A Yale Dermatology Perspective on Cutaneous T-Cell Lymphoma: Historical Reflection to Emerging Therapies.

Cutaneous T cell lymphoma (CTCL) is a form of non-Hodgkin lymphoma that can involve the skin, along with lymph nodes and blood. The two most common subtypes of CTCL are mycosis fungoides and Sézary syndrome, Since the initial description of mycosis fungoides by Dr. Jean-Louis Alibert in 1806, there have been significant advances in our understanding of the pathogenesis of CTCL, its diverse clinical and histologic variants, and the evolving treatment landscape.

Temporal Changes in Tick-Borne Pathogen Prevalence in Questing Ixodes ricinus Across Different Habitats in the North-Eastern Italian Alps.

Changes in land use, climate, and host community are leading to increased complexity in eco-epidemiological relationships and the emergence of zoonoses. This study investigates the changes in the prevalence of several Ixodes ricinus-transmitted pathogens in questing ticks over a 10-year interval (2011-2013, 2020) in natural and agricultural habitats of the Autonomous Province of Trento (North-eastern Alps), finding an average prevalence of infection of 27.1%.

Pervasive Induction of Regulatory Mutation Microclones in Sun-exposed Skin.

Carcinogen-induced mutations are thought near-random, with rare cancer-driver mutations underlying clonal expansion. Using high-fidelity Duplex Sequencing to reach a mutation frequency sensitivity of 4×10 per nt, we report that sun exposure creates pervasive mutations at sites with ∼100-fold UV-sensitivity in RNA-processing gene promoters - cyclobutane pyrimidine dimer (CPD) hyperhotspots - and these mutations have a mini-driver clonal expansion phenotype. Numerically, human skin harbored 10-fold more genuine mutations than previously reported, with neonatal skin containing 90,000 per cell; UV signature mutations increased 8,000-fold in sun-exposed skin, averaging 3×10 per nt.

SQuID (subcutaneous insulin in diabetic ketoacidosis) II: Clinical and operational effectiveness.

Objective: We previously demonstrated safe treatment of low- to moderate-severity (LTM) diabetic ketoacidosis (DKA) using the SQuID protocol (subcutaneous insulin in DKA) in a non-intensive care unit (ICU) observation setting, with decreased emergency department length of stay (EDLOS). Here, we expand eligibility to include sicker patients and admission to a regular medical floor and collected more detailed clinical data in a near-real-time fashion.

Methods: This is a real-world, prospective, observational cohort study in an urban academic hospital (March 4, 2023-March 4, 2024).

A novel method for determining ventilatory and gas exchange dynamics during exercise: the "chirp" waveform.

Quantitating exercise ventilatory and gas exchange dynamics affords insights into physiological control processes and cardiopulmonary dysfunction. We designed a novel waveform, the chirp waveform, to efficiently extract moderate-intensity exercise response dynamics. In the chirp waveform, work rate fluctuates sinusoidally with constant amplitude as sinusoidal period decreases progressively from ∼8.

Inclusion Goals: What Sex Education for LGBTQIA+ Adolescents?

According to the World Health Organization and the World Association for Sexual Health (WAS) Declaration of Sexual Rights, sex education aims to provide children and adolescents with comprehensive knowledge, skills, attitudes, and values, promoting equality and nondiscrimination while upholding freedom of thought and expression. However, current school curricula often focus on dichotomous sexual identity and hetero-cis-normative prevention strategies, neglecting the needs of gender minority (GM) and sexual minority (SM) youths. In family settings, discussions typically revolve around sexual risk reduction and basic contraception, omitting relational aspects and components of sexual identity such as orientations and gender expressions.

Beyond population size: Whole-genome data reveal bottleneck legacies in the peninsular Italian wolf.

Preserving genetic diversity and adaptive potential while avoiding inbreeding depression is crucial for the long-term conservation of natural populations. Despite demographic increases, traces of past bottleneck events at the genomic level should be carefully considered for population management. From this perspective, the peninsular Italian wolf is a paradigmatic case.

Enhanced Intratumoral Delivery of Immunomodulator Monophosphoryl Lipid A through Hyperbranched Polyglycerol-Coated Biodegradable Nanoparticles.

Immunomodulatory agents have significant potential to enhance cancer treatment but have demonstrated limited efficacy beyond the preclinical setting owing to poor pharmacokinetics and toxicity associated with systemic administration. Conversely, when locally delivered, immunomodulatory agents require repeated administration to optimize immune stimulation. To overcome these challenges, we encapsulated the toll-like receptor 4 agonist monophosphoryl lipid A (MPLA) within hyperbranched polyglycerol-coated biodegradable nanoparticles (NPs) engineered for gradual drug release from the NP core, resulting in a more persistent stimulation of antitumor immune responses while minimizing systemic side effects.

Camptothecin-loaded mesoporous silica nanoparticles functionalized with CpG oligodeoxynucleotide as a new approach for skin cancer treatment.

The therapeutic efficacy of camptothecin (CPT), a potent antitumor alkaloid, is hindered by its hydrophobic nature and instability, limiting its clinical use in treating cutaneous squamous cell carcinoma (SCC). This study introduces a novel nano drug delivery system (NDDS) utilizing functionalized mesoporous silica nanoparticles (FMSNs) for efficient CPT delivery. The FMSNs were loaded with CPT and subsequently coated with chitosan (CS) for enhanced stability and bioadhesion.

Generation and optimization of off-the-shelf immunotherapeutics targeting TCR-Vβ2+ T cell malignancy.

Current treatments for T cell malignancies encounter issues of disease relapse and off-target toxicity. Using T cell receptor (TCR)Vβ2 as a model, here we demonstrate the rapid generation of an off-the-shelf allogeneic chimeric antigen receptor (CAR)-T platform targeting the clone-specific TCR Vβ chain for malignant T cell killing while limiting normal cell destruction. Healthy donor T cells undergo CRISPR-induced TRAC, B2M and CIITA knockout to eliminate T cell-dependent graft-versus-host and host-versus-graft reactivity.

Mock community experiments can inform on the reliability of eDNA metabarcoding data: a case study on marine phytoplankton.

Environmental DNA metabarcoding is increasingly implemented in biodiversity monitoring, including phytoplankton studies. Using 21 mock communities composed of seven unicellular diatom and dinoflagellate algae, assembled with different composition and abundance by controlling the number of cells, we tested the accuracy of an eDNA metabarcoding protocol in reconstructing patterns of alpha and beta diversity. This approach allowed us to directly evaluate both qualitative and quantitative metabarcoding estimates.

Surpassing the nonlinear conversion efficiency of soliton microcombs.

Laser frequency combs are enabling some of the most exciting scientific endeavours in the twenty-first century, ranging from the development of optical clocks to the calibration of the astronomical spectrographs used for discovering Earth-like exoplanets. Dissipative Kerr solitons generated in microresonators currently offer the prospect of attaining frequency combs in miniaturized systems by capitalizing on advances in photonic integration. Most of the applications based on soliton microcombs rely on tuning a continuous-wave laser into a longitudinal mode of a microresonator engineered to display anomalous dispersion.

Impact of forest disturbance on microarthropod communities depends on underlying ecological gradients and species traits.

Windstorms and salvage logging lead to huge soil disturbance in alpine spruce forests, potentially affecting soil-living arthropods. However, the impacts of forest loss and possible interactions with underlying ecological gradients on soil microarthropod communities remain little known, especially across different environmental conditions. Here we used DNA metabarcoding approach to study wind-induced disturbances on forest communities of springtails and soil mites.

Multilayer integration in silicon nitride: decoupling linear and nonlinear functionalities for ultralow loss photonic integrated systems.

Silicon nitride is an excellent material platform for its extremely low loss in a large wavelength range, which makes it ideal for the linear processing of optical signals on a chip. Moreover, the Kerr nonlinearity and the lack of two-photon absorption in the near infrared enable efficient nonlinear optics, e.g.

FISH Panel for Leukemic Cutaneous T-Cell Lymphoma: Extended Patient Cohort Correlation with Blood Involvement and Clinical Outcomes.

The genomic basis of cutaneous T-cell lymphoma has been characterized by gene copy number alterations and genomic sequencing, but there are few clinical tests that are being widely used to inform the diagnosis and prognosis of leukemic cutaneous T-cell lymphoma that may arise as a progression from mycosis fungoides or de novo as Sézary syndrome. An 11-gene FISH panel of , , , , , , , and deletions and , (), and amplifications was previously found to encapsulate >95% of gene copy number variations in leukemic cutaneous T-cell lymphoma. Through a retrospective analysis of patients with leukemic cutaneous T-cell lymphoma seen at the Yale Cancer Center from 2014 to 2020, we gathered the relevant genes as they became available and correlated them to factors with prognostic relevance as a proof of concept to show the potential utility in further developing a limited gene panel for prognosis.

Ventilation and perceived exertion are sensitive to changes in exercise tolerance: arm+leg cycling vs. leg cycling.

Growing evidence suggests that respiratory frequency ( ) is a marker of physical effort and a variable sensitive to changes in exercise tolerance. The comparison between arm+leg cycling (Arm+leg) and leg cycling (Leg) has the potential to further test this notion because a greater exercise tolerance is expected in the Arm+leg modality. We systematically compared Arm+leg vs.