breast conservation and sentinel lymph node biopsy after neoadjuvant systemic therapy

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Transformer-based Atmospheric Density Forecasting

As the peak of the solar cycle approaches in 2025 and the ability of a single geomagnetic storm to significantly alter the orbit of Resident Space Objects (RSOs), techniques for atmospheric density forecasting are vital for space situational awareness. While linear data-driven methods, such as dynamic mode decomposition with control (DMDc), have been used previously for forecasting atmospheric density, deep learning-based forecasting has the ability to capture nonlinearities in data. By learning multiple layer weights from historical atmospheric density data, long-term dependencies in the dataset are captured in the mapping between the current atmospheric density state and control input to the atmospheric density state at the next timestep. This work improves upon previous linear propagation methods for atmospheric density forecasting, by developing a nonlinear transformer-based architecture for atmospheric density forecasting. Empirical NRLMSISE-00 and JB2008, as well as physics-based TIEGCM atmospheric density models are compared for forecasting with DMDc and with the transformer-based propagator.Comment: Conference: 24th Advanced Maui Optical and Space Surveillance Technologies At: Maui, Hawaii, United State

Successful optimization of reconstruction parameters in structured illumination microscopy

The impact of the different reconstruction parameters in super-resolution structured illumination microscopy (SIM) on image artifacts is carefully analyzed. These parameters comprise the Wiener filter parameter, an apodization function, zero-frequency suppression and modifications of the optical transfer function. A detailed investigation of the reconstructed image spectrum is concluded to be suitable for identifying artifacts. For this purpose, two samples, an artificial test slide and a more realistic biological system, were used to characterize the artifact classes and their correlation with the image spectra as well as the reconstruction parameters. In addition, a guideline for efficient parameter optimization is suggested and the implementation of the parameters in selected up-to-date processing packages (proprietary and open-source) is depicted. © 2018 The Author

Spatio-temporal dynamics and aetiology of proliferative leg skin lesions in wild British finches

Proliferative leg skin lesions have been described in wild finches in Europe although there have been no large-scale studies of their aetiology or epizootiology to date. Firstly, disease surveillance, utilising public reporting of observations of live wild finches was conducted in Great Britain (GB) and showed proliferative leg skin lesions in chaffinches (Fringilla coelebs) to be widespread. Seasonal variation was observed, with a peak during the winter months. Secondly, pathological investigations were performed on a sample of 39 chaffinches, four bullfinches (Pyrrhula pyrrhula), one greenfinch (Chloris chloris) and one goldfinch (Carduelis carduelis) with proliferative leg skin lesions and detected Cnemidocoptes sp. mites in 91% (41/45) of affected finches and from all species examined. Fringilla coelebs papillomavirus (FcPV1) PCR was positive in 74% (23/31) of birds tested: a 394 base pair sequence was derived from 20 of these birds, from all examined species, with 100% identity to reference genomes. Both mites and FcPV1 DNA were detected in 71% (20/28) of birds tested for both pathogens. Histopathological examination of lesions did not discriminate the relative importance of mite or FcPV1 infection as their cause. Development of techniques to localise FcPV1 within lesions is required to elucidate the pathological significance of FcPV1 DNA detection.We thank the members of the public and BTO Garden BirdWatch participants who reported garden bird morbidity and mortality incidents and our colleagues, Katie Beckmann, Shaheed Macgregor, Ricardo Castro Cesar de Sa, Lydia Franklinos and Tim Hopkins from the Zoological Society of London; Kirsi Peck from the Royal Society for the Protection of Birds; BTO staff members in the Garden BirdWatch team; the staff at Abbey Veterinary Services and the Animal & Plant Health Agency (Daniel Hicks, Richard Irvine, Alejandro Núñez and Scott Reid) for their assistance with this investigation. This work was financially supported by the following organisations; Birdcare Standards Association, British Trust for Ornithology, British Veterinary Association Animal Welfare Foundation, CJ Wildbird Foods, Cranswick Pet Products, UK Department for the Environment Food & Rural Affairs and Welsh Government through the Animal & Plant Health Agency’s Diseases of Wildlife Scheme Scanning Surveillance Programme (Project ED1600), Esmée Fairbairn Foundation, Gardman Ltd, Institute of Zoology, Royal Society for the Protection of Birds and the Universities Federation for Animal Welfare. RAJW was supported by the Moncloa of Excellence PICATA programme and Crafoord Foundation Sweden (grant number 20160971). Molecular and sequencing costs were funded by the Spanish Ministry of Science and Innovation, (Ref: CGL2013-41642-P/BOS)

Surgical closure of chest wall in noninflammatory locally advanced breast carcinoma with ulceration of the skin.

Abstract:  Patients with noninflammatory locally advanced breast cancer with ulceration of skin or muscle or parietal wall infiltration, better named "extended locally advanced breast cancer," may require cancer surgery and plastic reconstruction of the chest wall after multidisciplinary evaluation. The decision is made to improve quality of life, independently of prognosis, and severity of the disease. The aim of this study is to evaluate the best method for surgical closure of the chest wall and to check whether ablative surgery is an appropriate procedure in regards to the treatment of cancer. From October 1997 to June 2006, 27 patients with noninflammatory extended locally advanced breast cancer with ulceration of the skin, who were not candidate or did not respond to a neo-adjuvant treatment, underwent radical mastectomy and reconstructive surgery. Sixteen patients (59%) were affected by primary tumors of the breast, and eleven patients (41%) had local recurrence after mastectomy or conservative breast surgery. Two main techniques were used for breast reconstruction: transverse rectus-abdominis musculo cutaneous flap in 19 patients (70%), and a fasciocutaneous flap in eight patients (30%). The best procedure in each patient was chosen according to the extent of skin loss or previous radiotherapy to the chest wall. Fourteen patients (52%) died during the follow-up and the median length of survival was 16 months (range 3–79) in transverse rectus-abdominis musculo cutaneous group and 4 months (range 2–23) in fasciocutaneous flap group. The median length of follow-up after treatment for patients still alive was 32.5 months (range 0–96) in transverse rectus-abdominis musculo cutaneous flap group, and 18 months (range 8–41) in fasciocutaneous flap group. At the end of the follow-up, 10 patients were alive without evidence of disease and three patients developed metastatic lesion or local recurrence. The longest recorded disease free interval for a patient still alive and tumor free was 96 months. Only three patients (11%) had local complications: two wound infections and one partial necrosis of the transverse rectus-abdominis musculo cutaneous flap. Median hospital stay was 7 days (range 3–13) for transverse rectus-abdominis musculo cutaneous and 6 days (range 3–13) for fasciocutaneous flap. Our results confirmed that transverse rectus-abdominis musculo cutaneous group and fasciocutaneous flap flaps are good reconstructive options in patients with extended locally advanced breast cancer. Quality of life has improved in this group of patients, with acceptable survival periods and in some cases very important survival rates

Essential Genetic Interactors of SIR2 Required for Spatial Sequestration and Asymmetrical Inheritance of Protein Aggregates

Sir2 is a central regulator of yeast aging and its deficiency increases daughter cell inheritance of stress-and aging-induced misfolded proteins deposited in aggregates and inclusion bodies. Here, by quantifying traits predicted to affect aggregate inheritance in a passive manner, we found that a passive diffusion model cannot explain Sir2-dependent failures in mother-biased segregation of either the small aggregates formed by the misfolded Huntingtin, Htt103Q, disease protein or heat-induced Hsp104-associated aggregates. Instead, we found that the genetic interaction network of SIR2 comprises specific essential genes required for mother-biased segregation including those encoding components of the actin cytoskeleton, the actin-associated myosin V motor protein Myo2, and the actin organization protein calmodulin, Cmd1. Co-staining with Hsp104-GFP demonstrated that misfolded Htt103Q is sequestered into small aggregates, akin to stress foci formed upon heat stress, that fail to coalesce into inclusion bodies. Importantly, these Htt103Q foci, as well as the ATPase-defective Hsp104(Y662A)-associated structures previously shown to be stable stress foci, co-localized with Cmd1 and Myo2-enriched structures and super-resolution 3-D microscopy demonstrated that they are associated with actin cables. Moreover, we found that Hsp42 is required for formation of heat-induced Hsp104(Y662A) foci but not Htt103Q foci suggesting that the routes employed for foci formation are not identical. In addition to genes involved in actin-dependent processes, SIR2-interactors required for asymmetrical inheritance of Htt103Q and heat-induced aggregates encode essential sec genes involved in ER-to-Golgi trafficking/ER homeostasis

Chemical traits of cerebral amyloid angiopathy in familial British-, Danish-, and non-Alzheimerʼs dementias

Familial British dementia (FBD) and familial Danish dementia (FDD) are autosomal dominant forms of dementia caused by mutations in the integral membrane protein 2B (ITM2B, also known as BRI2) gene. Secretase processing of mutant BRI2 leads to secretion and deposition of BRI2-derived amyloidogenic peptides, ABri and ADan that resemble APP/β-amyloid (Aβ) pathology, which is characteristic of Alzheimer's disease (AD). Amyloid pathology in FBD/FDD manifests itself predominantly in the microvasculature by ABri/ADan containing cerebral amyloid angiopathy (CAA). While ABri and ADan peptide sequences differ only in a few C-terminal amino acids, CAA in FDD is characterized by co-aggregation of ADan with Aβ, while in contrast no Aβ deposition is observed in FBD. The fact that FDD patients display an earlier and more severe disease onset than FBD suggests a potential role of ADan and Aβ co-aggregation that promotes a more rapid disease progression in FDD compared to FBD. It is therefore critical to delineate the chemical signatures of amyloid aggregation in these two vascular dementias. This in turn will increase the knowledge on the pathophysiology of these diseases and the pathogenic role of heterogenous amyloid peptide interactions and deposition, respectively. Herein, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in combination with hyperspectral, confocal microscopy based on luminescent conjugated oligothiophene probes (LCO) to delineate the structural traits and associated amyloid peptide patterns of single CAA in postmortem brain tissue of patients with FBD, FDD as well as sporadic CAA without AD (CAA+) that show pronounced CAA without parenchymal plaques. The results show that CAA in both FBD and FDD consist of N-terminally truncated- and pyroglutamate-modified amyloid peptide species (ADan and ABri), but that ADan peptides in FDD are also extensively C-terminally truncated as compared to ABri in FBD, which contributes to hydrophobicity of ADan species. Further, CAA in FDD showed co-deposition with Aβ x-42 and Aβ x-40 species. CAA+ vessels were structurally more mature than FDD/FBD CAA and contained significant amounts of pyroglutamated Aβ. When compared with FDD, Aβ in CAA+ showed more C-terminal and less N-terminally truncations. In FDD, ADan showed spatial co-localization with Aβ3pE-40 and Aβ3-40 but not with Aβx-42 species. This suggests an increased aggregation propensity of Aβ in FDD that promotes co-aggregation of both Aβ and ADan. Further, CAA maturity appears to be mainly governed by Aβ content based on the significantly higher 500/580 patterns observed in CAA+ than in FDD and FBD, respectively. Together this is the first study of its kind on comprehensive delineation of Bri2 and APP-derived amyloid peptides in single vascular plaques in both FDD/FBD and sporadic CAA that provides new insight in non-AD-related vascular amyloid pathology. (Figure presented.

West Nile Virus in Golden Eagles, Spain, 2007

lthough West Nile virus (WNV) has not been isolated in Spain, several recent studies provide evidence for its circulation in this country (1–5). We report isolation of WNV in Spain from 2 golden eagles (Aquila chrysaetos).A captive-bred 2-year-old male golden eagle (GE-1) was released into the wild in central Spain. The bird’s location was monitored daily by telemetry, and it remained within a radius of 100 km from its original release point. On September 15, 2007 (1 month after release), it was found moribund and was moved to a rehabilitation and captive breeding center for endangered raptors. Upon admission, the bird was in fair condition but debilitated and aggressive. It then became increasingly disorientated, showed a head tilt, and died 5 days after admission, despite intensive supportive care and treatment for secondary infections.This study was supported in part by the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (OT01-002).Peer Reviewe

The impact of CD160 deficiency on alloreactive CD8 T cell responses and allograft rejection

.CD160 is a member of the immunoglobulin superfamily with a pattern of expression mainly restricted to cytotoxic cells. To assess the functional relevance of the HVEM/CD160 signaling pathway in allogeneic cytotoxic responses, exon 2 of the CD160 gene was targeted by CRISPR/Cas9 to generate CD160 deficient mice. Next, we evaluated the impact of CD160 deficiency in the course of an alloreactive response. To that aim, parental donor WT (wild-type) or CD160 KO (knock-out) T cells were adoptively transferred into non-irradiated semiallogeneic F1 recipients, in which donor alloreactive CD160 KO CD4 T cells and CD8 T cells clonally expanded less vigorously than in WT T cell counterparts. This differential proliferative response rate at the early phase of T cell expansion influenced the course of CD8 T cell differentiation and the composition of the effector T cell pool that led to a significant decreased of the memory precursor effector cells (MPECs) / short-lived effector cells (SLECs) ratio in CD160 KO CD8 T cells compared to WT CD8 T cells. Despite these differences in T cell proliferation and differentiation, allogeneic MHC class I mismatched (bm1) skin allograft survival in CD160 KO recipients was comparable to that of WT recipients. However, the administration of CTLA-4.Ig showed an enhanced survival trend of bm1 skin allografts in CD160 KO with respect to WT recipients. Finally, CD160 deficient NK cells were as proficient as CD160 WT NK cells in rejecting allogeneic cellular allografts or MHC class I deficient tumor cells. CD160 may represent a CD28 alternative costimulatory molecule for the modulation of allogeneic CD8 T cell responses either in combination with costimulation blockade or by direct targeting of alloreactive CD8 T cells that upregulate CD160 expression in response to alloantigen stimulation.S

Characterisation, prevalence and severity of skin lesions caused by ophidiomycosis in a population of wild snakes

Ophidiomycosis is an emerging infectious disease affecting wild snakes in the Northern Hemisphere. Recently confirmed in Great Britain, the prevalence, severity and significance of ophidiomycosis has yet to be characterised in free-living snakes at a population level in Europe. Therefore, a population of barred grass snakes (Natrix helvetica) in eastern England was monitored for three seasons (May 2019 to October 2021), to investigate the prevalence (25.5%; 191/750 snakes) and severity of skin lesions and their aetiology. The most frequently observed skin lesion characteristics were changes in scale colour, crusting, and scale margin erosion. The majority of such lesions (96.9%; 185/191 snakes) was observed on the ventral surface along the length of the body. The severity of skin lesions was considered mild in more than half of the cases (53.1%; 98/191 snakes). Predominantly, skin lesions were observed in adult snakes (72.8%; 139/191 snakes). Combined histological examinations and qPCR tests of skin lesions from N. helvetica sloughs and/or carcasses confirmed a diagnosis of ophidiomycosis. Further targeted surveillance, supported by molecular and histological examinations to confirm skin lesion aetiology, is required to determine the extent to which our findings reflect the occurrence of ophidiomycosis in populations within wider landscapes