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Publisher Correction: High-throughput fluorescence lifetime imaging flow cytometry
Analysis of the therapeutic efficacy of arthroscopic repair of the subscapularis tendon combined with coracoplasty
Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication
Determinants of perceived patient benefit in a longitudinal cohort study of patients with psoriasis and atopic dermatitis
AbstractThe Dermatology Life Quality Index (DLQI) should be used to assess treatment success in psoriasis (PSO). However, the DLQI does not assess the importance and achievement of treatment goals. The Patient Benefit Index (PBI) is a questionnaire that takes both into account. Currently, there is insufficient knowledge about the modulating variables of the PBI and whether it can complement the assessment of the DLQI. In a longitudinal cohort study, 82 patients with PSO were assessed before and up to sixteen weeks after a new treatment episode. The PBI was compared with patients with atopic dermatitis (AD) (n = 61). The effects of gender, age, type of therapy, improvement in body surface area (BSA), anxiety/depression, DLQI and individual coping were assessed. “Getting better skin quickly” was most important in PSO. Improved BSA, anxiety/depression, DLQI, male gender and initiation of biological therapy had the most positive effects. Partial mediation was found for the reduction of anxiety/depression and improved coping. The PBI may be considered an appropriate outcome measure of treatment success in PSO, complementing the DLQI. Patients with clinically relevant anxiety/depression and inadequate coping should be offered adjuvant psychosomatic treatment.
Accessing ultrastable glass via a bulk transformation
AbstractAs a medium to understand the nature of glass transition, ultrastable glasses have garnered increasing attention for their significance in fundamental science and technological applications. Most studies have produced ultrastable glasses through a surface-controlled process using physical vapor deposition. Here, we demonstrate an approach to accessing ultrastable glasses via the glass-to-glass transition, a bulk transformation that is inherently free from size constraints and anisotropy. The resulting ultrastable glass exhibits a significantly enhanced density (improved by 2.3%), along with high thermodynamic, kinetic, and mechanical stability. Furthermore, we propose that this method of accessing ultrastable glasses is general for metallic glasses, based on the examination of the competitive relationship between the glass-to-glass transition and crystallization. This strategy is expected to facilitate the proliferation of the ultrastable glass family, helping to resolve the instability issues of glass materials and devices and deepen our understanding of glasses and the glass transition.
Laboratory validation of patient-specific templating for total knee arthroplasty
AbstractPatient-specific templating (PST), which is a sister procedure to patient-specific instrumentation (PSI) but hospital-based, is relatively less complex and less expensive than robotics and navigation. However, there are some concerns about the PST including the process of preoperative planning, 3D printing and material, positioning of PST intraoperatively, availability, and clinical value. The purpose of this study was to validate the technical accuracy and reliability of the PST technique in the lab and to report the outcomes of clinical application. To test the reliability of the PST technique, five observers positioned the PST templates five times over the distal femur and proximal tibial whilst a navigation system was used to measure the level of bone cutting, coronal and sagittal alignment, and rotation in both femur and tibia. The mean alignment error in all planes was 0.67° (maximum 2.5°). Concerning the bone (femoral and tibial) cutting, the mean error was 0.32 mm (maximum 1 mm). The qualitative and quantitative analysis showed an overall agreement between observers (p < 0.05). The laboratory part of this study showed that the positioning of the PST over the proximal tibia and distal femur during TKA is reliable. There were statistically insignificant intraobserver and interobserver variations.
Heterochromatic gene silencing controls CD4+ T cell susceptibility to regulatory T cell-mediated suppression in a murine allograft model
AbstractProtective immune responses require close interactions between conventional (Tconv) and regulatory T cells (Treg). The extracellular mediators and signaling events that regulate the crosstalk between these CD4+ T cell subsets have been extensively characterized. However, how Tconv translate Treg-dependent suppressive signals at the chromatin level remains largely unknown. Here we show, using a murine bone marrow allograft model in which graft rejection is coordinated by CD4+ T cells and can be inhibited by Treg, that Treg-mediated T cell suppression involves Heterochromatin Protein 1 α (HP1α)-dependent gene silencing. Unexpectedly, our screen also reveals that T cells deficient for HP1γ or the methyltransferase SUV39H1 are better repressed by Treg than their wild-type counterparts. Mechanistically, our transcriptional and epigenetic profiling identifies HP1γ as a negative regulator of a gene network functionally associated with T-cell exhaustion, including those encoding the inhibitory receptors PD-1 and LAG-3. In conclusion, we identify HP1 variants as rheostats that finely tune the balance between tolerance and immunity. While HP1α converts immunosuppressive signals into heterochromatin-dependent gene silencing mechanisms, HP1γ adjusts Tconv sensitivity to inhibitory environmental signals.
Exploring the spatial patterns and influencing factors of rural tourism development in Hainan Province of China
Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients
Abstract Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels. In addition, transplant recipients exhibit decreased plasmablasts and transitional B cells, and increased senescent T cells. Blood and nasal transcriptional profiling demonstrate unexpected upregulation of innate immune signaling pathways and increased levels of several proinflammatory serum chemokines. Severe disease in transplant recipients, however, is characterized by a less robust induction of pro-inflammatory genes and chemokines. Together, our study reveals distinct immune features and altered viral dynamics in solid organ transplant recipients.
Combination of gray level features with deep transfer learning for copra classification using machine learning and neural networks
A feedback loop between Paxillin and Yorkie sustains Drosophila intestinal homeostasis and regeneration
A double closed loop digital hydraulic cylinder position system based on switching active disturbance rejection control
Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats
Abstract The COVID-19 pandemic exposed a global deficiency of systematic, data-driven guidance to identify high-risk individuals. Here, we illustrate the utility of routinely recorded medical history to predict the risk for 1741 diseases across clinical specialties and support the rapid response to emerging health threats such as COVID-19. We developed a neural network to learn from health records of 502,489 UK Biobank participants. Importantly, we observed discriminative improvements over basic demographic predictors for 1546 (88.8%) endpoints. After transferring the unmodified risk models to the All of US cohort, we replicated these improvements for 1115 (78.9%) of 1414 investigated endpoints, demonstrating generalizability across healthcare systems and historically underrepresented groups. Ultimately, we showed how this approach could have been used to identify individuals vulnerable to severe COVID-19. Our study demonstrates the potential of medical history to support guidance for emerging pandemics by systematically estimating risk for thousands of diseases at once at minimal cost.
Combining machine learning and single-cell sequencing to identify key immune genes in sepsis
Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia
AbstractTracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels. Taste signaling through the Trpm5 channel is essential for bacterial tuft cell activation and ATP release. We demonstrate that activated tuft cells recruit dendritic cells to the trachea and lung. ATP released by tuft cells initiates dendritic cell activation, phagocytosis and migration. Tuft cell stimulation also involves an adaptive immune response through recruitment of IL-17A secreting T helper cells. Collectively, the results provide a molecular framework defining tuft cell dependent regulation of both innate and adaptive immune responses in the airways to combat bacterial infection.
Designing cellulose based biochars for CO2 separation using molecular simulations
Deep mantle earthquakes linked to CO2 degassing at the Mid-Atlantic Ridge
Predictive value of an unsupervised web-based assessment of the neuropsychological function
AbstractNeuropsychological assessment has to consider the subjective and objective functional deficits of help-seeking individuals in several cognitive domains. Due to time constraints in clinical practice, several web-based approaches have been developed. The current study examined whether functional deficits in the mnestic and attentive domain can be predicted based on an unsupervised self-administered online assessment neuropsychological online screening (NOS): This screening includes self-reports and psychometric memory tests (face-name association, visual short-term memory). Data of help-seeking individuals (n = 213, mean age: 48.2 years) running an extensive in-person assessment were analyzed. A functional deficit in at least one cognitive domain was detected in 48 individuals. This classification was supported by the preceding online screening (sensitivity = 0.75, specificity = 0.80), and a linear regression model identified two significant predictors (free recall performance, form discrimination in visual short-term memory). The predictive quality was enhanced for individuals with selective deficits in the mnestic domain (n = 23: sensitivity = 0.78 and specificity = 0.78) as compared to the attentive domain (n = 25: sensitivity = 0.68 and specificity = 0.75). Our results show that a neuropsychological in-person assessment cannot be replaced by an unsupervised self-administered online test. However, a specific pattern of results in the online test might indicate the necessity of an extensive assessment in help-seeking individuals.
Seasonal changes of mélange thickness coincide with Greenland calving dynamics
Abstract Iceberg calving is a major contributor to Greenland’s ice mass loss. Ice mélange, tightly packed sea ice and icebergs, has been hypothesized to buttress the calving fronts. However, quantifying the mélange buttressing force from field observations remains a challenge. Here we show that such quantification can be achieved with a single field measurement: thickness of mélange at the glacier terminus. We develop a three-dimensional discrete element model of mélange along with a simple analytical model to quantify the mélange buttressing using mélange thickness data from ArcticDEM over 32 Greenland glacier termini. We observed a strong seasonality in mélange thickness: thin mélange (averaged thickness $$3{4}_{-15}^{+17}$$ 3 4 − 15 + 17 m) in summertime when terminus retreats, and thick mélange (averaged thickness $$11{9}_{-37}^{+31}$$ 11 9 − 37 + 31 m) in wintertime when terminus advances. The observed seasonal changes of mélange thickness strongly coincide with observed Greenland calving dynamics and the modeled buttressing effects.