bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-echinococcal effect of verapamil involving the regulation of the calcium/calmodulin-dependent protein kinase Ⅱ response in vitro and in a murine infection model
Authors: Gao Hai-Jun , Sun Xu-Dong , Luo Yan-Ping , Pang Hua-Sheng , Ma Xing-Ming , Zhang Ting , Jing Tao , Hu Wei , Shen Yu-Juan , Cao Jian-Ping 
Published: January 2021

Abstract
Background: Echinococcosis caused by the larvae of cestodes of the genus Echinococcus is a parasitic zoonosis that poses a serious threat to the health of humans and animals globally. Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and the assocaiated side effects after long-time use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil can suppress the growth of Echinococcus granulosus larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of verapamil on Echinococcus with a particular focus on the regulatory effect of verapamil on calcium/calmodulin-dependent protein kinase Ⅱ (Ca2+/CaM-CamKⅡ) in infected mice.Methods: The anti-echinococcal effects of verapamil on E. granulosus protoscoleces (PSC) in vitro and E. multilocularis metacestodes in infected mice were assessed. The morphological alterations in Echinococcus spp. induced by verapamil were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and Alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CamKⅡ in infected mice, and in the mRNA levels of CamKⅡ in E. granulosus PSC were evaluated after treatment with verapamil by immunohistochemistry and/or real-time quantitative polymerase chain reaction.Results: In vitro, E. granulosus PSC could be killed by verapamil at a concentration of 0.5 μg/mL or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied obvious calcium loss and downregulation of CamKⅡ mRNA expression. In vivo, the weight and the calcium content of E. multilocularis metacestodes from mice were reduced after treatment with 40 mg/kg verapamil, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CamKⅡ protein and mRNA expression in the livers of mice infected with E. multilocularis metacestodes was found after treatment with verapamil.Conclusions: Verapamil exerted a parasiticidal effect against Echinococcus both in vitro and in vivo through downregulating the expression of Ca2+/CaM-CamKⅡ, which were over-activated by parasitic infection. The results suggested that Ca2+/CaM-CamKⅡ may be a novel drug-target, and verapamil was shown to be a potential anti-echinococcal drug for controlling echinococcosis in the future.
SCUBE3 serves as an independent poor prognostic factor in breast cancer
Authors: Huo Qin , He Xi , Li Zhenwei , Yang Fan , He Shengnan , Shao Ling , Hu Ye , Chen Siqi , Xie Ni 
Published: January 2021

Abstract
Background: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in age, histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2+ (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95 % CI: 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95 % CI: 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.Conclusions: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.
Epicardial adipose tissue volume and coronary calcification among people living with diabetes: a cross-sectional study
Authors: Cosson Emmanuel , Nguyen Minh Tuan , Rezgani Imen , Tatulashvili Sopio , Sal Meriem , Berkane Narimane , Allard Lucie , Brillet Pierre-Yves , Bihan Hélène 
Published: January 2021

Abstract
Background: Epicardial adipose tissue (EAT) has anatomic and functional proximity to the heart and is considered a novel diagnostic marker and therapeutic target in cardiometabolic diseases. The aim of this study was to evaluate whether EAT volume was associated with coronary artery calcification (CAC) in people living with diabetes, independently of confounding factors.Methods: We included all consecutive patients with diabetes whose EAT volume and CAC score were measured using computed tomography between January 1, 2019 and September 30, 2020 in the Department of Diabetology-Endocrinology-Nutrition at Avicenne Hospital, France. Determinants of EAT volume and a CAC score ≥ 100 Agatston units (AU) were evaluated. Results: The study population comprised 409 patients (218 men). Mean (± standard deviation) age was 57±12 years, and 318, 56 and 35 had type 2 (T2D), type 1 (T1D), or another type of diabetes, respectively. Mean body mass index (BMI) was 29±6 kg/m², mean AET volume 93±38 cm3. EAT volume was positively correlated with age, BMI, pack-year smoking history and triglyceridaemia, but negatively correlated with HDL-cholesterol level. Furthermore, it was lower in people with retinopathy, but higher in men, in Caucasian people, in patients on antihypertensive and lipid-lowering medication, in people with nephropathy, and finally in individuals with a CAC ≥ 100 AU (CAC < 100 vs CAC ≥ 100: 89±35 vs 109±41 cm3, respectively, p<0.05). In addition to EAT volume, other determinants of CAC ≥ 100 AU (n=89, 22%) were age, T2D, ethnicity, antihypertensive and lipid-lowering medication, cumulative tobacco consumption, retinopathy, macular edema and macrovascular disease. Multivariable analysis considering all these determinants as well as gender and BMI showed that EAT volume was independently associated with CAC ≥ 100 AU (per 10 cm3 increase: OR 1.11 [1.02-1.20]). Conclusions: EAT volume was independently associated with CAC. As it may play a role in coronary atherosclerosis in patients with diabetes, reducing EAT volume through physical exercise, improved diet and pharmaceutical interventions may improve future cardiovascular risk outcomes in this population.
The rice cytosolic pentatricopeptide repeat protein OsPPR2-1 regulates OsGLK1 to control tapetal plastid development and programmed cell death
Authors: Zheng Shaoyan , Dong Jingfang , Lu Jingqin , Li Jing , Jiang Dagang , Ye Simiao , Bu Wenli , Liu Zhenlan , Zhou Hai , Zhuang Chuxiong 
Published: January 2021

Abstract
Most pentatricopeptide repeat (PPR) proteins localize to plastids or mitochondria, where they participate in RNA metabolism and post-transcriptionally regulate organelle gene expression. However, whether PPR proteins regulate the expression of nucleus-encoded genes remains unclear. Here, we uncovered a function for the rice (Oryza. sativa L.) PPR protein OsPPR2-1 (Os02g0110400) in pollen development and showed that, in contrast to most other PPR proteins, OPPR2-1 resides in the cytoplasm. Downregulating OsPPR2-1 expression led to abnormal plastid development in tapetal cells, prolonged programmed cell death (PCD), prolonged tapetum degradation, and significantly reduced pollen fertility. Transcriptome analysis revealed that the expression of OsGOLDEN-LIKE 1 (OsGLK1), encoding a transcription factor that regulates plastid development and maintenance, was significantly higher in plants with downregulated OsPPR2-1 expression compared to the wild type. Moreover, OsPPR2-1 bound to the OsGLK1 mRNA in RNA immunoprecipitation and RNA-electrophoretic mobility shift assays. An in vitro cleavage assay showed that OsPPR2-1 could degrade the OsGLK1 mRNA. Notably, knockdown of OsGLK1 partially restored pollen fertility in OsPPR2-1-knockdown plants and OsGLK1-overexpressing plants showed abnormal tapetum and plastid development, similar to the OsPPR2-1-knockdown plants. Together, our findings demonstrate that OsPPR2-1 regulates OsGLK1 expression, thereby controlling plastid development and PCD in the tapetum.
Selective Terminal Functionalization of Linear Alkanes
Authors: Marek Ilan , Bruffaerts Jeffrey , Buhnik-Rosenblau Keren , Cohen Anthony , Kesten Inbar , Cormier Morgan , Zhang Yuanfei , Ho Guo-Ming , Massad Itai , Edri Nurit , Halfon-Verner Hila , Glaser Fabian , Horev Guy , Kashi Yechezkel 
Published: January 2021

Abstract
Selective undirected functionalization of strong primary C-H bonds of linear alkanes, that do not possess directing groups, historically stands as one of the most challenging transformation in chemistry. In this Article, we report a two-step sequential strategy involving a biocatalytic dehydrogenation / remote hydrofunctionalization, as a unified and versatile approach to selectively convert linear alkanes into a large array of valuable functionalized aliphatic derivatives. The dehydrogenation is carried out by a mutant strain of Rhodococcus and the produced alkenes are subsequently engaged in a remote functionalization through a metal-catalyzed hydrometalation/migration sequence that subsequently react with a large variety of electrophiles. The judicious implementation of this combined biocatalytic and organometallic approach enabled us to develop a high-yielding protocol to site-selectively functionalize unreactive primary C–H bonds.
Paleoproteomics Reveals the Species Sources of Ancient Hair Textiles and Supports Historicity of Wool Manufacture in the Bronze Age Along the Silk Road
Authors: Wang Zhongyuan , Yang Hailiang , Zhai Yujie , Song Shanshan , Zhou Lian , Yang Hui , Zheng Hailing , Zhou Yang , Hu Zhiwen , Peng Zhiqin , Wang Bing 
Published: January 2021

Abstract
The Xinjiang region is a crossroad between the West and East on the Silk Road, where many exquisite hair textile relics in the Bronze Age were unearthed, therefore, it attracts the attention of scholars around the world. However, the limitation of information acquisition ability is still the main bottleneck to recognize the scientific value of ancient hair textile relics. In this study, paleoproteomics method was proposed to analyse the hair textile relics from Xiaohe and Shanpula cemetery in the Xinjiang region. To establish the databases of biomarkers and morphological features, five modern hair samples from representative animals (grey fox, raccoon dog, American mink, cape hare, and lamb) were selected and examined. Through searching the databases, the ancient hair textile samples from Xiaohe and Shanpula cemetery were all identified as wool. Ultimately, this work demonstrated the evidences supporting the existence of prosperous sheep husbandry, wool manufacture and cultural exchange along the Silk Road in the Bronze Age. The paleoproteomics, in combination with other methods, obtained more reliable and profound information from hair textile relics than ever before, and it goes without saying that they have bright prospects of being widely used in hair textile archaeology.
Risk Factors Associated With Cervical Spine Lesions in Patients With Rheumatoid Arthritis: The Role of Biological Agents
Authors: Uchino Yosuke , Kobayashi Naomi , Higashi Takayuki , Inoue Tetsuhiko , Mochida Yuichi , Inaba Yutaka 
Published: January 2021

Abstract
Purpose

To investigate the prevalence and risk factors of cervical lesions in patients with rheumatoid arthritis (RA) under current pharmacological treatments with biological agents.
Methods

One hundred and eighty-five consecutive patients with RA who underwent both cervical plain radiography and bone mineral density (BMD) scanning were enrolled. RA cervical lesions included atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS). We assigned patients with AAS, VS, or SAS to the cervical-lesion group, and all other patients to the non-cervical-lesion group. Radiological findings, BMD, and clinical data on RA were collected. We used multivariate logistic regression analyses to assess the risk factors of cervical lesions in patients with RA.
Results

The cervical-lesion and non-cervical-lesion groups included 106 and 79 patients, respectively. There were 79 patients with AAS, 31 with VS, and 41 with SAS. The cervical-lesion group had younger age of onset, longer RA disease duration, and lower femoral neck BMD than those in the non-cervical-lesion group. Multivariate analyses showed that the risk factors of RA cervical lesions were RA disease duration, prednisolone usage, biological agents, and femoral neck BMD. Femoral neck BMD in patients with VS was lower than in those without VS.
Conclusions

Cervical lesions were confirmed in 57% of the patients. RA duration, prednisolone usage, biological agents, and femoral neck BMD were significant risk factors of cervical lesions in patients with RA. The general status of osteoporosis might contribute to the development of VS.
Construction of a hippocampal cognitive map depends upon spatial context
Authors: Jiang Wan-Chen , Xu Shengjin , Dudman Joshua 
Published: January 2021

Abstract
The hippocampus encodes both spatial and non-spatial features of an environment thought to be critical to guide navigational trajectories and associative learning, respectively. These seemingly dichotomous roles have been reconciled in a proposed cognitive map - a representation of environment structure abstracted away from specific behavioral demands. However, the extent to which a cognitive map is independent of behavioral demands remains unclear because direct comparisons across environments with common structure but different spatial/behavioral context is lacking. Here we compare behaviors in mice trained to navigate to a hidden target in a physical arena and manipulate a joystick to a virtual target to collect a delayed reward. Comparison of behaviors with an artificial agent revealed a common algorithmic basis for learned foraging trajectories in both contexts. Imaging CA1 neural activity revealed a similar map-like encoding of active foraging; however, detailed analysis of ensemble activity, optogenetic inactivation, and modeling revealed a context-specific functional dissociation. In a navigational context, CA1 was critical for retrospective evaluation of spatial trajectories, but dispensable for initiation. In a non-navigational context, CA1 activity was critical for initiation and planning foraging trajectories. This work highlights how construction of a cognitive map to facilitate idiosyncratic behavioral demands7 is critical for foraging in diverse spatial contexts.
Disgust Versus Fear: Comparing the Generalization Pattern of Disgust and Fear
Authors: Wang Jinxia , Sun Xiaoying , Lu Jiachen , Dou Haoran , Lei Yi 
Published: January 2021

Abstract
A major limitation of fear generalization research entails the confusing unconditional stimulus—it can often induce not only fear but also disgust. Differences between the two threat-related emotions during conditioning and generalization are currently unknown. To address this issue, 32 college students completed threat conditioning tasks including conditioned stimuli paired with fear or disgust images. A block design was used to divide fear and disgust into two randomly ordered blocks, enabling examination of differences between fear and disgust by recording subjective expectations and eye movement in the generalization process. The results revealed that participants reported larger subjective expectations of fear-related GS1 (generalized stimuli) and GS2 than disgust-related GS1 and GS2, and fear led to longer reaction times than disgust in both conditioning and generalization phases. The pupil size and fixation duration for fear stimuli were larger than for disgust stimuli, suggesting that fear generalization has a steeper gradient than disgust generalization. Participants paid more attention to fear and were more inclined to avoid disgust stimuli. These findings provide new, albeit preliminary, evidence of the differences between fear and disgust stimuli in generalization, and may offer insight into the treatment of clinical anxiety and other fear- or disgust-related disorders.
Context-Aware Feature Attention Model for Coreference Resolution on Biomedical Texts
Authors: Li Yufei , Zhou Xiangyu , Ma Jie , Ma Xiaoyong , Li Chen 
Published: January 2021

Abstract
Background: Bio-entity Coreference resolution is an important task to gain a complete understanding of biomedical texts automatically. Previous neural network-based studies on this topic are domain system based methods which rely on some domain-specific information integration. However, for the identical mentions, this may lead to misleading information, as the model tends to get similar or even identical representations, which further leads to wrongful predictions. Results: we propose a new context-aware Feature Attention model to distinguish identical mentions effectively to better resolve coreference. The new model can represent identical mentions based on different contexts by adaptively exploiting features effectively. The proposed model substantially outperforms the state-of-the-art baselines on the BioNLP dataset with a 64.0% F1 score and further demonstrates superior performance on the differential representation and coreferential link of identical mentions. Conclusion: The context-aware Feature Attention model adaptively exploit features and represent identical mentions according to different contexts, which significantly makes the system obtain semantic information effectively and make more accurate predictions. Considering that this approach is still limited when context information is insufficient, we expect to utilize such information more fine-grained with the help of the external knowledge base in coreference resolution.
Primal-Dual for Classification with Rejection (PD-CR): A Novel Method for Classification and Feature Selection. An Application in Metabolomics Studies.
Authors: Chardin David , Barlaud Michel , Humbert Olivier , Burel-vandenbos Fanny , Pourcher Thierry , Rigau Valerie 
Published: January 2021

Abstract
Background: Supervised classification methods have been used for many years for feature selection in metabolomics and other omics studies. We developed a novel primal-dual based classification method (PD-CR) that can perform classification with rejection and feature selection on high dimensional datasets. PD-CR projects data onto a low dimension space and performs classification by minimizing an appropriate quadratic cost. It simultaneously optimizes the selected features and the prediction accuracy with a new tailored, constrained primal-dual method. The primal-dual framework is general enough to encompass various robust losses and to allow for convergence analysis. Here, we compared PD-CR to two commonly used methods : Partial Least Squares Discriminant Analysis (PLS-DA) and Random Forests. We analyzed two metabolomics datasets: one urinary metabolomics dataset concerning lung cancer patients and healthy controls; and a metabolomics dataset obtained from frozen glial tumor samples with mutated isocitrate dehydrogenase (IDH) or wild-type IDH. Results: PD-CR was more accurate than PLS-DA and Random Forests for classification using the 2 metabolomics datasets. It also selected biologically relevant metabolites. PD-CR has the advantage of providing a confidence score for each prediction, which can be used to perform classification with rejection. This substantially reduces the False Discovery Rate. Conclusion: The confidence score provided with PD-CR adds considerable value to the prediction as it includes a metric that is implicitly used by every physician when they make a medical decision: the probability to make the wrong choice. So far, one of the main obstacles to the use of machine learning in medicine resides in the fact that it is harder to trust the decision of a machine learning method than that of a physician when it comes to health issues. We believe that providing a confidence score associated to the decision would make these new tools more convincing if used in routine clinical practice.
Resolving cell state in iPSC-derived human neural samples with multiplexed fluorescence imaging
Authors: Tomov Martin , O'Neil Alison , Abbasi Hamdah , Cimini Beth , Carpenter Anne , Rubin Lee , Bathe Mark 
Published: January 2021

Abstract
Human induced pluripotent stem cell-derived (iPSC) neural cultures offer clinically relevant models of human diseases, including Amyotrophic Lateral Sclerosis, Alzheimer’s, and Autism Spectrum Disorder. In situ characterization of the spatial-temporal evolution of cell state in 2D and 3D culture models and organoids based on protein expression levels and localizations is essential to understanding neural cell differentiation, disease state phenotypes, and sample-to-sample variability. Here we apply PRobe-based Imaging for Sequential Multiplexing (PRISM) to facilitate multiplexed imaging with facile, rapid exchange of imaging probes to analyze iPSC-derived cortical and motor neuron cultures that are relevant to psychiatric and neurodegenerative disease models, using over ten protein targets. Our approach permits analysis of cell differentiation, cell composition, and functional marker expression in both standard 2D cultures and 3D spheroid and organoid sections. Further, our approach is amenable to automation, offering in principle ability to scale-up to dozens of protein targets and samples.