A spatial expression atlas of the adult human proximal small intestine.

The mouse small intestine shows profound variability in gene expression along the crypt-villus axis1,2. Whether similar spatial heterogeneity exists in the adult human gut remains unclear. Here we use spatial transcriptomics, spatial proteomics and single-molecule fluorescence in situ hybridization to reconstruct a comprehensive spatial expression atlas of the adult human proximal small intestine. We describe zonated expression and cell type representation for epithelial, mesenchymal and immune cell types. We find that migrating enterocytes switch from lipid droplet assembly and iron uptake at the villus bottom to chylomicron biosynthesis and iron release at the tip. Villus tip cells are pro-immunogenic, recruiting γδ T cells and macrophages to the tip, in contrast to their immunosuppressive roles in mouse. We also show that the human small intestine contains abundant serrated and branched villi that are enriched at the tops of circular folds. Our study presents a detailed resource for understanding the biology of the adult human small intestine.

From genes to modules, from cells to ecosystems.

Twenty years ago, molecular biology transitioned from predominantly studying genes as isolated elements to viewing them as part of complex modules, giving rise to the field of systems biology. This transition was made possible by technological advances that allowed to simultaneously measure the expression levels of thousands of genes in a single experiment and drove a shift toward analyses identifying gene sets, modules, and pathways involved in a biological process of interest. Today we are excitingly facing a similar turning point in cell biology, where single-cell technologies have enabled us to approach cells as cellular modules.

"The correlation between histopathological pattern and surgical treatment for palatal pleomorphic adenoma. Can we choose a more conservative approach?"

Pleomorphic adenoma (PA) is the most prevalent benign salivary gland tumor. Although rare, among the minor salivary glands, palatal PA exhibits the highest incidence. Unlike other benign tumors, PA infiltrates the surrounding tissues, posing challenges for complete removal through conservative measures. Surgeons often resort to aggressive surgical procedures involving resection of adjacent tissue to ensure clear margins and prevent recurrence. This study aims to analyze diverse histological characteristics of palatal PA, seeking statistical correlations for early prediction of tumor aggressiveness. The goal is to facilitate the preservation of the periosteum during surgical resection and attain conservative surgical margins. A retrospective histopathological investigation encompassed 18 patients diagnosed with palatal PA who underwent surgical treatment at Hadassah Medical Centre, Jerusalem, Israel. Evaluated parameters included tumor size, pseudocapsule thickness, tumor-periosteum distance, and the presence of pseudopodia and satellite nodules indicating tumor penetration. Statistical significance was set at P < 0.05. Tumors of varying sizes, whether large or small, lack consistent features. Neither tumor size, pseudocapsule thickness, nor tumor-periosteum distance displayed correlations with tumor penetration features. Palatal PA exhibits varied histological attributes impacting surgical technique. The absence of correlations among these attributes impedes early prediction of tumor aggressiveness, casting doubt on periosteum preservation. The periosteum is sufficiently robust to contain the tumor and should be excised. There is no data to support either ostectomy or a through-and-through surgical resection as part of the treatment.

Virtual histological staining of unlabeled autopsy tissue.

Traditional histochemical staining of post-mortem samples often confronts inferior staining quality due to autolysis caused by delayed fixation of cadaver tissue, and such chemical staining procedures covering large tissue areas demand substantial labor, cost and time. Here, we demonstrate virtual staining of autopsy tissue using a trained neural network to rapidly transform autofluorescence images of label-free autopsy tissue sections into brightfield equivalent images, matching hematoxylin and eosin (H&E) stained versions of the same samples. The trained model can effectively accentuate nuclear, cytoplasmic and extracellular features in new autopsy tissue samples that experienced severe autolysis, such as COVID-19 samples never seen before, where the traditional histochemical staining fails to provide consistent staining quality. This virtual autopsy staining technique provides a rapid and resource-efficient solution to generate artifact-free H&E stains despite severe autolysis and cell death, also reducing labor, cost and infrastructure requirements associated with the standard histochemical staining.

Low-Dose Colchicine Attenuates Sepsis-Induced Liver Injury: A Novel Method for Alleviating Systemic Inflammation.

Sepsis is a significant public health challenge. The immune system underlies the pathogenesis of the disease. The liver is both an active player and a target organ in sepsis. Targeting the gut immune system using low-dose colchicine is an attractive method for alleviating systemic inflammation in sepsis without inducing immunosuppression. The present study aimed to determine the use of low-dose colchicine in LPS-induced sepsis in mice. C67B mice were injected intraperitoneal with LPS to induce sepsis. The treatment group received 0.02 mg/kg colchicine daily by gavage. Short and extended models were performed, lasting 3 and 5 days, respectively. We followed the mice for biochemical markers of end-organ injury, blood counts, cytokine levels, and liver pathology and conducted proteomic studies on liver samples. Targeting the gut immune system using low-dose colchicine improved mice's well-being measured by the murine sepsis score. Treatment alleviated the liver injury in septic mice, manifested by a significant decrease in their liver enzyme levels, including ALT, AST, and LDH. Treatment exerted a trend to reduce creatinine levels. Low-dose colchicine improved liver pathology, reduced inflammation, and reduced the pro-inflammatory cytokine TNFα and IL1-ß levels. A liver proteomic analysis revealed low-dose colchicine down-regulated sepsis-related proteins, alpha-1 antitrypsin, and serine dehydratase. Targeting the gut immune system using low-dose colchicine attenuated liver injury in LPS-induced sepsis, reducing the pro-inflammatory cytokine levels. Low-dose colchicine provides a safe method for immunomodulation for multiple inflammatory disorders.

Two pandemics intertwined around one patient: Interstitial pneumonia as the first presentation of HIV/AIDS, be it Pneumocystis jirovecii, cytomegalovirus, SARS-CoV2 or all?-A case report.

Concerns have been mounting regarding the underdiagnosis of HIV among respiratory co-infections associated with the COVID-19 pandemic. The delay in recognizing HIV/AIDS may be attributed to the similarities in clinical, laboratory (lymphopenia) and imaging presentations, which are typical for advanced AIDS but could also be indicative of a COVID-19 infection. Herein, we present a case of a 38-year-old ultraorthodox Jew with a late diagnosis of AIDS in the context of COVID-19 infection. This occurred after several months of recurrent respiratory infections compounded by SARS-COV 2 infection, during which no HIV testing was conducted. As a result, a cascade of various opportunistic infections ensued, leading to an extended hospitalization period, ultimately culminating in the patient's demise despite receiving optimal treatment.

Giant Intracardiac Lipoma: A Case Report and the Role of Multimodality Cardiac Imaging.

Cardiac lipomas, especially ones originating from the left ventricle, are extremely rare. They may be asymptomatic or may present with various non-specific symptoms. Herein, we report a case of a giant lipoma of the left ventricle, with frequent ventricular premature beats on electrocardiogram. An echocardiogram demonstrated a large hyperechoic mass occupying a significant portion of the left ventricle. We further describe the diagnostic workup utilizing multimodality cardiac imaging and treatment options. Cardiac MRI demonstrated fat suppression, and cardiac CT showed a homogenous low-attenuation mass suggesting lipomatous matter. The mass was subsequently surgically removed for pathology examination in order to rule out liposarcoma. Histopathology demonstrated mature adipocytes, entrapped myocytes with hypertrophy, and interstitial fibrosis foci confirming the diagnosis of lipoma.

A Curious Case of Crystal Deposit Disease in the Petrous Bone.

Crystal deposit disease is a rare disorder with benign dense soft tissue calcium containing accumulations presenting as pseudogout or tumoral calcinosis. It rarely affects the head and neck region and even less to the petrous bone. We describe a case of para-articular tumoral calcinosis involving the external auditory canal wall in close proximity to the temporomandibular joint with extension towards the middle cranial fossa floor in a 73-year-old man presenting with otalgia and progressing mixed hearing loss. Subtotal petrosectomy with obliteration of the middle ear and mastoid was done with complete removal of the lesion. We discuss the course, treatment and final pathology with possible explanations for the pathophysiology in this particular case. Although tumoral calcinosis is uncommon, this entity should be considered in the differential diagnosis when an osteogenic temporal lesion is seen on computed tomography or magnetic resonance imaging. The treatment for this benign tumor includes complete excision of the lesion in symptomatic cases. Proper evaluation including anamnesis of the family history and previous trauma as well as serology should be done. The exact etiology and classification of crystal deposit diseases require further study.