bluuebunny/crossref_metadata_2025_split huggingface dataset:
High efficacy and safety of CD38 and BCMA bispecific CAR-T in relapsed or refractory multiple myeloma
Authors: Tang Yuanyan , Yin Haisen , Zhao Xinying , Jin Dan , Liang Yan , Xiong Tao , Li Lu , Tang Wen , Zhang Jiangzhao , Liu Min , Yu Zhuojun , Liu Huimin , Zang Sibin , Huang Zhiping 
Published: January 2022

Abstract
Background
B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy has obtained promising results in relapsed or refractory multiple myeloma (R/R MM), while some patients do not response, or relapse in short term after treatment. Combining with anti-CD38 might solve the problem of targeting BCMA alone. We aimed to assess the efficacy and safety of BCMA and CD38 (BCMA-CD38) bispecific CAR-T cells in R/R MM patients.

Methods
We did a single-center, single-arm clinical study at the Second Affiliated Hospital of Yangtze University in China. Patients meeting with the inclusion criteria were administered with fludarabine and cyclophosphamide before CAR-T cells infusion. Response and adverse events were assessed after infusion. This study was registered with the Chinese Clinical Trial Registration Center (ChiCTR1900026286).

Results
First, we found BCMA-CD38 CAR-T cells exhibited enhanced killing effect on BCMA+CD38+ cells in vitro, compared to BCMA CAR-T and CD38 CAR-T cells. We further demonstrated its anti-tumor activity in vivo. Then, we enrolled 16 R/R MM patients for safety and efficacy analyses. Of the 16 evaluable patients, 14 (87.5%) respond to the treatment, including 13 stringent complete response (sCR) and one partial response (PR), while two patients did not respond. At a median follow-up of 11.5 months, of the 13 patients who achieved sCR, 76.9% (10/13) did not relapse or progress during follow-up. Relapse occurred in 3 patients (Patient 2, 3 and 4) after achieving sCR. In sum, four patients died, of which one died of hemophagocytic lymphohistiocytosis syndrome secondary to severe cytokine release syndrome (CRS) and three died of disease progression or relapse. The 1-year progression-free survival rates was 68.8%. The 1-year overall survival rate was 75.0%. Extramedullary lesions were eliminated in 62.5% (5/8) patients. The most common symptoms after CAR-T infusion were cytopenia (16, 100%), fever (10, 62.5%), fatigue (8, 50.0%) and myalgias (8, 50.0%). Twelve patients (75.0%) were observed with various grades of CRS, of which five patients (31.3%) got serious CRS (Grade ≥ 3). The CAR+ cell expansion levels were associated with the severity of CRS. Transient clonal isotype switch was observed after CAR-T infusion.

Conclusion
Our results confirm that BCMA-CD38 CAR-T cells therapy is feasible in treating R/R MM patients, with high response rate, low recurrence rate and manageable CRS, which will be a promising treatment option for R/R MM.

Trial registration
ChiCTR1900026286, registered on September 29, 2019, retrospectively registered, URL: https://www.chictr.org.cn/showproj.aspx?proj=43805
Effect of different conditioning methods of traditional Chinese health exercise on lung function in healthy middle-aged and elderly people: study protocol for a randomized controlled trial
Authors: Li Wenlong , Song Yapei , Xiang Qiuping , Wang Xinlei , Wei Xiaoyun , Fan Tonggang 
Published: January 2022

Abstract
Background
Lung function is highly age-dependent as it decreases in varying degrees with age, even in healthy people. Decreased lung function results in less elastic lung tissue, reduced chest wall compliance, reduced area for gas exchange, and even a variety of chronic diseases. Traditional Chinese health exercise (TCHE) has three components: “breath regulation,” “body regulation,” and “heart regulation,” which play an important role in the improvement of lung function. However, which component has the most significant effect on lung functioning remains unclear. Therefore, depending on the modality of conditioning, TCHEs will be divided into three exercise intervention groups: breath regulation group, body regulation group, and heart regulation group, in order to explore the magnitude of the effect of the different modalities of conditioning on the improvement of lung function.

Methods
The prospective, parallel, single-blind, randomized controlled trial will evaluate the effects of different conditioning methods of TCHE on lung function in middle-aged and elderly people. The study subjects are healthy middle-aged and elderly adults, who will be randomly divided into the “breath regulation group,” “body regulation group,” “heart regulation group,” and “control group.” The control group will receive health education. Health education and exercise intervention in the three intervention groups will be provided for 6 months, 5 times a week, with each session lasting 60 min. The outcomes of interest include changes in the pulmonary function tests measured at baseline and 3 and 6 months after the beginning of the intervention. The primary outcome is the forced vital capacity (FVC), while the secondary outcomes include forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio, vital capacity (VC), and maximal voluntary ventilation (MVV).

Discussion
This study will assess the effects of different conditioning methods of TCHE on lung function in middle-aged and elderly people. The final findings of this study will validate the effectiveness and safety of TCHE on lung function interventions in middle-aged and elderly people.

Trial registration
China Clinical Trial Registry ChiCTR2100052687. Registered on November 3, 2021
Hematological malignancies in systemic lupus erythematosus: clinical characteristics, risk factors, and prognosis—a case-control study
Authors: Zhang Yuqi , Li Wei , Zhang Panpan , Guo Jinyan , Sun Jinlei , Lu Jiameng , Liu Shengyun 
Published: January 2022

Abstract
Background
Systemic lupus erythematosus (SLE) is a chronic and complex multi-system autoimmune disorder. Higher risks of hematological malignancies (HM) were observed in SLE patients, which was associated with higher mortality. The mechanism and risk factors of HM oncogenesis in SLE patients are still under investigation. The aim of this study was to explore clinical characteristics, risk factors, and prognosis of SLE patients with or without HM in the Chinese population.

Methods
A retrospective, case-controlled study was conducted in 72 SLE patients between January 2013 and December 2020. Clinical and laboratory data were collected and compared between the two groups of patients with HM and those without HM. Logistic regression analysis was performed to determine risk factors of HM oncogenesis. The survival rate was estimated by Kaplan-Meier methods and Cox proportional hazards regression analysis.

Results
Among 72 SLE patients in this study, fifteen complicated with HM and 57 without HM were identified. The incidence rate of HM was approximately 0.24% with elevated standardized incidence ratios of lymphoma and leukemia (27.559 and 12.708, respectively). Patients with HM were older when diagnosed with SLE, with a higher frequency of infection and splenomegaly, lower levels of hemoglobin and high-density lipoprotein compared with those without HM. Fewer patients with HM expressed positive anti-dsDNA antibody (26.7% vs 66.7%, P = 0.005) or received hydroxychloroquine treatment (40.0% vs 86.0%, P = 0.001). Older age at SLE diagnosis (OR=1.122, 95% CI: 1.037–1.214) was regarded as an independent risk factor of HM oncogenesis. Female (RR= 0.219, 95% CI: 0.070–0.681) and hydroxychloroquine (RR= 0.281, 95% CI: 0.094–0.845) were protective factors of mortality in SLE patients.

Conclusions
SLE patients with an older age are at an increased risk of HM carcinogenesis. The prognosis of male patients with SLE tends to be poorer whether complicated with HM. The association of antinuclear antibody spectrum, medication, and HM oncogenesis in SLE needs further investigation.
Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis
Authors: An Ning , Yang Chen , Wu Hong-Luan , Guo Yun , Huang Xi-Jie , Huang Tong-Sheng , Wu Zhi-Hong , Xue Jing , Chen Rui-Hong , Li Zhi-Hang , Pan Qing-Jun , Liu Hua-Feng 
Published: January 2022

Abstract
Background
Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified.

Method
HCQ was administered on spontaneous female MRL/lpr LN mice with severe proteinuria daily for 4 weeks. Moreover, the MRL/lpr mice with proteinuric LN were subjected to cisplatin-induced or unilateral ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) after 2 weeks of HCQ preadministration.

Results
As expected, HCQ treatment increased the survival ratio and downregulated the levels of serum creatinine in the mice with LN, ameliorated renal lesions, and inhibited renal interstitial inflammation. Unexpectedly, HCQ preadministration significantly increased susceptibility to and delayed the recovery of AKI complicated by LN, as demonstrated by an increase in PTEC apoptosis and expression of the tubular injury marker KIM-1 as well as the retardation of PTEC replenishment. HCQ preadministration suppressed the proliferation of PTECs by arresting cells in G1/S phase and upregulated the expression of cell cycle inhibitors. Furthermore, HCQ preadministration disrupted the PTEC autophagy-lysosomal pathway and accelerated PTEC senescence.

Conclusion
HCQ treatment may increase susceptibility and delay the recovery of AKI complicated by LN despite its ability to improve LN-related renal immune-mediated inflammatory lesions. The probable mechanism involves accelerated apoptosis and inhibited proliferation of PTECs via autophagy-lysosomal pathway disruption and senescence promotion.
Performance of an automated ultrasound device in identifying and tracing the heart in porcine cardiac arrest
Authors: Olszynski Paul , Marshall Rory A. , Olver T. Dylan , Oleniuk Trevor , Auser Cameron , Wilson Tracy , Atkinson Paul , Woods Rob 
Published: January 2022

Abstract
Background
While intra-arrest echocardiography can be used to guide and monitor chest compression quality, it is not currently feasible on the scene of out-of-hospital cardiac arrests. Rapid and automated sonographic localization of the heart may provide first-responders guidance to an optimal area of compression without requiring them to interpret ultrasound images. In this proof-of-concept porcine study, we sought to describe the performance of an automated ultrasound device in correctly identifying and tracing the borders of the heart in three distinct states: pre-arrest, arrest, and late arrest.

Methods
An automated ultrasound device (bladder scanner) was placed on the chests of 7 swine, along the left sternal border (4th–8th intercostal spaces). Scanner-generated images were recorded for each space during pre-arrest, arrest, and finally late arrest. 828 images of the LV and LV outflow tract were randomized and 150 (50/state) selected for analysis. Scanner tracings of the heart were then digitally obscured to facilitate tracing by expert reviewers who were blinded to the physiologic state. Reviewer tracings were compared to bladder scanner tracings; with concordance between these images determined via Sørensen–Dice index (SDI).

Results
When compared to human reviewers, the bladder scanner was able to identify and trace the borders during cardiac arrest. The bladder scanner performed best at the time of arrest (SDI 0.900 ± 0.059). As resuscitation efforts continued and time from initial arrest increased, the scanner’s performance decreased dramatically (SDI 0.597 ± 0.241 in late arrest).

Conclusion
An automated ultrasound device (bladder scanner) reliably traced porcine hearts during cardiac arrest. It is possible a device could be developed to indicate where compressions should be performed without requiring the operator to interpret ultrasound images. Further investigation into rapid, automated, sonographic localization of the heart to identify the area of compression in out-of-hospital cardiac arrest is warranted.
Response from Varani et al. to “Comment on ‘the IS6 family, a clinically important group of insertion sequences including IS26’ by Ruth M. Hall”
Authors: Varani Alessandro , He Susu , Siguier Patricia , Ross Karen , Chandler Michael 
Published: January 2022

AbstractThe IS6 family of insertion sequences is a large but coherent group which was originally named to avoid confusion between a number of identical or nearly identical IS that were identified at about the same time and given different names (IS15D, IS26, IS46, IS140, IS160, IS176). The underlying common mechanistic feature of all IS6 family members which have been investigated is that they appear to transpose by replicative transposition and form pseudo compound transposons with the flanking IS in direct repeat and in which associated genes are simply transferred to the target replicon and lost from the donor.In the accompanying letter Hall raises a number of very serious and wide-ranging criticisms of our recent review article concerning the IS6 family of insertion sequences. She clearly feels that we have undervalued her work and that we question or ignore certain of her in vivo results. This impression is almost certainly the result of the standard of proof we generally apply to mechanistic aspects of transposition where we think it important to identify transposition intermediates including the types of synaptic, strand cleavage and strand transfer complexes involved.
Acute worsening of native lung fibrosis after single lung transplantation for pulmonary fibrosis: two case reports
Authors: Goletto Tiphaine , Decaux Sixtine , Bunel Vincent , Weisenburger Gaëlle , Messika Jonathan , Najem Samer , Medraoui Chahine , Godet Cendrine , Debray Marie Pierre , Lortat-Jacob Brice , Mordant Pierre , Castier Yves , Bouadma Lila , Borie Raphael , Mal Hervé 
Published: January 2022

Abstract
Background
In patients receiving single lung transplantation for idiopathic pulmonary fibrosis, worsening of fibrosis of the native lung is usually progressive over time, with no significant effects on gas exchange.

Case presentation
Here, we describe the cases of two Caucasian male recipients of single lung transplants for idiopathic pulmonary fibrosis, 65 and 62 years of age, who exhibited acute worsening of lung fibrosis after an episode of serious viral infection (cytomegalovirus primo-infection in one case and COVID-19 in the other). In both cases, along with opacification of the native lung over several days, the patients presented acute respiratory failure that required the use of high-flow nasal oxygen therapy. Eventually, hypoxemic respiratory failure resolved, but with rapid progression of fibrosis of the native lung.

Conclusion
We conclude that acute worsening of fibrosis on the native lung secondary to a severe viral infection should be added to the list of potential complications developing on the native lung after single lung transplantation for idiopathic pulmonary fibrosis.
How deep is your model? Network topology selection from a model validation perspective
Authors: Nowaczyk Nikolai , Kienitz Jörg , Acar Sarp Kaya , Liang Qian 
Published: January 2022

AbstractDeep learning is a powerful tool, which is becoming increasingly popular in financial modeling. However, model validation requirements such as SR 11-7 pose a significant obstacle to the deployment of neural networks in a bank’s production system. Their typically high number of (hyper-)parameters poses a particular challenge to model selection, benchmarking and documentation. We present a simple grid based method together with an open source implementation and show how this pragmatically satisfies model validation requirements. We illustrate the method by learning the option pricing formula in the Black–Scholes and the Heston model.
Plasmatic MMP9 released from tumor-infiltrating neutrophils is predictive for bevacizumab efficacy in glioblastoma patients: an AVAglio ancillary study
Authors: Jiguet-Jiglaire Carine , Boissonneau Sebastien , Denicolai Emilie , Hein Victoria , Lasseur Romain , Garcia Josep , Romain Sylvie , Appay Romain , Graillon Thomas , Mason Warren , Carpentier Antoine F. , Brandes Alba A. , Ouafik L.’Houcine , Wick Wolfgang , Baaziz Ania , Gigan Julien P. , Argüello Rafael J. , Figarella-Branger Dominique , Chinot Olivier , Tabouret Emeline 
Published: January 2022

AbstractWe previously identified matrix metalloproteinase 2 (MMP2) and MMP9 plasma levels as candidate biomarkers of bevacizumab activity in patients with recurrent glioblastoma. The aim of this study was to assess the predictive value of MMP2 and MMP9 in a randomized phase III trial in patients with newly diagnosed glioblastoma and to explore their tumor source. In this post hoc analysis of the AVAglio trial (AVAGlio/NCT00943826), plasma samples from 577 patients (bevacizumab, n = 283; placebo, n = 294) were analyzed for plasma MMP9 and MMP2 levels by enzyme-linked immunosorbent assay. A prospective local cohort of 38 patients with newly diagnosed glioblastoma was developed for analysis of tumor characteristics by magnetic resonance imaging and measurement of plasma and tumor levels of MMP9 and MMP2. In this AVAglio study, MMP9, but not MMP2, was correlated with bevacizumab efficacy. Patients with low MMP9 derived a significant 5.2-month overall survival (OS) benefit with bevacizumab (HR 0.51, 95% CI 0.34–0.76, p = 0.0009; median 13.6 vs. 18.8 months). In multivariate analysis, a significant interaction was seen between treatment and MMP9 (p = 0.03) for OS. In the local cohort, we showed that preoperative MMP9 plasma levels decreased after tumor resection and were correlated with tumor levels of MMP9 mRNA (p = 0.03). However, plasma MMP9 was not correlated with tumor size, invasive pattern, or angiogenesis. Using immunohistochemistry, we showed that MMP9 was expressed by inflammatory cells but not by tumor cells. After cell sorting, we showed that MMP9 was expressed by CD45+ immune cells. Finally, using flow cytometry, we showed that MMP9 was expressed by tumor-infiltrating neutrophils. In conclusion, circulating MMP9 is predictive of bevacizumab efficacy and is released by tumor-infiltrating neutrophils.
Suicidal ideation, self-injury, aggressive behavior and substance use during intensive trauma-focused treatment with exposure-based components in adolescent and young adult PTSD patients
Authors: Fischer Anne , Rosner Rita , Renneberg Babette , Steil Regina 
Published: January 2022

Abstract
Background
Multiple traumata such as child sexual and/or physical abuse often result in complex psychopathologies and a range of associated dysfunctional behaviors. Although evidence-based interventions exist, some therapists are concerned that trauma-focused psychotherapy with exposure-based elements may lead to the deterioration of associated dysfunctional behaviors in adolescents and young adults. Therefore, we examined the course of suicidal ideation, self-injury, aggressive behavior and substance use in a group of abuse-related posttraumatic stress disorder (PTSD) patients during phase-based, trauma-focused PTSD treatment.

Methods
Daily assessments from a randomized controlled trial (RCT) of Developmentally adapted Cognitive Processing Therapy (D-CPT) were analyzed to test for differences in the stated dysfunctional behaviors between the four treatment phases. We conducted multilevel modeling and repeated measure ANOVAs.

Results
We did not find any significant differences between the treatment phases concerning the stated dysfunctional behaviors, either at the level of urge or at the level of actual actions. On the contrary, in some primary outcomes (self-injury, aggressive behavior), as well as secondary outcomes (distress caused by trauma, joy), we observed significant improvements.

Discussion
Overall, during D-CPT, adolescents and young adults showed no deterioration in dysfunctional behaviors, while even showing improvements in some, suggesting that trauma-focused treatment preceded by skills building was not deleterious to this population. Hence, the dissemination of effective interventions such as D-CPT should be fostered, whilst the concerns of the therapists regarding exposure-based components need to be addressed during appropriate training. Nevertheless, further studies with momentary assessment, extended measurement methods, a control group and larger sample sizes are needed to confirm our preliminary findings.

Trial registration
The trial was registered at the German Clinical Trial Registry (GCTR), DRKS00004787, 18 March 2013, https://www.drks.de/DRKS00004787.
Parathyroid hormone promotes maxillary expansion and reduces relapse in the repeated activation maxillary expansion rat model by regulating Wnt/β-catenin pathway
Authors: Xu Mengting , Li Yuan , Feng Xiaoxia , Zheng Wei , Zhao Zhihe , Li Yu 
Published: January 2022

Abstract
Background
Constricted maxillary bone is a common skeletal deformity, which may lead to crowding and posterior crossbite. Mid-palatal suture expansion is often used to increase the maxillary width, but its skeletal effects are limited and tend to relapse, even with prolonged retention. We hypothesized that parathyroid hormone (PTH) may reduce the relapse of maxillary expansion.

Methods
We established a novel rat maxillary expansion model using palatal tubes with an insertable “W”-shaped spring which can be repeatedly activated. A total of 32 male healthy Wistar rats were randomly divided into six groups: the control group, the PTH group, the expansion group, the expansion + PTH group, the expansion + relapse group and the expansion + PTH + relapse group. All animals in the first 4 groups were killed after 10 days and the 2 relapse groups were killed after 15 days. The maxillary arch widths and histological staining were used to assess the expansion and relapse effects. The immunohistochemical staining, micro-CT, RT-qPCR and Western blot were used to evaluate the bone remodeling during expansion.

Results
The suture width was increased by the expansion device, and the repeated activation maxillary expansion rat model showed better expansion effects than the conventional model. PTH significantly promoted the expansion width and reduced the relapse ratio. Meanwhile, in the expansion + PTH group, histological and immunohistochemical staining showed that osteoblasts, osteoclasts, new cartilage and osteoid were significantly increased, micro-CT showed increased bone mass, and PCR and Western blot results confirmed up-regulation of RANKL, β-catenin, type II collagen and OCN.

Conclusion
The novel repeated activation maxillary expansion rat model has better effects than the conventional model. PTH enhances the maxillary expansion and reduces its relapse by regulating Wnt/β-catenin and RANKL pathways. PTH administration may serve as an adjunctive therapy in addition to mechanical expansion for treatment of maxillary constriction.