bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spinal motoneuron firing properties mature from rostral to caudal during postnatal development of the mouse
Authors: Smith Calvin C. , Brownstone Robert M. 
Published: August 2020

Key points
Many mammals are born with immature motor systems that develop through a critical period of postnatal development.
In rodents, postnatal maturation of movement occurs from rostral to caudal, correlating with maturation of descending supraspinal and local spinal circuits.
We asked whether development of fundamental electrophysiological properties of spinal motoneurons follows the same rostro‐caudal sequence.
We show that in both regions, repetitive firing parameters increase and excitability decreases with development; however, these characteristics mature earlier in cervical motoneurons.
We suggest that in addition to autonomous mechanisms, motoneuron development depends on activity resulting from their circuit milieu.
AbstractAltricial mammals are born with immature nervous systems comprised of circuits that do not yet have the neuronal properties and connectivity required to produce future behaviours. During the critical period of postnatal development, neuronal properties are tuned to participate in functional circuits. In rodents, cervical motoneurons are born prior to lumbar motoneurons, and spinal cord development follows a sequential rostro‐caudal pattern. Here we asked whether birth order is reflected in the postnatal development of electrophysiological properties. We show that motoneurons of both regions have similar properties at birth and follow the same developmental profile, with maximal firing increasing and excitability decreasing into the third postnatal week. However, these maturative processes occur in cervical motoneurons prior to lumbar motoneurons, correlating with the maturation of premotor descending and local spinal systems. These results suggest that motoneuron properties do not mature by cell autonomous mechanisms alone, but also depend on developing premotor circuits.
Decomposing the educational gradient in allostatic load across European populations. What matters the most: differentials in exposure or in susceptibility?
Authors: Veronesi Giovanni , Kee Frank , Hicks Blanaid , Forrest Hannah , Tunstall-Pedoe Hugh , Kuulasmaa Kari , Sans Susana , Salomaa Veikko , Thorand Barbara , Di Castelnuovo Augusto , Soderberg Stefan , Cesana Giancarlo , Bobak Martin , De Ponti Roberto , Iacoviello Licia , Palmieri Luigi , Zeller Tanja , Blankenberg Stefan , Ferrario Marco M 
Published: August 2020

BackgroundWe investigate whether socially disadvantaged individuals are more susceptible to the detrimental effects of smoking and alcohol intake on allostatic load (AL), a marker of physiological ‘wear and tear’, resulting from adaptation to chronic stress.MethodsIn a cross-sectional analysis, 27 019 men and 26 738 women aged 35–74 years were identified from 21 European cohorts in the BiomarCaRE consortium. We defined three educational classes (EDs) according to years of schooling and an AL score as the sum of z-scores of eight selected biomarkers from the cardiovascular, metabolic and inflammatory systems. We used the Oaxaca-Blinder decomposition to disentangle the ED gradient in AL score into thedifferential exposure(DE, attributable to different distribution of smoking and alcohol intake across EDs) and thedifferential susceptibility(DS, attributable to a different effect of risk factors on AL across EDs) components.ResultsLess-educated men (mean AL difference: 0.68, 95% CI 0.57 to 0.79) and women (1.52, 95% CI 1.40 to 1.64) had higher AL scores. DE accounted for 7% and 6% of the gradient in men and women, respectively. In men, combining smoking and alcohol intake, DS accounted for 42% of the gradient (smoking DS coefficient=0.177, 26% of the gradient; alcohol DS coefficient=0.109; 16%, not statistically significant). DS contribution increased to 69% in metabolic markers. DS estimates were consistent across age groups, irrespective of comorbidities and robust to unmeasured confounding. No DS was observed in women.ConclusionsIn men, a DS mechanism substantially contributes to the educational class gradient in allostatic load.
Opioid use among veterans undergoing major joint surgery managed by a multidisciplinary transitional pain service
Authors: Buys Michael J , Bayless Kimberlee , Romesser Jennifer , Anderson Zachary , Patel Shardool , Zhang Chong , Presson Angela P , Brooke Benjamin S 
Published: August 2020

BackgroundChronic postsurgical pain and opioid use is a problem among patients undergoing many types of surgical procedures. A multidisciplinary approach to perioperative pain management known as a transitional pain service (TPS) may lower these risks.MethodsThis retrospective cohort study was conducted at the Salt Lake City VA Medical Center to compare patients undergoing elective primary or revision total knee, hip, or shoulder replacement or rotator cuff repair in the year before (2017) and after (2018) implementation of a TPS. The primary outcome is the proportion of patients taking opioids 90 days after surgery. Secondary outcomes include new chronic opioid use (COU) after surgery as well as the proportion of previous chronic opioid users who stopped or decreased opioid use after surgery.ResultsAt 90 days after surgery, patients enrolled in TPS were significantly less likely to be taking opioids (13.4% TPS vs 27.3% pre-TPS; p=0.002). This relationship remained statistically significant in a multivariable logistic regression analysis, where the TPS group had 69% lower odds of postoperative COU compared with the preintervention group (OR: 0.31; 95% CI: 0.14 to 0.66; p=0.03). Opioid-naive patients enrolled in TPS were less likely to have new COU after surgery (0.7% TPS vs 8.4% pre-TPS; p=0.004). Further, patients enrolled in TPS with existing COU prior to surgery were more likely to reduce or completely stop opioid use after surgery (67.5% TPS vs 45.3% pre-TPS; p=0.037) as compared with pre-TPS.ConclusionsThese data suggest that a TPS is an effective strategy for preventing new COU and reducing overall opioid use following orthopedic joint procedures in a Veterans Affairs hospital.
CT and surgical management of a uterine torsion associated with leiomyosarcoma in a dog
Authors: Carbonell Rossello Gabriel , Ferrandis Inma , Masso Juan Francisco Borrego , Jimenez Pelaez Manuel 
Published: August 2020

SUMMARYAn 11‐year‐old, 22‐kg, intact female crossbred dog presented with abdominal distention and marked chronic weight loss. Abdominal ultrasound revealed a large mass (>20‐cm diameter) in the mid‐abdomen; its origin could not be determined. CT of the abdomen revealed three masses associated with the uterus. A 720° uterine rotation along its long axis was noted. An exploratory laparotomy and en bloc ovariohysterectomy of the twisted uterus was performed and the dog recovered uneventfully. Histopathology confirmed three leiomyosarcomas within the uterine tissue. To the authors’ knowledge, this is the first case describing a uterine torsion associated with a leiomyosarcoma in a dog and diagnosed by CT.
High PD-1/PD-L1 Checkpoint Interaction Infers Tumor Selection and Therapeutic Sensitivity to Anti-PD-1/PD-L1 Treatment
Authors: Sánchez-Magraner Lissete , Miles James , Baker Claire L. , Applebee Christopher J. , Lee Dae-Jin , Elsheikh Somaia , Lashin Shaimaa , Withers Katriona , Watts Andrew G. , Parry Richard , Edmead Christine , Lopez Jose Ignacio , Mehta Raj , Italiano Antoine , Ward Stephen G. , Parker Peter J. , Larijani Banafshé 
Published: August 2020

AbstractMany cancers are termed immunoevasive due to expression of immunomodulatory ligands. Programmed death ligand-1 (PD-L1) and cluster of differentiation 80/86 (CD80/86) interact with their receptors, programmed death receptor-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), respectively, on tumor-infiltrating leukocytes eliciting immunosuppression. Immunotherapies aimed at blocking these interactions are revolutionizing cancer treatments, albeit in an inadequately described patient subset. To address the issue of patient stratification for immune checkpoint intervention, we quantitatively imaged PD-1/PD-L1 interactions in tumor samples from patients, employing an assay that readily detects these intercellular protein–protein interactions in the less than or equal to 10 nm range. These analyses across multiple patient cohorts demonstrated the intercancer, interpatient, and intratumoral heterogeneity of interacting immune checkpoints. The PD-1/PD-L1 interaction was not correlated with clinical PD-L1 expression scores in malignant melanoma. Crucially, among anti-PD-1–treated patients with metastatic non–small cell lung cancer, those with lower PD-1/PD-L1 interaction had significantly worsened survival. It is surmised that within tumors selecting for an elevated level of PD-1/PD-L1 interaction, there is a greater dependence on this pathway for immune evasion and hence, they exhibit more impressive patient response to intervention.Significance:Quantitation of immune checkpoint interaction by direct imaging demonstrates that immunotherapy-treated patients with metastatic NSCLC with a low extent of PD-1/PD-L1 interaction show significantly worse outcome.
Inhibition of Histone H3K27 Demethylases Inactivates Brachyury (TBXT) and Promotes Chordoma Cell Death
Authors: Cottone Lucia , Cribbs Adam P. , Khandelwal Garima , Wells Graham , Ligammari Lorena , Philpott Martin , Tumber Anthony , Lombard Patrick , Hookway Edward S. , Szommer Tamas , Johansson Catrine , Brennan Paul E. , Pillay Nischalan , Jenner Richard G. , Oppermann Udo , Flanagan Adrienne M. 
Published: August 2020

Abstract

Expression of the transcription factor brachyury (TBXT) is normally restricted to the embryo, and its silencing is epigenetically regulated. TBXT promotes mesenchymal transition in a subset of common carcinomas, and in chordoma, a rare cancer showing notochordal differentiation, TBXT acts as a putative oncogene. We hypothesized that TBXT expression is controlled through epigenetic inhibition to promote chordoma cell death. Screening of five human chordoma cell lines revealed that pharmacologic inhibition of the histone 3 lysine 27 demethylases KDM6A (UTX) and KDM6B (JMJD3) leads to cell death. This effect was phenocopied by dual genetic inactivation of KDM6A/B using CRISPR/Cas9. Inhibition of KDM6A/B with a novel compound KDOBA67 led to a genome-wide increase in repressive H3K27me3 marks with concomitant reduction in active H3K27ac, H3K9ac, and H3K4me3 marks. TBXT was a KDM6A/B target gene, and chromatin changes at TBXT following KDOBA67 treatment were associated with a reduction in TBXT protein levels in all models tested, including primary patient-derived cultures. In all models tested, KDOBA67 treatment downregulated expression of a network of transcription factors critical for chordoma survival and upregulated pathways dominated by ATF4-driven stress and proapoptotic responses. Blocking the AFT4 stress response did not prevent suppression of TBXT and induction of cell death, but ectopic overexpression of TBXT increased viability, therefore implicating TBXT as a potential therapeutic target of H3K27 demethylase inhibitors in chordoma. Our work highlights how knowledge of normal processes in fetal development can provide insight into tumorigenesis and identify novel therapeutic approaches.

Significance:
Pharmacologic inhibition of H3K27-demethylases in human chordoma cells promotes epigenetic silencing of oncogenic TBXT, alters gene networks critical to survival, and represents a potential novel therapy.
Loss of SWI/SNF Chromatin Remodeling Alters NRF2 Signaling in Non–Small Cell Lung Carcinoma
Authors: Song Shujie , Nguyen Vinh , Schrank Travis , Mulvaney Kathleen , Walter Vonn , Wei Darmood , Orvis Tess , Desai Nisarg , Zhang Jiren , Hayes D. Neil , Zheng Yanfang , Major Michael B. , Weissman Bernard E. 
Published: August 2020

Abstract

The NF-E2–related factor 2 (referred to as NRF2) transcription factor binds antioxidant responsive elements within the promoters of cytoprotective genes to induce their expression. Next-generation sequencing studies in lung cancer have shown a significant number of activating mutations within the NRF2 signaling pathway. Mutations in components of the SWI/SNF chromatin-remodeling complex, a general regulator of transcription using either BRG1 or BRM as the catalytic subunit, also frequently occur in lung cancers. Importantly, low BRG1 expression levels in primary human NSCLC correlated with increased NRF2-target gene expression. Here, we show that loss of SWI/SNF complex function activated a subset of NRF2-mediated transcriptional targets. Using a series of isogenic NSCLC lines with reduced or depleted BRG1 and/or BRM expression, we observed significantly increased expression of the NRF2-target genes HMOX1 and GSTM4. In contrast, expression of the NRF2 target genes NQO1 and GCLM modestly increased following BRM reduction. Chromatin immunoprecipitation showed that BRG1 knockdown led to increased NRF2 binding at its respective ARE sites in the HMOX1 promoter but not in NQO1 and GCLM. Our data demonstrate that loss of BRG1 or BRM in lung cancer results in activation of the NRF2/KEAP1 pathway and HMOX1 expression. Therefore, we provide an additional molecular explanation for why patients harboring BRG1 or BRM mutations show poor prognoses. A better understanding of this mechanism may yield novel insights into the design of targeted treatment modalities.

Implications:
Our study identifies a novel mechanism for how mutations in the SMARCA4 gene may drive progression of human lung adenocarcinomas.
Novel Panna Guide Wire Facilitates Percutaneous and Nonfluoroscopic Procedure for Atrial Septal Defect Closure
Authors: Kong Pengxu , Zhao Guangzhi , Zhang Zonggang , Zhang Weimin , Fan Taibing , Han Yu , Pang Kunjing , Wang Shouzheng , Zhang Fengwen , Wang Weiwei , Hu Shengshou , Pan Xiangbin 
Published: August 2020

Background:
Echo-guided percutaneous procedures have been reported reliable and advantageous. However, the learning curve is difficult for junior doctors. We aimed to evaluate the safety and efficacy of a novel guidewire (Panna wire) in percutaneous atrial septal defect closure under transthoracic echocardiography guidance only.

Methods:
The Panna wire is designed for echo-guide procedure with a retractable spindle-shaped tip. A multicenter, randomized, controlled trial was conducted to evaluate the safety and efficacy of the Panna wire versus the conventional guidewire for junior doctors with <100 cases experience. The primary outcome was operative success rate. The secondary outcomes were incidence of major adverse events, operation time, time needed to enter the left atrium, number of arrhythmia episodes, number of misguidance to tricuspid valve, and incidence of peripheral vascular complications.

Results:

Between July 2018 and September 2019, 100 patients with atrial septal defect were randomized to either the Panna wire group (n=52) or the conventional wire group (n=48) at 3 centers. The baseline clinical characteristics were similarly distributed. The operative success rate (primary outcome) was 100% in the Panna wire group versus 68.75% in the conventional wire group (
P
<0.001). No major adverse events occurred in either group. Significant differences in favor of the Panna wire group were found in operation time (
P
=0.004), time needed to enter the left atrium (
P
<0.001), number of arrhythmia episodes (
P
<0.001), and number of misguidance to tricuspid valve (
P
=0.005).

Conclusions:
The Panna wire is safe and effective and reduces the learning curve in percutaneous atrial septal defect closure under transthoracic echocardiography guidance only.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT04096924.
Shaping Taiwan’s History through Non-human Agents
Authors: Chang Ti-han 
Published: August 2020

Abstract
In the field of postcolonial Taiwanese literature, a literary tradition that an author follows often consists in contextualising issues of political identity, historical representation or social struggle via the narrative account of a human protagonist. This paper examines Wu Ming-yi’s postcolonial ecological novels, Shuimian de hangxian 睡眠的航線 [Routes in a Dream] (2007) and Danche shiqieji 單車失竊記 [The Stolen Bicycle] (2015), which not only break with this literary norm, but further invite readers to pay attention to the involvement of non-human agents in Taiwan’s colonial history. With an ecocritical reading of Wu’s works, the paper investigates the significant role of these non-human agents—including butterflies, elephants, a bird, fish–men and a bamboo forest—and further demonstrates that a non-anthropocentric narrative offered by these non-humans is also powerful in the shaping of historical representations and political identities of Taiwan.
Travel, Cultural Hybridity and Transnational Connections in Taiwanese Graphic Narratives
Authors: Zemanek Adina 
Published: August 2020

Abstract
This study adopts a discursive analytical perspective to elaborate on transnational connections and cultural diversity as strategies for defining Taiwaneseness in graphic narratives published between 1997 and 2016. It considers the following aspects represented in the analysed texts: (1) processes of self-identification while travelling abroad; (2) depictions of Taiwan centred on familiar spaces open to outside cultural influences, which become locally appropriated through daily activities that link them to individual emotions and weave them into personal and collective memories; and (3) reaching beyond Taiwan to highlight transnational encounters and connections, thus placing the island within a global or regional framework of reference. The article assesses the degree to which this transnational viewpoint reproduces, challenges or complements existing notions regarding Taiwan’s relations with China, Japan and the US, while also exploring relations established with other nodes of reference: Europe, New Zealand and Hong Kong. It also comments on the extent to which academic critical stances on Taiwan’s multiculturalism and warnings against overlooking existing ties between Taiwan and the PRC in contemporary definitions of nationhood may hold true for the research material.
Negotiating Legacies
Authors: Momesso Lara , Alsford Niki J.P. 
Published: August 2020

Abstract
This special issue concerns agency and negotiation in the context of the hierarchical relations between the People’s Republic of China (PRC), a global superpower, and Taiwan, a subordinated actor often relegated to a marginal position in contemporary global geopolitics. By exploring how Taiwan opposes, interrupts and re-creates its subordinate position vis-à-vis China, the authors of this special issue will shed light on the complexities of the ongoing Taiwan experience, shaped by different, often opposing, interests, positions and perspectives regarding its relationship with China. Yet, by exploring the experience of Taiwan with reference to its Chinese legacies, this special issue will also allow important reflections on China, not only in its hegemonic role regionally and globally, but also in its weaknesses when it deals with subordinated actors. This is a timely and important piece, which will allow alternative interpretations of contemporary events not only in Taiwan, for instance the recent national elections and related political developments, but also in the region, such as the protests which have been occurring in Hong Kong during the last four months.
Comparative Secularities: Tracing Social and Epistemic Structures beyond the Modern West
Authors: Kleine Christoph , Wohlrab-Sahr Monika 
Published: August 2020

Abstract
In view of the questionability of the concept “religion” as an analytical category for the investigation of pre-modern, non-Western cultures, how can one still pursue the history of religion or historical sociology of religion? Roughly speaking, scholars of religion can be placed between two poles with regard to this question: (1) those who reject the cross-cultural use of “religion” as a comparative concept and (2) those who believe they cannot do without it. We propose an approach that acknowledges the cultural dependence and historicity of concepts such as “religion” and the “secular,” while still conducting historical research on pre-colonial non-Western societies relevant to the study of both. Our approach aims to investigate the emergence of social and epistemic structures in various cultures—forms of differentiation and distinction—that have enabled the reorganisation of socio-cultural formations into religions and thus facilitated the formation of “multiple secularities” in global modernity.
Collaboration and Competition: The Twofold Logic of Science Diplomacy
Authors: Ruffini Pierre-Bruno 
Published: August 2020

Summary
From an attentive reading of the practitioner-driven literature, this essay questions the reasons why the dominant discourse on science diplomacy highlights practices based on international co-operation and the pursuit of shared interests but pays little attention to practices which are inspired by a spirit of competition. It advances hypotheses related to the professional profiles of those who built the definitions and shaped this discourse, and who are scientists. It underlines the need to provide a broader definition of science diplomacy, by recognising its double nature, both collaborative and competitive.
The EU Delegation Sarajevo as an Organisational Proxy of the EU’s Administrative Co-governance
Authors: Navrátil Matej 
Published: August 2020

Summary
This article argues that by using the European Union Delegation (EUD) in Sarajevo as an organisational proxy, the EU creates tools allowing it to participate in the enhancement of external administrative co-governance in Bosnia and Herzegovina. Inspired by the organisation theory approach, this article conceives of the EUD Sarajevo as a hybrid organisation. Such organisations are defined as a product of a combination of two sovereign organisations pursuing a common interest. They recombine multiple institutional logics, stimulate institutional change and spark innovative practices. The conceptualisation of the EUD Sarajevo as a hybrid organisation offers analytical insight for understanding the EU’s role in the society of states and allows us to theorise more concretely about the impact that a non-state actor has on the transformation of the institutions of diplomacy and sovereignty, which are foundational institutions of the international system of states.
Éléments du costume féminin italo-ostrogothique au nord de la mer Noire et la politique militaire de Justinien
Authors: Kazanski Michel 
Published: August 2020

Abstract
Une série d’objets de tradition vestimentaire italo-ostrogothique (boucles de ceinture et fibules) apparaissent en Crimée et sur la péninsule de Taman au VIe siècle. Ces objets témoignent du déplacement de groupes de population italo-ostrogothique vers le nord de la mer Noire. Il est possible que cette migration se soit déroulée dans le cadre de la politique militaire de Justinien, par exemple la déportation de prisonniers de guerre avec leurs familles et leurs installations sur les frontières lointaines de l’Empire romain d’Orient.