Dapsone is an important medication for the treatment of leprosy, but a life-threatening drug hypersensitivity syndrome develops in some patients. In this report from China, an
HLA-B
locus is ...identified as a strong genetic risk factor for the syndrome.
Dapsone (4-4′-sulfonyldianiline), which was first synthesized in 1908,
1
is both an antibiotic and an antiinflammatory agent. Dapsone alone or in combination with other drugs has been used for the prevention and treatment of infectious diseases (e.g., leprosy, malaria, and actinomycetoma, as well as
Pneumocystis jirovecii
pneumonia in persons with human immunodeficiency virus HIV infection) and chronic inflammatory diseases characterized by the infiltration of neutrophils or eosinophils (e.g., dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis, and erythema elevatum diutinum).
2
,
3
About 0.5 to 3.6% of persons treated with dapsone have a drug hypersensitivity syndrome,
3
–
5
which was first described by . . .
Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
Graphical abstract Highlight ► Cat urine odor induces fear behavior in rats. ► Injection muscimol into the BNST blocks the freezing induced by cat urine odor. ► The BNST, not BLA, is essential for ...innate fear responses in rats.
The cross section of the e+e−→Λc+Λ¯c− process is measured with unprecedented precision using data collected with the BESIII detector at /¯s=4574.5, 4580.0, 4590.0 and 4599.5 MeV. The nonzero cross ...section near the Λc+Λ¯c− production threshold is cleared. At center-of-mass energies /¯s=4574.5 and 4599.5 MeV, the higher statistics data enable us to measure the Λc polar angle distributions. From these, the Λc electric over magnetic form-factor ratios (|GE/GM|) are measured for the first time. They are found to be 1.14±0.14±0.07 and 1.23±0.05±0.03, respectively, where the first uncertainties are statistical and the second are systematic.
Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Here, we report a protocol for haploidentical allo-HSCT ...that combines granulocyte-colony stimulating factor primed bone marrow (G-BM) and peripheral blood stem cells (PBSC) without in vitro T-cell depletion (TCD). In this study, 171 patients, including 86 in high-risk group, underwent transplantation from haploidentical family donors. All patients achieved sustained, full donor chimerism. One hundred and eleven patients were alive in remission at a median of 682 (253-1502) days. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 23% and that of extensive chronic GVHD, 47%; these were not influenced by HLA disparity. Patients younger than 15 years had less grade III-IV acute GVHD than older patients (P=0.044). The 2-year probability of relapse was 12% for standard-risk disease and 39% for high-risk disease. The 2-year probability of leukemia-free survival (LFS) was 68% for standard-risk patients and 42% for high-risk patients (P=0.0009). Grade III-IV acute GVHD was associated with better LFS (P=0.0017). The results require confirmation and show that G-BM combined with PBSC from haploidentical family donors, without in vitro TCD, may be used as a good source of stem cells for allo-HSCT.
Braille system is widely used worldwide for communication by visually impaired people. However, there are still some visually impaired people who are unable to learn Braille system due to various ...factors, such as the age (too young or too old), brain damage, etc. A wearable and low-cost Braille recognition system may substantially help these people recognize Braille or assist them in Braille learning. In this work, we fabricated polydimethylsiloxane (PDMS)-based flexible pressure sensors to construct an electronic skin (E-skin) for the application of Braille recognition. The E-skin mimics human touch sensing function for collecting Braille information. Braille recognition is realized with a neural network based on memristors. We utilize a binary neural network algorithm with only two bias layers and three fully connected layers. Such neural network design remarkably reduces the calculation burden and, thus, the system cost. Experiments show that the system can achieve a recognition accuracy of up to 91.25%. This work demonstrates the possibility of realizing a wearable and low-cost Braille recognition system and a Braille learning-assistance system.
Constructing artificial helical structures through hierarchical self-assembly and exploring the underlying mechanism are important, and they help gain insight from the structures, processes, and ...functions from the biological helices and facilitate the development of material science and nanotechnology. Herein, the two enantiomers of chiral Au(I) complexes ( S )-1 and ( R )-1 were synthesized, and they exhibited impressive spontaneous hierarchical self-assembly transitions from vesicles to helical fibers. An impressive chirality inversion and amplification was accompanied by the assembly transition, as elucidated by the results of in situ and time-dependent circular dichroism spectroscopy and scanning electron microscope imaging. The two enantiomers could serve as ideal chiral templates to co-assemble with other achiral luminogens to efficiently induce the resulting co-assembly systems to show circularly polarized luminescence (CPL). Our work has provided a simple but efficient way to explore the sophisticated self-assembly process and presented a facile and effective strategy to fabricate architectures with CPL properties.
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