bluuebunny/crossref_metadata_2025_split huggingface dataset:
Underestimated and ignored? The impacts of microplastic on soil invertebrates—Current scientific knowledge and research needs
Authors: Möhrke Anne Christel Franka , Haegerbaeumer Arne , Traunspurger Walter , Höss Sebastian 
Published: October 2022

The accumulation of plastics in the environment is a major problem in the Anthropocene. As most plastic is produced, used and discarded on land, ∼4–23 times more plastics are deposited in soils than in the oceans. However, there is far too little knowledge on the ecological consequences of plastic pollution, especially for soil ecosystems. Microplastics (&lt;5 mm), whether derived from larger plastic pieces through physical, chemical and biological degradation or produced as primary particles, is of considerable interest, as they can be ingested by organisms at the basis of the trophic net and transferred to higher trophic levels. Nonetheless, although the assessment of microplastic effects on soil invertebrates is of undeniable relevance, most studies have focussed on nano- and microplastics in aquatic environments. This review examines the current state of knowledge regarding the effects of microplastics on soil invertebrates. As part of the soil biota, these organisms are of utmost importance for carbon cycling, respiration and biodiversity. Based on strict quality criteria, the data of 45 papers reporting ecotoxicological effects on soil invertebrates were analyzed, considering various test organisms and types of microplastic (in terms of polymer, shape and size). However, although different impacts were demonstrated, a deduction of general effect tendencies of microplastics in soils was difficult due to the scarcity of data and the use of diverse methodological setups. Moreover, almost all experiments were based on short-term single-species testing involving only a small number of species and single microplastic types. The review concludes with a discussion of the remaining knowledge gap and the needs for a standardized approach allowing an ecologically relevant risk assessment of the impacts of microplastic on invertebrates in terrestrial ecosystems.
CD38-specific nanobodies allow in vivo imaging of multiple myeloma under daratumumab therapy
Authors: Pape Luca Julius , Hambach Julia , Gebhardt Anna Josephine , Rissiek Björn , Stähler Tobias , Tode Natalie , Khan Cerusch , Weisel Katja , Adam Gerhard , Koch-Nolte Friedrich , Bannas Peter 
Published: October 2022

RationaleRecent studies have demonstrated the feasibility of CD38-specific antibody constructs for in vivo imaging of multiple myeloma. However, detecting multiple myeloma in daratumumab-pretreated patients remains difficult due to overlapping binding epitopes of the CD38-specific imaging antibody constructs and daratumumab. Therefore, the development of an alternative antibody construct targeting an epitope of CD38 distinct from that of daratumumab is needed. We report the generation of a fluorochrome-conjugated nanobody recognizing such an epitope of CD38 to detect myeloma cells under daratumumab therapy in vitro, ex vivo, and in vivo.MethodsWe conjugated the CD38-specific nanobody JK36 to the near-infrared fluorescent dye Alexa Fluor 680. The capacity of JK36AF680 to bind and detect CD38-expressing cells pretreated with daratumumab was evaluated on CD38-expressing tumor cell lines in vitro, on primary myeloma cells from human bone marrow biopsies ex vivo, and in a mouse tumor model in vivo.ResultsFluorochrome-labeled nanobody JK36AF680 showed specific binding to CD38-expressing myeloma cells pretreated with daratumumab in vitro and ex vivo and allowed for specific imaging of CD38-expressing xenografts in daratumumab-pretreated mice in vivo.ConclusionsOur study demonstrates that a nanobody recognizing a distinct, non-overlapping epitope of CD38 allows the specific detection of myeloma cells under daratumumab therapy in vitro, ex vivo, and in vivo.
Anakinra Pilot – a clinical trial to demonstrate safety, feasibility and pharmacokinetics of interleukin 1 receptor antagonist in preterm infants
Authors: Green Elys A. , Metz David , Galinsky Robert , Atkinson Rebecka , Skuza Elizbeth M. , Clark Megan , Gunn Alistair J , Kirkpatrick Carl M. , Hunt Rod W. , Berger Philip J. , Nold-Petry Claudia A. , Nold Marcel F. 
Published: October 2022

BackgroundBronchopulmonary dysplasia (BPD), its complication pulmonary hypertension (BPD-PH) and preterm brain and gut injury lead to significant morbidity and mortality in infants born extremely prematurely. There is extensive evidence that the pro-inflammatory cytokine interleukin 1 (IL-1) plays a key role in the pathophysiology of these illnesses. Two decades of clinical use in paediatric and adult medicine have established an excellent safety and efficacy record for IL-1 blockade with IL-1 receptor antagonist (IL-1Ra, medication name anakinra). Building on robust pre-clinical evidence, the Anakinra Pilot trial aims to demonstrate safety and feasibility of administering anakinra to preterm infants, and to establish pharmacokinetics in this population. Its ultimate goal is to facilitate large studies that will test whether anakinra can ameliorate early-life inflammation, thus alleviating multiple complications of prematurity.Methods and analysisAnakinra Pilot is an investigator-initiated, single arm, safety and feasibility dose-escalation trial in extremely preterm infants born between 24 weeks 0 days (240) and 276 weeks of gestational age (GA). Enrolled infants will receive anakinra intravenously over the first 21 days after birth, starting in the first 24 h after birth. In the first phase, dosing is 1 mg/kg every 48 h, and dosage will increase to 1.5 mg/kg every 24 h in the second phase. Initial anakinra dosing was determined through population pharmacokinetic model simulations. During the study, there will be a interim analysis to confirm predictions before undertaking dose assessment. Anakinra therapy will be considered safe if the frequency of adverse outcomes/events does not exceed that expected in infants born at 240-276 weeks GA.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT05280340.
The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis
Authors: Liu Shuhui , Yin Ruiying , Yang Ziwei , Wei Feili , Hu Jianhua 
Published: October 2022

BackgroundRhubarb is an important traditional Chinese medicine, and rhein is one of its most important active ingredients. Studies have found that rhein can improve ulcerative colitis by regulating gut microbes, but there are few reports on its effects on liver diseases. Therefore, this study aims to investigate these effects and underlying mechanisms.MethodsMice were given rhein (100 mg/kg), with both a normal control group and a model group receiving the same amount of normal saline for one week. Acute liver injury was induced in mice by intraperitoneal injection of D-GalN (800 mg/kg)/LPS (10 ug/kg). Samples (blood, liver, and stool) were then collected and assessed for histological lesions and used for 16S rRNA gene sequencing, high-performance liquid chromatography-mass spectrometry (LC-MS) and RNA-seq analysis.ResultsThe levels of ALT and AST in the Model group were abnormal higher compared to the normal control group, and the levels of ALT and AST were significantly relieved in the rhein group. Hepatic HE staining showed that the degree of liver injury in the rhein group was lighter than that in the model group, and microbiological results showed that norank_o:Clostridia_UCG-014, Lachnoclostridium, and Roseburia were more abundant in the model group compared to the normal control group. Notably, the rhein treatment group showed reshaped disturbance of intestinal microbial community by D-GalN/LPS and these mice also had higher levels of Verrucomicrobia, Akkermansiaceae and Bacteroidetes. Additionally, There were multiple metabolites that were significantly different between the normal control group and the model group, such as L-α-amino acid, ofloxacin-N-oxide, 1-hydroxy-1,3-diphenylpropan-2-one,and L-4-hydroxyglutamate semialdehyde, but that returned to normal levels after rhein treatment. The gene expression level in the model group also changed significantly, various genes such as Cxcl2, S100a9, Tnf, Ereg, and IL-10 were up-regulated, while Mfsd2a and Bhlhe41 were down-regulated, which were recovered after rhein treatment.ConclusionOverall, our results show that rhein alleviated D-GalN/LPS-induced acute liver injury in mice. It may help modulate gut microbiota in mice, thereby changing metabolism in the intestine. Meanwhile, rhein also may help regulate genes expression level to alleviate D-GalN/LPS-induced acute liver injury.
Clinical features and prognosis of MPO-ANCA and anti-GBM double-seropositive patients
Authors: Hu Xueling , Shen Chanjuan , Meng Ting , Ooi Joshua D. , Eggenhuizen Peter J. , Zhou Ya-ou , Luo Hui , Chen Jin-biao , Lin Wei , Gong Yizi , Xiong Qi , Xu Jia , Liu Ning , Xiao Xiangcheng , Tang Rong , Zhong Yong 
Published: October 2022

BackgroundSeveral lines of evidence implicate that there are distinct differences between patients with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) antibody double-seropositive patients (DPPs) and single-positive patients. Hence, we conducted a retrospective study from a single center in China to analyze the clinical and pathological features, and prognosis of DPPs.Methods109 patients with MPO-ANCA-associated vasculitis (MPO-AAV), 20 DPPs and 23 patients diagnosed with anti-GBM disease from a large center in China were included in this study. The ratio of patients with renal biopsy in three groups were 100%, 50% and 100%, respectively. Their clinical and pathological characteristics, and outcomes were analyzed. The intensity of immune deposits in the kidney at diagnosis was detected by immunofluorescence (IF). Furthermore, multivariate Cox hazard model analysis was used to assess the clinical and histological predictors of end-stage renal disease (ESRD) and death for DPPs.ResultsIn our study, we found that patients in the DPPs group were older than the other two groups (p = 0.007, MPO-AAV vs. DPPs; p &lt; 0.001, DPPs vs. anti-GBM). The DPPs group had a higher value of serum creatinine (p = 0.041) and lower estimated glomerular filtration rate (eGFR) (p = 0.032) compared with MPO-AAV patients. On the contrary, the DPPs group had a lower serum creatinine (p = 0.003) compared with patients with anti-GBM group. The proportion of patients with cardiac system involvement in the DPPs group was higher than anti-GBM patients (p = 0.014). Cellular crescents could be generally observed in renal biopsy of DPPs and patients with anti-GBM glomerulonephritis. In addition, Bowman’s capsule rupture was more common in DPPs than MPO-AAV patients (p = 0.001). MPO-AAV had a better renal and overall survival outcome than DPPs (p &lt; 0.001). There was no significant difference of renal and overall survival outcome between DPPs and patients with anti-GBM disease. The incidence of ESRD in DPPs was negatively associated with lymphocyte count (HR 0.153, 95% CI 0.027 to 0.872, p = 0.034) and eGFR (HR 0.847, 95% CI 0.726 to 0.989, p = 0.036). Elevated serum creatinine was confirmed as a risk factor of both renal (HR 1.003, 95% CI 1.000 to 1.005, p = 0.019) and patient survival in DPPs (HR1.461, 95% CI 1.050 to 2.033, p = 0.024).ConclusionIn summary, compared with anti-GBM disease, DPPs tended to involve multi-organ damage rather than limited to the kidney. It is highlighted that serologic DPPs have a worse renal and patient prognosis than MPO-AAV. Moreover, we found that the risk factors of renal survival of DPPs include low lymphocyte count, elevated serum creatinine and reduced eGFR, and serum creatinine can predict patient survival.
Patterns and predictors of recurrence after laparoscopic resection of rectal cancer
Authors: Yang Hong , Chen Lei , Wu Xiuxiu , Zhang Chenghai , Yao Zhendan , Xing Jiadi , Cui Ming , Jiang Beihai , Su Xiangqian 
Published: October 2022

PurposeThis study was designed to evaluate the patterns and predictors of recurrence in patients who underwent laparoscopic resection of rectal cancer.MethodsPatients with rectal cancer receiving laparoscopic resection between April 2009 and March 2016 were retrospectively analyzed. The association of recurrence with clinicopathological characteristics was evaluated using multivariate analyses.ResultsA total of 405 consecutive patients were included in our study. Within a median follow-up time of 62 months, 77 patients (19.0%) experienced disease recurrence: 10 (2.5%) had locoregional recurrence (LR), 61 (15.1%) had distant metastasis (DM), and 6 (1.5%) developed LR and DM synchronously. The lung was the most common site of metastasis. Multivariate analyses indicated that involved circumferential resection margin (CRM) was the only independent predictor for LR (OR=13.708, 95% CI 3.478-54.026, P&lt;0.001), whereas elevated baseline level of CA19-9 (OR=3.299, 95% CI 1.461-7.449, P=0.032), advanced pN stage (OR=2.292, 95% CI 1.177-4.462, P=0.015) and harvested lymph nodes less than 12 (OR=2.418, 95% CI 1.245-4.695, P=0.009) were independently associated with DM. Patients receiving salvage surgery showed superior 3-year survival compared with palliative treatment after relapse (90.9% vs. 20.5%; P=0.017). The estimated 5-year DFS and CSS for the entire cohort was 80.2% and 83.1%, respectively.ConclusionsDM was more common than LR after laparoscopic resection of rectal cancer, and there were several clinicopathological factors related to LR and DM. Involved CRM and suboptimal lymph node yield were adverse surgery-related factors of tumor recurrence, which should be paid more attention to during the operation.
Extended adjuvant endocrine therapy for women with hormone receptor-positive early breast cancer: A meta-analysis with trial sequential analysis of randomized controlled trials
Authors: Xie Ming , Zhong Yan , Yang Yide , Shen Fang , Nie Yue 
Published: October 2022

ObjectivesThe aim of the current study is to explore the association between extended adjuvant endocrine treatment and prognosis of women with hormone receptor-positive (HR+) early breast cancer.MethodsDatabases including PubMed, Web of Science, Embase and the Cochrane Library databases were electronically searched to identify randomized controlled trials (RCTs) that reported extended endocrine therapy for women with HR+ early breast cancer. The retrieval time was limited from inception to September 2022. Two reviewers independently screened literature, extracted data, and assessed risk bias of included studies. Meta-analysis was performed by using R software Version 4.1.2 and STATA Version 12.0.ResultsA total of 15 RCTs involving 29497 cases were included. The overall analysis showed that compared with the control, extended adjuvant endocrine therapy increased disease-free survival (DFS) (HR=0.814, 95% CI: 0.720-0.922, 95% PI: 0.556-1.194), overall survival (OS) (HR=0.885, 95% CI: 0.822-0.953, 95% PI: 0.771-1.035), relapse-free survival (RFS) (HR=0.833, 95% CI: 0.747-0.927, 95% PI: 0.575-1.159), distant metastatic-free survival (DMFS) (HR=0.824, 95% CI: 0.694-0.979, 95% PI: 0.300-2.089) and reduced new breast cancer cumulative incidence (NBCCI) (HR=0.484, 95% CI: 0.403-0.583, 95% PI: 0.359-0.654). For adverse events, extended adjuvant endocrine treatment was associated with a significantly higher risk of bone fracture (RR=1.446, 95% CI: 1.208-1.730, 95% PI: 1.154-1.854) and osteoporosis (RR=1.377, 95% CI: 1.018-1.862, 95% PI: 0.347-5.456).ConclusionOur study showed that extended adjuvant endocrine therapy increased DFS, OS, RFS, DMFS, the incidence of bone fracture and osteoporosis, and reduced NBCCI.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42022351295)
Evaluation of systemic inflammatory and nutritional indexes in locally advanced gastric cancer treated with adjuvant chemoradiotherapy after D2 dissection
Authors: Wang Shu-Bei , Chen Jia-Yi , Xu Cheng , Cao Wei-Guo , Cai Rong , Cao Lu , Cai Gang 
Published: October 2022

BackgroundMany studies have shown that the peripheral blood inflammatory index and nutritional index, such as the platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI), are independent prognostic factors for tumors. The present study aimed to investigate the prognostic role of these peripheral blood indexes before treatment in locally advanced gastric cancer (LAGC) treated with adjuvant chemoradiotherapy after D2 dissection.MethodsA total of 89 patients with LAGC who underwent D2 gastrectomy and adjuvant chemoradiotherapy at our hospital from 2010–2018 were eligible. Systemic inflammatory indicators before treatment were evaluated. Receiver operating characteristic curve (ROC), Kaplan–Meier analysis, and Cox regression were utilized for prognosis evaluation.ResultsThe median follow-up time was 29.1 (4.1–115.8) months. The overall survival at 3 years (OS) and the disease-free survival (DFS) were 78.9% and 59.1%, respectively. According to the ROC curve for 3-year DFS, the best cut-off values of pre-treatment NLR, PLR, LMR, SII, SIRI, PIV and PNI were 1.7, 109.3, 2.9, 369.2, 0.58, 218.7, and 48, respectively. Multivariate Cox regression analysis showed that NLR was an independent prognostic factor for DFS (HR 2.991, 95%CI 1.085–8.248, P = 0.034). Kaplan-Meier analysis showed that a higher NLR (&gt;1.70) was significantly associated with a poorer OS (3-year OS: 68.8% vs 92.9%, P = 0.045) and DFS (3-year DFS: 47.5% vs 80.9%, P = 0.005). In terms of the free locoregional recurrence rate (LRR), the prognosis of patients with high NLR was also significantly worse than those with low NLR (70.2% vs 96.0%, P = 0.017). Paraaortic lymph nodes were the most common site of LRR (7/14 patients). The seven cases of paraaortic lymph node metastasis occurred in patients with high NLR.ConclusionsIn our retrospective analysis, we found that pretreatment NLR could serve as a prognostic factor for survival in LAGC treated with adjuvant chemoradiotherapy after D2 dissection, especially for the prediction of LRR and paraaortic lymph node metastasis. Prospective studies are needed to confirm our findings.
Multidimensional characteristics, prognostic role, and preoperative prediction of peritoneal sarcomatosis in retroperitoneal sarcoma
Authors: Li Yang , Wu Jian-Hui , Li Cheng-Peng , Liu Bo-Nan , Tian Xiu-Yun , Qiu Hui , Hao Chun-Yi , Lv Ang 
Published: October 2022

BackgroundPeritoneal sarcomatosis (PS) could occur in patients with retroperitoneal sarcomas (RPS). This study aimed to expand the understanding of PS on its characteristics and prognostic role, and develop a nomogram to predict its occurrence preoperatively.MethodsData of 211 consecutive patients with RPS who underwent surgical treatment between 2011 and 2019 was retrospectively reviewed. First, the clinicopathological characteristics of PS were summarized and analyzed. Second, the disease-specific survival (DSS) and recurrence-free survival (RFS) of patients were analyzed to evaluate the prognostic role of PS. Third, preoperative imaging, nearly the only way to detect PS preoperatively, was combined with other screened risk factors to develop a nomogram. The performance of the nomogram was assessed.ResultsAmong the 211 patients, 49 (23.2%) patients had PS with an incidence of 13.0% in the primary patients and 35.4% in the recurrent patients. The highest incidence of PS occurred in dedifferentiated liposarcoma (25.3%) and undifferentiated pleomorphic sarcoma (25.0%). The diagnostic sensitivity of the preoperative imaging was 71.4% and its specificity was 92.6%. The maximum standardized uptake value (SUVmax) was elevated in patients with PS (P&lt;0.001). IHC staining for liposarcoma revealed that the expression of VEGFR-2 was significantly higher in the PS group than that in the non-PS group (P = 0.008). Survival analysis (n =196) showed significantly worse DSS in the PS group than in non-PS group (median: 16.0 months vs. not reached, P &lt; 0.001). In addition, PS was proven as one of the most significant prognostic predictors of both DSS and RFS by random survival forest algorithm. A nomogram to predict PS status was developed based on preoperative imaging combined with four risk factors including the presentation status (primary vs. recurrent), ascites, SUVmax, and tumor size. The nomogram significantly improved the diagnostic sensitivity compared to preoperative imaging alone (44/49, 89.8% vs. 35/49, 71.4%). The C-statistics of the nomogram was 0.932, and similar C-statistics (0.886) was achieved at internal cross-validation.ConclusionPS is a significant prognostic indicator for RPS, and it occurs more often in recurrent RPS and in RPS with higher malignant tendency. The proposed nomogram is effective to predict PS preoperatively.
BgNet: Classification of benign and malignant tumors with MRI multi-plane attention learning
Authors: Liu Hong , Jiao Meng-Lei , Xing Xiao-Ying , Ou-Yang Han-Qiang , Yuan Yuan , Liu Jian-Fang , Li Yuan , Wang Chun-Jie , Lang Ning , Qian Yue-Liang , Jiang Liang , Yuan Hui-Shu , Wang Xiang-Dong 
Published: October 2022

ObjectivesTo propose a deep learning-based classification framework, which can carry out patient-level benign and malignant tumors classification according to the patient’s multi-plane images and clinical information.MethodsA total of 430 cases of spinal tumor, including axial and sagittal plane images by MRI, of which 297 cases for training (14072 images), and 133 cases for testing (6161 images) were included. Based on the bipartite graph and attention learning, this study proposed a multi-plane attention learning framework, BgNet, for benign and malignant tumor diagnosis. In a bipartite graph structure, the tumor area in each plane is used as the vertex of the graph, and the matching between different planes is used as the edge of the graph. The tumor areas from different plane images are spliced at the input layer. And based on the convolutional neural network ResNet and visual attention learning model Swin-Transformer, this study proposed a feature fusion model named ResNetST for combining both global and local information to extract the correlation features of multiple planes. The proposed BgNet consists of five modules including a multi-plane fusion module based on the bipartite graph, input layer fusion module, feature layer fusion module, decision layer fusion module, and output module. These modules are respectively used for multi-level fusion of patient multi-plane image data to realize the comprehensive diagnosis of benign and malignant tumors at the patient level.ResultsThe accuracy (ACC: 79.7%) of the proposed BgNet with multi-plane was higher than that with a single plane, and higher than or equal to the four doctors’ ACC (D1: 70.7%, p=0.219; D2: 54.1%, p&lt;0.005; D3: 79.7%, p=0.006; D4: 72.9%, p=0.178). Moreover, the diagnostic accuracy and speed of doctors can be further improved with the aid of BgNet, the ACC of D1, D2, D3, and D4 improved by 4.5%, 21.8%, 0.8%, and 3.8%, respectively.ConclusionsThe proposed deep learning framework BgNet can classify benign and malignant tumors effectively, and can help doctors improve their diagnostic efficiency and accuracy. The code is available at https://github.com/research-med/BgNet.