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Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19–89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases.

Basal cell carcinoma is the most common malignancy in Caucasian individuals. Metastatic basal cell carcinoma is extremely rare (with a rate estimated as 0.03%). Actin has been detected in aggressive forms of basal cell carcinoma, but their expression in metastatic lesions is not known. We compared the expression of actin and actin-related cytoskeletal proteins in relatively less aggressive basal cell carcinoma (nodular), aggressive basal cell carcinoma (infiltrative/morpheaform), and metastatic basal cell carcinoma. We studied 12 cases of nodular basal cell carcinoma, 10 cases of infiltrative basal cell carcinoma, and 10 cases of metastatic basal cell carcinoma with immunohistochemistry for alpha-smooth muscle actin, calponin, myosin, and E-cadherin. Expression was interpreted as positive when at least 5% of the tumor exhibited at least weak expression. Five of the ten patients with metastatic basal cell carcinoma had an antecedent history of radiotherapy. Actin was present in 3 of 12 (25%) of the nodular, all 10 of the infiltrative, and 3 of 10 of the metastatic basal cell carcinomas (P<0.05 for metastatic vs infiltrative and nodular vs infiltrative). Calponin was present in 50% of the nodular, 60% of the infiltrative, and 30% of the metastatic basal cell carcinomas (not statistically significant). Myosin expression was not detected in any of the cases. E-cadherin was present in 75% of the nodular, 70% of the infiltrative, and all of the metastatic basal cell carcinomas (P<0.05 for metastatic vs nodular). Our results suggest that increased actin may contribute to local invasiveness, but it is lost in the metastatic phenotype. History of previous radiotherapy may contribute to development of the metastatic phenotype.

Increased global production of sorghum has the potential to meet many of the demands of a growing human population. Developing automation technologies for field scouting is crucial for long-term and low-cost production. Since 2013, sugarcane aphid (SCA) Melanaphis sacchari (Zehntner) has become an important economic pest causing significant yield loss across the sorghum production region in the United States. Adequate management of SCA depends on costly field scouting to determine pest presence and economic threshold levels to spray insecticides. However, with the impact of insecticides on natural enemies, there is an urgent need to develop automated-detection technologies for their conservation. Natural enemies play a crucial role in the management of SCA populations. These insects, primary coccinellids, prey on SCA and help to reduce unnecessary insecticide applications. Although these insects help regulate SCA populations, the detection and classification of these insects is time-consuming and inefficient in lower value crops like sorghum during field scouting. Advanced deep learning software provides a means to perform laborious automatic agricultural tasks, including detection and classification of insects. However, deep learning models for coccinellids in sorghum have not been developed. Therefore, our objective was to develop and train machine learning models to detect coccinellids commonly found in sorghum and classify them according to their genera, species, and subfamily level. We trained a two-stage object detection model, specifically, Faster Region-based Convolutional Neural Network (Faster R-CNN) with the Feature Pyramid Network (FPN) and also one-stage detection models in the YOLO (You Only Look Once) family (YOLOv5 and YOLOv7) to detect and classify seven coccinellids commonly found in sorghum (i.e., Coccinella septempunctata , Coleomegilla maculata , Cycloneda sanguinea , Harmonia axyridis , Hippodamia convergens , Olla v-nigrum , Scymninae). We used images extracted from the iNaturalist project to perform training and evaluation of the Faster R-CNN-FPN and YOLOv5 and YOLOv7 models. iNaturalist is an imagery web server used to publish citizen’s observations of images pertaining to living organisms. Experimental evaluation using standard object detection metrics, such as average precision ( AP ), AP @0.50, etc., has shown that the YOLOv7 model performs the best on the coccinellid images with an AP @0.50 as high as 97.3, and AP as high as 74.6. Our research contributes automated deep learning software to the area of integrated pest management, making it easier to detect natural enemies in sorghum.

CD137 (4-1BB; TNFSR9) is an activation-induced surface receptor that through costimulation effects provide antigen-primed T cells with augmented survival, proliferation and effector functions as well as metabolic advantages. These immunobiological mechanisms are being utilised for cancer immunotherapy with agonist CD137-binding and crosslinking-inducing agents that elicit CD137 intracellular signaling. In this study, side-by-side comparisons show that provision of CD137 costimulation in-cis with regard to the TCR-CD3-ligating cell is superior to that provided in-trans in terms of T cell activation, proliferation, survival, cytokine secretion and mitochondrial fitness in mouse and human. Cis ligation of CD137 relative to the TCR-CD3 complex results in more intense canonical and non-canonical NF-κB signaling and provides a more robust induction of cell cycle and DNA damage repair gene expression programs. Here we report that the superiority of cis versus trans CD137-costimulation is readily observed in vivo and is relevant for understanding the immunotherapeutic effects of CAR T cells and CD137 agonistic therapies currently undergoing clinical trials, which may provide costimulation either in cis or in trans. Costimulation has been shown to be required for optimal activation of T cells and it could be delivered either in trans with respect to the source of CD3-TCR ligation or in cis on the same cell. Here the authors show that CD137 costimulation is more effective when delivered in cis to enhance T cell proliferation and activation.

Cutaneous angiosarcoma (cAS) is a rare malignant neoplasm with variable clinical presentation. Although a distinct vascular tumour, cAS shares many overlapping histopathological features with other vasoformative and epithelioid tumours or ‘mimickers’. cAS shows aggressive behaviour and carries a grave prognosis, thus early diagnosis is of paramount importance to achieve the best possible outcomes. Recently, several genetic studies were conducted leading to the identification of novel molecular targets in the treatment of cAS. Herein, we present a comprehensive review of cAS with discussion of its clinical, histopathological and molecular aspects, the differential diagnosis, as well as current therapies including ongoing clinical trials.

Exosomes are small extracellular vesicles with a variable protein cargo in consonance with cell origin and pathophysiological conditions. Gestational diabetes mellitus (GDM) is characterized by different levels of chronic low-grade inflammation and vascular dysfunction; however, there are few data characterizing the serum exosomal protein cargo of GDM patients and associated signaling pathways. Eighteen pregnant women were enrolled in the study: 8 controls (CG) and 10 patients with GDM. Blood samples were collected from patients, for exosomes’ concentration. Protein abundance alterations were demonstrated by relative mass spectrometric analysis and their association with clinical parameters in GDM patients was performed using Pearson’s correlation analysis. The proteomics analysis revealed 78 significantly altered proteins when comparing GDM to CG, related to complement and coagulation cascades, platelet activation, prothrombotic factors and cholesterol metabolism. Down-regulation of Complement C3 (C3), Complement C5 (C5), C4-B (C4B), C4b-binding protein beta chain (C4BPB) and C4b-binding protein alpha chain (C4BPA), and up-regulation of C7, C9 and F12 were found in GDM. Our data indicated significant correlations between factors involved in the pathogenesis of GDM and clinical parameters that may improve the understanding of GDM pathophysiology. Data are available via ProteomeXchange with identifier PXD035673.

Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients.

Among patients who had had an acute coronary syndrome, the risk of death from coronary heart disease, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization at 2.8 years was lower among those randomly assigned to alirocumab than among those assigned to placebo.

The microstructural characteristic evolution was investigated during thermomechanical processing of Ti-29Nb-9Ta-10Zr (wt %) alloy, which consisted of, in a first stage, in a Multi-Pass Rolling with increasing thickness reduction of 20%, 40%, 60%, 80%, and 90%; in step two, the multi-pass rolled sample with the highest thickness reduction (90%) was subjected to a series of three variants of static short recrystallization and then to a final similar aging. The objective was to evaluate the microstructural features evolution during thermomechanical processing (phase’s nature, morphology, dimensions, and crystallographic characteristics) and to find the optimal heat treatment variant for refinement of the alloy granulation until ultrafine/nanometric level for a promising combination of mechanical properties. The microstructural features were investigated by X-ray diffraction and SEM techniques through which the presence of two phases was recorded: the β-Ti phase and the α″-Ti martensitic phase. The corresponding cell parameters, dimensions of the coherent crystallite and the micro-deformations at the crystalline network level for both recorded phases were determined. The majority β-Ti phase underwent a strong refinement during the Multi-Pass Rolling process until ultrafine/nano grain dimension (about 9.8 nm), with subsequent slow growing during recrystallization and aging treatments, hindered by the presence of sub-micron α″-Ti phase dispersed inside β-Ti grains. An analysis concerning the possible deformation mechanisms was performed.