria. Specialists had a specialist medical qualification related to diagnosing and managing pigmented skin lesions, whereas novices were dermatology junior doctors or registrars in trainee positions who had experience in examining and managing these lesions. Eligible patients were aged 18-99 years and had a modified Fitzpatrick I-III skin type; those in the diagnostic trial were undergoing routine excision or biopsy of one or more suspicious pigmented skin lesions bigger than 3 mm in the longest diameter, and those in the management trial had baseline total-body photographs taken within 1-4 years. We used two mobile phone-powered AI instruments incorporating a simple optical attachment: a new 7-class AI algorithm and the International Skin Imaging Collaboration (ISIC) AI algorithm, which was previously tested in a large online reader study. The reference standard for excised lesions in the diagnostic trial was histopathological examination; in the management trial, the reference standard was a descending hierarchy based on histopathological examination, comparison of baseline total-body photographs, digital monitoring, and telediagnosis. The main outcome of this study was to compare the accuracy of expert and novice diagnostic and management decisions with the two AI instruments. Possible decisions in the management trial were dismissal, biopsy, or 3-month monitoring. Decisions to monitor were considered equivalent to dismissal (scenario A) or biopsy of malignant lesions (scenario B). The trial was registered at the Australian New Zealand Clinical Trials Registry ACTRN12620000695909 (Universal trial number U1111-1251-8995). FINDINGS: The diagnostic study included 172 suspicious pigmented lesions (84 malignant) from 124 patients and the management study included 5696 pigmented lesions (18 malignant) from the whole body of 66 high-risk patients. The diagnoses of the 7-class AI algorithm were equivalent to the specialists' diagnoses (absolute accuracy difference 1·2% [95% CI -6·9 to 9·2]) and significantly superior to the novices' ones (21·5% [13·1 to 30·0]). The diagnoses of the ISIC AI algorithm were significantly inferior to the specialists' diagnoses (-11·6% [-20·3 to -3·0]) but significantly superior to the novices' ones (8·7% [-0·5 to 18·0]). The best 7-class management AI was significantly inferior to specialists' management (absolute accuracy difference in correct management decision -0·5% [95% CI -0·7 to -0·2] in scenario A and -0·4% [-0·8 to -0·05] in scenario B). Compared with the novices' management, the 7-class management AI was significantly inferior (-0·4% [-0·6 to -0·2]) in scenario A but significantly superior (0·4% [0·0 to 0·9]) in scenario B. INTERPRETATION: The mobile phone-powered AI technology is simple, practical, and accurate for the diagnosis of suspicious pigmented skin cancer in patients presenting to a specialist setting, although its usage for management decisions requires more careful execution. An AI algorithm that was superior in experimental studies was significantly inferior to specialists in a real-world scenario, suggesting that caution is needed when extrapolating results of experimental studies to clinical practice. FUNDING: MetaOptima Technology.

Comparison of 18F-FDG PET/CT and ultrasound in staging of patients with malignant melanoma.

OBJECTIVE: To evaluate the sensitivity and specificity of 2-18fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) and ultrasound (US) for staging patients with malignant melanoma. METHODS: In total, 258 patients (112 men and 146 women; mean age, 61 ± 16years) met the primary inclusion criteria for malignant melanoma without further malignancy proven by histopathology. This was a retrospective study of the diagnostic accuracy. All data were obtained from the hospital's patient and radiology information system. Patients formed a consecutive series and were examined by 18F-FDG PET/CT and 176 additionally by US (US as a whole [wUS], peripheral lymph nodes [pUS], abdomen [aUS]), with a total of 584 18F-FDG PET/CT and 697 US. 18F-FDG PET/CT and US revealed 824 and 726 lesions, respectively. Per-patient, per-examination, and per-lesion analyses were also performed. The reference standards used were histopathology or resection of lesions, and follow-up controls using other imaging methods. RESULTS: Significant differences (P < .05) were found in the per-examination for the sensitivity of 18F-FDG PET/CT (0.80) compared to wUS (0.63) and pUS (0.61), and the specificity of 18F-FDG PET/CT (0.96) compared to wUS (0.98) and aUS (0.99). In the PLA, there were significant differences in sensitivity and specificity for 18F-FDG PET/CT (0.83, 0.91) compared to wUS (0.61, 0.98), pUS (0.60, 0.98), and aUS (0.61, 0.99). CONCLUSION: 18F-FDG PET/CT is preferable to US for detecting both lymph node and abdominal metastases.

Development of a Framework for Scaling Up Community-Based Health Promotion: A Best Fit Framework Synthesis.

Community-based health promotion with a focus on people with social disadvantages is essential to address persistently existing health inequities. However, achieving an impact on public health requires scaling up such approaches beyond manifold funded pilot projects. The aim of this qualitative review is to provide an overview of scaling-up frameworks in health promotion and to identify key components for scaling up community-based health promotion. First, we conducted a systematic search for scaling-up frameworks for health promotion in PubMed, CINAHL, Scopus, Web of Science, PsycInfo, and SportDiscus. Based on the included frameworks, we created an a priori framework. Second, we searched for primary research studies in the same databases that reported scaling-up processes of community-based health promotion. We coded the data using the a priori framework. From 80 articles, a total of 12 frameworks were eligible, and 5 were included for data extraction. The analysis yielded 10 a priori defined key components: "innovation characteristics"; "clarify and coordinate roles and responsibilities"; "build up skills, knowledge, and capacity"; "mobilize and sustain resources"; "initiate and maintain regular communication"; "plan, conduct, and apply assessment, monitoring, and evaluation"; "develop political commitment and advocacy"; "build and foster collaboration"; "encourage participation and ownership"; and "plan and follow strategic approaches". We further identified 113 primary research studies; 10 were eligible. No new key components were found, but all a priori defined key components were supported by the studies. Ten key components for scaling up community-based health promotion represent the final framework. We further identified "encourage participation and ownership" as a crucial component regarding health equity.

FtsZ-mediated fission of a cuboid bacterial symbiont.

Less than a handful of cuboid and squared cells have been described in nature, which makes them a rarity. Here, we show how Candidatus Thiosymbion cuboideus, a cube-like gammaproteobacterium, reproduces on the surface of marine free-living nematodes. Immunostaining of symbiont cells with an anti-fimbriae antibody revealed that they are host-polarized, as these appendages exclusively localized at the host-proximal (animal-attached) pole. Moreover, by applying a fluorescently labeled metabolic probe to track new cell wall insertion in vivo, we observed that the host-attached pole started septation before the distal one. Similarly, Ca. T. cuboideus cells immunostained with an anti-FtsZ antibody revealed a proximal-to-distal localization pattern of this tubulin homolog. Although FtsZ has been shown to arrange into squares in synthetically remodeled cuboid cells, here we show that FtsZ may also mediate the division of naturally occurring ones. This implies that, even in natural settings, membrane roundness is not required for FtsZ function.