bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors of second hematopoietic allogeneic stem cell transplantation among hematological malignancy patients relapsed after first hematopoietic stem cell transplantation: A single center study
Authors: Lu Yue , Zhang Jian-Ping , Zhao Yan-Li , Xiong Min , Sun Rui-Juan , Cao Xing-Yu , Wei Zhi-Jie , Zhou Jia-Rui , Liu De-Yan , Yang Jun-Fang , Zhang Xian , Lu Dao-Pei , Lu Peihua 
Published: January 2023

IntroductionWe aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1).MethodsWe retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021.ResultsThe median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 —disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.ConclusionsAllo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 —disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.
CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells
Authors: Brault Julie , Liu Taylor , Liu Siyuan , Lawson Amanda , Choi Uimook , Kozhushko Nikita , Bzhilyanskaya Vera , Pavel-Dinu Mara , Meis Ronald J. , Eckhaus Michael A. , Burkett Sandra S. , Bosticardo Marita , Kleinstiver Benjamin P. , Notarangelo Luigi D. , Lazzarotto Cicera R. , Tsai Shengdar Q. , Wu Xiaolin , Dahl Gary A. , Porteus Matthew H. , Malech Harry L. , De Ravin Suk See 
Published: January 2023

IntroductionEx vivo gene therapy for treatment of Inborn errors of Immunity (IEIs) have demonstrated significant clinical benefit in multiple Phase I/II clinical trials. Current approaches rely on engineered retroviral vectors to randomly integrate copy(s) of gene-of-interest in autologous hematopoietic stem/progenitor cells (HSPCs) genome permanently to provide gene function in transduced HSPCs and their progenies. To circumvent concerns related to potential genotoxicities due to the random vector integrations in HSPCs, targeted correction with CRISPR-Cas9-based genome editing offers improved precision for functional correction of multiple IEIs. MethodsWe compare the two approaches for integration of IL2RG transgene for functional correction of HSPCs from patients with X-linked Severe Combined Immunodeficiency (SCID-X1 or XSCID); delivery via current clinical lentivector (LV)-IL2RG versus targeted insertion (TI) of IL2RG via homology-directed repair (HDR) when using an adeno-associated virus (AAV)-IL2RG donor following double-strand DNA break at the endogenous IL2RG locus. Results and discussionIn vitro differentiation of LV- or TI-treated XSCID HSPCs similarly overcome differentiation block into Pre-T-I and Pre-T-II lymphocytes but we observed significantly superior development of NK cells when corrected by TI (40.7% versus 4.1%, p = 0.0099). Transplants into immunodeficient mice demonstrated robust engraftment (8.1% and 23.3% in bone marrow) for LV- and TI-IL2RG HSPCs with efficient T cell development following TI-IL2RG in all four patients’ HSPCs. Extensive specificity analysis of CRISPR-Cas9 editing with rhAmpSeq covering 82 predicted off-target sites found no evidence of indels in edited cells before (in vitro) or following transplant, in stark contrast to LV’s non-targeted vector integration sites. Together, the improved efficiency and safety of IL2RG correction via CRISPR-Cas9-based TI approach provides a strong rationale for a clinical trial for treatment of XSCID patients.
Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials
Authors: Wang Zhongwang , Zhou Hui , Xu Jing , Wang Jinjin , Niu Ting 
Published: January 2023

BackgroundDuvelisib is the first FDA-approved oral dual inhibitor of phosphatidylinositol-3-kinase PI3K-delta (PI3K-δ) and PI3K-gamma (PI3K-γ). Although many clinical studies support the efficacy of duvelisib, the safety of duvelisib remains with great attention. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of duvelisib in treating different relapsed or refractory (RR) lymphoid neoplasm types.MethodsWe searched prospective clinical trials from PUBMED, EMBASE, Cochrane Library, and ClinicalTrials.gov. For efficacy analysis, Overall response rate (ORR), complete response rate (CR), partial response rate (PR), rate of stable disease (SDR), rate of progressive disease (PDR), median progression-free survival (mPFS), 12-/24-month PFS, and 12-month overall survival (OS) were assessed. For safety analysis, the incidences of any grade and grade ≥3 adverse events (AEs), serious AEs, and treatment-related discontinuation and death were evaluated. Subgroup analysis based on the disease type was performed.ResultsWe included 11 studies and 683 patients, including 305 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 187 B-cell indolent non-Hodgkin lymphoma (iNHL), 39 B-cell aggressive non-Hodgkin lymphoma (aNHL), and 152 T-cell non-Hodgkin lymphoma (T-NHL) patients. The pooled ORR in CLL/SLL, iNHL, aNHL and T-NHL was 70%, 70%, 28% and 47%, respectively. Additionally, the pooled ORR in CLL/SLL patients with or without TP53 mutation/17p-deletion (62% vs. 74%, p=0.45) and in follicular lymphoma (FL) or other iNHL (69% vs. 57%, p=0.38) had no significant differences. Mantle cell lymphoma (MCL) patients had higher pooled ORR than other aNHL (68% vs. 17%, p=0.04). Angioimmunoblastic TCL (AITL) patients had higher pooled ORR than other PTCL patients (67% vs. 42%, p=0.01). The pooled incidence of any grade, grade ≥3, serious AEs, treatment-related discontinuation and death was 99%, 79%, 63%, 33% and 3%, respectively. The most frequent any-grade AEs were diarrhea (47%), ALT/AST increase (39%), and neutropenia (38%). The most frequent grade ≥3 AEs were neutropenia (25%), ALT/AST increased (16%), diarrhea (12%), and anemia (12%).ConclusionGenerally, duvelisib could offer favorable efficacy in patients with RR CLL/SLL, iNHL, MCL, and AITL. Risk and severity in duvelisib treatment may be mitigated through proper identification and management.
Surface acoustic wave sensor for formaldehyde gas detection using the multi-source spray-deposited graphene/PMMA composite film
Authors: Wang Beibei , Zhou Lingling , Wang Xiaoqian 
Published: January 2023

A surface acoustic wave (SAW) formaldehyde sensor based on a graphene/polymethyl methacrylate (PMMA) composite film with high sensitivity, and short response and recovery time was proposed in this study. Using a novel multi-source spray deposition method, graphene sheets were uniformly dispersed in a PMMA film to fabricate sensitive films with a three-dimensional framework structure for use in SAW devices. The formaldehyde-sensing ability was enhanced by optimizing the film thickness and operating temperature. The highest performance was achieved for a graphene/PPMA film thickness of 2.2 μm at a temperature of 120°C.
Research on the underwater cutting mechanism of flux-cored arc cutting for aluminum alloy process
Authors: Yu Rui , Li Wenhang , Wang Jiayou , Wu Mingfang , Wang Jianxin , Wu Jing , Maksimov Sergii Yuri 
Published: January 2023

With the fast-growing demand of aluminum alloys in ships and deep-sea pressure structures, an accurate and efficient underwater cutting operation for aluminum alloy is significant. However, its underwater arc cutting mechanism is still not clear enough, which limits its further application. The challenges lie in poor underwater visibility and complex underwater environment. In this study, process experiments, underwater sensor, and numerical simulations were conducted during cutting process to investigate the cutting mechanism of 5,052 aluminum. Firstly, the effect of parameters were investigated on cutting current, voltage, and water depth on the underwater kerf formation. In addition, three typical kerf formations, including “V” type, “II” type and “∧” type, were found; Secondly, visual sensing system was setup to monitor the cutting arc trajectory and the combustion process during the cutting process. Specially, the underwater burning phenomenon was observed. Finally, Finite Element Analysis was performed to further analyze the underwater arc cutting kerf formation of aluminum alloy. A semi-ellipsoidal composite heat source was applied to simulate the underwater arc, and the aluminum thermal reaction-generated heat was introduced. A dynamic method named “birth and death elements” was utilized to simulate the removal of molten metal. The temperature test results show that the simulation process is feasible. All results showed that different cutting parameters led to different cutting mode and affected the kerf forming. 5,052 aluminum alloy in the deep water environment (≥50 m) kerf significantly narrowed. The kerf cross-section produces an inward concavity and the kerf surface is as wide as the cutting wire. The aluminum kerf forming process is greatly impacted by the process parameters and self-propagating high-temperature synthesis reaction during aluminum alloy cutting. The periodicity of the cutting process was computed by the numerical simulation with the arc motion trajectory monitored by the high-speed camera. The numerical results of temperature distribution and kerf shape were consistent with the experimental data, which revealed the cutting mechanism.
Numerical calculation of a 20MN heavy duty hydraulic press for analyzing the double frame pre-stressed steel wire winding
Authors: Zhang Yumin , Wang Xigui , Wang Yongmei 
Published: January 2023

The expected preloading effect of a hydraulic press frame parts (upper/lower semi-circular beams and columns) with pre-stressed by means of Winding Steel Wires which is directly related to the reliability and normal safe operation of the hydraulic press. The deformation of the Hydraulic Press Column (HPC) is an important indicator of the optimal preloading effect of the hydraulic press. A novelty of this project is to break through a bottleneck technology, the continuous cumulative deformation of a Hydraulic Press Column under seven time-varying steps is critical issues especially in theoretically calculated for a 20 MN double-frame hydraulic press with pre-stressed using WAW. A solid model with a pre-stressed frame is pre-designed by 3D software, and two simulation methods, equivalent pressure loading and equivalent temperature loading, are used to simulate and analyze the continuous cumulative deformation of the HPC under each step in Ansys Workbench software. By comparing the deformation and error analysis in the three cases above, the feasibility of the two simulation methods is verified, which leads to the advantages and disadvantages of each method in order to guide the subsequent design.
Pancreatic enzyme supplementation versus placebo for improvement of gastrointestinal symptoms in non-responsive celiac disease: A cross-over randomized controlled trial
Authors: Yoosuf Shakira , Barrett Caitlin G. , Papamichael Konstantinos , Madoff Sarah E. , Kurada Satya , Hansen Joshua , Silvester Jocelyn A. , Therrien Amelie , Singh Prashant , Dennis Melinda , Leffler Daniel A. , Kelly Ciaran P. 
Published: January 2023

BackgroundPancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to treat non-responsive celiac disease (NRCD) in clinical practice, clinical outcomes are variable and there is limited and low quality evidence to support this practice. The aim of this study was to assess the efficacy of pancreatic enzyme supplements (PES) for improvement of gastrointestinal symptoms in NRCD.MethodsProspective, randomized, placebo-controlled, double-blind, cross-over trial in adults with NRCD examining Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores on PES (pancrelipase co-administered with omeprazole) versus placebo (omeprazole only) during a 10-day treatment period. The study was registered under the clinical trials registry (https://clinicaltrials.gov/ number, NCT02475369) on 18 Jun 2015.ResultsTwelve participants (nine female) were included in the per-protocol analysis; one participant had low fecal elastase-1. Pancrelipase was not associated with significant change in CeD-GSRS compared to placebo (−0.03 versus −0.26; P = 0.366). There was a significant decrease in mean values of total CeD-GSRS scores (3.58 versus 2.90, P = 0.004), abdominal pain (2.92 versus 2.42, P = 0.009), and diarrhea sub-scores (3.44 versus 2.92, P = 0.037) during the run-in period with omeprazole.ConclusionIn this prospective, cross-over randomized, placebo-controlled study, PES did not improve symptoms in patients with NRCD. It is unclear whether this is a trial effect or related to administration of omeprazole.
Associations of the distance-saturation product and low-attenuation area percentage in pulmonary computed tomography with acute exacerbation in patients with chronic obstructive pulmonary disease
Authors: Chen Kuan-Yuan , Kuo Hsiao-Yun , Lee Kang-Yun , Feng Po-Hao , Wu Sheng-Ming , Chuang Hsiao-Chi , Chen Tzu-Tao , Sun Wei-Lun , Tseng Chien-Hua , Liu Wen-Te , Cheng Wun-Hao , Majumdar Arnab , Stettler Marc , Tsai Cheng-Yu , Ho Shu-Chuan 
Published: January 2023

BackgroundChronic obstructive pulmonary disease (COPD) has high global health concerns, and previous research proposed various indicators to predict mortality, such as the distance-saturation product (DSP), derived from the 6-min walk test (6MWT), and the low-attenuation area percentage (LAA%) in pulmonary computed tomographic images. However, the feasibility of using these indicators to evaluate the stability of COPD still remains to be investigated. Associations of the DSP and LAA% with other COPD-related clinical parameters are also unknown. This study, thus, aimed to explore these associations.MethodsThis retrospective study enrolled 111 patients with COPD from northern Taiwan. Individuals’ data we collected included results of a pulmonary function test (PFT), 6MWT, life quality survey [i.e., the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT)], history of acute exacerbation of COPD (AECOPD), and LAA%. Next, the DSP was derived by the distance walked and the lowest oxygen saturation recorded during the 6MWT. In addition, the DSP and clinical phenotype grouping based on clinically significant outcomes by previous study approaches were employed for further investigation (i.e., DSP of 290 m%, LAA% of 20%, and AECOPD frequency of ≥1). Mean comparisons and linear and logistic regression models were utilized to explore associations among the assessed variables.ResultsThe low-DSP group (&lt;290 m%) had significantly higher values for the mMRC, CAT, AECOPD frequency, and LAA% at different lung volume scales (total, right, and left), whereas it had lower values of the PFT and 6MWT parameters compared to the high-DSP group. Significant associations (with high odds ratios) were observed of the mMRC, CAT, AECOPD frequency, and PFT with low- and high-DSP groupings. Next, the risk of having AECOPD was associated with the mMRC, CAT, DSP, and LAA% (for the total, right, and left lungs).ConclusionA lower value of the DSP was related to a greater worsening of symptoms, more-frequent exacerbations, poorer pulmonary function, and more-severe emphysema (higher LAA%). These readily determined parameters, including the DSP and LAA%, can serve as indicators for assessing the COPD clinical course and may can serve as a guide to corresponding treatments.
Determining the cause of intrauterine fetal death in monochorionic twins: A case report
Authors: Xie Anxia , Cui Yan , Luo Gang , Chen Xianxia , Zhang Xuecheng , Han Jie , Tong Li , Ren Yanming , Wei Xiaoxing 
Published: January 2023

BackgroundDetermining the cause of intrauterine fetal death is essential for patients to manage their next pregnancy. However, in the majority of cases of fetal death, the cause remains unexplained despite comprehensive evaluation, especially in the cases of twins. Among twin pregnancies, conditions of monochorionic twinning, commonly regarded as monozygotic, are more complicated than dichorionic ones.Case summaryWe systematically evaluated the cause of fetal death for a Han Chinese woman with monochorionic twinning following in vitro fertilization/embryo transfer. Discrepant karyotypes were unexpectedly discovered between the twins. One fetus had an aneuploid male karyotype (46, XY), dup (9) (p24.3-q13), and the other had a normal female karyotype (46, XX). We considered that the male died of aberration of chromosome 9 and the female died of subsequent acute exsanguination through vascular anastomosis.ConclusionThis study demonstrated the importance of recognizing the presence of monochorionic dizygotic twinning and the challenges of clinical management for twins following in vitro fertilization/double embryo transfer.
Immunoregulatory functions of mature CD10+ and immature CD10– neutrophils in sepsis patients
Authors: Liu Ming , Wang Guan , Wang Lin , Wang Yuqi , Bian Yuqing , Shi Hang , Liu Jie 
Published: January 2023

IntroductionNeutrophil plays a more and more important role in sepsis with paralysis of immunoregulation. Till now, there was no biomarker to identify and isolate the mature and immature neutrophils in sepsis patients. CD10 shows on mature neutrophils at the latest stages of its differentiation. Our study aimed to investigate whether CD10 was a valid biomarker for distinguishing immature and mature neutrophil subgroups under septic conditions and their immunoregulatory effects on lymphocytes.MethodsTotally 80 healthy volunteers and 107 sepsis patients were recruited in this study. Fluorescence-conjugated anti-CD66b, and anti-CD10 monoclonal antibodies followed by incubation with specific anti-fluorochrome microbeads was used to isolate different subgroups of neutrophils. T cell apoptotic assays and T cell proliferation assays followed by flow cytometry analysis were used to evaluate the immunoregulatory effect of each subgroup of neutrophils.Results(1) The cytological morphology of CD10+ neutrophils was mature and that of CD10– neutrophils was immature in sepsis patients. (2) Mature CD10+ neutrophils inhibited the proliferation of T cell and immature CD10– neutrophils promoted the T cell proliferation.Conclusion(1) CD10 was a good biomarker to distinguish mature from immature neutrophils in sepsis patients. (2) Mature CD10+ and immature CD10– neutrophils displayed opposite immunoregulatory effects on T cells in sepsis patients.
Potato calcineurin B-like protein CBL4, interacting with calcineurin B-like protein-interacting protein kinase CIPK2, positively regulates plant resistance to stem canker caused by Rhizoctonia solani
Authors: Yang Shuai , Li Jie , Lu Jie , Wang Ling , Min Fanxiang , Guo Mei , Wei Qi , Wang Wenzhong , Dong Xuezhi , Mao Yanzhi , Hu Linshuang , Wang Xiaodan 
Published: January 2023

IntroductionCalcium sensor calcineurin B-like proteins (CBLs) and their interacting partners, CBL-interacting protein kinases (CIPKs), have emerged as a complex network in response to abiotic and biotic stress perception. However, little is known about how CBL-CIPK complexes function in potatoes.MethodsIn this study, we identified the components of one potato signaling complex, StCBL4–StCIPK2, and characterized its function in defense against Rhizoctonia solani causing stem canker in potato.ResultsExpressions of both StCBL4 and StCIPK2 from potato were coordinately induced upon R. solani infection and following exposure to the defense genes. Furthermore, transient overexpression of StCBL4 and StCIPK2 individually and synergistically increased the tolerance of potato plants to R. solani in Nicotiana benthamiana. Additionally, the transgenic potato has also been shown to enhance resistance significantly. In contrast, susceptibility to R. solani was exhibited in N. benthamiana following virus-induced gene silencing of NbCBL and NbCIPK2. Evidence revealed that StCBL4 could interact in yeast and in planta with StCIPK2. StCBL4 and StCIPK2 transcription was induced upon R. solani infection and this expression in response to the pathogen was enhanced in StCBL4- and StCIPK2-transgenic potato. Moreover, accumulated expression of pathogenesis-related (PR) genes and reactive oxygen species (ROS) was significantly upregulated and enhanced in both StCBL4- and StCIPK2- transgenic potato.DiscussionAccordingly, StCBL4 and StCIPK2 were involved in regulating the immune response to defend the potato plant against R. solani. Together, our data demonstrate that StCBL4 functions in concert with StCIPK2, as positive regulators of immunity, contributing to combating stem canker disease in potato.