Egebergmattingly1046

Histopathology is the gold standard method for staging and grading human tumors and provides critical information for the oncoteam's decision making. Highly-trained pathologists are needed for careful microscopic analysis of the slides produced from tissue taken from biopsy. This is a time-consuming process. A reliable decision support system would assist healthcare systems that often suffer from a shortage of pathologists. Recent advances in digital pathology allow for high-resolution digitalization of pathological slides. Digital slide scanners combined with modern computer vision models, such as convolutional neural networks, can help pathologists in their everyday work, resulting in shortened diagnosis times. In this study, 200 digital whole-slide images are published which were collected via hematoxylin-eosin stained colorectal biopsy. Alongside the whole-slide images, detailed region level annotations are also provided for ten relevant pathological classes. The 200 digital slides, after pre-processing, resulted in 101,389 patches. A single patch is a 512 × 512 pixel image, covering 248 × 248 μm2 tissue area. Versions at higher resolution are available as well. Hopefully, HunCRC, this widely accessible dataset will aid future colorectal cancer computer-aided diagnosis and research.Current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are administered parenterally and appear to be more protective in the lower versus the upper respiratory tract. Vaccines are needed that directly stimulate immunity in the respiratory tract, as well as systemic immunity. We used avian paramyxovirus type 3 (APMV3) as an intranasal vaccine vector to express the SARS-CoV-2 spike (S) protein. A lack of pre-existing immunity in humans and attenuation by host-range restriction make APMV3 a vector of interest. The SARS-CoV-2 S protein was stabilized in its prefusion conformation by six proline substitutions (S-6P) rather than the two that are used in most vaccine candidates, providing increased stability. APMV3 expressing S-6P (APMV3/S-6P) replicated to high titers in embryonated chicken eggs and was genetically stable, whereas APMV3 expressing non-stabilized S or S-2P were unstable. In hamsters, a single intranasal dose of APMV3/S-6P induced strong serum IgG and IgA responses to the S protein and its receptor-binding domain, and strong serum neutralizing antibody responses to SARS-CoV-2 isolate WA1/2020 (lineage A). Sera from APMV3/S-6P-immunized hamsters also efficiently neutralized Alpha and Beta variants of concern. Immunized hamsters challenged with WA1/2020 did not exhibit the weight loss and lung inflammation observed in empty-vector-immunized controls; SARS-CoV-2 replication in the upper and lower respiratory tract of immunized animals was low or undetectable compared to the substantial replication in controls. Thus, a single intranasal dose of APMV3/S-6P was highly immunogenic and protective against SARS-CoV-2 challenge, suggesting that APMV3/S-6P is suitable for clinical development.Due to the rise in bacterial resistance, the antibacterial extractions from Chinese herbs have been used more frequently for wound care. In this work, baicalin, an extraction from the Chinese herb Scutellaria baicalensis, was utilized as the antibacterial component in the poly(ε-caprolactone)/MXene (PCL/Ti3C2TX) hybrid nanofibrous membranes for wound dressing. The results revealed that the presence of Ti3C2TX aided in the diameter reduction of the electrospun nanofibers. The PCL hybrid membrane containing 3 wt% Ti3C2TX nanoflakes and 5 wt% baicalin exhibited the smallest mean diameter of 210 nm. Meanwhile, the antibacterial tests demonstrated that the PCL ternary hybrid nanofibers containing Ti3C2TX and baicalin exhibited adequate antibacterial activity against the Gram-positive bacterial S. aureus due to the good synergistic effects of Ti3C2TX naoflakes and baicalin. The addition of Ti3C2TX nanoflakes and baicalin could significantly improve the hydrophilicity of the membranes, resulting in the release of baicalin from the nanofibers. In addition, the cytotoxicity of the nanofibers on rat skeletal myoblast L6 cells confirmed their good compatibility with these PCL-based nanofibrous membrances. This work offers a feasible way to prepare antibacterial nanofibrous membranes using Chinese herb extraction for wound dressing applications.Considering brain structural alterations as neurodegenerative consequences of Parkinson's disease (PD), we sought to infer the progression of PD via the ordering of brain structural alterations from cross-sectional MRI observations. Having measured cortical thinning in gray matter (GM) regions and disintegrity in white matter (WM) regions as MRI markers of structural alterations for 130 patients with PD (69 ± 10 years, 72 men), stochastic simulation based on the probabilistic relationship between the brain regions was conducted to infer the ordering of structural alterations across all brain regions and the staging of structural alterations according to changes in clinical status. The ordering of structural alterations represented WM disintegrity tending to occur earlier than cortical thinning. The staging of structural alterations indicated structural alterations happening mostly before major disease complications such as postural instability and dementia. Later disease states predicted by the sequence of structural alterations were significantly related to more severe clinical symptoms. The relevance of the ordering of brain structural alterations to the severity of clinical symptoms suggests the clinical feasibility of predicting PD progression states.Somatic mutations are an inevitable component of ageing and the most important cause of cancer. The rates and types of somatic mutation vary across individuals, but relatively few inherited influences on mutation processes are known. selleckchem We perform a gene-based rare variant association study with diverse mutational processes, using human cancer genomes from over 11,000 individuals of European ancestry. By combining burden and variance tests, we identify 207 associations involving 15 somatic mutational phenotypes and 42 genes that replicated in an independent data set at a false discovery rate of 1%. We associate rare inherited deleterious variants in genes such as MSH3, EXO1, SETD2, and MTOR with two phenotypically different forms of DNA mismatch repair deficiency, and variants in genes such as EXO1, PAXIP1, RIF1, and WRN with deficiency in homologous recombination repair. In addition, we identify associations with other mutational processes, such as APEX1 with APOBEC-signature mutagenesis. Many of the genes interact with each other and with known mutator genes within cellular sub-networks. Considered collectively, damaging variants in the identified genes are prevalent in the population. We suggest that rare germline variation in diverse genes commonly impacts mutational processes in somatic cells.The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic α and β cells play a crucial role in glucose homeostasis. However, how α and β cells coordinate to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice, we recorded Ca2+ signals from islet α and β cells, and observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a brief period of glucose stimulation, α and β cells' oscillations were globally phase-locked. While the activation of α cells displayed a fixed time delay of ~20 s to that of β cells, β cells activated with a tunable period. Moreover, islet α cell number correlated with oscillation frequency. We built a mathematical model of islet Ca2+ oscillation incorporating paracrine interactions, which quantitatively agreed with the experimental data. Our study highlights the importance of cell-cell interaction in generating stable but tunable islet oscillation patterns.Vaccination prevents and controls foot-and-mouth disease (FMD). However, the current FMD vaccine remains disadvantageous since it cannot overcome maternally-derived antibody (MDA) interference in weeks-old animals, which suppress active immunity via vaccination. To address this, we developed the immune-enhancing O PA2-C3d and A22-C3d FMD vaccine strains that can stimulate receptors on the surface of B cells by inserting C3d (a B cell epitope) into the VP1 region of O PA2 (FMDV type O) and A22 (FMDV type A). We purified inactivated viral antigens from these vaccine strains and evaluated their immunogenicity and host defense against FMDV infection in mice. We also verified its efficacy in inducing an adaptive immune response and overcome MDA interference in MDA-positive (MDA(+), FMD-seropositive) and -negative (MDA(-), FMD-seronegative) pigs. These results suggest a key strategy for establishing novel FMD vaccine platform to overcome MDA interference and induce a robust adaptive immune response.The Phanerozoic Eon has witnessed considerable changes in the climate system as well as abundant animals and plant life. Therefore, the evolution of the climate system in this Eon is worthy of extensive research. Only by studying climate changes in the past can we understand the driving mechanisms for climate changes in the future and make reliable climate projections. Apart from observational paleoclimate proxy datasets, climate simulations provide an alternative approach to investigate past climate conditions of the Earth, especially for long time span in the deep past. Here we perform 55 snapshot simulations for the past 540 million years, with a 10-million-year interval, using the Community Earth System Model version 1.2.2 (CESM1.2.2). The climate simulation dataset includes global distributions of monthly surface temperatures and precipitation, with a 1° horizontal resolution of 0.9° × 1.25° in latitude and longitude. This open access climate dataset is useful for multidisciplinary research, such as paleoclimate, geology, geochemistry, and paleontology.Polaritons in hyperbolic van der Waals materials-where principal axes have permittivities of opposite signs-are light-matter modes with unique properties and promising applications. Isofrequency contours of hyperbolic polaritons may undergo topological transitions from open hyperbolas to closed ellipse-like curves, prompting an abrupt change in physical properties. Electronically-tunable topological transitions are especially desirable for future integrated technologies but have yet to be demonstrated. In this work, we present a doping-induced topological transition effected by plasmon-phonon hybridization in graphene/α-MoO3 heterostructures. Scanning near-field optical microscopy was used to image hybrid polaritons in graphene/α-MoO3. We demonstrate the topological transition and characterize hybrid modes, which can be tuned from surface waves to bulk waveguide modes, traversing an exceptional point arising from the anisotropic plasmon-phonon coupling. Graphene/α-MoO3 heterostructures offer the possibility to explore dynamical topological transitions and directional coupling that could inspire new nanophotonic and quantum devices.Super-enhancers regulate genes with important functions in processes that are cell type-specific or define cell identity. Mouse embryonic fibroblasts establish 40 senescence-associated super-enhancers regardless of how they become senescent, with 50 activated genes located in the vicinity of these enhancers. Here we show, through gene knockdown and analysis of three core biological properties of senescent cells that a relatively large number of senescence-associated super-enhancer-regulated genes promote survival of senescent mouse embryonic fibroblasts. Of these, Mdm2, Rnase4, and Ang act by suppressing p53-mediated apoptosis through various mechanisms that are also engaged in response to DNA damage. MDM2 and RNASE4 transcription is also elevated in human senescent fibroblasts to restrain p53 and promote survival. These insights identify key survival mechanisms of senescent cells and provide molecular entry points for the development of targeted therapeutics that eliminate senescent cells at sites of pathology.