Recipients after hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy are at increased risk for unfavorable outcomes after SARS-CoV-2 infection. The ...efficacy of COVID-19 vaccines remains undetermined in this vulnerable population, we therefore conducted a pooled analysis to evaluate the immune response after vaccination. A total of 46 studies were finally included, comprising 4757 HSCT and 174 CAR-T recipients. Our results indicated that HSCT and CAR-T recipients had an attenuated immune response to SARS-CoV-2 vaccination compared with healthy individuals, while time interval between transplant and vaccination, immunosuppressive therapy (IST) and lymphocyte counts at vaccination significantly affected the humoral response in HSCT recipients. In addition, seroconversion was significantly higher in patients with BCMA-based CAR-T than those with CD19-based CAR-T. Thus, an adapted vaccination strategy for HSCT and CAR-T recipients may be required, and further research on the effect of a booster dose of COVID-19 vaccine and the role of cellular response after vaccination is warranted. Keywords: Hematopoietic stem cell transplantation (HSCT), Chimeric antigen receptor T-cell (CAR-T) therapy, SARS-CoV-2 vaccination, Immune response
To make good use of the barrier effect of graphene nanosheets and to reduce the uneven dispersion of zinc particles caused by its sedimentation, coating with alternate structure containing rGO was ...developed to provide Cu a long-term corrosion protection. Ionic liquid was used to obtain a better dispersion of rGO in solvent, which was proved by TEM, SPM images and sedimentation experiment. The enhanced long-term anti-corrosion protection of alternate coating was revealed by electrochemical tests. OCP and EIS results showed enhanced barrier performance of epoxy-G compared with epoxy and improved sacrificial anode protection of epoxy-Zn-G compared with epoxy-Zn. Tidal range-corrosion simulation test was also performed to show that the alternate coating can stick on copper substrate without peeling off even in harsh corrosive environment for 432 h. Furthermore, EIS, XRD, and XPS spectra together proved that the excellent anti-corrosion property of alternate coating was originated from the combination of sacrificial anode protection provided by zinc-rich-epoxy layer with barrier protection provided by rGO-doping-epoxy layer. This combination makes it reality to protect copper substrate from corrosion for longer time immersion in 3.5 wt% NaCl solution compared with epoxy-Zn-G.
Display omitted
•An alternate epoxy-reduced graphene oxide/epoxy-Zinc multilayer coating is designed for enhancing anticorrosion.•The alternate structure can achieve an analogous sustained release effect of zinc particles.•The coating with alternate structure achieves longer protection than single structure in 3.5 wt% NaCl solution.•The coating with alternate structure shows strong adhesion strength in acidic environment for 432 h.
Metaplastic breast carcinoma (MpBC) typically consists of carcinoma of no special type (NST) with various metaplastic components. Although previous transcriptomic and proteomic studies have reported ...subtype-related heterogeneity, the intracase transcriptomic alterations between metaplastic components and paired NST components, which are critical for understanding the pathogenesis underlying the metaplastic processes, remain unclear.
Fifty-nine NST components and paired metaplastic components (spindle carcinomatous SPS, matrix-producing, rhabdoid RHA, and squamous carcinomatous SQC components) were microdissected from specimens obtained from 27 patients with MpBC for gene expression profiling using the NanoString Breast Cancer 360 Panel on a NanoString nCounter FLEX platform. BC360-defined signatures were scored using nSolver software.
Hierarchical clustering and principal component analysis revealed a heterogeneous gene expression profile (GEP) corresponding to the NST components, but the GEP of metaplastic components exhibited subtype dependence. Compared with the paired NST components, the SPS components demonstrated the upregulation of genes related to stem cells and epithelial-mesenchymal transition and displayed enrichment in claudin-low and macrophage signatures. Despite certain overlaps in the enriched functions and signatures between the RHA and SPS components, the specific differentially expressed genes differed. We observed the RHA-specific upregulation of genes associated with vascular endothelial growth factor signaling. The chondroid matrix-producing components demonstrated the upregulation of hypoxia-related genes and the downregulation of the immune-related MHC2 signature and the TIGIT gene. In the SQC components, TGF-β and genes associated with cell adhesion were upregulated. The differentially expressed genes among metaplastic components in the 22 MpBC cases with one or predominantly one metaplastic component clustered paired NST samples into clusters with correlation with their associated metaplastic types. These genes could be used to separate the 31 metaplastic components according to respective metaplastic types with an accuracy of 74.2%, suggesting that intrinsic signatures of NST may determine paired metaplastic type. Finally, the EMT activity and stem cell traits in the NST components were correlated with specimens displaying lymph node metastasis.
We presented the distinct transcriptomic alterations underlying metaplasia into specific metaplastic components in MpBCs, which contributes to the understanding of the pathogenesis underlying morphologically distinct metaplasia in MpBCs.
Abstract
Excavator is one of the most important construction machineries. Its working environment is complex and changeable. There is no perfect suspension system for excavator as cars, and the ...covering parts are mostly thin-wall welded parts. Therefore, the covering parts are easy to be damaged in the working process, which brings poor using experience problems to users. According to the user feedback survey, toolboxes are most prone to cracking in the cover. The quality of the toolbox determines the company’s reputation and brand competitiveness in the market to a certain extent. Therefore, it is important to study the vibration response of the toolbox. Aiming at the problem of box body cracking in the road test of a medium-sized excavator toolbox, this paper carried out modal simulation and test verification on the excavator toolbox, laying the foundation for the follow-up research.
The PI3K/AKT/mTOR pathway has long been known to play a major role in the growth and survival of cancer cells. Breast tumors often harbor
gene alterations, which therefore constitute a rational drug ...target. However, it has taken many years to demonstrate clinically-relevant efficacy of PI3K inhibition and eventually attain regulatory approvals. As data on PI3K inhibitors continue to mature, this review updates and summarizes the current state of the science, including the prognostic role of
alterations in breast cancer; the evolution of PI3K inhibitors; the clinical utility of the first-in-class oral selective PI3Kα inhibitor, alpelisib;
mutation detection techniques; and adverse effect management.
-mutated breast carcinomas predict survival benefit from PI3K inhibitor therapy. The pan-PI3K inhibitor, buparlisib and the beta-isoform-sparing PI3K inhibitor, taselisib, met efficacy endpoints in clinical trials, but pictilisib did not; moreover, poor tolerability of these three drugs abrogated further clinical trials. Alpelisib is better tolerated, with a more manageable toxicity profile; the principal adverse events, hyperglycemia, rash and diarrhea, can be mitigated by intensive monitoring and timely intervention, thereby enabling patients to remain adherent to clinically beneficial treatment. Alpelisib plus endocrine therapy shows promising efficacy for treating postmenopausal women with HR+/HER2- advanced breast cancer. Available evidence supporting using alpelisib after disease progression on first-line endocrine therapy with or without CDK4/6 inhibitors justifies
mutation testing upon diagnosing HR+/HER2- advanced breast cancer, which can be done using either tumor tissue or circulating tumor DNA. With appropriate toxicity management and patient selection using validated testing methods, all eligible patients can potentially benefit from this new treatment. Further clinical trials to assess combinations of hormone therapy with PI3K, AKT, mTOR, or CDK 4/6 inhibitors, or studies in men and women with other breast subtypes are ongoing.
Motivated by the high speed but insufficient precision of the existing fast point feature histogram algorithm, a new fast point feature histogram registration algorithm based on density optimization ...is proposed. In this method, a 44-section blank feature histogram is first established, and then a principal component analysis is implemented to calculate the normal of each point in the point cloud. By translating the coordinate system in the established local coordinate system, the normal angle of each point pair and its weighted neighborhood are obtained, and then a fast point feature histogram with 33 sections is established. The reciprocal of the volume density for the central point and its weighted neighborhood are calculated simultaneously. The whole reciprocal space is divided into 11 sections. Thus, a density fast point feature histogram with 44 sections is obtained. On inputting the testing models, the initial pose of the point cloud is adjusted using the traditional fast point feature histogram and the proposed algorithms, respectively. Then, the iterative closest point algorithm is incorporated to complete the fine registration test. Compared with the traditional fine registration test algorithm, the proposed optimization algorithm can obtain 44 feature parameters under the condition of a constant time complexity. Moreover, the proposed optimization algorithm can reduce the standard deviation by 8.6% after registration. This demonstrates that the proposed method encapsulates abundant information and can achieve a high registration accuracy.
The expanded GGGGCC hexanucleotide repeat in the non-coding region of the
C9orf72
gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). There ...are three main disease mechanisms: loss of function of C9ORF72 protein, gain of function from the accumulation of sense and antisense (GGGGCC)n in RNA, and from the production of toxic dipeptides repeat proteins (DPRs) by non-AUG initiated translation. While many of the downstream mechanisms have been identified, the specific pathogenic pathway is still unclear. In this article, we provide an overview on the currently available literature and propose several hypotheses: (1) The pathogenesis of
C9orf72
-associated ALS/FTD, which cannot be explained by a single mechanism, involves a dual mechanism of both loss and gain of function. (2) The loss of function and gain of function can cause TDP-43 aggregation and damage nucleocytoplasmic transport. (3) Neurodegeneration can be caused by an accumulation of toxic substances in neurons themselves. In addition, we suggest that microglia may cause neurodegeneration by releasing inflammatory factors to neurons. Finally, we summarize several of the most promising treatment strategies.
To introduce a case of a uterus "hernia-like" myoma within the uterine cavity that was successfully treated with hysteroscopy.
Step-by-step explanation of the case and surgical procedure using a ...video and slides. The Medical Ethics Committee of Women and Children's Hospital of Chongqing Medical University approved the study and decided for this video to be exempt from formal approval, and informed consent was obtained from the patient.
Hospital.
A 37-year-old woman, gravida 1, para 1, with a history of secondary infertility for 2 years and heavy menstrual bleeding for 7 months, which eventually resulted in anemia, was diagnosed with a type 1 (International Federation of Gynecology and Obstetrics leiomyoma subclassification system) myoma approximately 4 cm in diameter using ultrasonography. Her hemoglobin level was 8.6 g/dL (11.5-15.0 g/dL), red blood cell count was 3.6 ×10-12/L (3.8-5.1 ×10-12/L), and hematocrit was 26.7% (35%-45%).
Hysteroscopic myomectomy with bipolar resectoscope and transabdominal ultrasound guidance was used to resect the hernia-like myoma. Blunt dissection combined with oxytocin (20 U I.V.) and uterine dilation pressure reduction was used to induce the hernial content (myoma) protrusion into the uterine cavity.
The hernia-like myoma was completely resected by hysteroscopy, and all symptoms disappeared.
The hernia-like myoma was successfully and completely resected by hysteroscopy. The operative time was 37 minutes. No surgical-related or anesthesia-related complications occurred. During the follow-up period, the patient had regular menstrual cycles without hypermenorrhea, and her anemia had improved. The 5-month follow-up ultrasound examination and hysteroscopy revealed that the uterine cavity had recovered well. The patient conceived 7 months after the procedure and delivered at term (39 weeks 1 day) via cesarean section.
A hernia-like myoma covered with endometrium is a degenerative myoma that herniates into the myometrium and forms a hernia sac-like defect. Hysteroscopy is an effective and feasible method for treating hernia-like myoma.
The performance of traditional model-based constant false-alarm ratio (CFAR) detection algorithms can suffer in complex environments, particularly in scenarios involving multiple targets (MT) and ...clutter edges (CE) due to an imprecise estimation of background noise power level. Furthermore, the fixed threshold mechanism that is commonly used in the single-input single-output neural network can result in performance degradation due to changes in the scene. To overcome these challenges and limitations, this paper proposes a novel approach, a single-input dual-output network detector (SIDOND) using data-driven deep neural networks (DNN). One output is used for signal property information (SPI)-based estimation of the detection sufficient statistic, while the other is utilized to establish a dynamic-intelligent threshold mechanism based on the threshold impact factor (TIF), where the TIF is a simplified description of the target and background environment information. Experimental results demonstrate that SIDOND is more robust and performs better than model-based and single-output network detectors. Moreover, the visual explanation technique is employed to explain the working of SIDOND.
PDF
