vascular-organoid-generation-from-human-induced-pluripotent-stem-cells

Vascular Organoid Generation from Human-Induced Pluripotent Stem Cells

Vascular organoids derived from human induced pluripotent stem cells (hiPSCs) recapitulate the cell type diversity and complex architecture of human ...

Columbia University

Leukemia stem cells (LSCs) sustain the disease and contribute to relapse in acute myeloid leukemia (AML). Therapies that ablate LSCs may increase the chance of eliminating this cancer in patients. To this end, we used a bioreducible lipidoid-encapsulated Cas9/single guide RNA (sgRNA) ribonucleoprotein [lipidoid nanoparticle (LNP)-Cas9 RNP] to target the critical gene interleukin-1 receptor accessory protein () in human LSCs. To enhance LSC targeting, we loaded LNP-Cas9 RNP and the chemokine CXCL12α onto mesenchymal stem cell membrane-coated nanofibril (MSCM-NF) scaffolds mimicking the bone marrow microenvironment. In vitro, CXCL12α release induced migration of LSCs to the scaffolds, and LNP-Cas9 RNP induced efficient gene editing.  knockout reduced LSC colony-forming capacity and leukemic burden. Scaffold-based delivery increased the retention time of LNP-Cas9 in the bone marrow cavity. Overall, sustained local delivery of Cas9/IL1RAP sgRNA via CXCL12α-loaded LNP/MSCM-NF scaffolds provides an effective strategy for attenuating LSC growth to improve AML therapy.

Scaffold-mediated CRISPR-Cas9 delivery system for acute myeloid leukemia therapy.

Cutaneous T-cell lymphoma (CTCL) is a heterogenous group of non-Hodgkin lymphomas. Similar presentation to benign conditions, significant genetic variation, and lack of definitive biomarkers contributes to diagnostic delay. The etiology of CTCL is unknown, and environmental exposures, such as geographic, occupational, chemicals, sunlight, and insects have been investigated.

Clusters, crop dusters, and myth busters: a scoping review of environmental exposures and cutaneous T-cell lymphoma.

Fellowship directors (FDs) play a key role in shaping Mohs micrographic surgery (MMS). Studies characterizing director trends are lacking and may provide a framework for improving gender diversity.

Characterizing Gender and Leadership Trends Among Mohs Micrographic Surgery Fellowship Directors.

Truth-telling in dermatology: historical perspective and modern challenges to breaking bad news.

Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.

Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature.

Retrospective analysis of multiple myeloma drug use in cutaneous toxicity of monoclonal gammopathy of undetermined significance.

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a clonal plasma cell disorder that is considered preneoplastic, asymptomatic, and only requiring observation. However, MGUS may result in cutaneous complications, which are poorly understood, causing treatment delays and patient suffering. We present 30 patients with cutaneous findings associated with MGUS, characterizing clinical presentations, isoforms, treatments, and outcomes. These included: MGUS-associated 'rashes' (pruritic eczematous rashes), reactive and mucin-depositional conditions (pyoderma gangrenosum, scleromyxedema), M-protein-related deposition disorders (POEMS syndrome, Waldenstrom macroglobulinemia), and cutaneous lymphomas. Twelve of 30 (40%) patients received multiple myeloma drugs (MMDs). Eleven (92%) patients improved, and those not receiving MMDs rarely improved, suggesting that MMDs have efficacy for cutaneous manifestations of MGUS. Therefore, trialing MMDs may be warranted for patients with MGUS not responding to other therapies. Moreover, evaluation for monoclonal gammopathy in elderly patients with intractable pruritus or other chronic skin conditions that are non-responsive to skin-directed therapies should be considered.

Gammopathic dermopathy: characterization of cutaneous MGUS.

Skin cancer mortality rates continue to rise, and survival analysis is increasingly needed to understand who is at risk and what interventions improve outcomes. However, current statistical methods are limited by inability to synthesize multiple data types, such as patient genetics, clinical history, demographics, and pathology and reveal significant multimodal relationships through predictive algorithms. Advances in computing power and data science enabled the rise of artificial intelligence (AI), which synthesizes vast amounts of data and applies algorithms that enable personalized diagnostic approaches. Here, we analyze AI methods used in skin cancer survival analysis, focusing on supervised learning, unsupervised learning, deep learning, and natural language processing. We illustrate strengths and weaknesses of these approaches with examples. Our PubMed search yielded 14 publications meeting inclusion criteria for this scoping review. Most publications focused on melanoma, particularly histopathologic interpretation with deep learning. Such concentration on a single type of skin cancer amid increasing focus on deep learning highlight growing areas for innovation; however, it also demonstrates opportunity for additional analysis that addresses other types of cutaneous malignancies and expands the scope of prognostication to combine both genetic, histopathologic, and clinical data. Moreover, researchers may leverage multiple AI methods for enhanced benefit in analyses. Expanding AI to this arena may enable improved survival analysis, targeted treatments, and outcomes.

Current status of artificial intelligence methods for skin cancer survival analysis: a scoping review.

Reconstruction of Two Adjacent Defects on the Scalp.

A unique case of paraneoplastic lymphomatoid Papuloerythroderma of Ofuji with atypical clinical features.

Impact of Fitzpatrick skin type on narrowband UVB therapy outcomes in cutaneous T-cell lymphoma: A retrospective analysis.

Regular application of over-the-counter (OTC) sunscreen is considered the foundation of skin cancer prevention, yet OTC sunscreen is not eligible for reimbursement in almost all state Medicaid benefit plans. On review of 111 Medicaid preferred drug lists (PDLs) across 50 states and the District of Columbia (DC), only five plans were identified that incorporate coverage of sunscreen. Thus, many recipients of Medicaid, the majority of whom are individuals and families of lower socioeconomic status, may encounter financial difficulty and thus forego utilizing sun protective measures due to financial constraints. Here, we compare current Medicaid coverage of OTC sunscreen and discuss calculated and theoretical annual costs of this skin cancer prevention method.

Article	Year
Scaffold-mediated CRISPR-Cas9 delivery system for acute myeloid leukemia therapy. Science advances\| PubMed ID: 34138728	2021
Clusters, crop dusters, and myth busters: a scoping review of environmental exposures and cutaneous T-cell lymphoma. Italian journal of dermatology and venereology\| PubMed ID: 38015484	2023
Characterizing Gender and Leadership Trends Among Mohs Micrographic Surgery Fellowship Directors. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]\| PubMed ID: 38048171	2024
Truth-telling in dermatology: historical perspective and modern challenges to breaking bad news. Journal of the American Academy of Dermatology\| PubMed ID: 38395229	2024
Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature. The American Journal of dermatopathology\| PubMed ID: 38457671	2024
Retrospective analysis of multiple myeloma drug use in cutaneous toxicity of monoclonal gammopathy of undetermined significance. Journal of the American Academy of Dermatology\| PubMed ID: 38479611	2024
Gammopathic dermopathy: characterization of cutaneous MGUS. Leukemia & lymphoma\| PubMed ID: 38581379	2024
Current status of artificial intelligence methods for skin cancer survival analysis: a scoping review. Frontiers in medicine\| PubMed ID: 38711781	2024
Reconstruction of Two Adjacent Defects on the Scalp. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]\| PubMed ID: 38924507	2024
A unique case of paraneoplastic lymphomatoid Papuloerythroderma of Ofuji with atypical clinical features. JAAD case reports\| PubMed ID: 39077750	2024
Impact of Fitzpatrick skin type on narrowband UVB therapy outcomes in cutaneous T-cell lymphoma: A retrospective analysis. Journal of the American Academy of Dermatology\| PubMed ID: 39306003	2024
Elucidating disparities in sunscreen coverage among state Medicaid preferred drug lists. Pediatric dermatology\| PubMed ID: 39348046	2024

Caroline Chen

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