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Abstract: Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Nonreciprocity is a fundamental requirement of signal isolation in optical communication systems. However, on chip isolator designs require either post-processing steps or external magnetic biasing, which are impractical for commercial applications. This raises the need for standalone devices which support nonreciprocal functionality using standardized fabrication techniques. Here, we report the first design of an electromagnetic coil surrounding a waveguide which exclusively employed the complementary metal-oxide-semiconductor (CMOS) process flow. The coil supported an electric current up to 14 mA. In simulations, it generated an alternating magnetic flux density up to 1.16 mT inside a strip waveguide and thereby induced a rotation of 50.71 picodegrees for the fundamental transverse-magnetic mode at a wavelength of 1352 nm. Our analysis further revealed methods to increase the rotation by orders of magnitude. It demonstrated the scope of manufacturing processes and serves as a building block for the development of a commercially viable, on-chip optical isolator.

We demonstrate an optical time-gate isolator entirely fabricated on the silicon-on-insulator (SOI) platform based on a conventional traveling-wave Mach-Zehnder modulator (TW-MZM) design. The device achieves 18.2 dB (22.7 dB) time-averaged isolation when driven with 2.0-V pp (7.1-V pp ) differential clock signals at 6.8 GHz and biased at null. Under these conditions, the isolator blocks backward light at all time regardless of driver amplitude, but produces periodic modulation in the forward direction. Moreover, we embed our isolator in a digital communication link and measure a signal-to-noise ratio (SNR) penalty of only 0.5 dB due to the isolator at 13.6 Gbaud PAM-4 data rate. Our device can be integrated in larger circuits to protect laser sources or mitigate interference.

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management., (© 2020 by The American Society of Hematology.)