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The abscopal effect describes the ability of locally administered radiotherapy to induce systemic antitumor effects. Although mentioned for the first time in the 1950s, records of abscopal effects, considered to be immune-mediated, are scarce with radiotherapy alone. However, with the continued development and use of immunotherapy, reports on the abscopal effect have become increasingly frequent during the last decade. Here, we report a patient with advanced malignant pleural mesothelioma who had progressive disease while on the anti-PDL1 inhibitor pembrolizumab and showed an abscopal response after palliative radiotherapy.

Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) is important for invasion of reticulocytes and PvRBP2b antibodies correlate with protection. Here, Chan et al. isolate and characterize anti-PvRBP2b human monoclonal antibodies and describe mechanisms by which these antibodies inhibit invasion.

Engineered human tissues created by three-dimensional cell culture of human cells in a hydrogel are becoming emerging model systems for cancer drug discovery and regenerative medicine. Complex functional engineered tissues can also assist in the regeneration, repair, or replacement of human tissues. However, one of the main hurdles for tissue engineering, three-dimensional cell culture, and regenerative medicine is the capability of delivering nutrients and oxygen to cells through the vasculatures. Several studies have investigated different strategies to create a functional vascular system in engineered tissues and organ-on-a-chips. Engineered vasculatures have been used for the studies of angiogenesis, vasculogenesis, as well as drug and cell transports across the endothelium. Moreover, vascular engineering allows the creation of large functional vascular conduits for regenerative medicine purposes. However, there are still many challenges in the creation of vascularized tissue constructs and their biological applications. This review will summarize the latest efforts to create vasculatures and vascularized tissues for cancer research and regenerative medicine.

Hawkweeds (Pilosella spp.) have become a severe and rapidly invading weed in pasture lands and forest meadows of New Zealand. Detection of hawkweed infestations is essential for eradication and resource management at private and government levels. This study explores the potential of machine learning (ML) algorithms for detecting mouse-ear hawkweed (Pilosella officinarum) foliage and flowers from Unmanned Aerial Vehicle (UAV)-acquired multispectral (MS) images at various spatial resolutions. The performances of different ML algorithms, namely eXtreme Gradient Boosting (XGB), Support Vector Machine (SVM), Random Forest (RF), and K-nearest neighbours (KNN), were analysed in their capacity to detect hawkweed foliage and flowers using MS imagery. The imagery was obtained at numerous spatial resolutions from a highly infested study site located in the McKenzie Region of the South Island of New Zealand in January 2021. The spatial resolution of 0.65 cm/pixel (acquired at a flying height of 15 m above ground level) produced the highest overall testing and validation accuracy of 100% using the RF, KNN, and XGB models for detecting hawkweed flowers. In hawkweed foliage detection at the same resolution, the RF and XGB models achieved highest testing accuracy of 97%, while other models (KNN and SVM) achieved an overall model testing accuracy of 96% and 72%, respectively. The XGB model achieved the highest overall validation accuracy of 98%, while the other models (RF, KNN, and SVM) produced validation accuracies of 97%, 97%, and 80%, respectively. This proposed methodology may facilitate non-invasive detection efforts of mouse-ear hawkweed flowers and foliage in other naturalised areas, enabling land managers to optimise the use of UAV remote sensing technologies for better resource allocation.

Abstract Background Over the past decade Smartphone-based activation (SBA) of Community First Responders (CFR) to out-of-hospital cardiac arrests (OHCA) has gained much attention and popularity throughout Europe. Various programmes have been established, and interestingly there are considerable differences in technology, responder spectrum and the degree of integration into the prehospital emergency services. It is unclear whether these dissimilarities affect outcome. This paper reviews the current state in five European countries, reveals similarities and controversies, and presents consensus statements generated in an international conference with the intention to support public decision making on future strategies for SBA of CFR. Methods In a consensus conference a three-step approach was used: (i) presentation of current research from five European countries; (ii) workshops discussing evidence amongst the audience to generate consensus statements; (iii) anonymous real-time voting applying the modified RAND-UCLA Appropriateness method to adopt or reject the statements. The consensus panel aimed to represent all stakeholders involved in this topic. Results While 21 of 25 generated statements gained approval, consensus was only found for 5 of them. One statement was rejected but without consensus. Members of the consensus conference confirmed that CFR save lives. They further acknowledged the crucial role of emergency medical control centres and called for nationwide strategies. Conclusions Members of the consensus conference acknowledged that smartphone-based activation of CFR to OHCA saves lives. The statements generated by the consensus conference may assist the public, healthcare services and governments to utilise these systems to their full potential, and direct the research community towards fields that still need to be addressed.

Abstract Breast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences in mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab ancestry (ArA) compared to women of European ancestry (EA). In this study, we sought to identify molecular differences that could provide insight into the biology of ancestry-associated disparities in clinical outcomes. We applied a unique approach that combines the use of curated survival data from The Cancer Genome Atlas (TCGA) Pan-Cancer clinical data resource, improved single-nucleotide polymorphism-based inferred ancestry assignment, and a novel breast cancer subtype classification to interrogate the TCGA and a local Arab breast cancer dataset. We observed an enrichment of BasalMyo tumors in AA patients (38 vs 16.5% in EA, p = 1.30E − 10), associated with a significant worse overall (hazard ratio (HR) = 2.39, p = 0.02) and disease-specific survival (HR = 2.57, p = 0.03). Gene set enrichment analysis of BasalMyo AA and EA samples revealed differences in the abundance of T-regulatory and T-helper type 2 cells, and enrichment of cancer-related pathways with prognostic implications (AA: PI3K-Akt-mTOR and ErbB signaling; EA: EGF, estrogen-dependent and DNA repair signaling). Strikingly, AMPK signaling was associated with opposing prognostic connotation (AA: 10-year HR = 2.79, EA: 10-year HR = 0.34). Analysis of ArA patients suggests enrichment of BasalMyo tumors with a trend for differential enrichment of T-regulatory cells and AMPK signaling. Together, our findings suggest that the disparity in the clinical outcome of AA breast cancer patients is likely related to differences in cancer-related and microenvironmental features.

This paper focuses on the time-domain analysis of bandpass (BP) negative group delay (NGD) function. The innovative NGD investigation is based on the time-domain experimentation of an innovative topology of “lill”-shape passive microstrip circuit. The design principle of the proof of concept (POC) constituted by particular microstrip shapes is described. The NGD circuit is inspired from a recent fully distributed “li”-topology. Before the time-domain investigation, the BP NGD specifications of the circuit under study are academically defined. As practical application of the basic definition, a frequency domain validation of “lill”-circuit is presented in the first section of the paper. The POC circuit is specified by a -8 ns NGD value at 2.31 GHz NGD center frequency and a 27 MHz NGD bandwidth. The “lill”-circuit exhibits an attenuation loss of about -6.2 dB at the NGD center frequency. Then, the two-port black box model of “lill”-NGD-circuit represented by touchstone data of the measured S-parameters is exploited for the transient simulation. The measured group delay (GD) illustrates that the tested “lill”-circuit operates as a BP function regarding the NGD with NGD equal to -8.1 ns at the NGD center frequency. The time-domain demonstration of the BP NGD function was performed using a gaussian pulse modulating sine carrier. The innovative experimental setup with the possibility to plot simultaneously well synchronized input and output signals is explained. The BP NGD time-domain response is understood from commercial tool simulation using the touchstone S-parameters of the measured “lill”-circuit by using a Gaussian up-converted pulse having a 27 MHz frequency bandwidth. It was observed that the output signals are delayed when the sine carrier is out of NGD-band. However, the output signal envelope is in advanced of about -8 ns when the carrier is tuned to be approximately equal to the 2.31 GHz NGD center frequency. To confirm the time-domain typical behavior of BP NGD response, an input pulse signal having Gaussian waveform were considered during the test. However, the input signal spectrum must be determined in function of the NGD bandwidth. After tests, measured output signal envelopes presenting leading edge, trailing edge and peak in time-advance compared to the input ones are observed experimentally. The results of the present feasibility study open a potential microwave communication application of BP NGD function notably for systems operating with ISM and IEEE 802.11 standards.

A particularly original negative group delay (NGD) theory of $\Delta $ -topology is developed in the present paper. The NGD three-port topology is a passive circuit purely constituted by capacitors network. The model of the proposed $\Delta $ -topology impedance 3-D matrix is analytically established in function of the capacitor elements. Then, the S-matrix model is derived by using the Y-to-S transform. By considering the S-matrix frequency responses, a bandpass (BP) NGD analysis of the capacitive $\Delta $ -topology is originally elaborated. It is theoretically demonstrated that the passive $\Delta $ -topology is susceptible to behave as a BP NGD circuit under an analytical condition between the constituting capacitor values. The design feasibility of the BP NGD function is experimentally verified with lumped capacitor components-based $\Delta $ -circuit proof of concept. An electronic circuit board constituted by purely capacitive-network $\Delta $ -circuit is fabricated as an original $\Delta $ -circuit prototype. The tested board is constituted by arbitrary chosen capacitors, 100 nF, 10 nF and 0.1 nF. As expected, the calculation, simulation and measurement results, which are in very good agreement, confirm the BP NGD behavior. It is observed from measurement that it generates NGD of about −18.1 ns at a frequency of about 0.55 MHz and, lower and upper cut-off frequencies of about 0.33 MHz and 1.71 MHz. It is noteworthy that the transmission and reflection coefficients at very low frequency are independent of the capacitor values and analytically equal to 2/3 and 1/3, respectively.

This article aims to evaluate the potential of multitemporal and multiorbital remote sensing data acquired both in the microwave and optical domain to derive rapeseed biophysical parameters (crop height, dry mass, fresh mass, and plant water content). Dense temporal series of 98 Landsat-8 and Sentinel-2 images were used to derive normalized difference vegetation index (NDVI), green fraction cover (fCover), and green area index (GAI), while backscattering coefficients and radar vegetation index (RVI) were obtained from 231 mages acquired by synthetic aperture radar (SAR) onboard Sentinel-1 platform. Temporal signatures of these remote sensing indicators (RSI) were physically interpreted, compared with each other to ground measurements of biophysical parameters acquired over 14 winter rapeseed fields throughout the 2017–2018 crop season. We introduced new indicators based on the cumulative sum of each RSI that showed a significant improvement in their predictive power. Results particularly reveal the complementarity of SAR and optical data for rapeseed crop monitoring throughout its phenological cycle. They highlight the potential of the newly introduced indicator based on the VH polarized backscatter coefficient to estimate height (R2 = 0.87), plant water content (R2 = 0.77, from flowering to harvest), and fresh mass (R2 = 0.73) and RVI to estimate dry mass (R2 = 0.82). Results also demonstrate that multiorbital SAR data can be merged without significantly degrading the performance of SAR-based relationships while strongly increasing the temporal sampling of the monitoring. These results are promising in view of assimilating optical and SAR data into crop models for finer rapeseed monitoring.

A transient study of bandpass (BP) negative group delay (NGD) function is devoted in this paper. The transient analysis is applied to an original topology of NGD barcode-shape microstrip circuit. The performed investigation explains how to realize the transient analysis of tri-band NGD circuit. The time-domain (TD) parametrization of the test is established from the BP-NGD specifications of the circuit under test (CUT) based on the S-parameter model. The input signal is a Gaussian pulse characterized in function of the NGD bandwidth (BW) and center frequency. The feasibility of the BP-NGD transient study is illustrated with experimentation based on ultra-wide band (UWB) pulse generator. As proof-of-concept, barcode NGD circuit exhibiting tri-band NGD value-center frequency-bandwidth, (−5.9 ns, 2.128 GHz, 20 MHz), (−7.4 ns, 2.3 GHz, 14 MHz) and (−4.8 ns, 2.42 GHz, 14 MHz) has been fabricated and tested. The transient simulations and experiences confirm that the output signal envelopes of the barcode NGD prototype present leading and tailing edges in time-advance of input ones when the carrier frequency is set equal to the NGD center frequency.

This paper explores a new concept for the design of high scanning-range phased array antennas: the Interleaved Parasitic Arrays Antenna or IPAA. In this concept, we use periodic parasitic elements and the generator impedance to control the Active Voltage Standing Wave Ratio (AVSWR) over a wide scanning range. This new array architecture comes with a design methodology enabling a smooth step-by-step design process aiming at reducing the need for full-wave calculations. First, a numerical dual-polarization design is presented in detail to illustrate the methodology and to give the design keys to the reader. Then, a prototype working in the 5G C-band between 3.4 and 3.8 GHz (11% bandwidth) was designed using this methodology and measured for a 36-element array. It is meant to demonstrate and validate the mutual coupling management done by the interleaved parasitic arrays and the design process accuracy. Good correspondence between measurements and simulation was found and the proposed unit cell with its corresponding tile can be integrated in a larger phased array with active modules to perform beam steering over an important scanning range without deteriorating the AVSWR. The proposed unit cell is designed for a high-scanning range going from $\theta =0^{\circ }$ to $\theta = 70^{\circ }$ for every $\varphi $ -directions and shows an active reflection coefficient for an infinite array below −13.6dB.

The SARS-COV-2 pandemic has put pressure on intensive care units, so that predicting severe deterioration early is a priority. Here, the authors develop a multimodal severity score including clinical and imaging features that has significantly improved prognostic performance in two validation datasets compared to previous scores.

Roccella species constitute interesting models to address questions regarding lichen metabolite diversity across taxonomic, ecological and geographic gradients. Indeed, owing to their wide distribution, their taxonomic diversity and the narrow ecological niche they occupy, Roccella species are good candidates to study the drivers of lichen chemistry. This study focuses on the chemical profiling of five species: R. applanata , R. belangeriana , R. fuciformis , R. montagnei and R. phycopsis . These five species were sampled in a rather narrow longitudinal range (1°51′W to 47°17′E) covering the Eastern Atlantic and Western Indian Ocean areas along an extended latitudinal range (48°49′N to 22°23′S). High Pressure Liquid Chromatography (HPLC) analysis followed by mass spectrometry of 31 Roccella thalli revealed a number of interesting patterns through a multivariate (PCA) analysis, including the first detailed chemical profiles for two species from the Scattered Islands: R. applanata and R. belangeriana . Metabolite segregation amongst all studied Roccella species, including R. montagnei and R. belangeriana , gave some insight into the taxonomy of the latter two species, which we interpret as separate species. An additional analysis focusing on R. montagnei samples revealed chemical differences along both a latitudinal and ecological gradient (from Europa Island to São Tomé and Príncipe). Three mass spectra databases were built to dereplicate the ions, which gave an overview of the factors that could drive quantitative and qualitative metabolite composition in lichens. Additionally, several new Roccella species records are reported for the Scattered Islands, as well as São Tomé and Príncipe.

Reports of side effects of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasing worldwide. Capillary leak syndrome and vaccine-induced immune thrombotic thrombocytopenia are very rare but life-threatening adverse events that should be identified early and treated. However, isolated thrombocytopenia can indicate pseudothrombocytopenia. In certain people, ethylenediaminetetraacetic acid (EDTA) induces an in vitro platelet aggregation, resulting in misleading underestimation of platelet counts. It is essential to recognize pseudothrombocytopenia to prevent diagnostic errors, overtreatment, anxiety, and unnecessary invasive procedures. We present a case who developed generalized edema and persistent pseudothrombocytopenia after the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca).

RationaleTransition in psychiatry refers to the period where young people transit from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS). Discontinuity of care during this period is well-documented but little is known about provisions and transition characteristics and policies across Switzerland. The aim of this article is to describe the architecture of public mental health providers in Switzerland and compare it to EU countries.MethodTwo mapping surveys, developed previously for European countries, were adapted and sent to cantonal experts: the adapted European CAMHS Mapping Questionnaire (ECM-Q) assessing the architecture and functioning of CAMHS and the adapted Standardized Assessment Tool for Mental Health Transition (SATMeHT) to map CAMHS-AMHS interface.ResultsData were gathered from six cantons. Activity data and transition policies were comparable between Swiss regions and European countries. The percentage of young people below 19 years who were in care was above 2% in every responding canton with a higher proportion of boys than girls for patients

Hundreds of cytotoxic natural or synthetic lipidic compounds contain chiral alkynylcarbinol motifs, but the mechanism of action of those potential therapeutic agents remains unknown. Using a genetic screen in haploid human cells, we discovered that the enantiospecific cytotoxicity of numerous terminal alkynylcarbinols, including the highly cytotoxic dialkynylcarbinols, involves a bioactivation by HSD17B11, a short-chain dehydrogenase/reductase (SDR) known to oxidize the C-17 carbinol center of androstan-3-alpha,17-beta-diol to the corresponding ketone. A similar oxidation of dialkynylcarbinols generates dialkynylketones, that we characterize as highly protein-reactive electrophiles. We established that, once bioactivated in cells, the dialkynylcarbinols covalently modify several proteins involved in protein-quality control mechanisms, resulting in their lipoxidation on cysteines and lysines through Michael addition. For some proteins, this triggers their association to cellular membranes and results in endoplasmic reticulum stress, unfolded protein response activation, ubiquitin-proteasome system inhibition and cell death by apoptosis. Finally, as a proof-of-concept, we show that generic lipidic alkynylcarbinols can be devised to be bioactivated by other SDRs, including human RDH11 and HPGD/15-PGDH. Given that the SDR superfamily is one of the largest and most ubiquitous, this unique cytotoxic mechanism-of-action could be widely exploited to treat diseases, in particular cancer, through the design of tailored prodrugs.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has proven to be an efficient treatment option for patients with treatment-resistant depression (TRD). However, the success rate of this method is still low, and the treatment outcome is unpredictable. The objective of this study was to explore clinical and structural neuroimaging factors as potential biomarkers of the efficacy of high-frequency (HF) rTMS (20 Hz) over the left dorso-lateral pre-frontal cortex (DLPFC).MethodsWe analyzed the records of 131 patients with mood disorders who were treated with rTMS and were assessed at baseline at the end of the stimulation and at 1 month after the end of the treatment. The response is defined as a 50% decrease in the MADRS score between the first and the last assessment. Each of these patients underwent a T1 MRI scan of the brain, which was subsequently segmented with FreeSurfer. Whole-brain analyses [Query, Design, Estimate, Contrast (QDEC)] were conducted and corrected for multiple comparisons. Additionally, the responder status was also analyzed using binomial multivariate regression models. The explored variables were clinical and anatomical features of the rTMS target obtained from T1 MRI: target-scalp distance, DLPFC gray matter thickness, and various cortical measures of interest previously studied.ResultsThe results of a binomial multivariate regression model indicated that depression type (p = 0.025), gender (p = 0.010), and the severity of depression (p = 0.027) were found to be associated with response to rTMS. Additionally, the resistance stage showed a significant trend (p = 0.055). Whole-brain analyses on volume revealed that the average volume of the left part of the superior frontal and the caudal middle frontal regions is associated with the response status. Other MRI-based measures are not significantly associated with response to rTMS in our population.ConclusionIn this study, we investigated the clinical and neuroimaging biomarkers associated with responsiveness to high-frequency rTMS over the left DLPFC in a large sample of patients with TRD. Women, patients with bipolar depressive disorder (BDD), and patients who are less resistant to HF rTMS respond better. Responders present a lower volume of the left part of the superior frontal gyrus and the caudal middle frontal gyrus. These findings support further investigation into the use of clinical variables and structural MRI as possible biomarkers of rTMS treatment response.

Although Salmonella Typhimurium (STM) and Salmonella Paratyphi A (SPA) belong to the same phylogenetic species, share large portions of their genome and express many common virulence factors, they differ vastly in their host specificity, the immune response they elicit, and the clinical manifestations they cause. In this work, we compared their intracellular transcriptomic architecture and cellular phenotypes during human epithelial cell infection. While transcription induction of many metal transport systems, purines, biotin, PhoPQ and SPI-2 regulons was similar in both intracellular SPA and STM, we identified 234 differentially expressed genes that showed distinct expression patterns in intracellular SPA vs. STM. Surprisingly, clear expression differences were found in SPI-1, motility and chemotaxis, and carbon (mainly citrate, galactonate and ethanolamine) utilization pathways, indicating that these pathways are regulated differently during their intracellular phase. Concurring, on the cellular level, we show that while the majority of STM are non-motile and reside within Salmonella-Containing Vacuoles (SCV), a significant proportion of intracellular SPA cells are motile and compartmentalized in the cytosol. Moreover, we found that the elevated expression of SPI-1 and motility genes by intracellular SPA results in increased invasiveness of SPA, following exit from host cells. These findings demonstrate unexpected flagellum-dependent intracellular motility of a typhoidal Salmonella serovar and intriguing differences in intracellular localization between typhoidal and non-typhoidal salmonellae. We propose that these differences facilitate new cycles of host cell infection by SPA and may contribute to the ability of SPA to disseminate beyond the intestinal lamina propria of the human host during enteric fever.

This paper describes dynamical characterization of mechanical structures manufactured by Selective Laser Melting (SLM) process at various orientations. The samples are also compared to subtractive component. The additive metal samples were manufactured by a 3D printer (Renishaw AM 250, Renishaw) and were tested using vibration analysis of embedded-free beam installation. Experimental setup was replicated using the same geometry of samples printed at various orientations and submitted to low velocity impact. Accelerometers allowed recording mechanical responses of all the specimens, allowing characterizing the dynamic behavior of each component and the effect of the printing orientation and printing angles.

Understanding and characterising biochemical processes inside single cells requires experimental platforms that allow one to perturb and observe the dynamics of such processes as well as computational methods to build and parameterise models from the collected data. Recent progress with experimental platforms and optogenetics has made it possible to expose each cell in an experiment to an individualised input and automatically record cellular responses over days with fine time resolution. However, methods to infer parameters of stochastic kinetic models from single-cell longitudinal data have generally been developed under the assumption that experimental data is sparse and that responses of cells to at most a few different input perturbations can be observed. Here, we investigate and compare different approaches for calculating parameter likelihoods of single-cell longitudinal data based on approximations of the chemical master equation (CME) with a particular focus on coupling the linear noise approximation (LNA) or moment closure methods to a Kalman filter. We show that, as long as cells are measured sufficiently frequently, coupling the LNA to a Kalman filter allows one to accurately approximate likelihoods and to infer model parameters from data even in cases where the LNA provides poor approximations of the CME. Furthermore, the computational cost of filtering-based iterative likelihood evaluation scales advantageously in the number of measurement times and different input perturbations and is thus ideally suited for data obtained from modern experimental platforms. To demonstrate the practical usefulness of these results, we perform an experiment in which single cells, equipped with an optogenetic gene expression system, are exposed to various different light-input sequences and measured at several hundred time points and use parameter inference based on iterative likelihood evaluation to parameterise a stochastic model of the system.

Abstract Introduction Diabetes has long been implicated as a major risk factor for intervertebral disc (IVD) degeneration, interfering with molecular signaling and matrix biochemistry, which ultimately aggravates the progression of the disease. Glucose content has been previously shown to influence structural and compositional changes in engineered discs in vitro, impeding fiber formation and mechanical stability. Methods In this study, we investigated the impact of diabetic hyperglycemia on young IVDs by assessing biochemical composition, collagen fiber architecture, and mechanical behavior of discs harvested from 3‐ to 4‐month‐old db/db mouse caudal spines. Results We found that discs taken from diabetic mice with elevated blood glucose levels demonstrated an increase in total glycosaminoglycan and collagen content, but comparable advanced glycation end products (AGE) levels to wild‐type discs. Diabetic discs also contained ill‐defined boundaries between the nucleus pulposus and annulus fibrosus, with the latter showing a disorganized and unaligned collagen fiber network at this same boundary. Conclusions These compositional and structural changes had a detrimental effect on function, as the diabetic discs were twice as stiff as their wild‐type counterparts and demonstrated a significant resistance to deformation. These results indicate that diabetes may predispose the young disc to DDD later in life by altering patterns of extracellular matrix deposition, fiber formation, and motion segment mechanics independently of AGE accumulation.

BACKGROUND: The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program. METHODS: We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications. RESULTS: Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event (P

Abstract Differentiating pseudoprogression from true tumor progression has become a significant challenge in follow-up of diffuse infiltrating gliomas, particularly high grade, which leads to a potential treatment delay for patients with early glioma recurrence. In this study, we proposed to use a multiparametric MRI data as a sequence input for the convolutional neural network with the recurrent neural network based deep learning structure to discriminate between pseudoprogression and true tumor progression. In this study, 43 biopsy-proven patient data identified as diffuse infiltrating glioma patients whose disease progressed/recurred were used. The dataset consists of five original MRI sequences; pre-contrast T1-weighted, post-contrast T1-weighted, T2-weighted, FLAIR, and ADC images as well as two engineered sequences; T1post–T1pre and T2–FLAIR. Next, we used three CNN-LSTM models with a different set of sequences as input sequences to pass through CNN-LSTM layers. We performed threefold cross-validation in the training dataset and generated the boxplot, accuracy, and ROC curve, AUC from each trained model with the test dataset to evaluate models. The mean accuracy for VGG16 models ranged from 0.44 to 0.60 and the mean AUC ranged from 0.47 to 0.59. For CNN-LSTM model, the mean accuracy ranged from 0.62 to 0.75 and the mean AUC ranged from 0.64 to 0.81. The performance of the proposed CNN-LSTM with multiparametric sequence data was found to outperform the popular convolutional CNN with a single MRI sequence. In conclusion, incorporating all available MRI sequences into a sequence input for a CNN-LSTM model improved diagnostic performance for discriminating between pseudoprogression and true tumor progression.

Abstract Background Interest for the study of gut mycobiota in relation with human health and immune homeostasis has increased in the last years. From this perspective, new tools to study the immune/fungal interface are warranted. Systemic humoral immune responses could reflect the dynamic relationships between gut mycobiota and immunity. Using a novel flow cytometry technology (Fungi-Flow) to determine immunoglobulin (Ig) responses to fungi, we studied the relationships between gut mycobiota and systemic humoral anti-commensal immunity. Results The Fungi-Flow method allows a sensitive and specific measurement of systemic IgG responses against 17 commensal and environmental fungi from the two main divisions; Ascomycota and Basidiomycota. IgG responses exhibited a high inter-individual variability. Anti-commensal IgG responses were contrasted with the relative abundance, alpha-diversity, and intra-genus richness of fungal species in gut mycobiota of twenty healthy donors. Categorization of gut mycobiota composition revealed two differentiated fungal ecosystems. Significant difference of anti-Saccharomyces systemic IgG responses were observed in healthy donors stratified according to the fungal ecosystem colonizing their gut. A positive and significant correlation was observed between the variety of IgG responses against fungal commensals and intestinal alpha-diversity. At the level of intra-genus species richness, intense IgG responses were associated with a low intra-genus richness for known pathobionts, but not commensals. Conclusions Fungi-Flow allows an easy and reliable measure of personalized humoral responses against commensal fungi. Combining sequencing technology with our novel Fungi-Flow immunological method, we propose that there are at least two defined ecosystems in the human gut mycobiome associated with systemic humoral responses. Fungi-Flow opens new opportunities to improve our knowledge about the impact of mycobiota in humoral anti-commensal immunity and homeostasis. Video Abstract

Abstract Background Although exposure to cigarette smoking during pregnancy has been associated with alterations of DNA methylation in the cord blood or placental cells, whether such exposure before pregnancy could induce epigenetic alterations in the placenta of former smokers has never been investigated. Methods Our approach combined the analysis of placenta epigenomic (ENCODE) data with newly generated DNA methylation data obtained from 568 pregnant women, the largest cohort to date, either actively smoking during their pregnancy or formerly exposed to tobacco smoking. Results This strategy resulted in several major findings. First, among the 203 differentially methylated regions (DMRs) identified by the epigenome-wide association study, 152 showed “reversible” alterations of DNA methylation, only present in the placenta of current smokers, whereas 26 were also found altered in former smokers, whose placenta had not been exposed directly to cigarette smoking. Although the absolute methylation changes were smaller than those observed in other contexts, such as in some congenital diseases, the observed alterations were consistent within each DMR. This observation was further supported by a demethylation of LINE-1 sequences in the placentas of both current (beta-coefficient (β) (95% confidence interval (CI)), − 0.004 (− 0.008; 0.001)) and former smokers (β (95% CI), − 0.006 (− 0.011; − 0.001)) compared to nonsmokers. Second, the 203 DMRs were enriched in epigenetic marks corresponding to enhancer regions, including monomethylation of lysine 4 and acetylation of lysine 27 of histone H3 (respectively H3K4me1 and H3K27ac). Third, smoking-associated DMRs were also found near and/or overlapping 10 imprinted genes containing regions (corresponding to 16 genes), notably including the NNAT, SGCE/PEG10, and H19/MIR675 loci. Conclusions Our results pointing towards genomic regions containing the imprinted genes as well as enhancers as preferential targets suggest mechanisms by which tobacco could directly impact the fetus and future child. The persistence of significant DNA methylation changes in the placenta of former smokers supports the hypothesis of an “epigenetic memory” of exposure to cigarette smoking before pregnancy. This observation not only is conceptually revolutionary, but these results also bring crucial information in terms of public health concerning potential long-term detrimental effects of smoking in women.

Social distancing orders have been enacted worldwide to slow the coronavirus disease (COVID-19) pandemic, reduce strain on healthcare systems, and prevent deaths. To estimate the impact of the timing and intensity of such measures, we built a mathematical model of COVID-19 transmission that incorporates age-stratified risks and contact patterns and projects numbers of hospitalizations, patients in intensive care units, ventilator needs, and deaths within US cities. Focusing on the Austin metropolitan area of Texas, we found that immediate and extensive social distancing measures were required to ensure that COVID-19 cases did not exceed local hospital capacity by early May 2020. School closures alone hardly changed the epidemic curve. A 2-week delay in implementation was projected to accelerate the timing of peak healthcare needs by 4 weeks and cause a bed shortage in intensive care units. This analysis informed the Stay Home-Work Safe order enacted by Austin on March 24, 2020.

Cardiac diseases in the growing population of childhood cancer survivors are of major concern. Cardiotoxicity as a consequence of anthracyclines and chest radiotherapy continues to be relevant in the modern treatment era. Mitoxantrone has emerged as an important treatment-related risk factor and evidence on traditional cardiovascular risk factors in childhood cancer survivors is accumulating. International surveillance guidelines have been developed with the aim to detect and manage cardiac diseases early and prevent symptomatic disease. There is growing interest in risk prediction models to individualize prevention and surveillance. This State-of-the-Art Review summarizes literature from a systematic PubMed search focused on cardiac diseases after treatment for childhood cancer. Here, we discuss the prevalence, risk factors, prevention, risk prediction, and surveillance of cardiac diseases in survivors of childhood cancer.

Patient stratification based on biological variation in pancreatic ductal adenocarcinoma (PDAC) subtypes could help to improve clinical outcome. However, noninvasive assessment of the entire tumor microenvironment remains challenging. In this study, we investigate the biological basis of dynamic contrast‐enhanced (DCE), intravoxel incoherent motion (IVIM), and R2*‐derived magnetic resonance imaging (MRI) parameters for the noninvasive characterization of the PDAC tumor microenvironment and evaluate their prognostic potential in PDAC patients. Patients diagnosed with treatment‐naïve resectable PDAC underwent MRI. After resection, a whole‐mount tumor slice was analyzed for collagen fraction, vessel density, and hypoxia and matched to the MRI parameter maps. MRI parameters were correlated to immunohistochemistry‐derived tissue characteristics and evaluated for prognostic potential. Thirty patients were included of whom 21 underwent resection with whole‐mount histology available in 15 patients. DCE Ktrans and ve, ADC, and IVIM D correlated with collagen fraction. DCE kep and IVIM f correlated with vessel density and R2* with tissue hypoxia. Based on MRI, two main PDAC phenotypes could be distinguished; a stroma‐high phenotype demonstrating high vessel density and high collagen fraction and a stroma‐low phenotype demonstrating low vessel density and low collagen fraction. Patients with the stroma‐high phenotype (high kep and high IVIM D, n = 8) showed longer overall survival (not reached vs. 14 months, P = 0.001, HR = 9.1, P = 0.004) and disease‐free survival (not reached vs. 2 months, P

La problématique directrice de cette étude vise à dessiner l’ébauche d’une confrontation critique entre deux théories du sentir, celle de Hegel d’un côté, et celle de Straus de l’autre. Dans les deux cas, ces deux protagonistes décrivent le procès génético-sensitif d’émergence de la conscience. Tout d’abord, pour poser les jalons de cette comparaison, nous construirons une problématique historique qui s’ancrera dans un examen des principaux présupposés, essentiellement cartésiens, de la psychologie objective tels qu’ils sont présentés par Straus. D’emblée, il faut constater que, dans son histoire de la psychologie, Straus ne mentionne pas la théorie hégélienne du sentir, alors même que Straus connaît, pour le citer2, l’œuvre du philosophe de Stuttgart. Pourtant, dans son Anthropologie (premier moment de l’Esprit subjectif) Hegel dévoile des éléments dignes d’intérêt quant à un rapprochement avec la théorie straussienne du sentir. Cette problématique sera donc, dans un deuxième temps, suivie d’une problématique philosophique qui s’interrogera, à partir des théories straussienne et hégélienne, sur l’ontogenèse sensitive de la conscience. Nous chercherons à savoir dans quelle mesure Hegel, qui dans l’Anthropologie a l’idée d’une nouvelle science empirique, une physiologie psychique, anticipe la critique de Straus à l’égard de la psychologie contemporaine. Après quoi sera envisagée la théorie straussienne du sentir qui révèlera aussi l’extrême actualité de Hegelsur cette question. Enfin, nous conclurons en abordant les raisons d’après lesquelles tant l’anthropologie hégélienne que la phénoménologie de Straus se séparent foncièrement de tout type de phénoménologie fondée strictement sur le primat de l’intentionnalité et accablée à un je pense constituant, mais pas constitué.