bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour growth rate as a tool for response evaluation during PD-1 treatment for non-small cell lung cancer: a retrospective analysis
Authors: ten Berge Deirdre M.H.J. , Hurkmans Daniel P. , den Besten Ilse , Kloover Jeroen S. , Mathijssen Ron H.J. , Debets Reno , Smit Egbert F. , Aerts Joachim G.J.V. 
Published: December 2019

BackgroundImmune checkpoint inhibitors have emerged as a standard of care treatment for non-small cell lung cancer (NSCLC). To get insight into variations in tumour growth kinetics and their potential predictive values for outcome, we evaluated tumour growth rate (TGR) in patients receiving programmed cell death 1 (PD-1) checkpoint inhibitors.Patients and methodsDifferences in TGR before and after the start of treatment were calculated by entering the sum of the longest diameters from computer tomography scans before and after the initiation of therapy into a formula that assumes volumetric exponential tumour growth. TGR variations, possible predictors for TGR changes and its relationship to overall survival (OS) were studied. For comparison, tumour response was assessed using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.ResultsAmong the 58 evaluable patients, 37 patients (64%) showed deceleration of TGR and 16 patients (27%) showed an acceleration of TGR after initiation of therapy, with a significant difference in median OS of 18.0 monthsversus6.0 months (hazard ratio 0.35, 95% CI 0.18–0.71) between these groups. Four patients (7%) were defined as having hyperprogressive disease. In five patients (9%), tumour growth remained stable. These TGR categories were not significantly different according to age, sex, histology, smoking or previous radiotherapy. Of the patients defined as having progressive disease by RECIST version 1.1 at first follow-up, 40% showed response to checkpoint inhibitors by a decrease in TGR.ConclusionTumour growth kinetics can be used as a clinically relevant predictor for OS in anti-PD-1-treated patients with NSCLC, and may provide additional information to RECIST measurements.
The role of diagnostic hysteroscopy in diagnosis of incomplete uterine septum in patients with recurrent pregnancy loss in the era of transvaginal 3D ultrasound scan
Authors: Abuzeid O. , LaChance J. , Hebert J. , Abuzeid M. I. , Welch R. 
Published: December 2019

Abstract
Purpose
To determine the accuracy of transvaginal 3D ultrasound scan (TV 3D US) in detecting partial septate uterus (PSU) in patients with recurrent pregnancy loss (RPL).

Methods
This retrospective study included 113 patients with an initial diagnosis of unexplained RPL, who were subsequently found to have PSU on diagnostic hysteroscopy and who had TV 3D US prior to surgery. The diagnosis of PSU was made at the time of a diagnostic hysteroscopy based on ESHRE-ESGE classification of Müllerian anomalies. Based on hysteroscopic findings, patients were divided into two groups: those with PSU and a central point of indentation at an acute angle < 90° (PSUAA) [30.1%], and those who had PSU and a central point of indentation at an obtuse angle (PSUOA) [69.9%]. We compared the mean internal indentation length at the fundal midline (IILFM) in millimeters on TV 3D US and on diagnostic hysteroscopy. For the purpose of this study, a diagnosis of PSU on hysteroscopy was made if IILFM measured ≥ 10 mm.

Results
The mean IILFM (mm) on hysteroscopy was significantly higher than the mean IILFM (mm) measured on TV 3D US in patients with PSUAA (18.5 ± 6.5 vs 4.9 ± 4.4; P < 0.001), in patients with PSUOA (14.1 ± 3.8 vs 4.3 ± 3.4; P < 0.001), and in the overall population (15.3 ± 5.1 vs 4.1 ± 4.4; P < 0.001).

Conclusions
The data suggest that mean IILFM in patients with RPL and PSU can be underestimated on TV 3D US. Therefore, its diagnostic accuracy in such patients may need further evaluation.
Heating Efficiency of Triple Vortex State Cylindrical Magnetic Nanoparticles
Authors: Wong De Wei , Gan Wei Liang , Teo Yuan Kai , Lew Wen Siang 
Published: December 2019

AbstractA well-established method for treating cancerous tumors is magnetic hyperthermia, which uses localized heat generated by the relaxation mechanism of magnetic nanoparticles (MNPs) in a high-frequency alternating magnetic field. In this work, we investigate the heating efficiency of cylindrical NiFe MNPs, fabricated by template-assisted pulsed electrodeposition combined with differential chemical etching. The cylindrical geometry of the MNP enables the formation of the triple vortex state, which increases the heat generation efficiency by four times. Using time-dependent calorimetric measurements, the specific absorption rate (SAR) of the MNPs was determined and compared with the numerical calculations from micromagnetic simulations and vibrating sample magnetometer measurements. The magnetization reversal of high aspect ratios MNPs showed higher remanent magnetization and low-field susceptibility leading to higher hysteresis losses, which was reflected in higher experimental and theoretical SAR values. The SAR dependence on magnetic field strength exhibited small SAR values at low magnetic fields and saturates at high magnetic fields, which is correlated to the coercive field of the MNPs and a characteristic feature of ferromagnetic MNPs. The optimization of cylindrical NiFe MNPs will play a pivotal role in producing high heating performance and biocompatible magnetic hyperthermia agents.
Protective Effects of Carbon Dots Derived from Phellodendri Chinensis Cortex Carbonisata against Deinagkistrodon acutus Venom-Induced Acute Kidney Injury
Authors: Zhang Meiling , Cheng Jinjun , Sun Ziwei , Kong Hui , Zhang Yue , Wang Suna , Wang Xiaoke , Zhao Yan , Qu Huihua 
Published: December 2019

Abstract
Background
As an emerging nanomaterial, carbon dots (CDs) have been the focus of tremendous attention for biomedical applications. However, little information is available on their bioactivity of inhibiting acute kidney injury (AKI) induced by snake venom.

Methods
This study reports the development of a green, one-step pyrolysis process to synthesize CDs using Phellodendri Chinensis Cortex (PCC) as the sole precursor, and their potential application as a protectant against Deinagkistrodon acutus (D. acutus) venom-induced AKI was investigated for the first time. The AKI model was established by injecting D. acutus venom into the abdominal cavity of mice and the potential protective effects of PCC Carbonisata-CDs (PCCC-CDs) on renal abnormalities including dysfunction, inflammatory reactions, tissue damage, and thrombocytopenia at six time points (1, 3, and 12 h, and 1, 2, and 5 days) were investigated.

Results
These results demonstrated that PCCC-CDs significantly inhibited the kidney dysfunction (reduced serum creatinine (SCR), blood urea nitrogen (BUN), urinary total protein (UTP), and microalbuminuria (MALB) concentrations) and the production of chemoattractant (monocyte chemotactic protein 1 (MCP-1)), proinflammatory cytokines (interleukin (IL)-1β), and anti-inflammatory cytokine (IL-10) in response to intraperitoneal injection of D. acutus venom. The beneficial effect of PCCC-CDs on the envenomed mice was similar to that on the change in renal histology and thrombocytopenia.

Conclusions
These results demonstrated the remarkable protective effects of PCCC-CDs against AKI induced by D. acutus venom, which would not only broaden the biomedical applications of CDs but also provide a potential target for the development of new therapeutic drugs for AKI induced by D. acutus snakebite envenomation.
Ferumoxytol Attenuates the Function of MDSCs to Ameliorate LPS-Induced Immunosuppression in Sepsis
Authors: Xue Yaxian , Xu Yujun , Liu Xinghan , Sun Zhiheng , Pan Yuchen , Lu Xia , Liang Huaping , Dou Huan , Hou Yayi 
Published: December 2019

AbstractSepsis-induced immunosuppression is recognized as one of the main features responsible for therapeutic failures. Myeloid-derived suppressor cells (MDSCs), which are mainly characterized by their suppressive properties, have been reported to be expanded in sepsis. Ferumoxytol (FMT), an FDA-approved iron supplement, has been shown to possess immune-modulatory properties in tumors. However, it is unclear whether FMT alters the functions of MDSCs to reduce late-sepsis immunosuppression. Here, we showed an immunomodulatory effect of FMT on MDSCs to ameliorate lipopolysaccharide (LPS)–induced immunosuppression in the late stage of sepsis. Separation of cells with internalized FMT and detection of the intracellular iron content showed that MDSCs could uptake FMT. Low doses of FMT had no effects on the cell viability of MDSCs, but FMT inhibited the expansion of MDSCs in vitro. Moreover, FMT significantly downregulated the expression levels of Arg-1, S100A8, S100A9, and p47phox as well as ROS production in MDSCs. FMT decreased the percentage of granulocytic MDSCs (G-MDSCs) and promoted the differentiation of MDSCs into macrophages. Furthermore, FMT reduced white blood cell recruitment and alveolar wall thickening in the lungs and areas of necrosis in the liver as well as some biochemical markers of liver dysfunction. FMT decreased the percentage of G-MDSCs and monocytic MDSCs (M-MDSCs) in the spleens of LPS-induced septic mice. Of note, FMT reduced the T cell immunosuppressive functions of both G-MDSCs and M-MDSCs. Expectedly, FMT also significantly reduced Arg-1 and p47phox gene expression in splenic CD11b+Gr-1+cells isolated from LPS-challenged mice. These data indicate that FMT decreased the immunosuppressive functions of MDSCs by decreasing Arg-1 and ROS production, suggesting that FMT may reduce long-term immunosuppression in the late stage of sepsis.
Relation extraction between bacteria and biotopes from biomedical texts with attention mechanisms and domain-specific contextual representations
Authors: Jettakul Amarin , Wichadakul Duangdao , Vateekul Peerapon 
Published: December 2019

AbstractBackgroundThe Bacteria Biotope (BB) task is a biomedical relation extraction (RE) that aims to study the interaction between bacteria and their locations. This task is considered to pertain to fundamental knowledge in applied microbiology. Some previous investigations conducted the study by applying feature-based models; others have presented deep-learning-based models such as convolutional and recurrent neural networks used with the shortest dependency paths (SDPs). Although SDPs contain valuable and concise information, some parts of crucial information that is required to define bacterial location relationships are often neglected. Moreover, the traditional word-embedding used in previous studies may suffer from word ambiguation across linguistic contexts.ResultsHere, we present a deep learning model for biomedical RE. The model incorporates feature combinations of SDPs and full sentences with various attention mechanisms. We also used pre-trained contextual representations based on domain-specific vocabularies. To assess the model’s robustness, we introduced a mean F1 score on many models using different random seeds. The experiments were conducted on the standard BB corpus in BioNLP-ST’16. Our experimental results revealed that the model performed better (in terms of both maximum and average F1 scores; 60.77% and 57.63%, respectively) compared with other existing models.ConclusionsWe demonstrated that our proposed contributions to this task can be used to extract rich lexical, syntactic, and semantic features that effectively boost the model’s performance. Moreover, we analyzed the trade-off between precision and recall to choose the proper cut-off to use in real-world applications.
Low adaptive potential for tolerance to ethynylestradiol, but also low toxicity, in a grayling population (Thymallus thymallus)
Authors: Marques da Cunha Lucas , Maitre Diane , Wedekind Claus 
Published: December 2019

AbstractBackgroundThe presence of a novel pollutant can induce rapid evolution if there is additive genetic variance for the tolerance to the stressor. Continuous selection over some generations can then reduce the toxicity of the pollutant but also deplete the additive genetic variance for the tolerance and thereby slow down adaptation. One common pollutant that has been ecologically relevant for some time is 17alpha-ethynylestradiol (EE2), a synthetic compound of oral contraceptives since their market launch in the 1960s. EE2 is typically found in higher concentrations in rivers than in lakes. Recent experimental work revealed significant genetic variance for the tolerance to EE2 in two lake-spawning salmonid species but no such variance in river-spawning brown trout. We used another river-spawning salmonid, the European graylingThymallus thymallus, to study the toxicity of an ecologically relevant concentration of EE2. We also used a full-factorial in vitro breeding design and singly rearing of 1555 embryos and larvae of 40 sib groups to test whether there is additive genetic variance for the tolerance to this pollutant.ResultsWe found that exposure to EE2 reduced larval growth after hatching, but contrary to what has been found in the other salmonids, there were no significant effects of EE2 on embryo growth and survival. We found additive genetic variance for embryo viability, i.e. heritability for fitness. However, there was no significant additive variance for the tolerance to EE2.ConclusionsOur findings support the hypothesis that continuous selection has reduced the toxicity of EE2 and depleted genetic variance for tolerance to this synthetic stressor.
A phenomics-based approach for the detection and interpretation of shared genetic influences on 29 biochemical indices in southern Chinese men
Authors: Hu Yanling , Tan Aihua , Yu Lei , Hou Chenyang , Kuang Haofa , Wu Qunying , Su Jinghan , Zhou Qingniao , Zhu Yuanyuan , Zhang Chenqi , Wei Wei , Li Lianfeng , Li Weidong , Huang Yuanjie , Huang Hongli , Xie Xing , Lu Tingxi , Zhang Haiying , Yang Xiaobo , Gao Yong , Li Tianyu , Jiang Yonghua , Mo Zengnan 
Published: December 2019

Abstract
Background
Phenomics provides new technologies and platforms as a systematic phenome-genome approach. However, few studies have reported on the systematic mining of shared genetics among clinical biochemical indices based on phenomics methods, especially in China. This study aimed to apply phenomics to systematically explore shared genetics among 29 biochemical indices based on the Fangchenggang Area Male Health and Examination Survey cohort.

Result
A total of 1999 subjects with 29 biochemical indices and 709,211 single nucleotide polymorphisms (SNPs) were subjected to phenomics analysis. Three bioinformatics methods, namely, Pearson’s test, Jaccard’s index, and linkage disequilibrium score regression, were used. The results showed that 29 biochemical indices were from a network. IgA, IgG, IgE, IgM, HCY, AFP and B12 were in the central community of 29 biochemical indices. Key genes and loci associated with metabolism traits were further identified, and shared genetics analysis showed that 29 SNPs (P < 10− 4) were associated with three or more traits. After integrating the SNPs related to two or more traits with the GWAS catalogue, 31 SNPs were found to be associated with several diseases (P < 10− 8). Using ALDH2 as an example to preliminarily explore its biological function, we also confirmed that the rs671 (ALDH2) polymorphism affected multiple traits of osteogenesis and adipogenesis differentiation in 3 T3-L1 preadipocytes.

Conclusion
All these findings indicated a network of shared genetics and 29 biochemical indices, which will help fully understand the genetics participating in biochemical metabolism.
Transcriptome-wide association study identifies putative elicitors/suppressor of Puccinia graminis f. sp. tritici that modulate barley rpg4-mediated stem rust resistance
Authors: Sharma Poudel Roshan , Richards Jonathan , Shrestha Subidhya , Solanki Shyam , Brueggeman Robert 
Published: December 2019

AbstractBackgroundStem rust is an economically important disease of wheat and barley. However, studies to gain insight into the molecular basis of these host-pathogen interactions have primarily focused on wheat because of its importance in human sustenance. This is the first extensive study utilizing a transcriptome-wide association mapping approach to identify candidatePuccinia graminisf. sp.tritici(Pgt) effectors/suppressors that elicit or suppress barley stem rust resistance genes. Here we focus on identifyingPgtelicitors that interact with therpg4-mediated resistance locus (RMRL), the only effective source ofPgtrace TTKSK resistance in barley.ResultsThirty-sevenPgtisolates showing differential responses on RMRL were genotyped using Restriction Site Associated DNA-Genotyping by Sequencing (RAD-GBS), identifying 24 diverse isolates that were used for transcript analysis during the infection process.In plantaRNAseq was conducted with the 24 diverse isolates on the susceptible barley variety Harrington, 5 days post inoculation. The transcripts were mapped to thePgtrace SCCL reference genome identifying 114 K variants in predicted genes that would result in nonsynonymous amino acid substitutions. Transcriptome wide association analysis identified 33 variants across 28 genes that were associated with dominant RMRL virulence, thus, representing candidate suppressors of resistance. Comparative transcriptomics between the 9 RMRL virulent -vs- the 15 RMRL avirulentPgtisolates identified 44 differentially expressed genes encoding candidate secreted effector proteins (CSEPs), among which 38 were expressed at lower levels in virulent isolates suggesting that they may represent RMRL avirulence genes. Barley transcript analysis after colonization with 9 RMRL virulent and 15 RMRL avirulent isolates inoculated on the susceptible line Harrington showed significantly lower expression of host biotic stress responses specific to RMRL virulent isolates suggesting virulent isolates harbor effectors that suppress resistance responses.ConclusionsThis transcriptomic study provided novel findings that help fill knowledge gaps in the understanding of stem rust virulence/avirulence and host resistance in barley. The pathogen transcriptome analysis suggested RMRL virulence might depend on the lack of avirulence genes, but evidence from pathogen association mapping analysis and host transcriptional analysis also suggested the alternate hypothesis that RMRL virulence may be due to the presence of suppressors of defense responses.
Genome-wide identification and expression profiling of glutathione transferase gene family under multiple stresses and hormone treatments in wheat (Triticum aestivum L.)
Authors: Wang Ruibin , Ma Jingfei , Zhang Qian , Wu Chunlai , Zhao Hongyan , Wu Yanan , Yang Guangxiao , He Guangyuan 
Published: December 2019

Abstract
Background
Glutathione transferases (GSTs), the ancient, ubiquitous and multi-functional proteins, play significant roles in development, metabolism as well as abiotic and biotic stress responses in plants. Wheat is one of the most important crops, but the functions of GST genes in wheat were less studied.

Results
A total of 330 TaGST genes were identified from the wheat genome and named according to the nomenclature of rice and Arabidopsis GST genes. They were classified into eight classes based on the phylogenetic relationship among wheat, rice, and Arabidopsis, and their gene structure and conserved motif were similar in the same phylogenetic class. The 43 and 171 gene pairs were identified as tandem and segmental duplication genes respectively, and the Ka/Ks ratios of tandem and segmental duplication TaGST genes were less than 1 except segmental duplication gene pair TaGSTU24/TaGSTU154. The 59 TaGST genes were identified to have syntenic relationships with 28 OsGST genes. The expression profiling involved in 15 tissues and biotic and abiotic stresses suggested the different expression and response patterns of the TaGST genes. Furthermore, the qRT-PCR data showed that GST could response to abiotic stresses and hormones extensively in wheat.

Conclusions
In this study, a large GST family with 330 members was identified from the wheat genome. Duplication events containing tandem and segmental duplication contributed to the expansion of TaGST family, and duplication genes might undergo extensive purifying selection. The expression profiling and cis-elements in promoter region of 330 TaGST genes implied their roles in growth and development as well as adaption to stressful environments. The qRT-PCR data of 14 TaGST genes revealed that they could respond to different abiotic stresses and hormones, especially salt stress and abscisic acid. In conclusion, this study contributed to the further functional analysis of GST genes family in wheat.
Antimicrobial efficacy and toxicity of novel CAMPs against P. aeruginosa infection in a murine skin wound infection model
Authors: Yang Ming , Zhang Chunye , Hansen Sarah A. , Mitchell William J. , Zhang Michael Z. , Zhang Shuping 
Published: December 2019

Abstract
Background
Treatment of P. aeruginosa wound infection is challenging due to its inherent and acquired resistance to many conventional antibiotics. Cationic antimicrobial peptides (CAMPs) with distinct modes of antimicrobial action have been considered as the next-generation therapeutic agents. In the present study, a murine skin surgical wound infection model was used to evaluate the in vivo toxicity and efficacy of two newly designed antimicrobial peptides (CAMP-A and CAMP-B), as chemotherapeutic agents to combat P. aeruginosa infection.

Results
In the first trial, topical application of CAMPs on the wounds at a dose equivalent to 4 × MIC for 7 consecutive days did not cause any significant changes in the physical activities, hematologic and plasma biochemical parameters, or histology of systemic organs of the treated mice. Daily treatment of infected wounds with CAMP-A and CAMP-B for 5 days at a dose equivalent to 2× MIC resulted in a significant reduction in wound bacterial burden (CAMP-A: 4.3 log10CFU/g of tissue and CAMP-B: 5.8 log10CFU/g of tissue), compared to that of the mock-treated group (8.1 log10CFU/g of tissue). Treatment with CAMPs significantly promoted wound closure and induced epidermal cell proliferation. Topical application of CAMP-A on wounds completely prevented systemic dissemination of P. aeruginosa while CAMP-B blocked systemic infection in 67% of mice and delayed the onset of systemic infection by at least 2 days in the rest of the mice (33%). In a second trial, daily application of CAMP-A at higher doses (5× MIC and 50× MIC) didn’t show any significant toxic effect on mice and the treatments with CAMP-A further reduced wound bacterial burden (5× MIC: 4.5 log10CFU/g of tissue and 50× MIC: 3.8 log10CFU/g of tissue).

Conclusions
The data collectively indicated that CAMPs significantly reduced wound bacterial load, promoted wound healing, and prevented hepatic dissemination. CAMP-A is a promising alternative to commonly used antibiotics to treat P. aeruginosa skin infection.