bluuebunny/crossref_metadata_2025_split huggingface dataset:
Only as strong as the weakest link: structural analysis of the combined effects of elevated temperature and pCO2 on mussel attachment
Authors: Newcomb Laura A , George Matthew N , O’Donnell Michael J , Carrington Emily 
Published: August 2019

AbstractPredicting how combinations of stressors will affect failure risk is a key challenge for the field of ecomechanics and, more generally, ecophysiology. Environmental conditions often influence the manufacture and durability of biomaterials, inducing structural failure that potentially compromises organismal reproduction, growth, and survival. Species known for tight linkages between structural integrity and survival include bivalve mussels, which produce numerous byssal threads to attach to hard substrate. Among the current environmental threats to marine organisms are ocean warming and acidification. Elevated pCO2 exposure is known to weaken byssal threads by compromising the strength of the adhesive plaque. This study uses structural analysis to evaluate how an additional stressor, elevated temperature, influences byssal thread quality and production. Mussels (Mytilus trossulus) were placed in controlled temperature and pCO2 treatments, and then, newly produced threads were counted and pulled to failure to determine byssus strength. The effects of elevated temperature on mussel attachment were dramatic; mussels produced 60% weaker and 65% fewer threads at 25°C in comparison to 10°C. These effects combine to weaken overall attachment by 64–88% at 25°C. The magnitude of the effect of pCO2 on thread strength was substantially lower than that of temperature and, contrary to our expectations, positive at high pCO2 exposure. Failure mode analysis localized the effect of temperature to the proximal region of the thread, whereas pCO2 affected only the adhesive plaques. The two stressors therefore act independently, and because their respective target regions are interconnected (resisting tension in series), their combined effects on thread strength are exactly equal to the effect of the strongest stressor. Altogether, these results show that mussels, and the coastal communities they support, may be more vulnerable to the negative effects of ocean warming than ocean acidification.
Financial Toxicity as an Unforeseen Side Effect of Inflammatory Bowel Disease
Authors: Hobbs Misty , Thakur Kshitij 
Published: August 2019

Abstract
“Financial toxicity” refers to the adverse impacts of cost on a patient’s disease experience and outcomes. Although the focus of financial toxicity thus far has been in the context of cancer care, it is reasonable to suspect that other chronic illnesses are afflicted by this same concept. In this article, we discuss a case of financial toxicity in a patient with ulcerative colitis, which ultimately lead to not only insufficient disease management, but also paradoxically increased cost. Our case serves to illustrate the phenomenon of financial toxicity and its consequences in patients with inflammatory bowel disease.
Commonly Used Immunosuppressives Affect Mesenchymal Stem Cell Viability and Function: Should We Rethinking Clinical Trial Inclusion and Exclusion Criteria?
Authors: Lightner Amy L , Du Zeji , Peterson Timothy E , Shi Ao , Li Mark , Romero Arocha Sinibaldo Rafael , Behfar Atta 
Published: August 2019

Abstract

Background
Clinical trials utilizing mesenchymal stem cells (MCSs) for the treatment of perianal Crohn disease are expanding. Most enrolled Crohn patients are being actively treated with corticosteroids, immunomodulators, and biologic therapy for their luminal and perianal disease at the time of enrollment and treatment.

Aim
We sought to broaden the understanding of the effect of corticosteroids, immunomodulators, and biologic therapy on the viability and function of MCSs. This information is important for tailoring inclusion and exclusion criteria of clinical trials.

Methods
Human adipose–derived mesenchymal stem cells (hAMCSs) were harvested and isolated from healthy patient donors. At Passage 3, hAMCSs were treated with 7 commonly used immunosuppressive therapies used to treat Crohn disease at increasing concentrations: dexamethasone, methotrexate, azathioprine, 6-mercaptopurine, infliximab, vedolizumab, and ustekinumab. Cell proliferation, migration, and cytokine secretion were analyzed at Day 4.

Results
Dexamethasone and azathioprine and 6-mercaptopurien affected cell proliferation and migration. Dexamethasone even resulted in cell death at high physiologic concentrations. The same drugs also had the most profound impacts on IL-6, IL-8, and monocyte chemoattractant protein-1 secretion profiles. Biologic therapies, including anti-tumor necrosis factor, anti-interleukin, and anti-integrins, had the smallest impact on hAMSC proliferation, migration, and cytokine secretion profile.

Conclusions
In clinical trials with MCSs, a washout period may be recommended for corticosteroids and immunomodulators to minimize any effect of systemic immunosuppression on MSC function and efficacy.
Elevated Pretreatment Plasma Oncostatin M Is Associated With Poor Biochemical Response to Infliximab
Authors: Minar Phillip , Lehn Christina , Tsai Yi-Ting , Jackson Kimberly , Rosen Michael J , Denson Lee A 
Published: August 2019

Abstract

Background
We hypothesized that elevations of plasma Oncostatin M (OSM) would be associated with infliximab nonresponse.

Methods
Plasma OSM was measured in Crohn disease patients pre-infliximab with biochemical response (&gt;50% reduction in fecal calprotectin) as the primary outcome.

Results
The median OSM in biochemical responders was 86 (69–148) pg/mL compared with 166 (74–1766) pg/mL in nonresponders (P = 0.03). Plasma OSM &gt; 143.5 pg/mL was 71% sensitive and 78% specific for biochemical nonresponse (area under the curve 0.71). Early biochemical nonremission was also associated with an elevated neutrophil CD64 expression (odds ratio 8.9, P = 0.011).

Conclusions
Elevated preinfliximab plasma OSM and nCD64 surface expression were both associated with poor biochemical outcomes.
Oxidized low-density lipoproteins induce tissue factor expression in T-lymphocytes via activation of lectin-like oxidized low-density lipoprotein receptor-1
Authors: Cimmino Giovanni , Cirillo Plinio , Conte Stefano , Pellegrino Grazia , Barra Giusi , Maresca Lucio , Morello Andrea , Calì Gaetano , Loffredo Francesco , De Palma Raffaele , Arena Giulia , Sawamura Tatsuya , Ambrosio Giuseppe , Golino Paolo 
Published: August 2019

Abstract

Aims
T-lymphocytes plays an important role in the pathophysiology of acute coronary syndromes. T-cell activation in vitro by pro-inflammatory cytokines may lead to functional tissue factor (TF) expression, indicating a possible contribution of immunity to thrombosis. Oxidized low-density lipoproteins (oxLDLs) are found abundantly in atherosclerotic plaques. We aimed at evaluating the effects of oxLDLs on TF expression in T cells and the role of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1).

Methods and results
CD3+ cells were isolated from healthy volunteers. Gene, protein, and surface expression of TF, as well as of LOX-1, were assessed at different time-points after oxLDL stimulation. To determine whether oxLDL-induced TF was LOX-1 dependent, T cells were pre-incubated with an LOX-1 inhibiting peptide (L-RBP) or with an anti-LOX-1 blocking antibody. To exclude that TF expression was mediated by reactive oxygen species (ROS) generation, oxLDL-stimulated T cells were pre-incubated with superoxide dismutase + catalase or with 4-Hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), an intracellular free radical scavenger. Finally, to determine if the observed findings in vitro may have a biological relevance, the presence of CD3+/TF+/LOX-1+ cells was evaluated by immunofluorescence in human carotid atherosclerotic lesions. oxLDLs induced functionally active TF expression in T cells in a dose- and time-dependent manner, independently on ROS generation. No effect was observed in native LDL-treated T cells. LOX-1 expression was also induced by oxLDLs in a time- and dose-dependent manner. Pre-incubation with L-RBP or anti-LOX-1 antibody almost completely inhibited oxLDL-mediated TF expression. Interestingly, human carotid plaques showed significant infiltration of CD3+ cells (mainly CD8+ cells), some of which were positive for both TF and LOX-1.

Conclusion
oxLDLs induce functional TF expression in T-lymphocytes in vitro via interaction of oxLDLs with LOX-1. Human carotid atherosclerotic plaques contain CD3+/CD8+cells that express both TF and LOX-1, indicating that also in patients these mechanisms may play an important role.
Dispossession and the 1970s Trans-Genre: A Reading of Judy Grahn’s “The Psychoanalysis of Edward the Dyke”
Authors: Irwin Catherine 
Published: August 2019

AbstractWhile Judy Grahn’s 1978 prose poem “The Psychoanalysis of Edward the Dyke” has been examined through a cisgendered lesbian feminist lens, this essay argues that Grahn’s poem is more productively interpreted as a satirical trans-genre that critiques not just the clinical treatment of lesbians, but the clinical treatment of trans persons as well. Through a close reading, this essay analyzes the various social and medical encounters in “Edward the Dyke” to address how transphobic and homophobic discourses of this historical period are parodied and used as satirical elements to critique the clinical establishment. A reading of Grahn’s work as trans-genre contributes to a body of work that illustrates the dispossession of both gender variant lesbians and trans subjectivities and the historical intersections of non-normative genders and sexualities in literature.
At Will: The Queer Possibility of Jen Bervin’s Nets
Authors: Gold Alexandra J 
Published: August 2019

AbstractExploring Jen Bervin’s 2004 revision of the Shakespearean sonnets, this essay situates her project Nets within a visual and verbal tradition of erasure art past and contemporary and underscores her work’s queer potential. Through Bervin’s creative-critical intervention, Nets reorients the spatio-temporal boundaries of the Bard’s infamous sequence, unsettling its most entrenched assumptions of subjectivity and form. Her erasure not only unearths disparate meanings in but imagines alternative possibilities for Shakespeare’s sonnets, cultivating new pleasures and beauties therein. Doing so, Nets begins to reveal how erasure can function as a powerful poetic mode for those whose subjectivities and voices have long been excluded from official literary and cultural histories: how erasure becomes a bold act of will.
DeepScreening: a deep learning-based screening web server for accelerating drug discovery
Authors: Liu Zhihong , Du Jiewen , Fang Jiansong , Yin Yulong , Xu Guohuan , Xie Liwei 
Published: August 2019

Abstract
Deep learning contributes significantly to researches in biological sciences and drug discovery. Previous studies suggested that deep learning techniques have shown superior performance to other machine learning algorithms in virtual screening, which is a critical step to accelerate the drug discovery. However, the application of deep learning techniques in drug discovery and chemical biology are hindered due to the data availability, data further processing and lacking of the user-friendly deep learning tools and interface. Therefore, we developed a user-friendly web server with integration of the state of art deep learning algorithm, which utilizes either the public or user-provided dataset to help biologists or chemists perform virtual screening either the chemical probes or drugs for a specific target of interest. With DeepScreening, user could conveniently construct a deep learning model and generate the target-focused de novo libraries. The constructed classification and regression models could be subsequently used for virtual screening against the generated de novo libraries, or diverse chemical libraries in stock. From deep models training to virtual screening, and target focused de novo library generation, all those tasks could be finished with DeepScreening. We believe this deep learning-based web server will benefit to both biologists and chemists for probes or drugs discovery.
Evaluation of an automatic article selection method for timelier updates of the Comet Core Outcome Set database
Authors: Norman Christopher R , Gargon Elizabeth , Leeflang Mariska M G , Névéol Aurélie , Williamson Paula R 
Published: August 2019

AbstractCurated databases of scientific literature play an important role in helping researchers find relevant literature, but populating such databases is a labour intensive and time-consuming process. One such database is the freely accessible Comet Core Outcome Set database, which was originally populated using manual screening in an annually updated systematic review. In order to reduce the workload and facilitate more timely updates we are evaluating machine learning methods to reduce the number of references needed to screen. In this study we have evaluated a machine learning approach based on logistic regression to automatically rank the candidate articles. Data from the original systematic review and its four first review updates were used to train the model and evaluate performance. We estimated that using automatic screening would yield a workload reduction of at least 75% while keeping the number of missed references around 2%. We judged this to be an acceptable trade-off for this systematic review, and the method is now being used for the next round of the Comet database update.
RiceRelativesGD: a genomic database of rice relatives for rice research
Authors: Mao Lingfeng , Chen Meihong , Chu Qinjie , Jia Lei , Sultana Most Humaira , Wu Dongya , Kong Xiangdong , Qiu Jie , Ye Chu-Yu , Zhu Qian-Hao , Chen Xi , Fan Longjiang 
Published: August 2019

Abstract
Rice (Oryza sativa L.) is one of the most important crops worldwide. Its relatives, including phylogenetically related species of rice and paddy weeds with a similar ecological niche, can provide crucial genetic resources (such as resistance to biotic and abiotic stresses and high photosynthetic efficiency) for rice research. Although many rice genomic databases have been constructed, a database providing large-scale curated genomic data from rice relatives and offering specific gene resources is still lacking. Here, we present RiceRelativesGD, a user-friendly genomic database of rice relatives. RiceRelativesGD integrates large-scale genomic resources from 2 cultivated rice and 11 rice relatives, including 208 321 specific genes and 13 643 genes related to photosynthesis and responsive to external stimuli. Diverse bioinformatics tools are embedded in the database, which allow users to search, visualize and download the information of interest. To our knowledge, this is the first genomic database providing a centralized genetic resource of rice relatives. RiceRelativesGD will serve as a significant and comprehensive knowledgebase for the rice community.
RareLSD: a manually curated database of lysosomal enzymes associated with rare diseases
Authors: Akhter Sana , Kaur Harpreet , Agrawal Piyush , Raghava Gajendra P S 
Published: August 2019

AbstractRareLSD is a manually curated database of lysosomal enzymes associated with rare diseases that maintains comprehensive information of 63 unique lysosomal enzymes and 93 associated disorders. Each entry provides a complete information on the disorder that includes the name of the disease, organ affected, age of onset, available drug, inheritance pattern, defected enzyme and single nucleotide polymorphism. To facilitate users in designing drugs against these diseases, we predicted and maintained structures of lysosomal enzymes. Our information portal also contains information on biochemical assays against disease-associated enzymes obtained from PubChem. Each lysosomal entry is supported by information that includes disorders, inheritance pattern, drugs, family members, active inhibitors, etc. Eventually, a user-friendly web interface has been developed to facilitate the users in searching and browsing data in RareLSD with a wide range of options. RareLSD is integrated with sequence similarity search tools (e.g. BLAST and Smith-Waterman algorithm) for analysis. It is built on responsive templates that are compatible with most of browsers and screens including smartphones and gadgets (mobile, iPhone, iPad, tablets, etc.).
MicroRNA23a Overexpression in Crohn’s Disease Targets Tumour Necrosis Factor Alpha Inhibitor Protein 3, Increasing Sensitivity to TNF and Modifying the Epithelial Barrier
Authors: Felwick Richard K , Dingley Geraint J R , Martinez-Nunez Rocio , Sanchez-Elsner Tilman , Cummings J R Fraser , Collins Jane E 
Published: August 2019

Abstract

Background and Aims
Mucosal healing is important in Crohn’s disease therapies. Epithelial homeostasis becomes dysregulated in Crohn’s, with increased permeability, inflammation, and diarrhoea. MicroRNAs are small non-coding RNAs that regulate gene expression and show changes in inflammatory bowel disease. Tumour necrosis factor alpha [TNFα] inhibitor protein 3 is raised in Crohn’s and regulates TNFα-mediated activation of NFκB. We investigated TNFα regulation by microRNA in Crohn’s disease [CD], and studied effects on epithelial permeability and inflammation.

Methods
Colonic epithelium from CD and healthy donor biopsies was isolated using laser capture microdissection, and microRNA was quantified. Tumour necrosis factor alpha inhibitor protein 3 was characterised immunohistochemically on serial sections. Expression effect of microRNA was confirmed with luciferase reporter assays. Functional barrier permeability studies and innate cytokine release were investigated with cell and explant culture studies.

Results
MicroRNA23a levels significantly increased in colonic Crohn’s epithelium compared with healthy epithelium. Luciferase reporter assays in transfected epithelial cells confirmed that microRNA23a repressed expression via the 3’ untranslated region of tumour necrosis factor alpha inhibitor protein 3 mRNA, coinciding with increased NFκB-mediated transcription. Immunohistochemical staining of TNFAIP3 protein in colonic biopsies was reduced or absent in adjacent Crohn’s sections, correlating inversely with microRNA23a levels and encompassing some intercohort variation. Overexpression of microRNA23a increased epithelial barrier permeability in a colonic epithelial model and increased inflammatory cytokine release in cultured explant biopsies, mimicking Crohn’s disease characteristics.

Conclusions
MicroRNA23a overexpression in colonic Crohn’s epithelium represses tumour necrosis factor alpha inhibitor protein 3, enhancing sensitivity to TNFα, with increased intestinal permeability and cytokine release.
Improved regional myocardial blood flow and flow reserve after coronary revascularization as assessed by serial 15O-water positron emission tomography/computed tomography
Authors: Aikawa Tadao , Naya Masanao , Koyanagawa Kazuhiro , Manabe Osamu , Obara Masahiko , Magota Keiichi , Oyama-Manabe Noriko , Tamaki Nagara , Anzai Toshihisa 
Published: August 2019

Abstract

Aims
Myocardial perfusion imaging without and with quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) plays an important role in the diagnosis and risk stratification of patients with stable coronary artery disease (CAD). We aimed to quantify the effects of coronary revascularization on regional stress MBF and MFR and to determine whether the presence of subendocardial infarction was associated with these changes.

Methods and results
Forty-seven patients with stable CAD were prospectively enrolled. They underwent 15O-water positron emission tomography at baseline and 6 months after optimal medical therapy alone (n = 16), percutaneous coronary intervention (PCI) (n = 18), or coronary artery bypass grafting (CABG) (n = 13). Stenosis of ≥50% diameter was detected in 98/141 vessels (70%). The regional MFR was significantly increased from baseline to follow-up [1.84 (interquartile range, IQR 1.28–2.17) vs. 2.12 (IQR 1.69–2.63), P &lt; 0.001] in vessel territories following PCI or CABG due to an increase in the stress MBF [1.33 (IQR 0.97–1.67) mL/g/min vs. 1.64 (IQR 1.38–2.17) mL/g/min, P &lt; 0.001], whereas there was no significant change in the regional stress MBF or MFR in vessel territories without revascularization. A multilevel mixed-effects models adjusted for baseline characteristics, subendocardial infarction assessed by cardiovascular magnetic resonance imaging, and intra-patient correlation showed that the degree of angiographic improvement after coronary revascularization was significantly associated with increased regional stress MBF and MFR (P &lt; 0.05 for all).

Conclusion
Coronary revascularization improved the regional stress MBF and MFR in patients with stable CAD. The magnitude of these changes was associated with the extent of revascularization independent of subendocardial infarction.
Can Taxes Tame the Banks? Evidence from the European Bank Levies
Authors: Devereux Michael , Johannesen Niels , Vella John 
Published: August 2019

AbstractFollowing the 2007–2008 financial crisis, a large number of countries introduced levies on bank borrowing intended to reduce risk in the financial sector. This article studies the behavioural responses to bank levies and finds that banks exposed to levies increased their reliance on equity funding, but at the same time increased the risk of their assets; banks shifted risk from the liability side of their balance sheets to the asset side, which mitigated the impact of government intervention. Our analysis also shows that any reduction in total risk was concentrated among banks that pose no or little threat to financial stability.
Inevitable future: space colonization beyond Earth with microbes first
Authors: Lopez Jose V , Peixoto Raquel S , Rosado Alexandre S 
Published: August 2019

ABSTRACTBased on modern microbiology, we propose a major revision in current space exploration philosophy and planetary protection policy, especially regarding microorganisms in space. Mainly, microbial introduction should not be considered accidental but inevitable. We hypothesize the near impossibility of exploring new planets without carrying and/or delivering any microbial travelers. In addition, although we highlight the importance of controlling and tracking such contaminations—to explore the existence of extraterrestrial microorganisms—we also believe that we must discuss the role of microbes as primary colonists and assets, rather than serendipitous accidents, for future plans of extraterrestrial colonization. This paradigm shift stems partly from the overwhelming evidence of microorganisms’ diverse roles in sustaining life on Earth, such as symbioses and ecosystem services (decomposition, atmosphere effects, nitrogen fixation, etc.). Therefore, we propose a framework for new discussion based on the scientific implications of future colonization and terraforming: (i) focus on methods to track and avoid accidental delivery of Earth's harmful microorganisms and genes to extraterrestrial areas; (ii) begin a rigorous program to develop and explore ‘Proactive Inoculation Protocols’. We outline a rationale and solicit feedback to drive a public and private research agenda that optimizes diverse organisms for potential space colonization.