bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20
Authors: Antonia Ricardo J. , Karelehto Eveliina , Toriguchi Kan , Matli Mary , Warren Robert S. , Pfeffer Lawrence M. , Donner David B. 
Published: July 2022

AbstractTumour Necrosis Factor (TNF) potently induces a transient inflammatory response that must be downregulated once any invasive stimulus has resolved. Yet, how TNF‐induced inflammation is shut down in normal cells is incompletely understood. The present study shows that STAT3 was activated in mouse embryo fibroblasts (MEFs) by treatment with TNF or an agonist antibody to TNFR1. STAT3 activation was inhibited by pharmacological inhibition of the Jak2 tyrosine kinase that associates with TNFR1. To identify STAT3 target genes, global transcriptome analysis by RNA sequencing was performed in wild‐type MEFs and MEFs from STAT3 knockout (STAT3KO) mice that were stimulated with TNF, and the results were validated at the protein level by using multiplex cytokine assays and immunoblotting. After TNF stimulation, STAT3KO MEFs showed greater gene and protein induction of the inflammatory chemokines Ccl2, Cxcl1 and Cxcl10 than WT MEFs. These observations show that, by activating STAT3, TNF selectively modulates expression of a cohort of chemokines that promote inflammation. The greater induction by TNF of chemokines in STAT3KO than WT MEFs suggested that TNF induced an inhibitory protein in WT MEFs. Consistent with this possibility, STAT3 activation by TNFR1 increased the expression of Tnfaip3/A20, a ubiquitin modifying enzyme that inhibits inflammation, in WT MEFs but not in STAT3KO MEFs. Moreover, enforced expression of Tnfaip3/A20 in STAT3KO MEFs suppressed proinflammatory chemokine expression induced by TNF. Our observations identify Tnfaip3/A20 as a new downstream target for STAT3 which limits the induction of Ccl2, Cxcl1 and Cxcl10 and inflammation induced by TNF.
Dermoscopy of glomus tumour: a cross‐sectional study of 86 cases
Authors: Álvarez‐Salafranca M. , Bañuls J. , Thomas L. , Hirata S.H. , Argenziano G. , Medina C. , Lacarrubba F. , del Pozo L.J. , Ara M. , Zaballos P. 
Published: July 2022

AbstractBackgroundGlomus tumours (GTs) are benign cutaneous neoplasms derived from the neuromyoarterial apparatus with a strong predilection for acral sites, especially the subungual space. Current data regarding dermoscopy of these lesions are very limited.ObjectivesTo analyse the dermoscopic structures and patterns seen in a large series of subungual (SUGTs) and extraungual glomus tumours (EUGTs) and to determine their diagnostic significance.MethodsClinical and dermoscopic images of 86 histopathologically proven cases of GTs (47 SUGTs and 39 EUGTs) collected from 9 hospitals in Spain, France, Italy, and Brazil were evaluated for the presence of dermoscopic structures and patterns. Similarly, 189 and 185 dermoscopic images of other ungual tumours and other extraungual non‐pigmented tumours, respectively, were evaluated for the same structures and patterns. Finally, we evaluate diagnostic testing accuracy calculating sensitivity (S), specificity (Sp), and positive and negative predictive values of the different patterns for the diagnosis of GT.ResultsRegarding SUGTs, four patterns were built from the combination of different structures. The pattern composed of a structureless purplish/red subungual spot with or without vessels reached the highest S (S1, 78.8%). The combination of a structureless purplish/red subungual spot and longitudinal erythronychia (LE) (S2) is highly specific (96.3%). Patterns S3 (proximal purplish/red subungual spot, LE, and distal notch) and S4 (bed subungual spot and onycholysis) are the most specific and exclusive of matrix and bed tumours, respectively. The most consistent pattern in EUGTs is composed of a structureless purplish‐white to reddish‐white homogeneous area and linear unfocused vessels (E) (S: 61.5%, Sp: 95.7%). EUGTs did not show lacunae, unlike other vascular tumours.ConclusionsDermoscopy is helpful in improving the diagnostic accuracy of GTs, not only in SUGTs but also when these lesions arise out of the ungual apparatus.
Exploring ecosystem‐based management in the North Atlantic
Authors: Dickey‐Collas Mark , Link Jason S. , Snelgrove Paul , Roberts J. Murray , Anderson M. Robin , Kenchington Ellen , Bundy Alida , (Peg) Brady Margaret M. , Shuford Rebecca L. , Townsend Howard , Rindorf Anna , Rudd Murray A. , Johnson David , Johannesen Ellen 
Published: July 2022

AbstractThe United States, the EU and Canada established a trilateral working group on the ecosystem approach to ocean health and stressors under the Atlantic Ocean Research Alliance. Recognizing the Atlantic Ocean as a shared resource and responsibility, the working group sought to advance understanding of the Atlantic Ocean and its dynamic systems to improve ocean health, enhance ocean stewardship and promote the sustainable use and management of its resources. This included consideration of multiple ocean‐use sectors such as fishing, shipping, tourism and offshore energy. The working group met for 4 years and worked through eight steps that covered the development of common language as a basis for collaboration, challenges of stakeholder engagement, review of the governance mandates, exploring the links between sectors and ecosystems effects, identifying gaps in knowledge and uptake of science, identification of tools for ecosystem‐based management, customary best practice for tool development and communication of key research priorities. The key findings were that ecosystem‐based management enables new benefits and opportunities, and that we need to make the business case. Further findings were that adequate mandates and effective tools exist for ecosystem‐based management, and that ecosystem‐based management urgently requires integration of human dimensions, so we must diversify the conversation. In addition, it was found that stakeholders do not see their stake in ecosystem‐based management, so greater engagement with stakeholders and targeting of ocean literacy is required and a sustainable future requires a sustained investment in ecosystem‐based management, so long‐term commitment is key.
Adrenomedullin for biologic‐resistant Crohn's disease: A randomized, double‐blind, placebo‐controlled phase 2a clinical trial
Authors: Kita Toshihiro , Ashizuka Shinya , Takeda Teruyuki , Matsumoto Takayuki , Ohmiya Naoki , Nakase Hiroshi , Motoya Satoshi , Ohi Hidehisa , Mitsuyama Keiichi , Hisamatsu Tadakazu , Kanmura Shuji , Kato Naoya , Ishihara Shunji , Nakamura Masanao , Moriyama Tomohiko , Saruta Masayuki , Nozaki Ryoichi , Yamamoto Shojiro , Inatsu Haruhiko , Watanabe Koji , Kitamura Kazuo 
Published: July 2022

AbstractBackground and AimAdrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical trial to investigate the efficacy and safety of adrenomedullin in patients with Crohn's disease (CD).MethodsThis was a multicenter, double‐blind, placebo‐controlled phase 2a trial that evaluated 24 patients with biologic‐resistant CD in Japan. Patients were randomly assigned to three groups and were given an infusion of 10 or 15 ng/kg/min of adrenomedullin or placebo for 8 h per day for 7 days. The primary endpoint was the change in the CD activity index (CDAI) at 8 weeks. The main secondary endpoints included changes in CDAI from week 4 to week 24.ResultsNo differences in the primary or secondary endpoints were observed between the three groups by the 8th week. Changes in CDAI in the placebo group gradually decreased and disappeared at 24 weeks, but those in the adrenomedullin‐treated groups (10 or 15 ng/kg/min group) remained at steady levels for 24 weeks. Therefore, a significant difference was observed between the placebo and adrenomedullin‐treated groups at 24 weeks (P = 0.043) in the mixed‐effects model. We noted mild adverse events caused by the vasodilatory effect of adrenomedullin.ConclusionIn this trial, we observed a long‐lasting (24 weeks) decrease in CDAI in the adrenomedullin‐treated groups. Adrenomedullin might be beneficial for biologic‐resistant CD, but further research is needed.
Optimization and use of near infrared imaging to guide lymph node collection in rhesus macaques (Macaca mulatta)
Authors: Smedley Jeremy V. , Bochart Rachele M. , Fischer Miranda , Funderburgh Heidi , Kelly Vanessa , Crank Hugh , Armantrout Kim , Shiel Oriene , Robertson‐LeVay Mitchell , Sternberger Nikki , Schmaling Brian , Roberts Sheila , Sekiguchi Vicki , Reusz Michael , Schwartz Tiah , Meyer Kimberly A. , Webb Gabriela , Gilbride Roxanne M. , Dambrauskas Nicholas , Andrade Daniela , Wood Matthew , Labriola Caralyn , Axthelm Michael , Derby Nina , Varco‐Merth Ben , Fukazawa Yoshinori , Hansen Scott , Sacha Jonah B. , Sodora Donald L. , Sather D. Noah 
Published: July 2022

AbstractBackgroundIdentification of lymph nodes (LNs) draining a specific site or in obese macaques can be challenging.MethodsIndocyanine Green (ICG) was administered intradermal (ID), intramuscular, in the oral mucosa, or subserosal in the colon followed by Near Infrared (NIR) imaging.ResultsAfter optimization to maximize LN identification, intradermal ICG was successful in identifying 50–100% of the axillary/inguinal LN at a site. Using NIR, collection of peripheral and mesenteric LNs in obese macaques was 100% successful after traditional methods failed. Additionally, guided collection of LNs draining the site of intraepithelial or intramuscular immunization demonstrated significantly increased numbers of T follicular helper (Tfh) cells in germinal centers of draining compared to nondraining LNs.ConclusionThese imaging techniques optimize our ability to evaluate immune changes within LNs over time, even in obese macaques. This approach allows for targeted serial biopsies that permit confidence that draining LNs are being harvested throughout the study.
Improved Self‐Assessed Collaboration Through Interprofessional Education: Midwifery Students and Obstetrics and Gynecology Residents Learning Together
Authors: Avery Melissa D. , Mathiason Michelle , Andrighetti Tia , Autry Amy M. , Cammarano Dominic , Dau Kim Q. , Hoffman Samantha , Krause Susan Agard , Montgomery Owen , Perry Audrey , Sankey Heather Z. , Woodland Mark B. , Jennings John C. 
Published: July 2022

IntroductionResearch suggests that interprofessional education, bringing learners together to learn about, with, and from each other, improves health professions education and can improve health outcomes. Little research has measured outcomes of interprofessional education between midwifery students and obstetrics and gynecology residents. The purpose of this study was to examine self‐assessed interprofessional and collaborative competencies among midwifery students and obstetrics and gynecology residents.MethodsBaseline self‐assessed interprofessional and collaborative competencies were compared with follow‐up measurements to evaluate learners’ experiences over an 11‐month study period. Participants were midwifery students and obstetrics and gynecology residents who experienced interprofessional learning activities. The Interprofessional Education Collaborative Competency Self‐Assessment Survey (IPEC Survey) and Interprofessional Collaborative Competency Attainment Survey (ICCAS) were used.ResultsOf 256 learners at 4 demonstration sites, 223 (87%) completed the baseline, and 121 of 237 eligible learners (51%) completed the follow‐up surveys. The IPEC Survey total score (t = 2.31, P = .02) and interaction subscale (t = 2.85, P = .005) and ICCAS score (t = 4.04, P = .001) increased for midwifery students but not obstetrics and gynecology residents on the IPEC Survey (t = 0.32, P = .75) and ICCAS (t = −0.05, P = .96) measures. Midwifery students (87%) and residents (57%) reported improved overall ability to collaborate. Learners responding to 3 open‐ended questions valued team‐based experiences, including learning how to communicate with each other; appreciated learning each other's education and scope of practice; and recommended skills development including uncommon clinical events, case discussions, and direct clinical care.DiscussionThis study advanced knowledge about interprofessional education between midwifery students and obstetrics and gynecology residents. Midwifery students improved in self‐assessed interprofessional and collaborative competencies. Most learners reported better interprofessional collaboration skills and were positive about future interprofessional learning. This evaluation approach is available for other programs implementing or extending interprofessional education.
PICT‐1 regulates p53 splicing and sensitivity of medullary thyroid carcinoma cells to everolimus
Authors: Bareli Yifat , Shimon Ilan , Tobar Ana , Rubinfeld Hadara 
Published: July 2022

AbstractProtein interacting with carboxyl terminus 1 (PICT‐1) is a nucleolar protein shown to act as a tumor suppressor that interacts with PTEN, or in a contrasting manner to facilitate the accessibility of p53 to ubiquitination and degradation, thus to function as an oncogene. The aim of the study was to examine the potential role of PICT‐1 in neuroendocrine neoplasm (NEN) tumorigenesis and response to mTOR inhibitor treatment. PICT‐1 was overexpressed in medullary thyroid (TT) and pancreatic (BON1) NEN cell lines using lentiviral vector. Whereas in BON1 cells PICT‐1 overexpression exhibited no significant impact, in TT cells it induced the appearance of p53β lacking the C‐terminus end. This was accompanied by a robust decrease in p21 expression and elevation of cell viability. Remarkably, PICT‐1 overexpression completely reversed the reduction in cell viability of medullary thyroid neoplasm cells induced by everolimus, a therapeutic option for patients with progressive NENs. mTOR pathway investigations revealed that PICT‐1 overexpression induced a reduction in PTEN expression and a robust increase in the expression level of phospho‐Akt‐Ser47 only partially inhibited by everolimus. These findings suggest a possible role of PICT‐1 in the spliceosome machinery and provide functional involvement of PICT‐1 in the complex network of mTOR.
The ECB's asset purchase programme: Theory, effects, and risks
Authors: Benigno Pierpaolo , Canofari Paolo , Di Bartolomeo Giovanni , Messori Marcello 
Published: July 2022

AbstractIn response to the Covid‐19 crisis, the European Central Bank (ECB) has relaunched a massive asset purchase programme within its combined‐arms monetary strategy. This paper surveys and discusses the theory and the evidence of the central bank's unconventional monetary tools for the euro area. It analyses the role of the asset purchase programmes in the ECB's toolkit and the associated risks, focusing specifically on the gradual unwinding of these unconventional initiatives. Finally, the paper offers some insight into the possible evolution of the ECB's monetary policy.
Offset analgesia is increased intra‐orally
Authors: Szikszay Tibor M. , Lévénez Juliette L. M. , Adamczyk Wacław M. , Carvalho Gabriela F. , Luedtke Kerstin 
Published: July 2022

AbstractBackgroundOffset analgesia (OA) is commonly used to quantify endogenous pain inhibition. However, the potential role of afferent inputs and the subsequent peripheral factors from different body areas on the underlying mechanisms are still unclear.ObjectivesThe aim of this cross‐sectional study was to compare the magnitude of OA in four different body areas representing (a) glabrous and non‐glabrous skin, (b) trigeminal and extra‐trigeminal areas, and (c) intra‐ and extra‐oral tissue.MethodsOA was assessed at the oral mucosa of the lower lip, the skin of the cheek, the forearm and the palm of the hand in 32 healthy and pain‐free participants. OA testing included two trials: (1) a constant trial (30 s of constant heat stimulation at an individualised temperature of Pain50 [pain intensity of 50 out of 100]) and (2) an offset trial (10 s of individualised Pain50, followed by 5 s at Pain50 + 1°C and 15 s at Pain50). Participants continuously rated their pain during each trial with a computerised visual analogue scale.ResultsA significant OA response was recorded at the oral mucosa (p < .001, d = 1.24), the cheek (p < .001, d = 0.84) and the forearm (p < .001, d = 1.04), but not at the palm (p = .19, d = 0.24). Significant differences were shown for OA recorded at the cheek versus the mucosa (p = .02), and between palm and mucosa (p = .007), but not between the remaining areas (p > .05).ConclusionThis study suggests that intra‐oral endogenous pain inhibition assessed with OA is enhanced and supports the role of peripheral mechanisms contributing to the OA response.
Human–rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic–ischemic pathway melatonin‐sensitive
Authors: Weiss Michael D. , Carloni Silvia , Vanzolini Tania , Coppari Sofia , Balduini Walter , Buonocore Giuseppe , Longini Mariangela , Perrone Serafina , Sura Livia , Mohammadi Atefeh , Rocchi Marco Bruno Luigi , Negrini Massimo , Melandri Davide , Albertini Maria Cristina 
Published: July 2022

AbstractNeonatal encephalopathy (NE) is a pathological condition affecting long‐term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic–ischemic (HI) brain injury. However, unlike animal models that enable the study of the brain and the pathophysiologic cascade, only blood is available from human subjects. Therefore, due to the unavailability of neonatal brain tissue, assumptions about the pathophysiology in pathways and cascades are made in human subjects with NE. We analyzed animal and human specimens to improve our understanding of the pathophysiology in human neonates. A neonate with NE who underwent hypothermia and enrolled in a melatonin pharmacokinetic study was compared to HI rats treated/untreated with melatonin. MicroRNA (miRNA) analyses provided profiles of the neonate's plasma, rat plasma, and rat brain cortexes. We compared these profiles through a bioinformatics tool, identifying Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways common to HI brain injury and melatonin treatment. After evaluating the resulting pathways and the literature, to validate the method, the key proteins expressed in HI brain injury were investigated using cerebral cortexes. The upregulated miRNAs in human neonate and rat plasma helped identify two KEGG pathways, glioma and long‐term potentiation, common to HI injury and melatonin treatment. A unified neonatal cerebral melatonin‐sensitive HI pathway was designed and validated by assessing the expression of protein kinase Cα (PKCα), phospho (p)‐Akt, and p‐ERK proteins in rat brain cortexes. PKCα increased in HI‐injured rats and further increased with melatonin. p‐Akt and p‐ERK returned phosphorylated to their basal level with melatonin treatment after HI injury. The bioinformatics analyses validated by key protein expression identified pathways common to HI brain injury and melatonin treatment. This approach helped complete pathways in neonates with NE by integrating information from animal models of HI brain injury.
Associational effects, landscape context, and plant height affect white‐tailed deer (Odocoileus virginianus) browse selectivity in oak woodlands
Authors: Minette Justin H. , Keoshkerian Noah , Russell F. Leland 
Published: July 2022

AbstractQuestionsLarge spatial variation in damage intensity is a pervasive, but poorly explained, feature of herbivore–plant interactions. To predict herbivore effects on plant communities, ecologists need greater understanding of the mechanisms and relative importance of processes driving variation in damage at the spatial scales of individual plant, plant community, and landscape. We ask: (1) what are the relative strengths of traits of individual plants versus landscape context in affecting white‐tailed deer (Odocoileus virginianus) browsing on saplings in oak woodlands; and (2) is browsing intensity on post oak (Quercus stellata) influenced by associational effects related to density or frequency of more‐selected or less‐selected species?LocationDry oak‐dominated woodlands, Kansas, USA.MethodsWe sampled deer browsing on saplings in three woodlands, each containing five transects, with 21 10‐m2 plots per transect. Transects ran from woodland–grassland edges into woodlands. In each plot, we identified saplings to species, measured variables in individual‐plant (height) and landscape contexts (distance from edge and proximity to deer trails), and quantified proportion of stems browsed per sapling.ResultsBrowsing intensity varied greatly among the 18 tree species encountered. Browsing increased with sapling height and decreased with distance from woodland edges. The effect size of distance from edge was twice that of sapling height, although both effect sizes were small. Browsing on post oaks increased with local frequency of saplings of more‐selected species.ConclusionsOur comparison of individual‐plant versus landscape context variables and our assessment of associational effects supports a substantial role for coarse‐scale foraging decisions in explaining browsing damage. However, sapling species identity was most influential. Associational susceptibility of a less‐selected species, post oak, near more‐selected neighbors is consistent with a mobile herbivore choosing between patches. The pre‐eminence of frequency of more‐selected species in mediating associational susceptibility may reflect decreased handling time in pure patches and/or attempts to balance nutrients.
Linking large‐scale genetic structure of three Argynnini butterfly species to geography and environment
Authors: Polic Daniela , Yıldırım Yeşerin , Lee Kyung Min , Franzén Markus , Mutanen Marko , Vila Roger , Forsman Anders 
Published: July 2022

AbstractUnderstanding which factors and processes are associated with genetic differentiation within and among species remains a major goal in evolutionary biology. To explore differences and similarities in genetic structure and its association with geographical and climatic factors in sympatric sister species, we conducted a large‐scale (>32° latitude and >36° longitude) comparative phylogeographical study on three Argynnini butterfly species (Speyeria aglaja, Fabriciana adippe and F. niobe) that have similar life histories, but differ in ecological generalism and dispersal abilities. Analyses of nuclear (ddRAD‐sequencing derived SNP markers) and mitochondrial (COI sequences) data revealed differences between species in genetic structure and how genetic differentiation was associated with climatic factors (temperature, solar radiation, precipitation, wind speed). Geographical proximity accounted for much of the variation in nuclear and mitochondrial structure and evolutionary relationships in F. adippe and F. niobe, but only explained the pattern observed in the nuclear data in S. aglaja, for which mitonuclear discordance was documented. In all species, Iberian and Balkan individuals formed genetic clusters, suggesting isolation in glacial refugia and limited postglacial expansion. Solar radiation and precipitation were associated with the genetic structure on a regional scale in all species, but the specific combinations of environmental and geographical factors linked to variation within species were unique, pointing to species‐specific responses to common environments. Our findings show that the species share similar colonization histories, and that the same ecological factors, such as niche breadth and dispersal capacity, covary with genetic differentiation within these species to some extent, thereby highlighting the importance of comparative phylogeographical studies in sympatric sister species.