Advances in the application of CRISPR-Cas technology in rapid detection of pathogen nucleic acid

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) are widely used as gene editing tools in biology, microbiology, and other fields. CRISPR is composed of highly conserved repetitive sequences and spacer sequences in tandem. The spacer sequence has homology with foreign nucleic acids such as viruses and plasmids; Cas effector proteins have endonucleases, and become a hotspot in the field of molecular diagnosis because they recognize and cut specific DNA or RNA sequences. Researchers have developed many diagnostic platforms with high sensitivity, high specificity, and low cost by using Cas proteins (Cas9, Cas12, Cas13, Cas14, etc.) in combination with signal amplification and transformation technologies (fluorescence method, lateral flow technology, etc.), providing a new way for rapid detection of pathogen nucleic acid. This paper introduces the biological mechanism and classification of CRISPR-Cas technology, summarizes the existing rapid detection technology for pathogen nucleic acid based on the trans cleavage activity of Cas, describes its characteristics, functions, and application scenarios, and prospects the future application of this technology

B lymphocytes as effector cells in the immunotherapy of cancer

Over the years, the role of B cells in the host immune response to malignancy has been overshadowed by our focus on T cells. Nevertheless, B cells play important roles as antigen‐presenting cells and in the production of antibodies. Furthermore, B cells can function as effector cells that mediate tumor destruction on their own. This review will highlight the various functions of B cells that are involved in the host response to tumor. J. Surg. Oncol. 2012;105:431–435. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90339/1/22093_ftp.pd

Embedment Strength of Cross-Laminated Timber for Smooth Dowel-type Fasteners

Embedment strength is a significant property in the dowel type connection in timber structure, i.e. cross-laminated timber (CLT). The CLT design properties are different from those of sawn timber (ST) and glued-laminated timber (GLT) because of the orthogonal structure, which may particularly have influence on the design of connections. The layup feature, i.e. the thickness ratio of transverse layer (TRTL) was considered as an effective factor on CLT embedment strength in this study, except for other factors, i.e. wood density, smooth dowel diameter, and loading angle. Approximate 660 embedment tests were performed according to ASTM D5764 half-hole test method. A few of existing design models for CLT embedment strength were evaluated using experimental data. It was found that different factors had different effect tendency and each factor had statistically significant impact on CLT embedment strength. The embedment strength and failure modes of CLT were obviously different from those of GLT due to the existence of transverse layer in CLT. The existing design equations should be improved. Based on the test results, a new design equation was proposed which had better prediction

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

Expert Consensus on Microtransplant for Acute Myeloid Leukemia in Elderly Patients -Report From the International Microtransplant Interest Group

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment

Machine Learning Prediction Model for Boundary Transverse Reinforcement of Shear Walls

Due to their roles as efficient lateral force-resisting systems, reinforced concrete shear walls exert a tremendous degree of influence on the overall seismic performance of buildings. The ability to predict the boundary transverse reinforcement of shear walls is critical to the seismic design process, as well as in the overall evaluation and retrofitting of existing buildings. Contemporary empirical models attain low predictive accuracy, with an inability to capture nonlinearity between boundary transverse reinforcement and different influencing variables. This study proposes a boundary transverse reinforcement prediction model for shear walls with boundary elements based on the demand of ductility. Using the extreme gradient boosting machine learning algorithm and 501 samples, some 52 input variables are considered, and a subset with six features is selected, monitored, and analyzed using both internal methods (gain and cover) and external methods. The results (R2=0.884) display superior predictive capacity compared with existing models. Interpretation and error analysis are performed. Safety analysis is conducted to obtain references for use in practical engineering. Overall, this study presents a more accurate tool for use in seismic design and provides references for the evaluation and retrofitting of existing buildings. Our contributions hold significant implications for enhancing the safety and resilience of reinforced concrete structures

Prediction of Transverse Reinforcement of RC Columns Using Machine Learning Techniques

Transverse reinforcement of reinforced concrete (RC) columns contributes greatly to the ductility deformation capacity of RC structures. The existing models to predict the amount of transverse reinforcement required are all empirical models with low accuracy and large dispersion and have not considered the real ductility demand of individual components. This paper proposes a ductility design method of RC structure based on component drift ratio demand obtained from nonlinear structural dynamic analysis. To establish the best transverse reinforcement ratio prediction model for RC columns, based on an experimental database consisting of 498 columns, 12 machine learning (ML) models are trained. To solve the over-fitting problem caused by the current situation of “few samples and big errors” of the experimental database, feature engineering aiming at dimension reduction is systematically carried out through an iterative process. Through comprehensive performance evaluation on the testing set, an XGBoost model is selected. To interpret the “black box” ML model, the SHAP method and partial dependence plots are used to analyse the correlation between the input parameters and the transverse reinforcement ratio. The interpretation results are consistent with mechanical laws and engineering experience, which prove the reliability of the selected ML model. Compared with two existing empirical models, the proposed XGBoost model shows higher accuracy and smaller deviation. After safety probability analysis, the trained XGBoost model is transformed into C code and integrated into seismic design software for productive practice. An open-source data-driven model to predict the transverse reinforcement ratio required for RC columns is provided worldwide, with the flexibility to account for additional experimental results

Embedment Strength of Cross-Laminated Timber for Smooth Dowel-type Fasteners

Embedment strength is a significant property in the dowel type connection in timber structure, i.e. cross-laminated timber (CLT). The CLT design properties are different from those of sawn timber (ST) and glued-laminated timber (GLT) because of the orthogonal structure, which may particularly have influence on the design of connections. The layup feature, i.e. the thickness ratio of transverse layer (TRTL) was considered as an effective factor on CLT embedment strength in this study, except for other factors, i.e. wood density, smooth dowel diameter, and loading angle. Approximate 660 embedment tests were performed according to ASTM D5764 half-hole test method. A few of existing design models for CLT embedment strength were evaluated using experimental data. It was found that different factors had different effect tendency and each factor had statistically significant impact on CLT embedment strength. The embedment strength and failure modes of CLT were obviously different from those of GLT due to the existence of transverse layer in CLT. The existing design equations should be improved. Based on the test results, a new design equation was proposed which had better prediction