Simultaneous mapping of cathodoluminescence spectra and backscatter diffraction patterns in a scanning electron microscope.

Electron backscatter diffraction and cathodoluminescence are complementary scanning electron microscopy modes widely used in the characterisation of semiconductor films, respectively revealing the strain state of a crystalline material and the effect of this strain on the light emission from the sample. Conflicting beam, sample and detector geometries have meant it is not generally possible to acquire the two signals together during the same scan. Here, we present a method of achieving this simultaneous acquisition, by collecting the light emission through a transparent sample substrate. We apply this combination of techniques to investigate the strain field and resultant emission wavelength variation in a deep-ultraviolet micro-LED. For such compatible samples, this approach has the benefits of avoiding image alignment issues and minimising beam damage effects.

Effect of ß-glucans on rainbow trout (Oncorhynchus mykiss) IgM+ B cells.

ß-glucans are carbohydrates present in the cell wall of many fungi, which are often used as immunostimulants in feeds for farmed species. Their capacity to activate innate immune responses directly acting on innate cell populations has been widely documented in fish. However, whether they can affect the functionality of adaptive immune cells has been scarcely explored. In this context, in the current work, we have determined the effects of ß-glucans on rainbow trout blood IgM+ B cells in the presence or absence of 2,4,6-trinitrophenyl hapten conjugated to lipopolysaccharide (TNP-LPS), a model antigen. For this, rainbow trout peripheral blood leukocytes were incubated with different doses of ß-glucans or media alone in the presence or absence of TNP-LPS for 48 h. The size, levels of expression of surface MHC II, antigen processing and phagocytic capacities and proliferation of IgM+ B cells were then studied by flow cytometry. The number of IgM-secreting cells in the cultures was also estimated by ELISpot. ß-glucans significantly decreased the levels of surface MHC II expression and the antigen processing capacities of these cells, especially in the presence of TNP-LPS, while they increased their phagocytic activity. On their own, ß-glucans slightly activated the proliferation of IgM+ B cells but reduced that induced by TNP-LPS. In contrast, ß-glucans significantly increased the number of cells secreting IgM in the cultures. This effect of ß-glucans on the IgM-secreting capacity of B cells was also confirmed through a feeding experiment, in which the IgM-secreting capacity of blood leukocytes obtained from fish fed a ß-glucan-supplemented diet for one month was compared to that of leukocytes obtained from fish fed a control diet. Altogether, these findings contribute to increase our knowledge regarding the effects of ß-glucans on fish adaptive responses.

COVID-19 Infection in Ultramarathon Runners: Findings of the Ultrarunners Longitudinal TRAcking Study.

OBJECTIVE: Ultramarathon runners are a unique patient population who have been shown to have a lower rate of severe chronic medical conditions. This study aimed to determine the effect that COVID-19 infection has had on this population and their running behavior. DESIGN: The Ultrarunners Longitudinal TRAcking (ULTRA) Study is a large longitudinal study of ultramarathon runners. Questions on health status, running behavior, and COVID-19 infection were included in the most recent survey. SETTING: Community survey. PARTICIPANTS: Seven hundred thirty-four ultramarathon runners participated in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Personal, exercise, and COVID-19 infection history. RESULTS: 52.7% of study participants reported having been symptomatic from a COVID-19 infection, with 6.7% testing positive multiple times. Participants required a total of 4 days of hospitalization. The most common symptoms included fever (73.6%), fatigue (68.5%), sore throat (68.2%), runny nose (67.7%), and cough (67.4%). Cardiovascular symptoms, which are of particular interest in the running population, included shortness of breath (46.3%), tachycardia (44.7%), chest pain (36.2%), and wheezing (33.3%). A total of 50 subjects (6.8%) reported long COVID (symptoms lasting more than 12 weeks). CONCLUSIONS: Severe COVID-19 infection has been rare in this population of ultramarathon runners, although symptomatic infection that affects running is common. To support the well-being of this group of highly active athletes, clinicians should appreciate that cardiovascular symptoms are common and the long-term significance of these symptoms in runners is unknown. LEVEL OF EVIDENCE: Level 2 prospective study.

Plasma metabolites in childhood Burkitt lymphoma cases and cancer-free controls in Uganda.

INTRODUCTION: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma associated with Plasmodium falciparum and Epstein-Barr virus, both of which affect metabolic pathways. The metabolomic patterns of BL is unknown. MATERIALS AND METHODS: We measured 627 metabolites in pre-chemotherapy treatment plasma samples from 25 male children (6-11 years) with BL and 25 cancer-free area- and age-frequency-matched male controls from the Epidemiology of Burkitt Lymphoma in East African Children and Minors study in Uganda using liquid chromatography-tandem mass spectrometry. Unconditional, age-adjusted logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for the BL association with 1-standard deviation increase in the log-metabolite concentration, adjusting for multiple comparisons using false discovery rate (FDR) thresholds and Bonferroni correction. RESULTS: Compared to controls, levels for 42 metabolite concentrations differed in BL cases (FDR < 0.001), including triacylglyceride (18:0_38:6), alpha-aminobutyric acid (AABA), ceramide (d18:1/20:0), phosphatidylcholine ae C40:6 and phosphatidylcholine C38:6 as the top signals associated with BL (ORs = 6.9 to 14.7, P < 2.4✕10- 4). Two metabolites (triacylglyceride (18:0_38:6) and AABA) selected using stepwise logistic regression discriminated BL cases from controls with an area under the curve of 0.97 (95% CI: 0.94, 1.00). CONCLUSION: Our findings warrant further examination of plasma metabolites as potential biomarkers for BL risk/diagnosis.

Sap flow through partially embolized xylem vessel networks.

Sap is transported through numerous conduits in the xylem of woody plants along the path from the soil to the leaves. When all conduits are functional, vessel lumen diameter is a strong predictor of hydraulic conductivity. As vessels become embolized, sap movement becomes increasingly affected by factors operating at scales beyond individual conduits, creating resistances that result in hydraulic conductivity diverging from diameter-based estimates. These effects include pit resistances, connectivity, path length, network topology, and vessel or sector isolation. The impact of these factors varies with the level and distribution of emboli within the network, and manifest as alterations in the relationship between the number and diameter of embolized vessels with measured declines in hydraulic conductivity across vulnerability to embolism curves. Divergences between measured conductivity and diameter-based estimates reveal functional differences that arise because of species- and tissue-specific vessel network structures. Such divergences are not uniform, and xylem tissues may diverge in different ways and to differing degrees. Plants regularly operate under nonoptimal conditions and contain numerous embolized conduits. Understanding the hydraulic implications of emboli within a network and the function of partially embolized networks are critical gaps in our understanding of plants occurring within natural environments.

Functional group tolerant hydrogen borrowing C-alkylation.

Hydrogen borrowing is an attractive and sustainable strategy for carbon-carbon bond formation that enables alcohols to be used as alkylating reagents in place of alkyl halides. However, despite intensive efforts, limited functional group tolerance is observed in this methodology, which we hypothesize is due to the high temperatures and harsh basic conditions often employed. Here we demonstrate that room temperature and functional group tolerant hydrogen borrowing can be achieved with a simple iridium catalyst in the presence of substoichiometric base without an excess of reagents. Achieving high yields necessitates the application of anaerobic conditions to counteract the oxygen sensitivity of the catalytic iridium hydride intermediate, which otherwise leads to catalyst degradation. Substrates containing heteroatoms capable of complexing the catalyst exhibit limited room temperature reactivity, but the application of moderately higher temperatures enables extension to a broad range of medicinally relevant nitrogen rich heterocycles. These newly developed conditions allow alcohols possessing functional groups that were previously incompatible with hydrogen borrowing reactions to be employed.

The tumor microbiome reacts to hypoxia and can influence response to radiation treatment in colorectal cancer.

Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation's ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA-seq data from the Oncology Research Information Exchange Network (ORIEN) database of colorectal cancer (CRC) patients treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 CRC cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, where tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-trophic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia appears to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes.

Spectroscopic Manifestations Of (Anti)Aromaticity In Oxidized And Reduced Porphyrin And Norcorrole.

Aromaticity and antiaromaticity are foundational principes in organic chemistry, regularly invoked to explain stability, structure, and magnetic and electronic properties. There are ongoing challenges in assigning molecules as aromatic or antiaromatic using optical spectroscopy. Here we report spectroelectrochemical and computational analyses of porphyrin (18π neutral, aromatic) and norcorrole (16π neutral, antiaromatic), and their oxidized (16π porphyrin dication) and reduced (norcorrole 18π dianion) forms. Our results show that while the visible spectra are characteristic of (anti)aromaticity consistent with Hückel's rules, the IR spectra are much less informative, owing to the relative rigidity of norcorrole. The results have implications for the assignment of (anti)aromaticity in both ground-state and time-resolved excited-state spectra.

Spectral characterization of a blue light-emitting micro-LED platform on skin-associated microbial chromophores.

The therapeutic application of blue light (380 - 500nm) has garnered considerable attention in recent years as it offers a non-invasive approach for the management of prevalent skin conditions including acne vulgaris and atopic dermatitis. These conditions are often characterised by an imbalance in the microbial communities that colonise our skin, termed the skin microbiome. In conditions including acne vulgaris, blue light is thought to address this imbalance through the selective photoexcitation of microbial species expressing wavelength-specific chromophores, differentially affecting skin commensals and thus altering the relative species composition. However, the abundance and diversity of these chromophores across the skin microbiota remains poorly understood. Similarly, devices utilised for studies are often bulky and poorly characterised which if translated to therapy could result in reduced patient compliance. Here, we present a clinically viable micro-LED illumination platform with peak emission 450 nm (17 nm FWHM) and adjustable irradiance output to a maximum 0.55 ± 0.01 W/cm2, dependent upon the concentration of titanium dioxide nanoparticles applied to an accompanying flexible light extraction substrate. Utilising spectrometry approaches, we characterised the abundance of prospective blue light chromophores across skin commensal bacteria isolated from healthy volunteers. Of the strains surveyed 62.5% exhibited absorption peaks within the blue light spectrum, evidencing expression of carotenoid pigments (18.8%, 420-483 nm; Micrococcus luteus, Kocuria spp.), porphyrins (12.5%, 402-413 nm; Cutibacterium spp.) and potential flavins (31.2%, 420-425 nm; Staphylococcus and Dermacoccus spp.). We also present evidence of the capacity of these species to diminish irradiance output when combined with the micro-LED platform and in turn how exposure to low-dose blue light causes shifts in observed absorbance spectra peaks. Collectively these findings highlight a crucial deficit in understanding how microbial chromophores might shape response to blue light and in turn evidence of a micro-LED illumination platform with potential for clinical applications.

Type VI Collagen Deficiency Causes Enhanced Periodontal Tissue Destruction.

The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrillogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6-deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared toward the inflammatory response. We also observed that cultured COL6-deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber turnover and ECM organization as well as migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrillogenesis and affecting the immune response in periodontitis. These insights advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease.

Dual spatio-temporal regulation of axon growth and microtubule dynamics by RhoA signaling pathways.

RhoA plays a crucial role in neuronal polarization, where its action restraining axon outgrowth has been thoroughly studied. We now report that RhoA has not only inhibitory but also a stimulatory effect on axon development depending on when and where exerts its action and the downstream effectors involved. In cultured hippocampal neurons, FRET imaging revealed that RhoA activity selectively localizes in growth cones of undifferentiated neurites, while in developing axons it displays a biphasic pattern, being low in nascent axons and high in elongating ones. RhoA-Rho kinase (ROCK) signaling prevents axon initiation but has no effect on elongation, while formin inhibition reduces axon extension without significantly altering initial outgrowth. Besides, RhoA-mDia promotes axon elongation by stimulating growth cone microtubule stability and assembly, as opposed to RhoA-ROCK that restrains growth cone microtubule assembly and protrusion.

Coherent control of an optical tweezer phonon laser.

The creation and manipulation of coherence continues to capture the attention of scientists and engineers. The optical laser is a canonical example of a system that, in principle, exhibits complete coherence. Recent research has focused on the creation of coherent, laser-like states in other physical systems. The phonon laser is one example where it is possible to amplify self-sustained mechanical oscillations. A single mode phonon laser in a levitated optical tweezer has been demonstrated through appropriate balance of active feedback gain and damping. In this work, coherent control of the dynamics of an optical tweezer phonon laser is used to share coherence between its different modes of oscillation, creating a multimode phonon laser. The coupling of the modes is achieved by periodically rotating the asymmetric optical potential in the transverse focal plane of the trapping beam via trap laser polarization rotation. The presented theory and experiment demonstrate that coherence can be transferred across different modes of an optical tweezer phonon laser, and are a step toward using these systems for precision measurement and quantum information processing.

Separation-dependent near-field effects in Mie scattering spectra of two optically trapped aerosol droplets.

The backscattering of ultraviolet and visible light by a model organic (squalane) aerosol droplet (1.0

Standardizing quality utilization of interventional radiology treatments of blunt splenic injury: SQUIRTS study.

OBJECTIVES: Nonoperative management (NOM) of blunt splenic injury (BSI) is well accepted in appropriate patients. Splenic artery embolization (SAE) in higher-grade injuries likely plays an important role in increasing the success of NOM. We previously implemented a protocol requiring referral of all BSI grades III-V undergoing NOM for SAE. It is unknown the risk of complications as well as longitudinal outcomes. We aimed to examine the splenic salvage rate and safety profile of the protocol. We hypothesized the splenic salvage rate would be high and complications would be low. METHODS: A retrospective study was performed at our Level 1 trauma center over a 9-year period. Injury characteristics and outcomes in patients sustaining BSI grades III-V were collected. Outcomes were compared for NOM on protocol (SAE) and off protocol (no angiography or angiography but no embolization). Complications for angiographies were examined. RESULTS: Between January 2010 and February 2019, 570 patients had grade III-V BSI. NOM was attempted in 359 (63 %) with overall salvage rate of 91 % (328). Of these, 305 were on protocol while 54 were off protocol (41 no angiography and 13 angiography but no SAE). During the study period, for every grade of injury a pattern was seen of a higher salvage rate in the on-protocol group when compared to the off-protocol group (Grade III, 97 %(181/187) vs. 89 %(32/36), Grade IV, 91 %(98/108) vs. 69 %(9/13) and Grade V, 80 %(8/10 vs. 0 %(0/5). The overall salvage rate was 94 %(287) on protocol vs. 76 %(41) off protocol (p < 0.001, Cochran-Mantel-Haenszel test). Complications occurred in only 8 of the 318 who underwent angiography (2 %). These included 5 access complications and 3 abscesses. CONCLUSION: The use of a protocol requiring routine splenic artery embolization for all high-grade spleen injuries slated for non-operative management is safe with a very low complication rate. NOM with splenic angioembolization failure rate is improved as compared to non-SAE patients' at all higher grades of injury. Thus, SAE for all hemodynamically stable patients of all high-grade types should be considered as a primary form of therapy for such injuries.

Mef2d potentiates type-2 immune responses and allergic lung inflammation.

Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.

Sustainability in a broad sense: An essential aspect of scientific conferences.

This article reflects on sustainability in the context of scientific conferences with emphasis on environmental, diversity, inclusivity, and intellectual aspects. We argue that it is imperative to embrace sustainability as a broad concept during conference organization. In-person conferences have an obvious environmental impact but mitigating strategies can be implemented, such as incentivizing low-emission travel, offering fellowships to support sustainable traveling, and promoting use of public transport or car-pooling. Utilizing eco-conscious venues, catering, and accommodations, along with minimizing resource wastage, further reduces environmental impact. Additional considerations include facilitating hybrid format conferences that allow both in-person and online attendance. Hybrid conferences enhance global participation whilst reducing resource consumption and environmental impact. Often-overlooked benefits can arise from the simple recording of talks to enable asynchronous viewing for people unable to attend in person, in addition to providing a legacy of knowledge that, for example, could support the training of early career researchers (ECRs) or newcomers in the field. The longevity of a research field, intellectual sustainability, requires an inclusive conference atmosphere, offering optimal opportunities for ECRs, minority groups, and researchers from emerging countries. Diversity and inclusivity not only enrich conference experiences but also enhances creativity and innovation.

Salivary Gland Tissue Recombination Can Modify Cell Fate.

Although mesenchyme is essential for inducing the epithelium of ectodermal organs, its precise role in organ-specific epithelial fate determination remains poorly understood. To elucidate the roles of tissue interactions in cellular differentiation, we performed single-cell RNA sequencing and imaging analyses on recombined tissues, where mesenchyme and epithelium were switched ex vivo between two types of embryonic mouse salivary glands: the parotid gland (a serous gland) and the submandibular gland (a predominantly mucous gland). We found partial induction of molecules that define gland-specific acinar and myoepithelial cells in recombined salivary epithelium. The parotid epithelium recombined with submandibular mesenchyme began to express mucous acinar genes not intrinsic to the parotid gland. While myoepithelial cells do not normally line parotid acini, newly induced myoepithelial cells densely populated recombined parotid acini. However, mucous acinar and myoepithelial markers continued to be expressed in submandibular epithelial cells recombined with parotid mesenchyme. Consequently, some epithelial cells appeared to be plastic, such that their fate could still be modified in response to mesenchymal signaling, whereas other epithelial cells appeared to be already committed to a specific fate. We also discovered evidence for bidirectional induction: transcriptional changes were observed not only in the epithelium but also in the mesenchyme after heterotypic tissue recombination. For example, parotid epithelium induced the expression of muscle-related genes in submandibular fibroblasts that began to mimic parotid fibroblast gene expression. These studies provide the first comprehensive unbiased molecular characterization of tissue recombination approaches exploring the regulation of cell fate.

Prevalence of right-to-left shunt in stroke patients with cancer.

BACKGROUND AND OBJECTIVES: Cancer is associated with an increased risk of acute ischemic stroke (AIS) and venous thromboembolism. The role of a cardiac right-to-left shunt (RLS) as a surrogate parameter for paradoxical embolism in cancer-related strokes is uncertain. We sought to investigate the relationship between the presence of an RLS and cancer in AIS patients. METHODS: We included consecutive AIS patients hospitalized at our tertiary stroke center between January 2015 and December 2020 with available RLS status as detected on transesophageal echocardiography (TEE). Active cancers were retrospectively identified and the association with RLS was assessed with multivariable logistic regression and inverse probability of treatment weighting to minimize the ascertainment bias of having a TEE obtained. RESULTS: Of the 2236 AIS patients included, 103 (4.6%) had active cancer, of whom 24 (23%) were diagnosed with RLS. An RLS was present in 774 out of the 2133 AIS patients without active cancer (36%). After adjustment and weighting, the absence of RLS was associated with active cancer (adjusted odds ratio (aOR) 2.29; 95% confidence interval (CI), 1.14-4.58). When analysis was restricted to patients younger than 60 years of age or those with a high-risk RLS (Risk of Paradoxical Embolism Score ⩾ 6), there was no association between RLS and cancer (aOR, 3.07; 95% CI, 0.79-11.88 and aOR, 0.56; 95% CI, 0.10-3.10, respectively). CONCLUSION: RLS was diagnosed less frequently in AIS patients with cancer than in cancer-free patients, suggesting that arterial sources may play a larger role in cancer-related strokes than paradoxical venous embolization. Future studies are needed to validate these findings and evaluate potential therapeutic implications, such as the general indication, or lack thereof, for patent foramen ovale (PFO) closure in this patient population.

Probing the Antiaromaticity and Coordination Chemistry of Bowl-Shaped Zinc(II) Norcorrole.

Zinc norcorrole was prepared as its pyridine complex (ZnNc·pyridine) by metalation of freebase norcorrole. The ZnNc·pyridine complex is distinctly bowl-shaped, as demonstrated by both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. NMR spectroscopy showed characteristic ring current deshielding effects, with different magnitudes on either face of the bowl-shaped complex. Exchanging the pyridine ligand with the bidentate ligand DABCO results in the formation of a stable (ZnNc)2·DABCO sandwich complex, which was also characterized by crystallography and NMR spectroscopy. The NMR resonances of the axial ligands in all of the complexes demonstrate that the paratropic ring current in zinc norcorrole is approximately 40 nA/T, which is comparable in magnitude to the diatropic ring current in porphyrin. Analysis of the ligand-exchange processes on addition of DABCO to ZnNc·pyridine showed that ZnNc coordinates to axial nitrogen-containing ligands with approximately 1000-fold higher binding constants than analogous zinc porphyrins.