bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Narrative Origins of Language
Authors: Ferretti Francesco 
Published: March 2021

Abstract
Central to this chapter is the idea that the investigation of the origin of language is strictly tied to the analysis of the traits that distinguish human communication from that of animals. A cognitive approach to the study of the origin of language is employed. The proposal is that the analysis of the traits that distinguish human communication from that of animals must be guided by an investigation of the processing devices that allowed our ancestral relatives to manage the transition from animal communication to language. The argument put forward is that the distinguishing feature of language is how it supports the ability to tell stories; and that the cognitive devices responsible for the transition from animal communication to language (space and time navigational systems, plus mindreading) are the same cognitive devices dedicated to discursive level processing in human communication. Given that the issue of the origins of language is closely related to the analysis of the differences between the way in which humans and non-human animals communicate, the first issue to be addressed regards the question of what is specific about language as a system of communication.
The Case for Peele’s Authorship of Titus Andronicus 4.1: Cross-Examining Attribution Methods in a Disputed Scene
Authors: Hulse Mark C 
Published: March 2021

Abstract
William Weber (2014) argues that Shakespeare authored Titus Andronicus 4.1 as evidenced by verbal collocation data and auxiliary investigations into the vocabulary, rhetoric, and classical content of the scene. Anna Pruitt (2017) corroborates this view using n-gram testing, and critical opinion has shifted against the older orthodoxy assigning the scene to George Peele. Yet despite efforts to select a limited set of Shakespearean works for their experiments, the datasets compiled by Weber and Pruitt from the LION database are invalidated by the imbalanced canon sizes of the two authorship candidates. This oversight compromises their quantitative arguments, as does their neglecting The Troublesome Reign of King John. This article demonstrates that when equitable canons are implemented 4.1’s vocabulary is strongly indicative of Peele’s hand, in clear opposition to the current consensus view. Additionally, the scene contains classical allusiveness that is distinct from that of Shakespeare with regard to sources, effect, and scope, further reinforcing the case for Peele’s authorship. The article then revisits the un-Shakespearean metrical properties of 4.1 and testimonial evidence in support of an earlier Titus play, arguing that Peele’s ownership of the scene can greatly inform our model of Shakespeare’s timeline and alleged innovations in the revenge tragedy genre during his earliest career phase. Recent critiques of automated searching in attribution studies show why integrated methods that unite quantitative and qualitative techniques remain indispensable, and the 2014 and 2017 studies’ erroneous conclusions provide a cautionary tale for future research in the field.
Reliability, validity and responsiveness of physical activity monitors in patients with inflammatory myopathy
Authors: Rockette-Wagner Bonny , Saygin Didem , Moghadam-Kia Siamak , Oddis Chester , Landon-Cardinal Océane  , Allenbach Yves , Dzanko Sedin , Koontz Diane , Neiman Nicole , Aggarwal Rohit 
Published: March 2021

Abstract

Objective
Idiopathic inflammatory myopathies (IIMs) cause proximal muscle weakness, which affects the ability to carry out the activities of daily living. Wearable physical activity monitors (PAMs) objectively assess continuous activity and potentially have clinical usefulness in the assessment of IIMs. We examined the psychometric characteristics for PAM outcomes in IIMs.

Methods
Adult IIM patients were prospectively evaluated (at baseline, 3 months and 6 months) in an observational study. A waist-worn PAM (ActiGraph GT3X-BT) assessed average step counts/minute, peak 1-minute cadence, and vector magnitude/minute. Validated myositis core set measures (CSMs) including manual muscle testing (MMT), physician global disease activity (MD global), patient global disease activity (Pt global), extramuscular disease activity (Ex-muscular global), HAQ-DI (HAQ disability index), muscle enzymes, and patient-reported physical function were evaluated. Test–retest reliability, construct validity, and responsiveness were determined for PAM measures and CSMs, using Pearson correlations and other appropriate analyses.

Results
A total of 50 adult IIM patients enrolled [mean (s.d.) age, 53.6 (14.6); 60% female, 94% Caucasian]. PAM measures showed strong test–retest reliability, moderate-to-strong correlations at baseline with MD global (r = −0.37 to −0.48), Pt global (r=−0.43 to −0.61), HAQ-DI (r = −0.47 to −0.59) and MMT (r = 0.37–0.52), and strong discriminant validity for categorical MMT and HAQ-DI. Longitudinal associations with MD global (r=−0.38 to −0.44), MMT (r = 0.50–0.57), HAQ-DI (r = −0.45 to −0.55) and functional tests (r = 0.30–0.65) were moderate to strong. PAM measures were responsive to MMT improvement ≥10% and moderate-to-major improvement on ACR/EULAR myositis response criteria. Peak 1-minute cadence had the largest effect size and standardized response means.

Conclusion
PAM measures showed promising construct validity, reliability, and longitudinal responsiveness; especially peak 1-minute cadence. PAMs are able to provide valid outcome measures for future use in IIM clinical trials.
Genetics-Based Approach to Identify Novel Genes Regulated by the Aryl Hydrocarbon Receptor in Mouse Liver
Authors: Jurgelewicz Amanda , Dornbos Peter , Warren Melanie , Nault Rance , Arkatkar Anooj , Lin Hui , Threadgill David W , Zacharewski Tim , LaPres John J 
Published: March 2021

Abstract
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor in the Per-Arnt-Sim superfamily of environmental sensors that is linked to several metabolic diseases, including nonalcoholic fatty liver disease. Much remains unknown regarding the impact of genetic variation in AHR-driven disease, as past studies have focused on a small number of inbred strains. Recently, the presence of a wide range of interindividual variability amongst humans was reported in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototypical ligand of the AHR. In this study, a panel of 14 diverse mouse strains was exposed to TCDD for 10 days to characterize the AHR-mediated response across genetic backgrounds. Responses to TCDD are heavily dependent on genetic background. Although mice carry 1 of 4 Ahr alleles known to impact the affinity to AHR-ligands, we observed significant intra-allelic variability suggesting the presence of novel genetic modifiers of AHR signaling. A regression-based approach was used to scan for genes regulated by the AHR and/or associated with TCDD-induced phenotypes. The approach identified 7 genes, 2 of which are novel, that are likely regulated by the AHR based on association with hepatic TCDD burden (p ≤ .05). Finally, we identified 1 gene, Dio1, which was associated with change in percent body fat across the diverse set of strains (p ≤ .05). Overall, the results in this study exemplify the power of genetics-based approaches in identifying novel genes that are putatively regulated by the AHR.
Methylation of ERβ 5′‐untranslated region attenuates its inhibitory effect on ERα gene transcription and promotes the initiation and progression of papillary thyroid cancer
Authors: Xu Lin‐Wan , Gou Xi , Yang Jun‐Yan , Jiang Rong , Jiang Xue , Chen George G. , Liu Zhi‐Min 
Published: March 2021

AbstractNormal thyroid tissue displays a prevalent expression of ERβ than ERα, which drastically turns upside down in the initiation and progression of papillary thyroid cancer (PTC). The underlying molecular mechanism of this phenomenon remains unclear. Here, we demonstrated that ERα and ERβ were coexpressed in human thyroid tissues and cells. ERα mRNA (A‐1) and ERβ mRNA (0N‐1), transcribed from Promoter A of ERα gene and Promoter 0N of ERβ gene, respectively, were the major mRNA isoforms which mainly contributed to total ERα mRNA and total ERβ mRNA in human thyroid‐derived cell lines and tissues. The expression levels of ERα mRNA (A‐1) and total ERα mRNA were gradually increased, and those of ERβ mRNA (0N‐1) and total ERβ mRNA were decreased by degree in the initiation and progression of PTC. No aberrant DNA methylation of ERα 5′‐untranslated region was involved in its up‐regulation; however, aberrant DNA methylation in Promoter 0N and Exon 0N of ERβ gene was found to be involved in its down‐regulation in the initiation and progression of PTC. ERβ can repress ERα gene transcription via recruitment of NCoR and displacement of RNA polymerase II at the Sp1 site in ERα Promoter A‐specific region in thyroid‐derived cells. It is suggested that DNA methylation of CpG islands in Promoter 0N and Exon 0N of ERβ gene leads to a decreased ERβ gene expression, which attenuates its inhibitory effect on ERα gene transcription and results in an increased ERα gene expression, cell proliferation, initiation, and progression of PTC.
Efficient G protein coupling is not required for agonist‐mediated internalization and membrane reorganization of the adenosine A3 receptor
Authors: Stoddart Leigh A. , Kilpatrick Laura E. , Corriden Ross , Kellam Barrie , Briddon Stephen J. , Hill Stephen J. 
Published: March 2021

AbstractOrganization of G protein‐coupled receptors at the plasma membrane has been the focus of much recent attention. Advanced microscopy techniques have shown that these receptors can be localized to discrete microdomains and reorganization upon ligand activation is crucial in orchestrating their signaling. Here, we have compared the membrane organization and downstream signaling of a mutant (R108A, R3.50A) of the adenosine A3 receptor (A3AR) to that of the wild‐type receptor. Fluorescence Correlation Spectroscopy (FCS) studies with a fluorescent agonist (ABEA‐X‐BY630) demonstrated that both wild‐type and mutant receptors bind agonist with high affinity but in subsequent downstream signaling assays the R108A mutation abolished agonist‐mediated inhibition of cAMP production and ERK phosphorylation. In further FCS studies, both A3AR and A3AR R108A underwent similar agonist‐induced increases in receptor density and molecular brightness which were accompanied by a decrease in membrane diffusion after agonist treatment. Using bimolecular fluorescence complementation, experiments showed that the R108A mutant retained the ability to recruit β‐arrestin and these receptor/arrestin complexes displayed similar membrane diffusion and organization to that observed with wild‐type receptors. These data demonstrate that effective G protein signaling is not a prerequisite for agonist‐stimulated β‐arrestin recruitment and membrane reorganization of the A3AR.
Resident immune cells of the avascular lens: Mediators of the injury and fibrotic response of the lens
Authors: Menko A. Sue , DeDreu JodiRae , Logan Caitlin M. , Paulson Heather , Levin Alex V. , Walker Janice L. 
Published: March 2021

AbstractTissues typically harbor subpopulations of resident immune cells that function as rapid responders to injury and whose activation leads to induction of an adaptive immune response, playing important roles in repair and protection. Since the lens is an avascular tissue, it was presumed that it was absent of resident immune cells. Our studies now show that resident immune cells are a shared feature of the human, mouse, and chicken lens epithelium. These resident immune cells function as immediate responders to injury and rapidly populate the wound edge following mock cataract surgery to function as leader cells. Many of these resident immune cells also express MHCII providing them with antigen presenting ability to engage an adaptive immune response. We provide evidence that during development immune cells migrate on the ciliary zonules and localize among the equatorial epithelial cells of the lens adjacent to where the ciliary zonules associate with the lens capsule. These findings suggest that the vasculature‐rich ciliary body is a source of lens resident immune cells. We identified a major role for these cells as rapid responders to wounding, quickly populating each wound were they can function as leaders of lens tissue repair. Our findings also show that lens resident immune cells are progenitors of myofibroblasts, which characteristically appear in response to lens cataract surgery injury, and therefore, are likely agents of lens pathologies to impair vision like fibrosis.
RNF8‐ubiquitinated KMT5A is required for RNF168‐induced H2A ubiquitination in response to DNA damage
Authors: Lu Xiaopeng , Xu Min , Zhu Qian , Zhang Jun , Liu Ge , Bao Yantao , Gu Luo , Tian Yuan , Wen He , Zhu Wei‐Guo 
Published: March 2021

AbstractHistone modifications play critical roles in DNA damage repair to safeguard genome integrity. However, how different histone modifiers coordinate to build appropriate chromatin context for DNA damage repair is largely unknown. Here, we report a novel interplay between the histone methyltransferase KMT5A and two E3 ligases RNF8 and RNF168 in establishing the histone modification status for DNA damage repair. KMT5A is a newly identified substrate of RNF8 in vitro and in vivo. In response to DNA double‐strand breaks (DSBs), RNF8 promotes KMT5A recruitment onto damaged chromatin in a ubiquitination‐dependent manner. RNF8‐induced KMT5A ubiquitination increases the binding capacity of KMT5A to RNF168. Interestingly, KMT5A not only drives a local increase in H4K20 monomethylation at DSBs, but also promotes RNF168’s activity in catalyzing H2A ubiquitination. We proved that the interaction between the H2A acidic patch and KMT5A R188/R189 residues is critical for KMT5A‐mediated regulation of H2A ubiquitination. Taken together, our results highlight a new role for KMT5A in linking H4K20 methylation and H2A ubiquitination and provide insight into the histone modification network during DNA damage repair.
Melatonin prevents diabetes‐associated cognitive dysfunction from microglia‐mediated neuroinflammation by activating autophagy via TLR4/Akt/mTOR pathway
Authors: Cui Yixin , Yang Mengmeng , Wang Yilin , Ren Jianmin , Lin Peng , Cui Chen , Song Jia , He Qin , Hu Huiqing , Wang Kexin , Sun Yu 
Published: March 2021

AbstractCognitive dysfunction often occurs in diabetes mellitus patients. This study aimed to investigate the efficacy of melatonin (MLT) in improving diabetes‐associated cognitive decline and the underlying mechanism involved. Type 2 diabetic mice and palmitic acid (PA)‐stimulated BV‐2 cells were treated by MLT, and the potential mechanisms among MLT, cognition, and autophagy were explored. The results showed that type 2 diabetic mice showed obvious learning and memory impairments in the Morris water maze test compared with normal controls, which could be ameliorated by MLT treatment. Meanwhile, MLT administration significantly improved neuroinflammation and regulated microglial apoptosis. Furthermore, autophagy inhibitor 3‐methyladenine (3‐MA) increased the microglial inflammation and apoptosis, indicating that the treatment effect of MLT was mediated by autophagy. Lastly, MLT treatment significantly decreased the levels of toll‐like receptors 4 (TLR4), phosphorylated‐protein kinase B (Akt), and phosphorylated‐mechanistic target of rapamycin (mTOR), indicating that blocking TLR4/Akt/mTOR pathway might be an underlying basis for the anti‐inflammatory and anti‐apoptosis effects of MLT. Collectively, our study suggested that MLT could improve learning and memory in type 2 diabetic mice by activating autophagy via the TLR4/Akt/mTOR pathway, thereby inhibiting neuroinflammation and microglial apoptosis.
Fish NF‐κB couples TCR and IL‐17 signals to regulate ancestral T‐cell immune response against bacterial infection
Authors: Wei Xiumei , Li Cheng , Zhang Yu , Li Kang , Li Jiaqi , Ai Kete , Li Kunming , Zhang Jiansong , Yang Jialong 
Published: March 2021

AbstractAs fish constitute the first evolutionary group with primordial T cells, they are of importance for understanding the origin and evolution of adaptive immunity. Yet, the knowledge about how ancestral T cells function remains limited. Therefore, the teleost model Nile tilapia (Oreochromis niloticus) was used in this study to investigate the regulatory mechanisms of T‐cell immunity in fish. We identified an evolutionarily conserved canonical NF‐κB signaling pathway in Nile tilapia, which participates in primary adaptive immune response during Streptococcus agalactiae infection. Blockade of NF‐κB activity severely impairs T‐cell activation and expansion, rendering the animals more vulnerable to pathogen attack. Meanwhile, NF‐κB signaling is indispensable for fish T cells to produce IL‐17A during the antibacterial immune response. Moreover, IL‐17A binds its receptor IL‐17RA, initiates the ACT1–TRAF6–TAK1 axis, and triggers NF‐κB‐dependent T‐cell activation, thus forming a positive feedback loop of T‐cell immunity in Nile tilapia. Furthermore, IL‐17A seems to promote innate immunity by regulating pro‐inflammatory cytokines via TRAF6–NF–κB axis, indicating the presence of an NF‐κB‐dependent IL‐17A signaling pathway for coordinating adaptive and innate immunity in fish. Our results suggest that fish NF‐κB couples TCR and IL‐17 signals to modulate ancestral T‐cell immunity against bacterial infection, and the regulation of T‐cell immunity by NF‐κB and IL‐17 is a strategy that existed prior to the divergence of the tetrapod lineage from teleost fish. This study, therefore, provides a new perspective on the evolution of adaptive immunity.
Refracture Rate of Both Bone Forearm Fractures: A Retrospective Comparison of Casting Alone Versus Casting and Extended Functional Bracing
Authors: Soumekh Lisa , Sylvanus Tonye , Karlen Aaron , Wahl Caitlin , Huser Aaron J. , Truong Walter H. 
Published: March 2021

Background:
One of the most common pediatric fractures is a midshaft both bone forearm fracture. The preferred nonoperative treatment is cast immobilization for 6 to 8 weeks; however, 4% to 8% refracture within 6 months. There are no comparative studies evaluating the efficacy of bracing after cast immobilization. We hypothesized that children treated with prolonged functional bracing would have a lower rate of refracture than casting alone or short-term bracing.

Methods:
This is a retrospective review of children younger than 15 years of age treated nonoperatively following radius and ulnar shaft fractures treated at 3 tertiary pediatric hospitals. We excluded distal radius/ulna fractures, isolated fractures of the radius/ulna, and fractures near the elbow. Logistic regression analysis on casting plus functional bracing was run to determine if age, translation, or the number of days in brace were associated with refracture. The incidence of refracture was compared between groups.

Results:
A total of 1549 patients were screened and 426 were included in the study [111 casting only (CO), 259 casting plus functional brace <8 wk (CFB <8 wk), 56 casting plus functional brace ≥8 wk (CFB ≥8 wk)]. In comparing the groups, CO was the youngest (4.4 y vs. 6.3 and 8.4 y). The initial translation and angulation of the radius and ulna were significantly greater in the CFB ≥8 weeks group. Regression analyses shows no association between refracture and initial fracture characteristics including age, translation, or the number of days in brace. The CO group had 3 refractures (2.7%), the CFB <8 weeks group had 13 (5%) and the CFB ≥8 weeks group had 1 (1.8%); demonstrating no statistical significance.

Conclusion:
Extended fracture bracing, following a period of cast immobilization, did not lead to a statistically significant difference in refracture rate. Contrary to previous cases series, the benefit of bracing seems nominal. Larger, prospective studies are needed to better understand targets for treatment.

Level of Evidence:
This is the first level III retrospective comparison study of its kind.
2021 European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement
Authors: Stergiou George S. , Palatini Paolo , Parati Gianfranco , O’Brien Eoin , Januszewicz Andrzej , Lurbe Empar , Persu Alexandre , Mancia Giuseppe , Kreutz Reinhold ,   on behalf of the European Society of Hypertension Council and the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability
Published: March 2021

Collaborators:
Lucas Aparicio (Argentina), Kei Asayama (Japan), Roland Asmar (France), Grzegorz Bilo (Italy), Jean-Marc Boivin (France), Alejandro de la Sierra (Spain), Eamon Dolan (Ireland), Jan Filipovsky (Czech Republic), Geoffrey Head (Australia), Yutaka Imai (Japan), Kazuomi Kario (Japan), Anastasios Kollias (Greece), Efstathios Manios (Greece), Klaus Matthias (Germany), Richard McManus (UK), Anastasia Mihailidou (Australia), Paul Muntner (USA), Martin Myers (Canada), Teemu Niiranen (Finland), Angeliki Ntineri (Greece), Takayoshi Ohkubo (Japan), Aleksander Prejbisz (Poland), Athanase Protogerou (Greece), Menno Pruijm (Switzerland), Aletta Schutte (Australia), Daichi Shimbo (USA), Joseph Schwartz (USA), James Sharman (Australia), Andrew Shennan (UK), Jan Staessen (Belgium), Markus van der Giet (Germany), Liffert Vogt (The Netherlands), Jiguang Wang (China), Paul Whelton (USA), William White (USA).
Chronologic Analysis of Tear Dynamics on Blinking Using Quantitative Manometry in Healthy Humans
Authors: Sato Yohei , Mimura Masashi , Fujita Yasushi , Oku Hidehiro , Ikeda Tsunehiko 
Published: March 2021

Purpose:
To analyze the tear dynamics during blinking by measuring the inner pressure of the upper lacrimal drainage system.

Methods:
This observational study involved 11 healthy bi- or tricenarian volunteers. Direct manometry was performed using a fiber optic pressure sensor inserted into the conjunctival sac, upper/lower canaliculus (5 mm from punctum), and inferior lacrimal sac (15 mm from punctum) during both involuntary and intentional tight blinking. Pressure was measured 200 times/second during 3 separate blinks and then chronologically analyzed.

Results:
In all subjects of all locations during both types of blinking, the inner pressures during the stationary eyelid closing/opening were positive/approximately zero, while a positive/negative pressure spike was observed during the eyelid closing/opening movement. The averages of the maximum pressure in the spike during the intentional tight blinking (tPmax: mm Hg) in the conjunctival sac, upper/lower canaliculus, and lacrimal sac were 8.00, 12.39/12.93, and 10.59, respectively, while for the minimum (tPmin: mm Hg), the pressures were −3.18, −3.91/−3.43, and −3.31, respectively. The tPmax and tPmin in the lacrimal duct were positively correlated with that of the conjunctival sac, which suggested synchronism of the drainage system. However, the tPmax in the canaliculus was significantly higher than that of the conjunctival sac, which suggested that tears do not flow from the conjunctival sac into the lacrimal duct during eyelid closure.

Conclusions:
The upper lacrimal drainage system functions as one united lumen in the lacrimal pump. The positive /negative pressure spike is essential for the lacrimal pump to efficiently eject/aspirate the tear from the lacrimal/conjunctival sac.