bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine-dependent early synaptic and motor dysfunctions induced by α-synuclein in the nigrostriatal circuit
Authors: Tozzi Alessandro , Sciaccaluga Miriam , Loffredo Vittorio , Megaro Alfredo , Ledonne Ada , Cardinale Antonella , Federici Mauro , Bellingacci Laura , Paciotti Silvia , Ferrari Elena , La Rocca Antonino , Martini Alessandro , Mercuri Nicola B , Gardoni Fabrizio , Picconi Barbara , Ghiglieri Veronica , De Leonibus Elvira , Calabresi Paolo 
Published: July 2021

Abstract
Misfolding and aggregation of α-synuclein are specific features of Parkinson’s disease and other neurodegenerative diseases defined as synucleinopathies. Parkinson’s disease progression has been correlated with the formation and extracellular release of α-synuclein aggregates, as well as with their spread from neuron to neuron. Therapeutic interventions in the initial stages of Parkinson’s disease require a clear understanding of the mechanisms by which α-synuclein disrupts the physiological synaptic and plastic activity of the basal ganglia. For this reason, we identified two early time points to clarify how the intrastriatal injection of α-synuclein-preformed fibrils in rodents via retrograde transmission induces time-dependent electrophysiological and behavioural alterations. We found that intrastriatal α-synuclein-preformed fibrils perturb the firing rate of dopaminergic neurons in the substantia nigra pars compacta, while the discharge of putative GABAergic cells of the substantia nigra pars reticulata is unchanged. The α-synuclein-induced dysregulation of nigrostriatal function also impairs, in a time-dependent manner, the two main forms of striatal synaptic plasticity, long-term potentiation and long-term depression. We also observed an increased glutamatergic transmission measured as an augmented frequency of spontaneous excitatory synaptic currents. These changes in neuronal function in the substantia nigra pars compacta and striatum were observed before overt neuronal death occurred. In an additional set of experiments, we were able to rescue α-synuclein-induced alterations of motor function, striatal synaptic plasticity and increased spontaneous excitatory synaptic currents by subchronic treatment with l-DOPA, a precursor of dopamine widely used in the therapy of Parkinson’s disease, clearly demonstrating that a dysfunctional dopamine system plays a critical role in the early phases of the disease.
Clinical characteristics of headache after vaccination against COVID-19 (coronavirus SARS-CoV-2) with the BNT162b2 mRNA vaccine: a multicentre observational cohort study
Authors: Göbel Carl H , Heinze Axel , Karstedt Sarah , Morscheck Mascha , Tashiro Lilian , Cirkel Anna , Hamid Qutayba , Halwani Rabih , Temsah Mohamad-Hani , Ziemann Malte , Görg Siegfried , Münte Thomas , Göbel Hartmut 
Published: July 2021

Abstract
The novel coronavirus SARS-CoV-2 causes the infectious disease COVID-19. Newly developed mRNA vaccines can prevent the spread of the virus. Headache is the most common neurological symptom in over 50% of those vaccinated. Detailed information about the clinical characteristics of this form of headache has not yet been described. The aim of the study is to examine in detail the clinical characteristics of headaches occurring after vaccination against COVID-19 with the BNT162b2 mRNA COVID-19 vaccine for the first time. In a multicentre observational cohort study, data on the clinical features and corresponding variables were recorded using a standardized online questionnaire. The questionnaire was circulated to 12 000 residential care homes of the elderly as well as tertiary university hospitals in Germany and the United Arab Emirates. The primary outcomes of this study are the clinical features of headache after vaccination. Comorbidities, treatment with medication and sociodemographic variables are also analysed. A total of 2349 participants reported headaches after vaccination with the BNT162b2 mRNA COVID-19 vaccine. Headaches occur an average of 18.0 ± 27.0 h after vaccination and last an average duration of 14.2 ± 21.3 h. Only 9.7% of those affected also report headaches resulting from previous vaccinations. In 66.6% of the participants, headache occurs as a single episode. A bilateral location is indicated by 73.1% of the participants. This is most often found on the forehead (38.0%) and temples (32.1%). A pressing pain character is indicated by 49.2% and 40.7% report a dull pain character. The pain intensity is most often moderate (46.2%), severe (32.1%) or very severe (8.2%). The most common accompanying symptoms are fatigue (38.8%), exhaustion (25.7%) and muscle pain (23.4%). Headaches after COVID-19 vaccination show an extensive complex of symptoms. The constellation of accompanying symptoms together with the temporal and spatial headache characteristics delimit a distinctive headache phenotype.
Self-Determination and the Right of Peoples to Participate in International Law-Making
Authors: Jones Natalie 
Published: July 2021

Abstract
In recent decades, peoples have frequently asserted a right to participate in the international legal order, and have participated in various international law-making and regulatory processes carried out under the auspices of intergovernmental organizations. However, while self-determination has long been understood to encompass a right to participation at the national level, the case for this legal right at the international level has not been comprehensively discussed. I present an account of the development of the law of self-determination and argue that by its logic, the law of self-determination can be interpreted as justifying a collective right of peoples to participate in international law-making. The article proposes a formulation of the right including its corresponding duties. The article’s key contribution is to offer an understanding of how practice by states and international organizations to grant indigenous peoples enhanced status in intergovernmental fora may be seen to logically follow from the law of self-determination.
Chronic Disease and Immunosuppression Increase the Risk for Nonvaccine Serotype Pneumococcal Disease: A Nationwide Population-based Study
Authors: Naucler Pontus , Galanis Ilias , Petropoulos Alexandros , Granath Fredrik , Morfeldt Eva , Örtqvist Åke , Henriques-Normark Birgitta 
Published: July 2021

Abstract

Background
Demography is changing, with people living longer with comorbidities. In this nationwide population-based study, we investigated the serotype-specific invasive pneumococcal disease (IPD) risk in individuals with comorbidities, and effects of the pneumococcal conjugated vaccine (PCV) child immunization program.

Methods
Cases included 14 096 IPD episodes in Sweden during 2006–2015. Controls (n = 137 289), matched to cases by age, sex, region, and calendar time, were selected from the general population. Comorbidity data was obtained through health registers and grouped as immunocompromising (IC) or chronic medical conditions (CMC).

Results
The prevalence of CMC and IC among elderly cases was 33.9% and 39.4%. New risks identified for IPD were sarcoidosis, inflammatory polyarthropathies, systemic connective tissue, and neurological diseases. The odds ratio (OR) for IPD caused by non-PCV13 compared with PCV13 serotypes was higher in individuals with CMC/IC. Serotypes associated with the highest risk were 16F, 15C, 35F, 19F, and 23A (OR 3–5 for CMC, &gt;10 for IC). Most comorbidities increased post-vaccination, and absolute increases of IPD caused by non-PCV13, PPV23–non-PCV13, and non-PCV13/non-PPV23 serotypes were higher in individuals with IC/CMC compared with healthy persons. Non-PCV13 serotypes 6C, 9N, 11A, 22F, 23A and 35F increased more in those with comorbidities. Mortality due to non-PCV13 serotypes increased in individuals with IC/CMC, while remaining stable in persons without comorbidities.

Conclusions
The PCV child immunization program associates with an increased disease burden of non-vaccine serotypes in individuals with comorbidities. These data are important for vaccine design and optimization of current vaccination strategies.
Hayek’s twin ideas: reconciling methodological individualism and group selection
Authors: Schaefer Alexander 
Published: July 2021

Abstract
Hayek repeatedly refers to ‘the twin ideas of evolution and spontaneous order’. Yet, critics argue that Hayek’s theory of cultural group selection is inconsistent with his theory of spontaneous order. To assess these criticisms, this paper situates Hayek’s social theory in the contemporary discussion surrounding multilevel selection. Hayek’s theory posits two main levels—rules and order—that exhibit upward and downward causation. An examination of Hayek’s theory of cultural group selection and his account of methodological individualism reveals that neither one can provide a fully adequate explanation of social phenomena. Neither individualistic nor group-selectionist analyses allow the theorist to fully account for social order, but taken together they provide a more complete explanation. Far from being substitutes, therefore, both types of analysis are complementary aspects of Hayek’s social theory. Understanding Hayek’s theory in this way allows us to glimpse how he might weigh in on contemporary debates surrounding multilevel selection in human societies.
Ultra-proactive Therapeutic Drug Monitoring of Infliximab Based on Point of Care Testing in Inflammatory Bowel Disease: Results of a Pragmatic Trial
Authors: Bossuyt Peter , Pouillon Lieven , Claeys Sophie , D’Haens Soetkin , Hoefkens Eveline , Strubbe Beatrijs , Marichal Denis , Peeters Harald 
Published: July 2021

Abstract

Background
With point of care testing [POCT] for infliximab [IFX], ultraproactive therapeutic drug monitoring [TDM] with ad-hoc dose optimisation is possible in patients with inflammatory bowel disease [IBD].

Aim
To compare the clinical outcomes of an ultraproactive TDM algorithm of IFX based on POCT with reactive TDM in patients with IBD, in a pragmatic clinical trial.

Methods
All patients with IBD and maintenance IFX treatment were included between June and August 2018 in two centres. Centre A applied an ultra-proactive TDM algorithm incorporating POCT, and centre B applied reactive TDM. Primary endpoint was failure of IFX therapy after 1 year. Secondary endpoints included sustained clinical remission and mucosal remission.

Results
In total 187 patients [n = 115/72 cohort A/B] were included. Cohort A had more trough level [TL] measurements compared with cohort B [8.8 vs 1/patient/year; p &lt;0.0001], leading to a significant higher number of dose optimisations. POCT testing was required in 27% after the first round of ultra-proactive TDM and in a mean of 6.3% (standard deviation [SD] 1.9) in the subsequent rounds. Ad-hoc extra dosing was needed in 13% of the POCT. After 1 year, no difference was seen between cohort A and cohort B in IFX failure [19% vs 10%; p = 0.08], nor in sustained clinical remission [75% vs 83%; p = 0.17]. Mucosal remission was evaluated in 71 patients [38%], and was more frequent in the reactive TDM cohort [p = 0.02].

Conclusions
Ultra-proactive TDM in patients with IBD and maintenance IFX treatment leads to equal clinical outcomes as reactive TDM after 1 year of follow-up.
Off-pump coronary artery bypass grafting is safe and effective in patients with severe left ventricular dysfunction
Authors: Marin-Cuartas Mateo , Deo Salil V , Ramirez Paulina , Verevkin Alexander , Leontyev Sergey , Borger Michael A , Davierwala Piroze M 
Published: July 2021

Abstract

OBJECTIVES
Severe left ventricular dysfunction (LVD) is associated with increased risk following coronary artery bypass grafting (CABG). Due to a dearth of reports on the choice of CABG technique in patients with LVD, this study aims to compare the outcomes of off-pump CABG (OPCAB) and conventional CABG (ONCAB) in such patients.

METHODS
Retrospective single-centre propensity-matched analysis comparing early- and long-term outcomes of OPCAB and ONCAB in patients with severe LVD. Primary outcome was long-term all-cause mortality.

RESULTS
Between 2002 and 2014, a total of 1161 consecutive patients with severe LVD underwent isolated CABG [442 patients underwent OPCAB and 719 ONCAB (430 matched pairs)]. Incomplete revascularization was observed more frequently among OPCAB than ONCAB patients (35.3% vs 21.6%; P &lt; 0.01). The overall 30-day mortality was 5% and was comparable between the matched groups [OR 0.64 (0.34–1.22); P = 0.18]. OPCAB patients had shorter median hospital stay (11 vs 12 days; P = 0.02) and lower packed red blood cell transfusion rates [2.7 (2.21–3.19) vs 4.4 (3.56–5.24); P &lt; 0.01]. Estimated adjusted survival was 86.0% vs 85.8%, 69.1% vs 65.5% and 59.9% vs 49.1% at 1, 5 and 10 years for OPCAB and ONCAB patients, respectively (P = 0.99). Long-term risk of mortality was similar between groups [hazard ratio (HR) 0.94 (0.66–1.32); P = 0.7]. Incomplete revascularization was weakly associated with increased risk of long-term all-cause mortality [HR 1.33 (0.99–1.77); P = 0.05].

CONCLUSIONS
OPCAB is safe and effective in patients with severe LVD. Although incomplete revascularization is more commonly observed in patients undergoing OPCAB, it is not associated with increased late mortality.
Functional diversity of microbial communities in inactive seafloor sulfide deposits
Authors: Dong Xiyang , Zhang Chuwen , Li Wenli , Weng Shengze , Song Weizhi , Li Jiangtao , Wang Yong 
Published: July 2021

ABSTRACTThe seafloor sulfide structures of inactive vents are known to host abundant and diverse microorganisms potentially supported by mineralogy of sulfides. However, little is known about the diversity and distribution of microbial functions. Here, we used genome-resolved metagenomics to predict microbial metabolic functions and the contribution of horizontal gene transfer to the functionality of microorganisms inhabiting several hydrothermally inactive seafloor deposits among globally distributed deep-sea vent fields. Despite of geographically distant vent fields, similar microbial community patterns were observed with the dominance of Gammaproteobacteria, Bacteroidota and previously overlooked Candidatus Patescibacteria. Metabolically flexible Gammaproteobacteria are major potential primary producers utilizing mainly sulfur, iron and hydrogen as electron donors coupled with oxygen and nitrate respiration for chemolithoautotrophic growth. In addition to heterotrophic microorganisms like free-living Bacteroidota, Ca. Patescibacteria potentially perform fermentative recycling of organic carbon. Finally, we provided evidence that many functional genes that are central to energy metabolism have been laterally transferred among members within the community and largely within the same class. Taken together, these findings shed light on microbial ecology and evolution in inactive seafloor sulfide deposits after the cessation of hydrothermal activities.
Distinct requirements for Pho, Sfmbt, and Ino80 for cell survival in Drosophila
Authors: Elizarev Pavel , Finkl Katja , Müller Jürg 
Published: July 2021

Abstract
The Drosophila proteins Pleiohomeotic (Pho) and its paralog Pho-like (Phol) are the homologs of the mammalian transcription factor YY1. Pho and Phol are subunits of the Polycomb group protein complex PhoRC and they are also stably associated with the INO80 nucleosome remodeling complex. Drosophila lacking both Pho and Phol arrest development as larvae with small misshaped imaginal discs. The basis of this phenotype is poorly understood. We find that in pho phol mutant animals cells retain the capacity to proliferate but show a high incidence of apoptotic cell death that results in tissue hypoplasia. Clonal analyses establish that cells stringently require Pho and Phol to survive. In contrast, the PhoRC subunit Sfmbt and the ATP-dependent nucleosome remodeling factor Ino80 are not essential for cell viability. Pho and Phol, therefore, execute their critical role for cell survival through mechanisms that do not involve Sfmbt function or INO80 nucleosome remodeling.
Appendiceal Orifice Inflammation in Severe Ulcerative Colitis and Its Resolution With Infliximab and Plant-based Diet as First-line Therapy
Authors: Chiba Mitsuro , Ishii Hajime , Sageshima Masato , Iwabuchi Akira 
Published: July 2021

Lay Summary
Appendiceal orifice inflammation, which is often observed in mild or moderate distal ulcerative colitis, was observed in a case of severe UC. Appendiceal orifice inflammation resolved after new induction therapy for severe UC: infliximab and a plant-based diet as first-line therapy.
Developing perennial fruit crop models in APSIM Next Generation using grapevine as an example
Authors: Zhu Junqi , Parker Amber , Gou Fang , Agnew Rob , Yang Linlin , Greven Marc , Raw Victoria , Neal Sue , Martin Damian , Trought Michael C T , Huth Neil , Brown Hamish Edward 
Published: July 2021

AbstractA new model for grapevines (Vitis vinifera) is the first perennial fruit crop model using the Agricultural Production System sIMulator (APSIM) Next Generation framework. Modules for phenology, light interception, carbohydrate allocation, yield formation and berry composition were adapted or added into APSIM Next Generation to represent the nature of fruit-bearing vines. The simulated grapevine phenological cycle starts with the dormancy phase triggered by a critical photoperiod in autumn, and then goes through the subsequent phenophases sequentially and finally returns to dormancy for a new cycle. The canopy microclimate module within APSIM Next Generation was extended to allow for row crop light interception. The carbohydrate arbitrator was enhanced to consider both sink strength and sink priority to reflect carbohydrate reserve as a concurrent competing sink. Weather conditions and source–sink ratio at critical developmental stages were used to determine potential grapevine yield components, e.g. bunch number, berry number and berry fresh weight. The model was calibrated and tested extensively using four detailed data sets. The model captured the variations in the timing of measured budburst, flowering and véraison over 15 seasons across New Zealand for five different varieties. The calculated seasonal dynamics of light interception by the row and alley were consistent with field observations. The model also reproduced the dynamics of dry matter and carbohydrate reserve of different organs, and the wide variation in yield components caused by seasonal weather conditions and pruning regimes. The modelling framework developed in this work can also be used for other perennial fruit crops.
The adaptability of regulatory T cells and Foxp3
Authors: Hori Shohei , Murakami Ryuichi 
Published: July 2021

Abstract
Regulatory T (Treg) cells that express the lineage-defining transcription factor Foxp3 play a pivotal role in establishing and maintaining immune and tissue homeostasis. Foxp3 serves as a highly connected ‘hub’, interacting with numerous genomic sites and partner proteins, in the molecular network that orchestrates multiple facets of Treg cell differentiation and function. Treg cells are distributed throughout the body from lymphoid tissues to most non-lymphoid tissues, where they exert anti-inflammatory and protective functions appropriate for the tissue and immune environment. They are thus capable of adapting to diverse and changing environments by dynamically integrating extrinsic cues with the intrinsic molecular network. In this review, we discuss recent advances in our understanding of the cell-intrinsic and -extrinsic mechanisms underlying the adaptability of Treg cells and we propose a crucial role for the Foxp3-centered molecular network, which operates in a multimodal and adaptive manner in response to environmental signals.
“Videogames Saved My Life”: Everyday Resistance and Ludic Recovery among US Military Veterans
Authors: Hirst Aggie 
Published: July 2021

AbstractWhile the explosion of videogames as a global entertainment medium has been explored in International Relations (IR) and associated fields in some detail in recent years, the proliferation of games in military settings remains under-researched. This paper examines the uses to which US military veterans put videogames following service, showing that they play an important role in healing and rehabilitation processes through community building, therapeutic relief, and suicide prevention. Drawing in detail on interviews conducted with veterans and support workers between 2017 and 2019, the paper shows that grassroots gaming groups promote forms of communication, connectivity, and community which the military's stigmatizing reintegration and mental health programs often do not. The core argument developed is that while they do not embrace an antimilitarist ethos, through their promotion of mental and physical recovery, veterans’ gaming groups can be read as important sites of everyday resistance to the violences enacted by the US military on its personnel. Unsettling critical scholarly assumptions about what resistance looks like, and where it takes place, the paper ultimately demonstrates that it is possible to challenge the embodied alienations of militarism from within.
Indicators and Success Stories: The UN Sustaining Peace Agenda, Bureaucratic Power, and Knowledge Production in Post-War Settings
Authors: Martin de Almagro Maria 
Published: July 2021

Abstract
Most discussions on knowledge production in peacebuilding and conflict management have focused on the study of epistemic communities and strategic coalitions of global and local actors. This article shifts the focus away from who produces knowledge to the underexplored question of how knowledge is generated, repackaged, deployed, or ignored. Combining sociology of knowledge approaches with feminist governmentality scholarship, I critically interrogate the role of reports as knowledge production artifacts and report writing as bureaucratic practices that serve to design and implement UN Peacebuilding Fund (PBF) projects on Sustaining Peace. Specifically, I analyze the role of reports and reporting in four PBF projects on gender and reconciliation in Liberia, and I show how through the mechanisms of persuasion and homogenization, reports serve not only to measure success and failure and to produce contextualized knowledge, but also to exert symbolic power, (re)producing authoritative knowledge on women, gender and reconciliation, and giving legitimacy to external interventions. Studying how knowledge is produced instead of who produces it enables us to apprehend the entanglement of the local and the global and overcome simplistic binaries and oppositions, all while paying attention to how the production of knowledge, and its silences, remains embedded in global power relations.
Filth Fly Impacts to Animal Production in the United States and Associated Research and Extension Needs
Authors: Machtinger Erika T , Gerry Alec C , Murillo Amy C , Talley Justin L 
Published: July 2021

AbstractMany flies are considered serious pests of livestock, poultry, and equids. These pests can negatively impact animal welfare and contribute to considerable production losses. Management of filth fly pests in particular, including the house fly (Musca domestica L.), stable fly (Stomoxys calcitrans (L.)), horn fly (Haematobia irritans (L.)), face fly (Musca autumnalis De Geer) (Diptera: Muscidae), and little or lesser house fly (Fannia canicularis (L.) (Diptera: Fanniidae)), has been a research and Extension priority of veterinary entomologists for many decades. However, ongoing changes to animal husbandry and production practices, coupled with an increasing development of behavioral and physiological resistance to insecticides require renewed focus on new and more effective management strategies. This article is the first in a series of updates to these historical reports and the purpose is to serve as a resource for veterinary practitioners, consultants, funding agencies, veterinary entomologists, industry, commodity groups, and the scientific community working towards control of these pests. Companion articles will review individual filth fly species of importance to animal agriculture in the United States