Single-nucleus chromatin accessibility identifies a critical role for TWIST1 in idiopathic pulmonary fibrosis myofibroblast activity

In idiopathic pulmonary fibrosis (IPF) myofibroblasts are key effectors of fibrosis and architectural distortion by excessive deposition of extracellular matrix and their acquired contractile capacity. Single-cell RNA-sequencing has precisely defined the IPF myofibroblast transcriptome, but identifying critical transcription factor activity by this approach is imprecise. We performed and integrated snATAC-seq and scRNA-seq from human IPF and donor control explants to identify differentially accessible chromatin regions and enriched transcription factor motifs within lung cell populations. TWIST1 and other E-box transcription factor motifs were significantly enriched in IPF myofibroblasts compared to both IPF non-myogenic and control fibroblasts. TWIST1 expression was also selectively upregulated in IPF myofibroblasts. Overexpression of Twist1 in lung COL1A2-expressing fibroblasts in bleomycin-injured mice was associated with increased collagen synthesis. Our studies utilizing human multiomic single-cell analyses combined with in vivo murine disease models confirm a critical regulatory function for TWIST1 in IPF myofibroblast activity in the fibrotic lung. Understanding the global process of opening TWIST1 and other E-box TF motifs that govern myofibroblast differentiation may identify new therapeutic interventions for fibrotic pulmonary diseases.

Architectural Distortion-Based Digital Mammograms Classification Using Depth Wise Convolutional Neural Network

Architectural distortion is the third most suspicious appearance on a mammogram representing abnormal regions. Architectural distortion (AD) detection from mammograms is challenging due to its subtle and varying asymmetry on breast mass and small size. Automatic detection of abnormal ADs regions in mammograms using computer algorithms at initial stages could help radiologists and doctors. The architectural distortion star shapes ROIs detection, noise removal, and object location, affecting the classification performance, reducing accuracy. The computer vision-based technique automatically removes the noise and detects the location of objects from varying patterns. The current study investigated the gap to detect architectural distortion ROIs (region of interest) from mammograms using computer vision techniques. Proposed an automated computer-aided diagnostic system based on architectural distortion using computer vision and deep learning to predict breast cancer from digital mammograms. The proposed mammogram classification framework pertains to four steps such as image preprocessing, augmentation and image pixel-wise segmentation. Architectural distortion ROI`s detection, training deep learning, and machine learning networks to classify AD`s ROIs into malignant and benign classes. The proposed method has been evaluated on three databases, the PINUM, the CBIS-DDSM, and the DDSM mammogram images, using computer vision and depth-wise 2D V-net 64 convolutional neural networks and achieved 0.95, 0.97, and 0.98 accuracies, respectively. Experimental results reveal that our proposed method outperforms as compared with the ShuffelNet, MobileNet, SVM, K-NN, RF, and previous studies.

Imaging and pathologic features of non-calcified ductal carcinoma in situ: can sonography predict upgrade?

Objectives: The purpose of this study was to evaluate the imaging and pathologic features and upgrade rate of non-calcified ductal carcinoma in situ (NCDCIS). The study tested the hypothesis that lesions with sonographic findings have higher upgrade rate compared to lesions seen on mammography or MRI only. Methods: This retrospective study included patients with ductal carcinoma in situ diagnosed by image-guided core breast biopsy from December 2009 to April 2018. Patients with microcalcifications on mammography or concurrent ipsilateral cancer on core biopsy were excluded. An upgrade was defined as surgical pathology showing microinvasive or invasive cancer. Results: A total of 71 lesions constituted the study cohort. Sixty two percent of cases (44/71) had a mammographic finding, and 38% (27/71) of mammographically occult lesions had findings on either ultrasound, MRI, or both. Of the 67 cases that underwent sonography, a mass was noted in 56/67 (83.6%) cases and no sonographic correlate was identified in 11/67 (16.4%) cases. Twenty-one percent (15/71) of lesions were upgraded on final surgical pathology. The upgrade rate of patients with sonographic correlate was 27% (15/56) versus with mammographic findings only was 0% (0/11). Conclusion: Ductal carcinoma in situ (DCIS) should be considered in the differential diagnosis of architectural distortion, asymmetries, focal asymmetries, and masses, even in the absence of microcalcifications. NCDCIS diagnosed by ultrasound may be an independent risk factor for upgrade. Advances in knowledge: Radiologists must be aware of imaging features of DCIS and consider increased upgrade rate when NCDCIS is diagnosed by ultrasound.

Reversibility of clinical and computed tomographic lesions mimicking pulmonary fibrosis in a young cat

Background In humans with idiopathic pulmonary fibrosis (IPF), specific thoracic computed tomographic (CT) features in the correct clinical context may be used in lieu of histologic examination. Cats develop an IPF-like condition with similar features to humans. As few cats have invasive lung biopsies, CT has appeal as a surrogate diagnostic, showing features consistent with architectural remodeling supporting “end-stage lung”. Case presentation A 1-year-old female spayed Domestic Shorthair cat presenting with progressive respiratory clinical signs and thoracic CT changes (reticular pattern, parenchymal bands, subpleural interstitial thickening, pleural fissure thickening, subpleural lines and regions of increased attenuation with traction bronchiectasis and architectural distortion) consistent with reports of IPF was given a grave prognosis for long-term survival. The cat was treated with prednisolone, fenbendazole, pradofloxacin and clindamycin. Five months later, while still receiving an anti-inflammatory dose of prednisolone, the cat was re-evaluated with owner-reported absent respiratory clinical signs. Thoracic CT demonstrated resolution of lung patterns consistent with fibrosis. Conclusions Fibrotic lung disease is irreversible. Despite this cat having compatible progressive respiratory signs and associated lung patterns on thoracic CT scan, these abnormalities resolved with non-specific therapy and time, negating the possibility of IPF. While the cause of the distinct CT lesions that ultimately resolved was not determined, infection was suspected. Experimental Toxocara cati infection shows overlapping CT features as this cat and is considered a treatable disease. Improvement of CT lesions months after experimental heartworm-associated respiratory disease in cats has been documented. Reversibility of lesions suggests inflammation rather than fibrosis was the cause of the thoracic CT lesions. This cat serves as a lesson that although thoracic CT has been advocated as a surrogate for histopathology in people with IPF, additional studies in cats are needed to integrate CT findings with signalment, other clinicopathologic features and therapeutic response before providing a diagnosis or prognosis of fibrotic lung disease.

Erosive acute colitis associated with intestinal spirochetosis

Background Although usually believed to be harmless, intestinal spirochetosis may active erosive colitis associated with intestinal spirochetosis that may mimic idiopathic chronic inflammatory bowel disease. Case presentation. A 49-year-old homosexual male patient sought medical assistance due to asthenia, rectal bleeding, tenesmus, and diarrhea for one month. He had been using corticosteroids for nine months to treat sciatic nerve pain. Colonoscopy showed rectum and distal sigmoid with diffuse erythema with many surface erosions. Rectal biopsy showed inflammatory changes including chronic changes such as architectural distortion and basal plasmacytosis, and active inflammation including crypt microabscesses. In all large bowel sample, dense colonization of intestinal spirochetosis was observed. Patient also had a positive PCR testing for Chlamydia trachomatis. The patient was treated with metronidazole for 14 days, ciprofloxacin for 14 days and azithromycin (single dose). Symptoms improved and the patient is asymptomatic after two months of follow-up. Conclusion In some high-risk groups, intestinal spirochetosis may cause colonic manifestations with overlapping features with intestinal bowel diseases. Awareness of this association is importance since proper antibiotic therapy against Brachyspira (metronidazole) is highly effective. Coinfection with other sexually transmitted infections is common and proper treatment is required.

PD-L1 Expression in Patients with Idiopathic Pulmonary Fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is the most common and severe form within the group of idiopathic interstitial pneumonias. It is characterized by repetitive alveolar injury in genetically susceptible individuals and abnormal wound healing, leading to dysregulated bronchiolar proliferation and excessive deposition of extracellular matrix, causing complete architectural distortion and fibrosis. Epithelial-to-mesenchymal transition is considered an important pathogenic event, a phenomenon also observed in various malignant neoplasms, in which tumor cells express programmed death-ligand one (PD-L1). The aim of this study was to assess the presence of PD-L1 in patients with IPF and other interstitial lung diseases (ILDs). Method: Patients with a clinically and radiologically suspected idiopathic interstitial pneumonia or other ILDs undergoing transbronchial cryobiopsy to confirm the diagnosis at the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, were included in this prospective observational study. Cellular membrane PD-L1 expression in epithelial cells was determined using the DAKO PD-L1 IHC 22C3 PharmDx Kit. Results: Membrane-bound PD-L1 (mPD-L1) was found in twelve (28%) of the forty-three patients with IPF and in five (9%) of the fifty-five patients with other ILDs (p = 0.015). When adjusting for age, gender and smoking status, the odds ratio of having IPF when expressing mPD-L1 in alveolar and/or bronchiolar epithelial cells was 4.3 (CI: 1.3–14.3). Conclusion: Expression of mPD-L1 in epithelial cells in the lung parenchymal zones was detected in a consistent subgroup of patients with IPF compared to other interstitial pneumonias. Larger studies are needed to explore the role of mPD-L1 in patients with IPF.

Male Breast Cancer Review. A Rare Case of Pure DCIS: Imaging Protocol, Radiomics and Management

Ductal carcinoma in situ (DCIS) of male breast is a rare lesion, often associated with invasive carcinoma. When the in situ component is present in pure form, histological grade is usually low or intermediate. Imaging is difficult as gynaecomastia is often present and can mask underlying findings. We report a rare case of pure high-grade DCIS in a young male patient, with associated intraductal papilloma and atypical ductal hyperplasia. Digital breast tomosynthesis (DBT) showed an area of architectural distortion at the union of outer quadrants of the left breast without gynaecomastia. Triple assessment suggested performing a nipple-sparing mastectomy, which revealed the presence of a focal area of high-grade DCIS of 2 mm. DCIS, even of high grade, is difficult to detect with mammography and even more rare, especially when associated with other proliferative lesions. DBT with 2D synthetic reconstruction is useful as the imaging step of a triple assessment and it should be performed in both symptomatic and asymptomatic high-risk men to differentiate between malignant and benign lesions. We propose a diagnostic model to early detect breast cancer in men, optimizing resources according to efficiency, effectiveness and economy, and look forward to radiomics as a powerful tool to help radiologists.

Three-dimensional tomosynthesis versus two-dimensional mammography in detection and characterization of different breast lesions

Background Breast cancer is considered the most serious lesion among different breast lesions. Mammography is the corner stone for screening for detection of breast cancer. It has been modified to digital mammography (DM) and then to digital breast tomosynthesis (DBT). Tomosynthesis is an emerging technique for diagnosis and screening of breast lesions. The aim of this study is to interrogate whether the addition of DBT to DM helps in better detection and characterization of different breast lesions. Methods This is a prospective study carried on 38 female patients according to our inclusion criteria. All patients were evaluated by using DM alone and thereafter with the addition of DBT to DM. Recall rate was calculated, and the imaging findings of each case were correlated with the final diagnosis and follow-up. Results DM identified 32 lesions while DBT with DM identified 37 lesions. On DM alone, 17 lesions were characterized as masses, 5 as focal asymmetry, 2 as architectural distortion, 7 as microcalcification and 1 as macrocalcification. With the addition of DBT, 27 lesions were characterized as masses, 1 as focal asymmetry, 1 as architectural distortion, 7 as microcalcification and 1 as macrocalcification. So, there were better detection and characterization of lesions with the addition of DBT than DM alone. The sensitivity, specificity, AUC, positive and negative predictive values were significantly higher with the addition of DBT to DM (100%, 90.5%, 0.952, 90% and 100%, respectively) than with DM (77.8%, 80.9%, 0.794, 77.8% and 80.9%, respectively) for all breast lesions. Conclusions The addition of DBT to DM helps in better detection and characterization of different breast lesions. This leads to early detection of breast cancer, improvement of the performance of radiologists and saving time by reduction of recall rate.