Biological tissues are highly organized structures where spatial-temporal gradients (e.g., nutrients, hypoxia, cytokines) modulate multiple physiological and pathological processes including inflammation, tissue regeneration, embryogenesis, and cancer progression. Current in vitro technologies struggle to capture the complexity of these transient microenvironmental gradients, do not provide dynamic control over the gradient profile, are complex and poorly suited for high throughput applications. Therefore, we have designed Griddent, a user-friendly platform with the capability of generating controllable and reversible gradients in a 3D microenvironment. Our platform consists of an array of 32 microfluidic chambers connected to a 384 well-array through a diffusion port at the bottom of each reservoir well. The diffusion ports are optimized to ensure gradient stability and facilitate manual micropipette loading. This platform is compatible with molecular and functional spatial biology as well as optical and fluorescence microscopy. In this work, we have used this platform to study cancer progression.

PURPOSE: The role of circulating tumor DNA (ctDNA) monitoring in predicting treatment response and survival outcomes in early-stage and metastatic solid tumors has shown promising results. The value of early ctDNA dynamics in solid tumors treated with immune checkpoint inhibitors (ICIs) merits further investigation. Our study aims to assess the role of early ctDNA changes, measured 3-4 weeks after initiating ICI therapy, in predicting clinical outcomes in patients with advanced-stage melanoma. METHODS: We performed a multi-institutional analysis of real-world data from testing patients with unresectable stage III/IV melanoma using a personalized, tumor-informed ctDNA assay (Signatera) during the course of treatment with anti–PD-1-based therapy. ctDNA levels were assessed before the start of treatment and at 3-4 weeks before the second treatment dose. The change in ctDNA (decrease v increase) between the two points was assessed to evaluate the odds of objective response and disease control and to evaluate the risk of progression-free survival (PFS) and overall survival (OS). RESULTS: One hundred seventeen patients were evaluated. Regression analysis revealed that a decrease in ctDNA was associated with increased odds of disease control (odds ratio [OR], 30.56 [95% CI, 10.64 to 87.84], P < .001) and objective response (OR, 23.54 [95% CI, 8.58 to 64.57], P < .001). Patients with a decrease in ctDNA had an increased PFS (hazard ratio [HR], 0.18 [95% CI, 0.11 to 0.31], P < .001) and OS (HR, 0.28 [95% CI, 0.13 to 0.56], P < .001) probability. CONCLUSION: We found that early ctDNA dynamics after only 3-4 weeks of ICI initiation in patients with advanced-stage melanoma appears to be a candidate strategy to predict overall treatment response, risk of progression, and long-term survival. Larger prospective studies are warranted to validate the utility of early ctDNA changes in treatment monitoring.

During brain metastasis, tumor cells interact with the surrounding stroma, including neurons and astrocytes, to create a tumor-promoting microenvironment. However, the molecular and cellular factors driving tumor-neural stroma interactions remain unclear. Here, we developed a co-culture model of metastatic melanoma by combining metastatic melanoma cells with dissociated human iPSC-derived cerebral organoids, consisting of neurons and astrocytes, in a microfluidic device. We cultured these astrocytes and neurons in a 3D hydrogel that contained a domain with metastatic melanoma cells. This approach generated a spatially organized co-culture system with no physical boundary between the tumor and stromal compartments. Then, we leveraged several imaging modalities to study tumor-stroma interactions and changes in the microenvironment. Using non-destructive, luminescence-based methods, we spatially resolved changes in cell viability, metabolite concentration, and other biochemical parameters. We also used luminescence to analyze the effect of radionuclides on tumor cell viability and used PET imaging to monitor their diffusion across the system.

Malaria and babesiosis are significant parasitic infections, requiring timely diagnosis to avoid severe complications. This study retrospectively compared hematology thin smears (HS) with parasitology thick and thin blood smears (PS), the gold standard for diagnosis, to evaluate HS’s performance in detecting Plasmodium and Babesia infections. Of 529 cases with paired HS and PS testing, HS demonstrated 93.3% sensitivity and 99.8% specificity, with 97.7% positive and 99.4% negative predictive values. When only considering new diagnoses, HS and PS were 100% concordant. No significant difference was found in percent parasitemia between HS and PS, highlighting HS as a reliable diagnostic tool in settings where PS or other diagnostic modalities may not be readily available. IMPORTANCE: This study demonstrates that hematology thin smears—often available in laboratories that may not have other means of diagnosing blood parasite infections such as parasitology thick and thin smears, rapid diagnostics tests, or polymerase chain reaction—are an accurate and reliable way to diagnose Plasmodium and Babesia infections in a low prevalence setting.

Immune checkpoint inhibitors (ICI) have quickly emerged as standard therapy in multiple cancers, yet their application in organ transplant recipients (OTRs) remains challenging due to risk of graft rejection. In this case, report, we highlight the successful use of a lymphocyte activation gene 3 (LAG-3) inhibitor, relatlimab, in combination with nivolumab (a programmed cell death protein 1 [PD-1] inhibitor) for the treatment of metastatic melanoma in a kidney transplant recipient. The patient developed a complete metabolic response to therapy. LAG-3 expression was notably positive in the renal graft, but negative in the metastatic melanoma tumor tissue. Although the outcome resulted in rapid renal graft rejection, this underscores the need for further research into LAG-3's dual role in cancer therapy and allograft rejection in organ transplant recipients.

Cutaneous sensory syndromes (CSS) are a heterogeneous group of disorders characterized by itch, burning, pain, or other dysesthesias on normal or minimally altered skin. They share convergent biology that includes aberrant small-fiber input, spinal and supraspinal sensitization, and neuroimmune crosstalk that perpetuates the itch-scratch cycle. This narrative review synthesizes current concepts and practical management across seven types of CSS encountered in adult practice: scalp dysesthesia, vulvodynia, scrotodynia, brachioradial pruritus, notalgia paresthetica, burning mouth syndrome, and psychogenic itch. We first outline a clinically focused pathophysiology from peripheral pruriceptors through dorsal horn circuits to cortical networks and descending control, and we integrate the brain-skin axis and autonomic influences. We then present a pragmatic evaluation framework that emphasizes targeted history, symptom mapping, red flags, a minimal laboratory panel, selective imaging or biopsy, and patch testing when product exposure suggests contact allergy. Management is organized around education and trigger modification, topical neuromodulators for focal disease, class-level systemic neuromodulators when symptoms are frequent or widespread, and psychoderm integration that addresses attention, mood, sleep, and behavioral loops. Disorder specific sections highlight distinctive clinical clues and low risk first steps, with adjuncts for refractory cases. This narrative review provides a concise, mechanism-informed roadmap to improve diagnosis, counseling, and outcomes in CSS.