Extracorporeal Photochemotherapy: Mechanistic Insights Driving Recent Advances and Future Directions.

Dendritic cells (DCs) are professional antigen-presenting cells, necessary for the initiation and maintenance of antigen-specific immunity and tolerance. Decades of research have been driven by hopes to harness the immunological capabilities of DCs and achieve physiological partnership with the immune system for therapeutic ends. Potential applications for DC-based immunotherapy include treatments for cancer, autoimmune disorders, and infectious diseases. However, DCs have poor availability in peripheral and lymphoid tissues and have poor survivability in culture, leading to the development of multiple strategies to generate and manipulate large numbers of DCs ex vivo. Among these is Extracorporeal Photopheresis (ECP), a widely used cancer immunotherapy. Recent advancements have uncovered that stimulation of monocyte-to-DC maturation via physiologic inflammatory signaling lies at the mechanistic core of ECP. Here, we describe the landscape of DC-based immunotherapy, the historical context of ECP, the current mechanistic understanding of ex vivo monocyte-to-DC maturation in ECP, and the implications of this understanding on making scientifically driven improvements to modern ECP protocols and devices.

Recurrent Coxsackievirus Infection in a Patient with Lamellar Ichthyosis.

We describe a case of coxsackievirus (CV) A6 infection in a patient with lamellar ichthyosis followed by subsequent CV A8 infection within the same year. Atypical cutaneous features characterized the infection. This observation, combined with the rapidity with which reinfection occurred, suggests that the natural history of CV infection may be altered in patients with underlying ichthyoses.

Advances in PET/CT Imaging for Breast Cancer Patients and Beyond.

Breast cancer is the most common cancer in women around the world and the fifth leading cause of cancer-related death [...].

Recent Advances in the Field of Artificial Intelligence for Precision Medicine in Patients with a Diagnosis of Metastatic Cutaneous Melanoma.

Standard-of-care medical imaging techniques such as CT, MRI, and PET play a critical role in managing patients diagnosed with metastatic cutaneous melanoma. Advancements in artificial intelligence (AI) techniques, such as radiomics, machine learning, and deep learning, could revolutionize the use of medical imaging by enhancing individualized image-guided precision medicine approaches. In the present article, we will decipher how AI/radiomics could mine information from medical images, such as tumor volume, heterogeneity, and shape, to provide insights into cancer biology that can be leveraged by clinicians to improve patient care both in the clinic and in clinical trials. More specifically, we will detail the potential role of AI in enhancing detection/diagnosis, staging, treatment planning, treatment delivery, response assessment, treatment toxicity assessment, and monitoring of patients diagnosed with metastatic cutaneous melanoma. Finally, we will explore how these proof-of-concept results can be translated from bench to bedside by describing how the implementation of AI techniques can be standardized for routine adoption in clinical settings worldwide to predict outcomes with great accuracy, reproducibility, and generalizability in patients diagnosed with metastatic cutaneous melanoma.

PET/CT and SPECT/CT Imaging of HER2-Positive Breast Cancer.

HER2 (Human Epidermal Growth Factor Receptor 2)-positive breast cancer is characterized by amplification of the HER2 gene and is associated with more aggressive tumor growth, increased risk of metastasis, and poorer prognosis when compared to other subtypes of breast cancer. HER2 expression is therefore a critical tumor feature that can be used to diagnose and treat breast cancer. Moving forward, advances in HER2 in vivo imaging, involving the use of techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), may allow for a greater role for HER2 status in guiding the management of breast cancer patients. This will apply both to patients who are HER2-positive and those who have limited-to-minimal immunohistochemical HER2 expression (HER2-low), with imaging ultimately helping clinicians determine the size and location of tumors. Additionally, PET and SPECT could help evaluate effectiveness of HER2-targeted therapies, such as trastuzumab or pertuzumab for HER2-positive cancers, and specially modified antibody drug conjugates (ADC), such as trastuzumab-deruxtecan, for HER2-low variants. This review will explore the current and future role of HER2 imaging in personalizing the care of patients diagnosed with breast cancer.

Castleman Disease Mimicking Pancreatic Neuroendocrine Tumour: Interpretation of Positron Emission Tomography in Pancreatic Incidentaloma.

We report a rare case of an incidental pancreatic lesion that proved to be Castleman disease in a peripancreatic lymph node, which mimicked a high-grade pancreatic neuroendocrine tumour (PNET) based on findings on positron emission tomography (PET). The disease was discovered as an incidental finding on CT imaging of the abdomen and was investigated and managed as PNET. Surgical resection was performed with distal pancreatectomy and splenectomy, however, histology revealed the lesion was a lymph node affected by Castleman disease. Often termed the great mimic, Castleman disease is a rare lymphoproliferative disorder that is often mistaken for other primary lesions of the organ due to its location and should be considered a differential of fluorodeoxyglucose (FDG)-avid PET lesions on imaging.

Metastatic Breast Cancer Presenting as Acute Appendicitis.

Breast cancer is one of the most commonly diagnosed cancers in Australia. With the development in screening, diagnosis, and treatment, people are living longer with metastatic disease of the breast. This malignancy commonly metastasizes to the lung, brain, bone, and liver. However, due to the increased survival of patients living with breast cancer, metastases may present with complications that have not been seen before. We describe a case of a 55-year-old female with a background of metastatic breast cancer to the brain who presented to the emergency department with acute appendicitis. At surgery, a malignant mass was found in the cecum obstructing the appendix, and histopathology revealed metastatic breast cancer.

Social isolation delays the positive effects of running on adult neurogenesis.

Social isolation can exacerbate the negative consequences of stress and increase the risk of developing psychopathology. However, the influence of living alone on experiences generally considered to be beneficial to the brain, such as physical exercise, remains unknown. We report here that individual housing precludes the positive influence of short-term running on adult neurogenesis in the hippocampus of rats and, in the presence of additional stress, suppresses the generation of new neurons. Individual housing also influenced corticosterone levels--runners in both housing conditions had elevated corticosterone during the active phase, but individually housed runners had higher levels of this hormone in response to stress. Moreover, lowering corticosterone levels converted the influence of short-term running on neurogenesis in individually housed rats from negative to positive. These results suggest that, in the absence of social interaction, a normally beneficial experience can exert a potentially deleterious influence on the brain.

Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen.

Targeting antigen to dendritic cells (DCs) is a powerful and novel strategy for vaccination. Priming or loading DCs with antigen controls whether subsequent immunity will develop and hence whether effective vaccination can be achieved. The goal of our present work was to increase the potency of DC-based antitumor vaccines by overcoming inherent limitations associated with antigen stability and cross-presentation. Nanoparticles prepared from the biodegradable polymer poly(lactic-co-glycolic acid) have been extensively used in clinical settings for drug delivery and are currently the subject of intensive investigation as antigen delivery vehicles for vaccine applications. Here we describe a nanoparticulate delivery system with the ability to simultaneously carry a high density of protein-based antigen while displaying a DC targeting ligand on its surface. Utilizing a targeting motif specific for the DC-associated surface ligand DEC-205, we show that targeted nanoparticles encapsulating a MART-127-35 peptide are both internalized and cross-presented with significantly higher efficiency than isotype control-coated nanoparticles in human cells. In addition, the DEC-205-labeled nanoparticles rapidly escape from the DC endosomal compartment and do not colocalize with markers of early (EEA-1) or late endosome/lysosome (LAMP-1). This indicates that encapsulated antigens delivered by nanoparticles may have direct access to the class I cytoplasmic major histocompatibility complex loading machinery, overcoming the need for "classical" cross-presentation and facilitating heightened DC stimulation of anti-tumor CD8(+) T-cells. These results indicate that this delivery system provides a flexible and versatile methodology to deliver melanoma-associated antigen to DCs, with both high efficiency and heightened potency.

Dynamic coupling between the lateral occipital-cortex, default-mode, and frontoparietal networks during bistable perception.

The lateral occipital cortex (LOC), a visual area known to be involved in object recognition, was dynamically coupled with each of two distributed patterns of neural activity depending upon the percept (default or alternative) elicited by a bistable figure. The two distributed patterns included core nodes of the default-mode and frontoparietal networks (FPN), and they were most highly coupled to each other during the alternative percept, whereas they were less coupled during the default percept. Surprisingly, the regions associated with the nonengaged percept exhibited the highest connectivity to the LOC. Together, these findings reveal a dynamic organization between the default mode and the FPNs, and the incoming bottom-up visual stream during perceptual binding of visual images.

Verrucous carcinoma masquerading as a giant fibroepithelial polyp.

The authors report a case of a verrucous carcinoma (VC) of the buttocks clinically simulating a giant (6.5 cm in length and 5.4 cm in greatest diameter) fibroepithelial polyp (FEP) capped by a large cutaneous horn. The growth had been present for 15 years and had never been biopsied despite numerous physical exams. VC typically presents distinctly as a large cauliflower-like growth with histological features of acanthosis, parakeratosis, minimal cytological atypia, and deep pushing epithelial borders. It is considered a low-grade, well-differentiated variant of squamous cell cancer and is commonly associated with human papillomavirus (HPV). Anogenital VC has been associated more with "low-risk" (type 6 and 11) than "high-risk" (16 and 18) HPV types. Presentation of VC as a FEP is unusual and demonstrates the necessity of maintaining a high level of clinical suspicion of anogenital growths, particularly those involving atypical features such as ulceration or the presence of a cutaneous horn.

Running induces widespread structural alterations in the hippocampus and entorhinal cortex.

Physical activity enhances hippocampal function but its effects on neuronal structure remain relatively unexplored outside of the dentate gyrus. Using Golgi impregnation and the lipophilic tracer DiI, we show that long-term voluntary running increases the density of dendritic spines in the entorhinal cortex and hippocampus of adult rats. Exercise was associated with increased dendritic spine density not only in granule neurons of the dentate gyrus, but also in CA1 pyramidal neurons, and in layer III pyramidal neurons of the entorhinal cortex. In the CA1 region, changes in dendritic spine density are accompanied by changes in dendritic arborization and alterations in the morphology of individual spines. These findings suggest that physical activity exerts pervasive effects on neuronal morphology in the hippocampus and one of its afferent populations. These structural changes may contribute to running-induced changes in cognitive function.