Delayed skin reaction after mRNA-1273 vaccine against SARS-CoV-2: a rare clinical reaction.

Background: The coronavirus disease 2019 (COVID-19) is associated with a wide clinical spectrum of skin manifestations, including urticarial, vesicular, vasculitic and chilblain-like lesions. Recently, delayed skin reactions have been reported in 1% individuals following mRNA vaccination against SARS-CoV-2. The exact pathophysiology and the risk factors still remain unclear.

Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies.

Malignant sweat gland tumours are rare, with the most common form being Eccrine porocarcinoma (EP). To investigate the mutational landscape of EP, we performed whole-exome sequencing (WES) on 14 formalin-fixed paraffin-embedded samples of matched primary EP and healthy surrounding tissue. Mutational profiling revealed a high overall median mutation rate.

Exploring Cyclic Sulfamidate Building Blocks for the Synthesis of Sequence-Defined Macromolecules.

The preparation of sequence-defined macromolecules using cyclic sulfamidates on solid-phase is outlined. The challenges surrounding an AB+CD approach are described with focus on understanding the formation of ring-opened side products when using amide coupling reagents. To avoid undesired side product formation, a strategy of iterative ring-openings of cyclic sulfamidates on solid-phase is explored.

Integrative Genomic Analyses of Patient-Matched Intracranial and Extracranial Metastases Reveal a Novel Brain-Specific Landscape of Genetic Variants in Driver Genes of Malignant Melanoma.

Background: Development of brain metastases in advanced melanoma patients is a frequent event that limits patients' quality of life and survival. Despite recent insights into melanoma genetics, systematic analyses of genetic alterations in melanoma brain metastasis formation are lacking. Moreover, whether brain metastases harbor distinct genetic alterations beyond those observed at different anatomic sites of the same patient remains unknown.

3D Printing-Enabled DNA Extraction for Long-Read Genomics.

Long-read genomics technologies such as nanopore sequencing and genome mapping in nanochannels extract genomic information in the kilobase to megabase pair range from single DNA molecules, thereby overcoming read-length limitations in next-generation DNA sequencing. Long-read technologies start with long DNA molecules as the input and thus benefit from universal sample preparation methods that are fast and shear-free and present a scope of automation and direct upstream integration. We describe a 3D printing-assisted poly(dimethylysiloxane)-based DNA sample preparation device, where diffusive chemical lysis followed by electrophoresis produces circa 100 ng of long DNA directly from cells with less than 5 min of labor.

Hidradenitis Suppurativa is Associated with Symptoms of Keratoconjunctivitis Sicca.

Aim Of The Study: Hidradenitis suppurativa (HS) and psoriasis vulgaris (PSO) are chronic inflammatory dermatoses in which proinflammatory cytokines, such as IL-17, play a central role. The prevalence of keratoconjunctivitis sicca (KCS) is commonly higher in PSO than in healthy individuals. This study was thus set up to investigate the prevalence of KCS among patients with HS.

Macrophages/Microglia Represent the Major Source of Indolamine 2,3-Dioxygenase Expression in Melanoma Metastases of the Brain.

The manifestation of brain metastases in patients with advanced melanoma is a common event that limits patient's survival and quality of life. The immunosuppressive properties of the brain parenchyma are very different compared to the rest of the body, making it plausible that the current success of cancer immunotherapies is specifically limited here. In melanoma brain metastases, the reciprocal interplay between immunosuppressive mediators such as indoleamine 2, 3-dioxygenase (IDO) or programmed cell death-ligand 1 (PD-L1) in the context of neoplastic transformation are far from being understood.

Mandible handling in the surgical treatment of oral squamous cell carcinoma: lessons from clinical results after marginal and segmental mandibulectomy.

Objective: The aim of this retrospective, single-center study was to analyze long-term results after marginal and segmental mandibulectomies in patients with oral squamous cell carcinoma (OSCC).

Study Design: The study included 259 patients treated for OSCC with mandibulectomy between 1996 and 2010. Data acquisition consisted of analysis of operation reports, re-evaluation of histologic bone specimens, and collection of clinical follow-up data.

Extension distribution for DNA confined in a nanochannel near the Odijk regime.

DNA confinement in a nanochannel typically is understood via mapping to the confinement of an equivalent neutral polymer by hard walls. This model has proven to be effective for confinement in relatively large channels where hairpin formation is frequent. An analysis of existing experimental data for Escherichia coli DNA extension in channels smaller than the persistence length, combined with an additional dataset for λ-DNA confined in a 34 nm wide channel, reveals a breakdown in this approach as the channel size approaches the Odijk regime of strong confinement.

Long-read single-molecule maps of the functional methylome.

We report on the development of a methylation analysis workflow for optical detection of fluorescent methylation profiles along chromosomal DNA molecules. In combination with Bionano Genomics genome mapping technology, these profiles provide a hybrid genetic/epigenetic genome-wide map composed of DNA molecules spanning hundreds of kilobase pairs. The method provides kilobase pair-scale genomic methylation patterns comparable to whole-genome bisulfite sequencing (WGBS) along genes and regulatory elements.

Measuring the wall depletion length of nanoconfined DNA.

Efforts to study the polymer physics of DNA confined in nanochannels have been stymied by a lack of consensus regarding its wall depletion length. We have measured this quantity in 38 nm wide, square silicon dioxide nanochannels for five different ionic strengths between 15 mM and 75 mM. Experiments used the Bionano Genomics Irys platform for massively parallel data acquisition, attenuating the effect of the sequence-dependent persistence length and finite-length effects by using nick-labeled genomic DNA with contour length separations of at least 30 m (88 325 base pairs) between nick pairs.

Odijk excluded volume interactions during the unfolding of DNA confined in a nanochannel.

We report experimental data on the unfolding of human and genomic DNA molecules shortly after injection into a 45 nm nanochannel. The unfolding dynamics are deterministic, consistent with previous experiments and modeling in larger channels, and do not depend on the biological origin of the DNA. The measured entropic unfolding force per friction per unit contour length agrees with that predicted by combining the Odijk excluded volume with numerical calculations of the Kirkwood diffusivity of confined DNA.

Sequence-Dependent Persistence Length of Long DNA.

Using a high-throughput genome-mapping approach, we obtained circa 50 million measurements of the extension of internal human DNA segments in a 41  nm×41  nm nanochannel. The underlying DNA sequences, obtained by mapping to the reference human genome, are 2.5-393 kilobase pairs long and contain percent GC contents between 32.

Modeling the relaxation of internal DNA segments during genome mapping in nanochannels.

We have developed a multi-scale model describing the dynamics of internal segments of DNA in nanochannels used for genome mapping. In addition to the channel geometry, the model takes as its inputs the DNA properties in free solution (persistence length, effective width, molecular weight, and segmental hydrodynamic radius) and buffer properties (temperature and viscosity). Using pruned-enriched Rosenbluth simulations of a discrete wormlike chain model with circa 10 base pair resolution and a numerical solution for the hydrodynamic interactions in confinement, we convert these experimentally available inputs into the necessary parameters for a one-dimensional, Rouse-like model of the confined chain.

Immune dysregulation in patients with PTEN hamartoma tumor syndrome: Analysis of FOXP3 regulatory T cells.

Background: Patients with heterozygous germline mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) experience autoimmunity and lymphoid hyperplasia.

Objectives: Because regulation of the phosphoinositide 3-kinase (PI3K) pathway is critical for maintaining regulatory T (Treg) cell functions, we investigate Treg cells in patients with heterozygous germline PTEN mutations (PTEN hamartoma tumor syndrome [PHTS]).

Methods: Patients with PHTS were assessed for immunologic conditions, lymphocyte subsets, forkhead box P3 (FOXP3) Treg cell levels, and phenotype.

Chronic UVB-irradiation actuates perpetuated dermal matrix remodeling in female mice: Protective role of estrogen.

Chronic UVB-exposure and declined estradiol production after menopause represent important factors leading to extrinsic and intrinsic aging, respectively. Remodeling of the extracellular matrix (ECM) plays a crucial role in both responses. Whether the dermal ECM is able to recover after cessation of UVB-irradiation in dependence of estradiol is not known, however of relevance when regarding possible treatment options.

Measurements of DNA barcode label separations in nanochannels from time-series data.

We analyzed time-series data for fluctuations of intramolecular segments of barcoded E. coli genomic DNA molecules confined in nanochannels with sizes near the persistence length of DNA. These dynamic data allowed us to measure the probability distribution governing the distance between labels on the DNA backbone, which is a key input into the alignment methods used for genome mapping in nanochannels.

[Juvenile systemic lupus erythematosus with unusual manifestation of lupus-associated panniculitis].

Juvenile systemic lupus erythematosus (JSLE) is a rare multisystem autoimmune disease with broad heterogeneity of clinical manifestations. Diagnosing JSLE is often very challenging. This life-threatening, unpredictable, and relapsing disease, which may affect various organ systems, requires interdisciplinary, lifelong care.

Topological events in single molecules of E. coli DNA confined in nanochannels.

We present experimental data concerning potential topological events such as folds, internal backfolds, and/or knots within long molecules of double-stranded DNA when they are stretched by confinement in a nanochannel. Genomic DNA from E. coli was labeled near the 'GCTCTTC' sequence with a fluorescently labeled dUTP analog and stained with the DNA intercalator YOYO.