Bortezomib in relapsed/refractory immune thrombotic thrombocytopenic purpura: A single-centre retrospective cohort and systematic literature review.

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological condition. Initial treatment involves plasma exchange (PLEX), corticosteroids, caplacizumab and rituximab. In relapsed and refractory cases despite initial treatments, further immune-modulating therapy includes the proteasome inhibitor, bortezomib. Evidence for bortezomib in this setting is limited to case reports and case series. We report our experience and perform a systematic review of the literature. We identified 21 publications with 28 unique patients in addition to our cohort of eight patients treated with bortezomib. The median age of patients was 44 years (IQR: 27-53) and 69% female. They were usually in an initial, refractory presentation of iTTP where they had received PLEX, corticosteroids, rituximab and another line of therapy. After bortezomib administration, 72% of patients had a complete response, with 85% maintaining a durable response without relapse at the last follow-up.

A Scan of Pleiotropic Immune Mediated Disease Genes Identifies Novel Determinants of Baseline FVIII Inhibitor Status in Hemophilia-A.

Hemophilia-A (HA) is caused by heterogeneous loss-of-function factor (F)VIII gene (F8)-mutations and deficiencies in plasma-FVIII-activity that impair intrinsic-pathway-mediated coagulation-amplification. The standard-of-care for severe-HA-patients is regular infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called "FVIII-inhibitors (FEIs)" and become refractory. We used the PATH study and ImmunoChip to scan immune-mediated-disease (IMD)-genes for novel and/or replicated genomic-sequence-variations associated with baseline-FEI-status while accounting for non-independence of data due to genetic-relatedness and F8-mutational-heterogeneity. The baseline-FEI-status of 450 North American PATH subjects-206 with black-African-ancestry and 244 with white-European-ancestry-was the dependent variable. The F8-mutation-data and a genetic-relatedness matrix were incorporated into a binary linear-mixed model of genetic association with baseline-FEI-status. We adopted a gene-centric-association-strategy to scan, as candidates, pleiotropic-IMD-genes implicated in the development of either ³2 autoimmune-/autoinflammatory-disorders (AADs) or ³1 AAD and FEIs. Baseline-FEI-status was significantly associated with SNPs assigned to NOS2A (rs117382854; p=3.2E-6) and B3GNT2 (rs10176009; p=5.1E-6), which have functions in anti-microbial-/-tumoral-immunity. Among IMD-genes implicated in FEI-risk previously, we identified strong associations with CTLA4 assigned SNPs (p=2.2E-5). The F8-mutation-effect underlies ~15% of the total heritability for baseline-FEI-status. Additive genetic heritability and SNPs in IMD-genes account for >50% of the patient-specific variability in baseline-FEI-status. Race is a significant determinant independent of F8-mutation-effects and non-F8-genetics.

PBFT optimization algorithm based on community contributions.

Community governance is the basic unit of social governance, and it is also an important direction for building a social governance pattern of co-construction, co-governance and sharing. Previous studies have solved the problems of data security, information traceability and participant enthusiasm in the process of community digital governance by building a community governance system based on blockchain technology and incentive mechanisms. The application of blockchain technology can solve the problems of low data security, difficulty in sharing and tracing and low enthusiasm on the part of multiple subjects regarding participation in community governance. The process of community governance involves the cooperation of multiple government departments and multiple social subjects. Under the blockchain architecture, the number of alliance chain nodes will reach 1000 with the expansion of community governance. The existing consensus algorithms for coalition chains are difficult to meet the high concurrent processing requirements under such large-scale nodes. An optimization algorithm has improved the consensus performance to a certain extent, but the existing systems still cannot meet the data needs of the community and are not suitable for community governance scenarios. Since the community governance process only involves the participation of relevant departments in users, all nodes in the network are not required to participate in the consensus under the blockchain architecture. Therefore, a practical Byzantine fault tolerance (PBFT) optimization algorithm based on community contribution (CSPBFT) is proposed here. First, consensus nodes are set according to different roles of participants in community activities, and participants are given different consensus permissions. Second, the consensus process is divided into different stages, and the amount of data processed by each consensus step is reduced. Finally, a two-level consensus network is designed to perform different consensus tasks, and reduce unnecessary communication between nodes to reduce the communication complexity of consensus among nodes. Compared with the PBFT algorithm, CSPBFT reduces the communication complexity from O(N2) to O(N2/C3). Finally, the simulation results show that, through rights management, network level setting and consensus phase division, when the number of nodes in the CSPBFT network is 100-400, the consensus throughput can reach 2000 TPS. When the node in the network is 1000, the instantaneous concurrency is guaranteed to be above 1000 TPS, which can meet the concurrent needs of the community governance scenario.

Short Video Addiction on the Interaction of Creative Self-Efficacy and Career Interest to Innovative Design Profession Students.

In recent years, a variety of emerging online media, such as TikTok, Kuaishou, YouTube and other short video application platforms, have appeared. The problem of short video addiction has become an issue to education experts and the general public, as students' excessive use of short video has become increasingly serious with many hidden concerns to the students' learning effectiveness. In addition, to meet the growing demand for innovative design talents worldwide, the Taiwan government has been committed to promoting policies related to the cultivation of innovative and creative talents nowadays, particularly for innovative design profession students who often use the Internet and short videos for learning. Therefore, the study aims to use questionnaires to understand the habits and addiction of the innovative design profession students in using short videos, and to further investigate the relation of short video addiction to the students' creative self-efficacy (CSE) and career interests. A total of 561 valid questionnaires were collected after eliminating invalid questionnaires and reliability analysis. Structural equation modeling and model validation were conducted afterwards. The results showed that short video addiction had a negative effect on CSE; CSE had a positive effect on career interests; and CSE had an indirect effect between short video addiction and career interests.

Building operation and maintenance scheme based on sharding blockchain.

Blockchain can ensure data security and reliability during the stage of building operation and maintenance (BOM), provide reliable data for decision-making. However, existing schemes based on single-chain architecture have the problems of storage limitation and scalability, and ignore the impact of event's priority and real-time on blockchain transaction. Therefore, for BOM, this paper provides a BOM framework based on sharding blockchain (SBC-BOMF), which constructs two-layer architecture based on master-chain and multiple shards, relieves the storage pressure of blockchain nodes and improves the concurrency capability. Priority-based transaction handling strategy is designed to achieve reasonable and rapid response for multi-level transactions. Finally, an actual BOM project is taken as example to illustrate the effectiveness of proposed scheme; experiments are conducted for performance testing and evaluation. Results show that proposed scheme can effectively solve the scalability problem caused by the application of blockchain in BOM, reduce storage overhead, and realize efficient handling for blockchain transactions.

Construction of SARS-CoV-2 receptor binding domain molecular probe and its application in the isolation of neutralizing antibodies / 中国热带医学

@#Abstract: Objective　To construct SARS-CoV-2 receptor binding domain molecular probe for monoclonal memory B cell sorting and obtain RBD specific neutralizing antibodies from peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents by single-cell sorting. Methods　The SARS-CoV-2 RBD sequence was downloaded from GenBank, and the Avi tag and 6-histidine tags were added at the C-terminal. After codon optimization, it was chemically synthesized, cloned into the pDRVI1.0 vector, expressed after transfection of 293F cells, and biotinylated consequently. RBD-specific B cells were sorted out with this probe1 from the PBMCs of convalescents recovered from COVID-19. After B cells were lysed, the variable regions of heavy chain and light chain were amplified, cloned into the antibody expression vector, and transfected into 293F cells to express the antibody. Then the antibody was purified from the supernatant using protein A column and SARS-CoV-2 pseudovirus was used to test their neutralizing activity. Results　RBD-Avi probe was produced and successfully biotinylated sequentially with an efficiency of 30%-50%. Western blot analysis revealed that the biotinylated probe was recognized by the antibodies purified from COVID-19 convalescent plasma. Using this probe, 7 and 16 RBD-specific memory B cells were successfully isolated from the PBMCs of two convalescent individuals, accounting for 0.24% and 0.17% of the total cell population, respectively. After amplifying the variable regions of antibody heavy and light chains from the lysed B cells, 7 and 12 pairs of antibody heavy-light chains were obtained. A total of 16 antibodies were expressed in the convalescent individuals, and most of the purified antibodies showed neutralizing activity against the pseudovirus, with IC50 values of 6 antibodies below 1 μg/mL. The IC50 values of XJ-A9 and SCF-F1 against the wild-type pseudovirus were 0.07 μg/mL and 0.35 μg/mL, respectively. Conclusion　The SARS-CoV-2 RBD molecular probe constructed in this study has good antigenicity, and the isolated antibodies present neutralizing activity against wild-type SARS-CoV-2 pseudovirus.

Successful use of lenalidomide to treat refractory acquired von Willebrand disease associated with monoclonal gammopathy.

Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS.

Research on multi-person collaborative design of BIM drawing based on blockchain.

The existing multi-person collaborative design scheme of Building Information Modeling (BIM) integrated with blockchain faces problems such as poor reliability of BIM drawing, inconsistent drawing information, redundant information, and inaccurate protection of copyright interests. This paper proposes a multi-person collaborative design model for BIM drawing that combines blockchain and InterPlanetary File System (IPFS). This model uses blockchain to store drawing design information to protect the copyright interests of designers and combines IPFS to ensure the reliability of drawing. A cycle division mechanism is designed to solve the problem of drawing information synchronization when multiple people collaborate in design. The Semantic Differential Transaction (SDT) method is used to achieve incremental update of drawing and reduce the information redundancy of the blockchain. Finally, a comparative analysis and validation evaluation of the scheme is carried out, and the usability of the scheme is illustrated with an illustrative example. The results show that: (1) proposed scheme is feasible for multi-person collaborative design; (2) proposed scheme can effectively ensure the reliability of drawing and reduce the redundancy of blockchain information, so as to achieve copyright protection for designers.

Identification and characterization of tsyl1, a thermosensitive chlorophyll-deficient mutant in rice (Oryza sativa).

Chloroplast development and chlorophyll biosynthesis are affected by temperature. However, the underlying molecular mechanism of this phenomenon remains elusive. Here, we isolated and characterized a thermosensitive yellow-green leaf mutant named tsyl1 (thermosensitive yellow leaf 1) from an ethylmethylsulfone (EMS)-mutagenized pool of rice. The mutant exhibits a yellow-green leaf phenotype and decreased leaf chlorophyll contents throughout development. At the mature stage of the tsyl1 mutant, the plant height, tiller number, number of spikelets per panicle and 1000 seed weight were decreased significantly compared to those of wild-type plants, but the seed setting rate and panicle length were not. The mutant phenotype was controlled by a single recessive nuclear gene on the short arm of rice chromosome 11. Map-based cloning of TSYL1, followed by a complementation experiment, showed a G base deletion at the coding region of LOC_Os11g05552, leading to the yellow-green phenotype. The TSYL1 gene encodes a signal recognition particle 54 kDa (SRP54) protein that is conserved in all organisms. The expression of tsyl1 was induced by high temperature. Furthermore, the expression of chlorophyll biosynthesis- and chloroplast development-related genes was influenced in tsyl1 at different temperatures. These results indicated that the TSYL1 gene plays a key role in chlorophyll biosynthesis and is affected by temperature at the transcriptional level.

L2 Enjoyment of English as a Foreign Language Students: Does Teacher Verbal and Non-verbal Immediacy Matter?

This review explored the investigations on the role of teacher immediacy in English as a Foreign Language (EFL) learners' foreign language enjoyment. Earlier investigations have proved that teacher immediacy, such as posture, body language, vocal variety, gestures, and smile, can significantly affect learners' positive emotions like foreign language enjoyment. It means that teachers should try both to control the feelings of their learners and manage their feelings to enhance enjoyment among learners. Moreover, studies have shown that teacher immediacy is significantly related to learner motivation which is a basis for increasing foreign language enjoyment among learners. However, specific strategies can be employed to increase learner motivation, which in return increases learner foreign language enjoyment. Furthermore, the study presented the implications and future directions of this line of research for different people, such as EFL teachers, teacher educators, and foreign language scholars. The ideas can improve their awareness of teacher-student relationships, in particular, teacher immediacy and its role in learners' foreign language enjoyment.

Utilization of emicizumab in acquired hemophilia A: A case report.

BACKGROUND: Acquired Hemophilia A (AHA) is a rare autoimmune disorder associated with the development of autoantibodies against factor VIII (FVIII). Although obtaining hemostatic control through the use of recombinant factor VIIa, activated prothrombin complex concentrate and recombinant porcine FVIII are cornerstones in the clinical management of AHA, these therapies have several disadvantages, including a higher risk for the development of thromboembolic events, unpredictable efficacy and short half-lives. While emicizumab has been FDA licensed for use in bleeding prophylaxis for patients with Congenital Hemophilia A (CHA) with and without inhibitors, it has not been approved for use in AHA, with only a few reports describing its use in this context. CASE REPORT: We report our experience with the use of emicizumab in an 83-year old male with AHA, complicated by the onset of atrial fibrillation following admission, drug-induced thrombocytopenia, infectious complications, and the identification of a low-grade lymphoproliferative disorder, in which emicizumab prophylaxis was used for bleeding prophylaxis in the context of persistently elevated inhibitor titers without evidence of thrombotic events or thrombotic microangiopathy.

Corrigendum: New Breakthroughs and Innovation Modes in English Education in Post-pandemic Era.

[This corrects the article DOI: 10.3389/fpsyg.2022.839440.].

Increasing Chinese EFL Learners' Grit: The Role of Teacher Respect and Support.

Owing to the pivotal role of grit in scholastic success, factors that help learners become gritty are worth to be studied. Accordingly, this research sought to inspect the impact of teacher respect and teacher support on Chinese EFL learners' grit. In doing so, three reliable measures of the variables were sent to 613 Chinese EFL learners. Using Spearman correlation tests, strong connections were discovered between teacher respect, teacher support, and Chinese EFL learners' grit. Multiple regression analysis was then performed to inspect the role of teacher respect and teacher support in increasing Chinese EFL learners' grit. As a result, both teacher respect and teacher support were found to be highly influential in increased learner grit. The limitations and implications are discussed.

Robust PVC Identification by Fusing Expert System and Deep Learning.

Premature ventricular contraction (PVC) is one of the common ventricular arrhythmias, which may cause stroke or sudden cardiac death. Automatic long-term electrocardiogram (ECG) analysis algorithms could provide diagnosis suggestion and even early warning for physicians. However, they are mutually exclusive in terms of robustness, generalization and low complexity. In this study, a novel PVC recognition algorithm that combines deep learning-based heartbeat template clusterer and expert system-based heartbeat classifier is proposed. A long short-term memory-based auto-encoder (LSTM-AE) network was used to extract features from ECG heartbeats for K-means clustering. Thus, the templates were constructed and determined based on clustering results. Finally, the PVC heartbeats were recognized based on a combination of multiple rules, including template matching and rhythm characteristics. Three quantitative parameters, sensitivity (Se), positive predictive value (P+) and accuracy (ACC), were used to evaluate the performances of the proposed method on the MIT-BIH Arrhythmia database and the St. Petersburg Institute of Cardiological Technics database. Se on the two test databases was 87.51% and 87.92%, respectively; P+ was 92.47% and 93.18%, respectively; and ACC was 98.63% and 97.89%, respectively. The PVC scores on the third China Physiological Signal Challenge 2020 training set and hidden test set were 36,256 and 46,706, respectively, which could rank first in the open-source codes. The results showed that the combination strategy of expert system and deep learning can provide new insights for robust and generalized PVC identification from long-term single-lead ECG recordings.

Scurvy: a rare cause of haemarthrosis.

A male in his 60s with a history of previously treated locally advanced head and neck cancer presented to the emergency department with atraumatic left knee pain and upper and lower extremity ecchymoses that had been present for 3 weeks. His initial laboratory results showed a normocytic anaemia, normal platelet count, slightly abnormal coagulation studies and normal inflammatory markers. Arthrocentesis of the left knee revealed haemarthrosis, and additional laboratory workup found an undetectable serum vitamin C (ascorbic acid) level consistent with scurvy. It was determined that scurvy had predisposed the patient to injury, leading to haemarthrosis. Following vitamin C supplementation, dietary and activity modifications, and acetaminophen as needed, the patient's serum vitamin C level normalised and his left knee pain and swelling improved. Scurvy is a rare cause of haemarthrosis, but it should be recognised in at-risk patients since treatment is effective.

New Breakthroughs and Innovation Modes in English Education in Post-pandemic Era.

The outbreak of COVID-19 has brought drastic changes to English teaching as it has shifted from the offline mode before the pandemic to the online mode during the pandemic. However, in the post-pandemic era, there are still many problems in the effective implementation of the process of English teaching, leading to the inability of achieving better results in the quality and efficiency of English teaching and effective cultivation of students' practical application ability. In recent years, English speaking has attracted the attention of experts and scholars. Therefore, this study constructs an interactive English-speaking practice scene based on a virtual character. A dual-modality emotion recognition method is proposed that mainly recognizes and analyzes facial expressions and physiological signals of students and the virtual character in each scene. Thereafter, the system adjusts the difficulty of the conversation according to the current state of students, toward making the conversation more conducive to the students' understanding and gradually improving their English-speaking ability. The simulation compares nine facial expressions based on the eNTERFACE05 and CAS-PEAL datasets, which shows that the emotion recognition method proposed in this manuscript can effectively recognize students' emotions in interactive English-speaking practice and reduce the recognition time to a great extent. The recognition accuracy of the nine facial expressions was close to 90% for the dual-modality emotion recognition method in the eNTERFACE05 dataset, and the recognition accuracy of the dual-modality emotion recognition method was significantly improved with an average improvement of approximately 5%.

Lymphomatoid granulomatosis of the central nervous system (CNS-LYG) posing a management challenge.

Isolated central nervous system lymphomatoid granulomatosis (CNS-LYG) can mimic aggressive glioblastomas. We describe a complex presentation of CNS-LYG coexisting with immune thrombocytopenia successfully managed with rituximab and ultra-low-dose radiation therapy.

Protein Phosphatase 2A Activation Via ApoER2 in Trophoblasts Drives Preeclampsia in a Mouse Model of the Antiphospholipid Syndrome.

[Figure: see text].