Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

Abstract Background Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. Case presentation We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Conclusions Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Trial registration Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT0279955

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ABSTRACT. Objective. We evaluated the whole-spine computed tomography (CT) findings in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome to improve our understanding of this rare disease. Methods. Whole-spine CT images obtained in 69 patients with SAPHO were reviewed. For each individual, a total of 25 vertebrae were evaluated for the distribution of affected vertebrae, CT manifestations of vertebral lesions, symmetry and location of distribution of the lesions on vertebrae, involvement pattern, and narrowing of adjacent intervertebral disc space. Paravertebral ligamentous ossifications, apophyseal joint disorders, and costovertebral joint disorders were also evaluated. Results. All the 69 patients with SAPHO exhibited abnormalities on whole-spine CT. Sixty-four had vertebral lesions, 52 had paravertebral ossifications, and 47 had both. The vertebral lesions were observed in 441 vertebrae, with a predilection for thoracic spine. The lesions exhibited a mixture of cortical erosion, reactive osteosclerosis of surrounding cancellous bone, and syndesmophyte. They may be confined to the vertebral corner (65.1%) or be extensive, involving the endplate (34.9%). Corner lesions could start in any part of the epiphyseal ring. The lesions were asymmetrically distributed. The affected vertebrae were more consecutively involved in a "kissing" appearance (78.2%). Intervertebral disc spaces were usually normal or mildly narrowed. There were 320 foci of paravertebral ossifications observed, with a predilection for the supraspinous ligament. Paravertebral ossifications were delicate and segmental. Ossifications throughout annulus fibrosis and apophyseal joint were not observed. Conclusion. Our investigation of the distributional, morphological features and the involvement pattern of spinal lesions in patients with SAPHO demonstrated distinct CT characteristics

:5; Personal non-commercial use only

ABSTRACT. Objective. We evaluated the whole-spine computed tomography (CT) findings in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome to improve our understanding of this rare disease. Methods. Whole-spine CT images obtained in 69 patients with SAPHO were reviewed. For each individual, a total of 25 vertebrae were evaluated for the distribution of affected vertebrae, CT manifestations of vertebral lesions, symmetry and location of distribution of the lesions on vertebrae, involvement pattern, and narrowing of adjacent intervertebral disc space. Paravertebral ligamentous ossifications, apophyseal joint disorders, and costovertebral joint disorders were also evaluated. Results. All the 69 patients with SAPHO exhibited abnormalities on whole-spine CT. Sixty-four had vertebral lesions, 52 had paravertebral ossifications, and 47 had both. The vertebral lesions were observed in 441 vertebrae, with a predilection for thoracic spine. The lesions exhibited a mixture of cortical erosion, reactive osteosclerosis of surrounding cancellous bone, and syndesmophyte. They may be confined to the vertebral corner (65.1%) or be extensive, involving the endplate (34.9%). Corner lesions could start in any part of the epiphyseal ring. The lesions were asymmetrically distributed. The affected vertebrae were more consecutively involved in a "kissing" appearance (78.2%). Intervertebral disc spaces were usually normal or mildly narrowed. There were 320 foci of paravertebral ossifications observed, with a predilection for the supraspinous ligament. Paravertebral ossifications were delicate and segmental. Ossifications throughout annulus fibrosis and apophyseal joint were not observed. Conclusion. Our investigation of the distributional, morphological features and the involvement pattern of spinal lesions in patients with SAPHO demonstrated distinct CT characteristics

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Giant flexoelectric response of uniformly dispersed BT-PVDF composite films induced by SDS-assisted treatment

Summary: Polymer-ceramic composites are commonly used as flexoelectric films. In existing studies, the flexoelectric effect of composites are generally improved by adjusting the material structures or adding ferroelectric materials. Further improvement of flexoelectric response has encountered a bottleneck. Considering from a new perspective, this study innovatively proposes to prepare the uniformly dispersed BT-PVDF composite films with giant flexoelectric response by surfactant SDS-assisted treatment. According to the engineering applications, tilt sensors have been fabricated with the SDS/BT-PVDF composite films. The prepared tilt sensors can accurately sense the tilt change in a small-angle range (0–10°) between the coaxial connecting parts, the response signal changes significantly (49.25–72.35 mV/°), and the response speed can reach 0.166 s. The research provides a new idea for improving the flexoelectric response and also paves a way for developing tilt sensors through a low-cost, facile, and reliable method, showing potential applications including bending sensing and structural health monitoring

Performance verification and clinical evaluation of the NAP-Fluo Cycler system for detecting five genital tract pathogens based on microfluidic technology

Introduction: Sexually transmitted infections (STIs) are among the most common infectious diseases worldwide, often leading to coinfections. Timely detection of genital tract pathogens in at-risk populations is crucial for preventing STIs. We evaluated the NAP-Fluo Cycler System, an innovative microfluidic nucleic acid detection platform, for its ability to simultaneously identify Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Ureaplasma urealyticum (UU), Mycoplasma genitalium (MG), and Mycoplasma hominis (MH) in urethral or cervical secretions. Materials and methods: The limits of detection (LODs), repeatability, specificity, and interference resistance of the system were evaluated using standard strains, a panel of 24 pathogens, and seven interferents. We used the system to analyze 302 clinical samples and compared the results with those of five approved commercial reference kits. Results: The system achieved LODs of 500 IFU/mL, 500 CFU/mL, and 500 CCU/mL for CT, NG, and UU/MG/MH, respectively, demonstrating high stability (coefficient of variation <1.1 %), specificity, and resistance to interference. Among 302 clinical samples, 237 tested positive with single, dual, and triple infection rates of 35.6 %, 16.2 %, and 3.0 %, respectively. The reference kits detected 138 positive samples. The concordance rates with commercial reference kits were 100 % for UU, NG, and MH; 94.85 % for CT; and 80.00 % for MG. Conclusions: This system offers a streamlined, rapid, and multiplex detection method that reduces testing time and complexity. Although it performs well with pure strains, it has limitations when using clinical samples of CT and MG, suggesting the need for further refinement before its widespread use in the clinic

Validation Study to Determine the Accuracy of Widespread Promoterless EGFP Reporter at Assessing CRISPR/Cas9-Mediated Homology Directed Repair

An accurate visual reporter system to assess homology-directed repair (HDR) is a key prerequisite for evaluating the efficiency of Cas9-mediated precise gene editing. Herein, we tested the utility of the widespread promoterless EGFP reporter to assess the efficiency of CRISPR/Cas9-mediated homologous recombination by fluorescence expression. We firstly established a promoterless EGFP reporter donor targeting the porcine GAPDH locus to study CRISPR/Cas9-mediated homologous recombination in porcine cells. Curiously, EGFP was expressed at unexpectedly high levels from the promoterless donor in porcine cells, with or without Cas9/sgRNA. Even higher EGFP expression was detected in human cells and those of other species when the porcine donor was transfected alone. Therefore, EGFP could be expressed at certain level in various cells transfected with the promoterless EGFP reporter alone, making it a low-resolution reporter for measuring Cas9-mediated HDR events. In summary, the widespread promoterless EGFP reporter could not be an ideal measurement for HDR screening and there is an urgent need to develop a more reliable, high-resolution HDR screening system to better explore strategies of increasing the efficiency of Cas9-mediated HDR in mammalian cells