bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors for clinical effectiveness of baricitinib in rheumatoid arthritis patients in routine clinical practice: data from a Japanese multicenter registry
Authors: Takahashi Nobunori , Asai Shuji , Kobayakawa Tomonori , Kaneko Atsushi , Watanabe Tatsuo , Kato Takefumi , Nishiume Tsuyoshi , Ishikawa Hisato , Yoshioka Yutaka , Kanayama Yasuhide , Watanabe Tsuyoshi , Hirano Yuji , Hanabayashi Masahiro , Yabe Yuichiro , Yokota Yutaka , Suzuki Mochihito , Sobue Yasumori , Terabe Kenya , Ishiguro Naoki , Kojima Toshihisa 
Published: December 2020

AbstractThis study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan–Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.
Metabolomic analysis and mass spectrometry imaging after neonatal stroke and cell therapies in mouse brains
Authors: Tanaka Emi , Ogawa Yuko , Fujii Ritsuko , Shimonaka Tomomi , Sato Yoshiaki , Hamazaki Takashi , Nagamura-Inoue Tokiko , Shintaku Haruo , Tsuji Masahiro 
Published: December 2020

AbstractIschemic brain injury provokes complex, time-dependent downstream pathways that ultimately lead to cell death. We aimed to demonstrate the levels of a wide range of metabolites in brain lysates and their on-tissue distribution following neonatal stroke and cell therapies. Postnatal day 12 mice underwent middle cerebral artery occlusion (MCAO) and were administered 1 × 105 cells after 48 h. Metabolomic analysis of the injured hemisphere demonstrated that a variety of amino acids were significantly increased and that tricarboxylic acid cycle intermediates and some related amino acids, such as glutamate, were decreased. With the exception of the changes in citric acid, neither mesenchymal stem/stromal cells nor CD34+ cells ameliorated these changes. On-tissue visualization with matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) imaging revealed that the signal intensity of glutamate was significantly decreased in the infarct area, consistent with the metabolomic analysis, while its intensity was significantly increased in the peri-infarct area after MCAO. Although cell therapies did not ameliorate the changes in metabolites in the infarct area, mesenchymal stem cells ameliorated the increased levels of glutamate and carnitine in the peri-infarct area. MALDI-MS imaging showed the location-specific effect of cell therapies even in this subacute setting after MCAO. These methodologies may be useful for further investigation of possible treatments for ischemic brain injury.
Development of immunohistochemistry and in situ hybridisation for the detection of SARS-CoV and SARS-CoV-2 in formalin-fixed paraffin-embedded specimens
Authors: Lean Fabian Z. X. , Lamers Mart M. , Smith Samuel P. , Shipley Rebecca , Schipper Debby , Temperton Nigel , Haagmans Bart L. , Banyard Ashley C. , Bewley Kevin R. , Carroll Miles W. , Brookes Sharon M. , Brown Ian , Nuñez Alejandro 
Published: December 2020

AbstractThe rapid emergence of SARS-CoV-2, the causative agent of COVID-19, and its dissemination globally has caused an unprecedented strain on public health. Animal models are urgently being developed for SARS-CoV-2 to aid rational design of vaccines and therapeutics. Immunohistochemistry and in situ hybridisation techniques that facilitate reliable and reproducible detection of SARS-CoV and SARS-CoV-2 viral products in formalin-fixed paraffin-embedded (FFPE) specimens would be of great utility. A selection of commercial antibodies generated against SARS-CoV spike protein and nucleoprotein, double stranded RNA, and RNA probe for spike genes were evaluated for the ability to detect FFPE infected cells. We also tested both heat- and enzymatic-mediated virus antigen retrieval methods to determine the optimal virus antigen recovery as well as identifying alternative retrieval methods to enable flexibility of IHC methods. In addition to using native virus infected cells as positive control material, the evaluation of non-infected cells expressing coronavirus (SARS, MERS) spike as a biosecure alternative to assays involving live virus was undertaken. Optimized protocols were successfully applied to experimental animal-derived tissues. The diverse techniques for virus detection and control material generation demonstrated in this study can be applied to investigations of coronavirus pathogenesis and therapeutic research in animal models.
Hemipteran defensive odors trigger predictable color biases in jumping spider predators
Authors: Vickers Michael E. , Taylor Lisa A. 
Published: December 2020

AbstractMultimodal warning displays often pair one signal modality (odor) with a second modality (color) to avoid predation. Experiments with bird predators suggest these signal components interact synergistically, with aversive odors triggering otherwise hidden aversions to particular prey colors. In a recent study, this phenomenon was found in a jumping spider (Habronattus trimaculatus), with the defensive odor from a coreid bug (Acanthocephala femorata) triggering an aversion to red. Here, we explore how generalizable this phenomenon is by giving H. trimaculatus the choice between red or black prey in the presence or absence of defensive odors secreted from (1) eastern leaf-footed bugs (Leptoglossus phyllopus, Hemiptera), (2) grass stinkbugs (Mormidea pama, Hemiptera), (3) Asian ladybird beetles (Harmonia axyridis, Coleoptera), and (4) eastern lubber grasshoppers (Romalea microptera, Orthoptera). As expected, in the presence of the hemipteran odors, spiders were less likely to attack red prey (compared to no odor). Unexpectedly, the beetle and grasshopper odors did not bias spiders away from red. Our results with the hemipteran odors were unique to red; follow-up experiments indicated that these odors did not affect biases for/against green prey. We discuss our findings in the context of generalized predator foraging behavior and the functions of multimodal warning displays.
First assessment of POPs and cytochrome P450 expression in Cuvier’s beaked whales (Ziphius cavirostris) skin biopsies from the Mediterranean Sea
Authors: Baini Matteo , Panti Cristina , Fossi Maria Cristina , Tepsich Paola , Jiménez Begoña , Coomber Frazer , Bartalini Alice , Muñoz-Arnanz Juan , Moulins Aurelie , Rosso Massimiliano 
Published: December 2020

AbstractThe Cuvier's beaked whale (Ziphius cavirostris) is one of the least known cetacean species worldwide. The decreasing population trend and associated threats has led to the IUCN categorising the Mediterranean subpopulation as Vulnerable on the Red List of Threatened Species. This study aimed to investigate for the first time the ecotoxicological status of Cuvier's beaked whale in the NW Mediterranean Sea. The study sampled around the 20% of the individuals belonging to the Ligurian subpopulation, collecting skin biopsies from free-ranging specimens. The levels of polychlorinated biphenyl (PCBs), polybrominated diphenyl ethers (PBDEs) and induction of cytochrome's P450 (CYP1A1 and CYP2B isoforms) were evaluated. Results highlighted that the pattern of concentration for the target contaminants was PCBs > PBDEs and the accumulation values were linked to age and sex, with adult males showing significantly higher levels than juvenile. Concerns raised by the fact that 80% of the individuals had PCB levels above the toxicity threshold for negative physiological effects in marine mammals. Therefore, these findings shed light on this silent and serious threat never assessed in the Mediterranean Cuvier’s beaked whale population, indicating that anthropogenic pressures, including chemical pollution, may represent menaces for the conservation of this species in the Mediterranean Sea.
Growth, ionic homeostasis, and physiological responses of cotton under different salt and alkali stresses
Authors: Guo Huijuan , Huang Zhijie , Li Meiqi , Hou Zhenan 
Published: December 2020

AbstractTo better understand the mechanism of salt tolerance, we analyzed cotton growth and the ionomes in different tissues under different types of salt–alkali stress. Cotton was exposed to the soil salt and alkali stresses, NaCl, Na2SO4, and Na2CO3 + NaHCO3, in a pot study. Salt and alkali stress significantly inhibited cotton growth, significantly reduced root length, surface area, and volume, and significantly increased relative electrical conductivity (REC) and malondialdehyde (MDA) content but also significantly increased antioxidant enzyme activities, and proline (Pro) content. The REC in leaves was higher under salt stress than under alkali stress, but the effects on Pro were in the order Na2CO3 + NaHCO3 > NaCl > Na2SO4. Principal component analysis showed a significant difference in ion composition under the different types of salt–alkali stress. Under the three types of salt–alkali stress, concentrations of Na and Mo increased significantly in different organs of cotton plants. Under NaCl stress, the absorption of Ca was inhibited, the transport capacity of P, Mg, and Cu was reduced, and the ion balance was maintained by promoting the uptake and transport of Zn, Mn, Al, and Mo. Under Na2SO4 stress, the absorption of P and Ca was inhibited, the transport capacity of Mg, B, and Cu was reduced, and the ion balance was maintained by promoting the uptake and transport of S, Zn, Fe, Mo, Al, and Co. Under Na2CO3 + NaHCO3 stress, the absorption of P and S was inhibited, the transport capacity of Mg and B was reduced, but that of Al and Fe increased, and the ion balance was maintained by promoting the uptake and transport of Mn, Mo, Ni, and Co. The relative expression of GhSOS1 and GhNHX1 in leaves increased significantly under salt stress but decreased under alkali stress. These results suggest that cotton is well-adapted to salt–alkali stress via the antioxidant enzyme system, adjustment of osmotic substances, and reconstruction of ionic equilibrium; neutral salt stress primarily disrupts the ion balance, whereas alkali stress decreases the ability to regulate Na and inhibits the absorption of mineral elements, as well as disrupts the ion balance; and the changes in the expression of salt tolerance-related genes may partially explain the accumulation of Na ions in cotton under salt–alkali stress.
Comparative transcriptomics indicates endogenous differences in detoxification capacity after formic acid treatment between honey bees and varroa mites
Authors: Genath Antonia , Sharbati Soroush , Buer Benjamin , Nauen Ralf , Einspanier Ralf 
Published: December 2020

AbstractFormic acid (FA) has been used for decades to control Varroa destructor, one of the most important parasites of the western honey bee, Apis mellifera. The rather unselective molecular mode of action of FA and its possible effects on honeybees have long been a concern of beekeepers, as it has undesirable side effects that affect the health of bee colonies. This study focuses on short-term transcriptomic changes as analysed by RNAseq in both larval and adult honey bees and in mites after FA treatment under applied conditions. Our study aims to identify those genes in honey bees and varroa mites differentially expressed upon a typical FA hive exposure scenario. Five detoxification-related genes were identified with significantly enhanced and one gene with significantly decreased expression under FA exposure. Regulated genes in our test setting included members of various cytochrome P450 subfamilies, a flavin-dependent monooxygenase and a cytosolic 10-formyltetrahydrofolate dehydrogenase (FDH), known to be involved in formate metabolism in mammals. We were able to detect differences in the regulation of detoxification-associated genes between mites and honey bees as well as between the two different developmental stages of the honey bee. Additionally, we detected repressed regulation of Varroa genes involved in cellular respiration, suggesting mitochondrial dysfunction and supporting the current view on the mode of action of FA—inhibition of oxidative phosphorylation. This study shows distinct cellular effects induced by FA on the global transcriptome of both host and parasite in comparison. Our expression data might help to identify possible differences in the affected metabolic pathways and thus make a first contribution to elucidate the mode of detoxification of FA.
Neutrophil-to-lymphocyte ratio is an independent predictor for survival outcomes in cervical cancer: a systematic review and meta-analysis
Authors: Zou Peijun , Yang E. , Li Zhengyu 
Published: December 2020

AbstractThis updated meta-analysis sought to explore whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could serve as an independent predictor for survival outcomes in patients with cervical cancer. We searched PubMed, Embase, Web of science and Scopus for studies on the association of pretreatment serum NLR with overall survival (OS) and progression-free survival (PFS) among patients with cervical cancer. Included studies with a hazard ratio (HR) and 95% confidence interval (CI) or a p-value were weighted by generic inverse-variance and pooled in a random effects meta-analysis. Subgroup analyses were conducted according to regions, NLR cut-off values and treatments. Publication bias was analyzed by Egger’s and Begg’s tests. A total of 14 studies comprising 6041 patients were included. The median cut-off value for NLR was 2.46 (range from 1.60 to 3.80). The higher NLR was associated to worse OS (HR 1.86, 95% CI 1.44–2.40) and PFS (HR 1.67, 95% CI 1.25–2.23), compared with lower NLR. This association still exited when analyzed according to regions, NLR cut-off values. Moreover, Significant association between NLR and OS was observed in studies which included patients with early stage disease and receiving radical surgeries. High NLR is independently associated with decreased OS and PFS in patients with cervical cancer. Pretreatment NLR is of independent value to predict the survival outcomes in patients with cervical cancer, regardless of regions and primary treatments.
Natural history of social and sexual behavior in fruit flies
Authors: Dukas Reuven 
Published: December 2020

AbstractThe past 2 decades have seen fruit flies being widely adopted for research on social behavior and aggression. This fruitful research, however, has not been well tied to fruit flies’ natural history. To address this knowledge gap, I conducted a field study. My goal was to inform future research conducted in artificial surroundings, and to inspire new investigations that can rely more heavily on fruit flies’ actual natural behavior. My two main novel findings were first, that flies in the field showed significant sociability, as they formed social groups rather than dispersed randomly among fruits of similar quality. Second, males showed fair levels of aggression towards each other as indicated by a lunging rate of 17 per hour, and lower rates of wing threat and boxing. Courtship was the most prominent activity on fruits, with females rejecting almost all males’ advances. This resulted in an estimated mating rate of 0.6 per female per day. Flies showed a striking peak of activity early in the mornings, even at cold temperatures, followed by inactivity for much of the day and night. Flies, however, handled well high temperatures approaching 40 °C by hiding away from fruit and concentrating activity in the cooler, early mornings. My field work highlights a few promising lines of future research informed by fruit flies’ natural history. Most importantly, we do not understand the intriguing dynamics that generate significant sociability despite frequent aggressive interactions on fruits. Males’ responses to female rejection signals varied widely, perhaps because the signals differed in information content perceived by flies but not humans. Finally, flies tolerated cold early mornings perhaps owing to fitness benefits associated with increased mating and feeding opportunities at this time. Flies were adept at handling very high temperatures under the natural daily temperature fluctuations and availability of shelters, and this can inform more realistic research on the effects of global warming on animals in their natural settings.
Genetic ancestry, skin pigmentation, and the risk of cutaneous squamous cell carcinoma in Hispanic/Latino and non-Hispanic white populations
Authors: Jorgenson Eric , Choquet Hélène , Yin Jie , Hoffmann Thomas J. , Banda Yambazi , Kvale Mark N. , Risch Neil , Schaefer Catherine , Asgari Maryam M. 
Published: December 2020

AbstractAlthough cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in individuals of European ancestry, the incidence of cSCC in Hispanic/Latinos is also increasing. cSCC has both a genetic and environmental etiology. Here, we examine the role of genetic ancestry, skin pigmentation, and sun exposure in Hispanic/Latinos and non-Hispanic whites on cSCC risk. We observe an increased cSCC risk with greater European ancestry (P = 1.27 × 10−42) within Hispanic/Latinos and with greater northern (P = 2.38 × 10−65) and western (P = 2.28 × 10−49) European ancestry within non-Hispanic whites. These associations are significantly, but not completely, attenuated after considering skin pigmentation-associated loci, history of actinic keratosis, and sun-protected versus sun-exposed anatomical sites. We also report an association of the well-known pigment variant Ala111Thr (rs1426654) at SLC24A5 with cSCC in Hispanic/Latinos. These findings demonstrate a strong correlation of northwestern European genetic ancestry with cSCC risk in both Hispanic/Latinos and non-Hispanic whites, largely but not entirely mediated through its impact on skin pigmentation.
Microfluidic platform enables tailored translocation and reaction cascades in nanoliter droplet networks
Authors: Bachler Simon , Haidas Dominik , Ort Marion , Duncombe Todd A. , Dittrich Petra S. 
Published: December 2020

AbstractIn the field of bottom-up synthetic biology, lipid membranes are the scaffold to create minimal cells and mimic reactions and processes at or across the membrane. In this context, we employ here a versatile microfluidic platform that enables precise positioning of nanoliter droplets with user-specified lipid compositions and in a defined pattern. Adjacent droplets make contact and form a droplet interface bilayer to simulate cellular membranes. Translocation of molecules across membranes are tailored by the addition of alpha-hemolysin to selected droplets. Moreover, we developed a protocol to analyze the translocation of non-fluorescent molecules between droplets with mass spectrometry. Our method is capable of automated formation of one- and two-dimensional droplet networks, which we demonstrated by connecting droplets containing different compound and enzyme solutions to perform translocation experiments and a multistep enzymatic cascade reaction across the droplet network. Our platform opens doors for creating complex artificial systems for bottom-up synthetic biology.
Reverse Chromatin Immunoprecipitation (R-ChIP) enables investigation of the upstream regulators of plant genes
Authors: Wen Xuejing , Wang Jingxin , Zhang Daoyuan , Ding Yu , Ji Xiaoyu , Tan Zilong , Wang Yucheng 
Published: December 2020

AbstractDNA binding proteins carry out important and diverse functions in the cell, including gene regulation, but identifying these proteins is technically challenging. In the present study, we developed a technique to capture DNA-associated proteins called reverse chromatin immunoprecipitation (R-ChIP). This technology uses a set of specific DNA probes labeled with biotin to isolate chromatin, and the DNA-associated proteins are then identified using mass spectrometry. Using R-ChIP, we identified 439 proteins that potentially bind to the promoter of the Arabidopsis thaliana gene AtCAT3 (AT1G20620). According to functional annotation, we randomly selected 5 transcription factors from these candidates, including bZIP1664, TEM1, bHLH106, BTF3, and HAT1, to verify whether they in fact bind to the AtCAT3 promoter. The binding of these 5 transcription factors was confirmed using chromatin immunoprecipitation quantitative real-time PCR and electrophoretic mobility shift assays. In addition, we improved the R-ChIP method using plants in which the DNA of interest had been transiently introduced, which does not require the T-DNA integration, and showed that this substantially improved the protein capture efficiency. These results together demonstrate that R-ChIP has a wide application to characterize chromatin composition and isolate upstream regulators of a specific gene.
Clinical Science Editorial 2020 – a year gone by and the year ahead
Authors: Touyz Rhian M. 
Published: December 2020

Abstract
As this extraordinary year, blemished by COVID-19, comes to an end, I look back as Editor-in-Chief to the many great successes and new initiatives of Clinical Science. Despite the challenges we all faced during 2020, our journal has remained strong and vibrant. While we have all adapted to new working conditions, with life very different to what it was pre-COVID-19, the one thing that remains intact and secure is the communication of scientific discoveries through peer-reviewed journals. I am delighted to share with you some of the many achievements of our journal over the past year and to highlight some exciting new activities planned for 2021.