bluuebunny/crossref_metadata_2025 huggingface dataset:
26. Preventing and Countering Violent Extremism
Authors: Koehler Daniel
Published: August 2022

This chapter presents an overview of how to prevent and counter violent extremism programmes (P/CVE). It highlights issues on evaluation and quality standards, staff training, gender-specific P/CVE, evidence-based methods, and solid theories of change. The chapter differentiates Eastern and Western P/CVE. It shows how ideological discourse was dominant in the West, while civil society partners and non-ideological components became the main area of consideration in the East. P/CVE became the cornerstone of numerous counterterrorism strategies, but it still needs to be flexible and adaptable to needs. The chapter also recognises how prisons can turn into hotbeds of violent radicalization, and targeted assassinations of terrorists can turn them into martyrs.
4. Historical Materialism
Authors: Herring Eric
Published: August 2022

This chapter begins with an overview of the social scientific, philosophical, and political dimensions of historical materialism (HM). This overview is followed by an elaboration of what HM involves, including its diversity, value, and potential but avoidable pitfalls. Key HM concepts are set out and used to show how capitalism generally and in its recent neoliberal form aims to generate insecurity for labour and security for capital. Rather than being a narrow approach to security that focuses on economics, at its best, HM is a holistic approach that provides a way of putting into perspective and relating the many components of security. It goes on to explore the relationships between HM and approaches to security in wider contexts (realism, liberalism, social constructivism, and gender) and then to various perspectives on security (securitization and the sectoral approach, peace studies, Critical Security Studies, and human security). Accompanying the text are Think Point 4.1 on using HM to understand arms production and the arms trade, and Think Point 4.2 on using HM to understand the connections between development and security. The conclusion provides an overall assessment of the contribution of HM to the scholarship and politics of security and insecurity.
15. Regime Security
Authors: Krieg Andreas
Published: August 2022

This chapter examines the nature of regime security in the weak states in the developing world in contrast to public or state security in the developed world. The chapter shows that the insecurities that confront regimes in the developing world mostly emanate from internal rather than external threats and are linked to the inability or unwillingness of these regimes to provide security inclusively as a public good to local communities. In order to understand the regime insecurity loop in the developing world, the chapter commences by introducing the difference between public and regime security. It continues by defining the major threats to regime security before exemplifying how regimes in the developing world are trying to manage these threats through accommodation and coercion. The regime insecurity loop will be illustrated on the basis of the Assad regime in Syria. The chapter concludes by outlining the prospects of regime security in the developing world amid an increased transnationalization of security affairs.
2. The European Union: Establishment and Development
Authors: Phinnemore David
Published: August 2022

The focus of this chapter is the emergence of the European Communities in the 1950s, their evolution in the three decades thereafter, and the establishment and early development of the European Union (EU) in the 1990s. The chapter explores key developments in the first five decades of European integration and some of the tensions that have shaped them. It considers the ambitions of the architects and supporters of the European Communities and how their hopes and aspirations played out as integration became a reality in the 1950s and 1960s. It looks at how their ambitions grew and how the process then lost momentum in the 1970s before the idea of ‘European union’ was rekindled in the 1980s with the Single European Act (1986) and the Single Market project. These acted as catalysts for a new era of dynamic European integration with the now expanded Communities at its core. The chapter then explores how, through the adoption and implementation of the Treaty on European Union (1992), the European Union was established. The chapter assesses the unique and incomplete form of the new ‘union’ and examines the impact on it of reforms introduced by the Treaty of Amsterdam (1997) and the Treaty of Nice (2000) as the EU sought to prepare itself for the further enlargement and the challenges of the initial years of the twenty-first century.
7. Governance in the European Union
Authors: Christiansen Thomas
Published: August 2022

This chapter provides an overview of the ‘governance turn’ in the study of European integration. Opening with a discussion of the reasons why governance as a concept and as a practice has become so prevalent in Europe, the chapter goes on to discuss the various ways in which the governance approach has evolved. Two strands of this literature—‘multilevel governance’ and the ‘regulatory state’—are examined in greater detail here. The chapter then introduces some of the important normative debates to which the ‘governance turn’ has given rise, before concluding with some observations about the relevance of the governance approach in the current phase of European integration.
8. Europeanization
Authors: Börzel Tanja A. , Panke Diana
Published: August 2022

The chapter first explains what Europeanization means and outlines the main approaches to studying this phenomenon. The second section describes why this concept has become so prominent in research on the European Union (EU) and its member states. In the third section, the chapter reviews the state of the art with particular reference to how the EU affects states (‘top-down’ Europeanization). It illustrates the theoretical arguments with empirical examples. Similarly, the fourth section examines how states can influence the EU (‘bottom-up’ Europeanization) and provides some theoretical explanations for the empirical patterns observed. This is followed by a section that presents an overview of research that looks at linkages between bottom-up and top-down Europeanization, and considers the future of Europeanization research with regard to the EU’s recent and current crises and challenges. This chapter argues that Europeanization will remain an important field of EU research for the foreseeable future.
10. The European Commission
Authors: Egeberg Morten
Published: August 2022

This chapter provides a general introduction to the European Commission, the main executive body of the European Union (EU). It argues that it is more productive to compare the Commission to national executives or to a government than to a secretariat of a traditional international organization. It begins with a summary of the Commission’s functions within the EU’s policy process. It then considers the question of Commission influence and autonomy, before moving on to look at the structure, demography, and decision behaviour within the organization—that is, at the role of the President of the Commission and the Commissioners, at the Commissioners’ personal staffs, and at the Commission administration. It then examines the committees and administrative networks that link the Commission to national administrations and interest groups, and the recent growth of EU agencies. The chapter concludes by emphasizing that the Commission is much more of a European(ized) and supranational institution than it was at its inception.
11. The European Council and the Council of the European Union
Authors: Lewis Jeffrey
Published: August 2022

This chapter examines the components that constitute the Council system: the European Council and the Council of the EU. Together, these institutions form the part of the Union that unabashedly represents national interests in the European integration process. The EU Council is a site of intense negotiation, compromise-building, and at times acrimonious disagreement among the member states. The EU Council is not a single body, but a composite of national officials working at different levels of political seniority and policy specialization. From the heads of state and government to the ministers, down to the expert-level fonctionnaires (officials), the EU Council and the European Council embed governments of the EU into a networked club of collective decision-making that penetrates into the national capitals and domestic politics of the member states. In authority, scope, and procedural methods, the Council system represents the most advanced, intensive forum of international cooperation between sovereign nation states in the modern world.
16. Policy-making in the European Union
Authors: Best Edward
Published: August 2022

This chapter provides an overview of how policy is made in the European Union (EU), focusing on the main procedures involved and the varying roles of the EU institutions. It begins by describing the range of powers that have been given to the EU by the member states in different policy areas, and the multiple modes of governance that are involved. The concept of the policy cycle is used as a framework to explain the stages in EU law-making. The ordinary legislative procedure is presented in some detail, and a case study illustrates the whole cycle from problem definition to implementation. The roles of the institutions in other kinds of policy process are then presented. Policy coordination is explained, with particular attention to economic governance and the European Semester. Finally, the chapter looks at external relations and the common foreign and security policy.
19. The European Union’s Foreign, Security, and Defence Policies
Authors: Juncos Ana E. , Friis Anna Maria
Published: August 2022

EU cooperation in foreign, security, and defence policy has developed rapidly since the launch of the Common Foreign and Security Policy (CFSP) in the early 1990s. The first section of this chapter charts the first steps towards a common policy in this area, including the development of the Common Security and Defence Policy (CSDP) and the gradual militarization of the EU. The chapter then reviews the key theoretical debates on the EU’s role as a foreign and security actor. The subsequent section analyses the main actors involved in the CFSP, focusing in particular on the role of the member states and EU institutions in the development of the policy. The next section of the chapter evaluates the range of military and civilian CSDP operations and missions that the EU has undertaken to date, before examining the key challenges that the EU faces in this area.
AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice
Authors: Jia Ruixuan , Meng Xiang , Chen Shaohong , Zhang Fan , Du Juan , Liu Xiaozhen , Yang Liping
Published: August 2022

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal degenerative disease characterized by yellow-white crystal deposits in the posterior pole, degeneration of the retinal pigment epithelium (RPE), and sclerosis of the choroid. Mutations in the cytochrome P450 4V2 gene (CYP4V2) cause BCD, which is associated with lipid metabolic disruption. The use of gene-replacement therapy in BCD has been hampered by the lack of disease models. To advance CYP4V2 gene-replacement therapy, we generated BCD patient-specific induced pluripotent stem cell (iPSC)–RPE cells and Cyp4v3 knockout (KO) mice as disease models and AAV2/8-CAG-CYP4V2 as treatment vectors. We demonstrated that after adeno-associated virus (AAV)-mediated CYP4V2 gene-replacement therapy BCD–iPSC–RPE cells presented restored cell survival and reduced lipid droplets accumulation; restoration of vision in Cyp4v3 KO mice was revealed by elevated electroretinogram amplitude and ameliorated RPE degeneration. These results suggest that AAV-mediated gene-replacement therapy in BCD patients is a promising strategy.
Glycine-rich RNA-binding cofactor RZ1AL is associated with tomato ripening and development
Authors: Li Xindi , Yang Yongfang , Zeng Ni , Qu Guiqin , Fu Daqi , Zhu Benzhong , Luo Yunbo , Ostersetzer-Biran Oren , Zhu Hongliang
Published: August 2022

Tomato ripening is a complex and dynamic process coordinated by many regulatory elements, including plant hormones, transcription factors, and numerous ripening-related RNAs and proteins. Although recent studies have shown that some RNA-binding proteins are involved in the regulation of the ripening process, understanding of how RNA-binding proteins affect fruit ripening is still limited. Here, we report the analysis of a glycine-rich RNA-binding protein, RZ1A-Like (RZ1AL), which plays an important role in tomato ripening, especially fruit coloring. To analyze the functions of RZ1AL in fruit development and ripening, we generated knockout cr-rz1al mutant lines via the CRISPR/Cas9 gene-editing system. Knockout of RZ1AL reduced fruit lycopene content and weight in the cr-rz1al mutant plants. RZ1AL encodes a nucleus-localized protein that is associated with Cajal-related bodies. RNA-seq data demonstrated that the expression levels of genes that encode several key enzymes associated with carotenoid biosynthesis and metabolism were notably downregulated in cr-rz1al fruits. Proteomic analysis revealed that the levels of various ribosomal subunit proteins were reduced. This could affect the translation of ripening-related proteins such as ZDS. Collectively, our findings demonstrate that RZ1AL may participate in the regulation of carotenoid biosynthesis and metabolism and affect tomato development and fruit ripening.
Pleural solitary fibrous tumour with brain metastasis: an aggressive tumour and pathologic conundrum
Authors: Williams Catherine , French Daniel , Christie Sean , Castonguay Mathieu , Wallace Alison
Published: August 2022

Solitary fibrous tumours of the pleura are a rare finding; those with brain metastases are rarer still. Here, we present the evolution of a pleural solitary fibrous tumour in a 70-year-old male treated surgically, and subsequent brain metastasis requiring emergent craniotomy and excision. The patient received adjuvant radiotherapy to the brain and had no recurrence of brain metastases; however, 1 year surveillance imaging demonstrated metastases to the lungs, liver and spleen for which he received chemotherapy but eventually succumbed to the disease process. Solitary fibrous tumours are most often slow-growing, relatively benign neoplasms. However, up to 10% are malignant. This case highlights the importance of surgical resection of these benign tumours with malignant potential.
The protein phosphatase 2A catalytic subunit StPP2Ac2b is involved in the control of potato tuber sprouting and source–sink balance in tubers and sprouts
Authors: Muñiz García María N , Cortelezzi Juan I , Capiati Daniela A
Published: August 2022

Sprouting negatively affects the quality of stored potato tubers. Understanding the molecular mechanisms that control this process is important for the development of potato varieties with desired sprouting characteristics. Serine/threonine protein phosphatase type 2A (PP2A) has been implicated in several developmental programs and stress responses in plants. PP2A comprises a catalytic (PP2Ac), a scaffolding (A), and a regulatory (B) subunit. In cultivated potato, six PP2Ac isoforms were identified, named StPP2Ac1, 2a, 2b, 3, 4, and 5. In this study we evaluated the sprouting behavior of potato tubers overexpressing the catalytic subunit 2b (StPP2Ac2b-OE). The onset of sprouting and initial sprout elongation is significantly delayed in StPP2Ac2b-OE tubers; however, sprout growth is accelerated during the late stages of development, due to a high degree of branching. StPP2Ac2b-OE tubers also exhibit a pronounced loss of apical dominance. These developmental characteristics are accompanied by changes in carbohydrate metabolism and response to gibberellic acid, and a differential balance between abscisic acid, gibberellic acid, cytokinins, and auxin. Overexpression of StPP2Ac2b alters the source–sink balance, increasing the source capacity of the tuber, and the sink strength of the sprout to support its accelerated growth.
Astrochemical model to study the abundances of branched carbon-chain molecules in a hot molecular core with realistic binding energies
Authors: Srivastav Satyam , Sil Milan , Gorai Prasanta , Pathak Amit , Sivaraman Bhalamurugan , Das Ankan
Published: August 2022

Straight-chain (normal-propyl cyanide, $\rm {n-C_3H_7CN}$) and branched-chain (iso-propyl cyanide, $\rm {i-C_3H_7CN}$) alkyl cyanides are recently identified in the massive star-forming regions (Sgr B2(N) and Orion). These branched-chain molecules indicate that the key amino acids (side-chain structures) may also be present in a similar region. The process by which this branching could propagate towards the higher order (butyl cyanide, $\rm {C_4H_9CN}$) is an active field of research. Since the grain catalysis process could have formed a major portion of these species, considering a realistic set of binding energies are indeed essential. We employ quantum chemical calculations to estimate the binding energy of these species considering water as a substrate because water is the principal constituent of this interstellar ice. We find significantly lower binding energy values for these species than were previously used. It is noticed that the use of realistic binding energy values can significantly change the abundance of these species. The branching is more favourable for the higher order alkyl cyanides with the new binding energies. With the inclusion of our new binding energy values and one essential destruction reaction ($\rm {i-C_3H_7CN+H \rightarrow CH_3C(CH_3)CN + H_2}$, having an activation barrier of 947 K), abundances of $\rm {t-C_4H_9CN}$ dramatically increased.
Effect of the UV dose on the formation of complex organic molecules in astrophysical ices: irradiation of methanol ices at 20 K and 80 K
Authors: Tenelanda-Osorio Laura I , Bouquet Alexis , Javelle Thomas , Mousis Olivier , Duvernay Fabrice , Danger Grégoire
Published: August 2022

Methanol is a ubiquitous complex organic molecule (COM) in the interstellar medium, thought to be a precursor of larger COMs when it is submitted to different energetic processes, that can trigger chemical reactions in solid and gas phases. Using laboratory experiments, we report the characterization of the evolution of photoproducts generated by the UV irradiation of methanol ice at different UV doses and temperatures (20 and 80 K). We used gas chromatography coupled to mass spectrometry (GC-MS) to analyse the volatile organic compounds (VOCs) recovered during the warming of the photoprocessed methanol ice. We identified 21 molecules (with up to five carbon atoms, including alcohols, aldehydes, ketones, ester, and ethers) and followed their abundance as a function of the UV fluence and ice temperatures. With increasing UV fluence, an increase in the production of heavier COMs is observed, while species with 1 or 2 carbon atoms are depleted or do not increase. Species within a same chemical family show the same pattern of evolution, with heavier molecules present in smaller quantities. Ketones and esters are the chemical families that lead to more complex molecules and start forming at the earliest stages of irradiation. Their formation pathways are driven by radical recombinations with CO as the main building blocks. Aldehydes are formed before their alcohol counterparts, implying they do not form through alcohol dehydrogenation, but via radical recombination around HCO. Ethers seem to be the precursors of a large set of COMs, and alcohols present a steady profile throughout irradiation.
Constraining IGM enrichment and metallicity with the C iv forest correlation function
Authors: Tie Suk Sien , Hennawi Joseph F , Kakiichi Koki , Bosman Sarah E I
Published: August 2022

The distribution and abundance of metals in the diffuse intergalactic medium (IGM) have implications for galaxy formation and evolution models, and has been argued to be sensitive to the Universe’s reionization history. However, reduced sensitivity in the near-IR implies that probing IGM metals at z > 4 is currently out of reach with the traditional method of detecting individual absorbers. We present a new technique based on clustering analysis that enables the detection of these weak IGM absorbers. We investigate the two-point correlation function (2PCF) of the ${\rm C\, {\small IV}}$ forest as a probe of IGM metallicity and enrichment topology by simulating the z = 4.5 IGM with models of inhomogeneous metal distributions. The 2PCF of the ${\rm C\, {\small IV}}$ forest demonstrates a clear peak at a characteristic separation corresponding to the doublet separation of the ${\rm C\, {\small IV}}$ line.The peak amplitude scales quadratically with metallicity, while enrichment topology affects both the shape and amplitude of the 2PCF. For models consistent with the distribution of metals at z ∼ 3, we find that we can constrain [C/H] to within 0.2 dex, log$\, M_{\rm {min}}$ to within 0.4 dex, and R to within 15 per cent. We show that CGM absorbers can be reliably identified and masked, thus recovering the underlying IGM signal. The auto-correlation of the metal-line forest presents a compelling avenue to constrain the IGM metallicity and enrichment topology with high precision at z > 4, thereby pushing such measurements into the Epoch of Reionization.
Evaluating the prevalence of spurious correlations in pulsar timing array data sets
Authors: Zic Andrew , Hobbs George , Shannon R M , Reardon Daniel , Goncharov Boris , Bhat N D Ramesh , Cameron Andrew , Dai Shi , Dawson J R , Kerr Matthew , Manchester R N , Mandow Rami , Marshman Tommy , Russell Christopher J , Thyagarajan Nithyanandan , Zhu X-J
Published: August 2022

Pulsar timing array collaborations have recently reported evidence for a noise process with a common spectrum among the millisecond pulsars in the arrays. The spectral properties of this common-noise process are consistent with expectations for an isotropic gravitational-wave background (GWB) from inspiralling supermassive black hole binaries. However, recent simulation analyses based on Parkes Pulsar Timing Array data indicate that such a detection may arise spuriously. In this paper, we use simulated pulsar timing array data sets to further test the robustness of the inference methods for spectral and spatial correlations from a GWB. Expanding on our previous results, we find strong support (Bayes factors exceeding 105) for the presence of a common-spectrum noise process in data sets where no common process is present, under a wide range of timing noise prescriptions per pulsar. We show that these results are highly sensitive to the choice of Bayesian priors on timing noise parameters, with priors that more closely match the injected distributions of timing noise parameters resulting in diminished support for a common-spectrum noise process. These results emphasize shortcomings in current methods for inferring the presence of a common-spectrum process, and imply that the detection of a common process is not a reliable precursor to detection of the GWB. Future searches for the nanohertz GWB should remain focused on detecting spatial correlations, and make use of more tailored specifications for a common-spectrum noise process.
Spectral and timing analysis of Be/X-ray binary EXO 2030+375 during its giant 2021 outburst
Authors: Tamang Ruchi , Ghising Manoj , Tobrej Mohammed , Rai Binay , Paul Bikash Chandra
Published: August 2022

We report the X-ray spectral and timing analysis of the high mass X-ray binary EXO 2030+375 during the 2021 type II outburst. We have incorporated NuSTAR, NICER, Swift/BAT, and Fermi/GBM observations to carry out a comprehensive analysis of the source. Pulse profiles in different energy ranges and time intervals have been generated and analysed. We have performed a brief comparison of the observations amidst the peak outburst condition and also during the decaying state of the outburst. Pulse profiles are found to evolve with time and energy. An iron emission line at (6–7) keV is observed in the X-ray continuum. Distinct absorption features were observed in the spectra corresponding to the peak outburst state while such features were not detected during the later decaying phase of the outburst. We have estimated the characteristic spin-up time-scale to be ∽ 60 yr. The continuum flux of the system and the varying luminosities covering the entire outburst period have been used to interpret the characteristics of the source. We have summarized the variability of various parameters along with their underlying physical implications.
Explaining mercury via a single giant impact is highly unlikely
Authors: Franco P , Izidoro A , Winter O C , Torres K S , Amarante A
Published: August 2022

The classical scenario of terrestrial planet formation is characterized by a phase of giant impacts among Moon-to-Mars mass planetary embryos. While the classic model and its adaptations have produced adequate analogues of the outer three terrestrial planets, Mercury’s origin remains elusive. Mercury’s high-core mass fraction compared to the Earth’s is particularly outstanding. Among collisional hypotheses, this feature has been long interpreted as the outcome of an energetic giant impact among two massive protoplanets. Here, we revisit the classical scenario of terrestrial planet formation with focus on the outcome of giant impacts. We have performed a large number of N-body simulations considering different initial distributions of planetary embryos and planetesimals. Our simulations tested the effects of different giant planet configurations, from virtually circular to very eccentric configurations. We compare the giant impacts produced in our simulations with those that are more likely to account for the formation of Mercury and the Moon according to smoothed hydrodynamic simulations. Impact events that could lead to Moon’s formation are observed in all our simulations with up to ∼20 per cent of all giant impacts, consistent with the range of the expected Moon-forming event conditions. On the other hand, Mercury-forming events via a single giant impact are extremely rare, accounting for less than ∼1 per cent of all giant impacts. Our results suggest that producing Mercury as a remnant of a single giant impact that strips out the mantle of a differentiated planetary object with Earth-like iron-silicate ratio is challenging and alternative scenarios may be required (e.g. multiple collisions).
Efficient detection and assembly of non-reference DNA sequences with synthetic long reads
Authors: Meleshko Dmitry , Yang Rui , Marks Patrick , Williams Stephen , Hajirasouliha Iman
Published: August 2022

Recent pan-genome studies have revealed an abundance of DNA sequences in human genomes that are not present in the reference genome. A lion’s share of these non-reference sequences (NRSs) cannot be reliably assembled or placed on the reference genome. Improvements in long-read and synthetic long-read (aka linked-read) technologies have great potential for the characterization of NRSs. While synthetic long reads require less input DNA than long-read datasets, they are algorithmically more challenging to use. Except for computationally expensive whole-genome assembly methods, there is no synthetic long-read method for NRS detection. We propose a novel integrated alignment-based and local assembly-based algorithm, Novel-X, that uses the barcode information encoded in synthetic long reads to improve the detection of such events without a whole-genome de novo assembly. Our evaluations demonstrate that Novel-X finds many non-reference sequences that cannot be found by state-of-the-art short-read methods. We applied Novel-X to a diverse set of 68 samples from the Polaris HiSeq 4000 PGx cohort. Novel-X discovered 16 691 NRS insertions of size > 300 bp (total length 18.2 Mb). Many of them are population specific or may have a functional impact.
A meta-analysis of the association betweenHelicobacter pyloriinfection and risk of hepatic encephalopathy
Authors: Li Junwei , Yu Hongwei , Wang Yuexia , Wang Bin , Zhang Rongguang , Chen Shuaiyin , Duan Guangcai
Published: August 2022

Background

Although the association between Helicobacter pylori (H. pylori) infection and hepatic encephalopathy (HE) has been confirmed through some research, the results of these relevant studies still remain controversial. We conducted an updated meta-analysis based on published studies to address this issue.

Methods

A systematic search was conducted, reviewing all studies about the association between H. pylori infection and HE, through November 2021. The outcome measures were presented as odds ratios (ORs) with 95% confidence intervals (CIs).

Results

In total, 13 studies provided data from 2784 subjects. H. pylori infection increased the risk of HE by 32% (OR = 2.32, 95% CI: 1.78–3.04). The effect became greater after hepatic encephalopathy was divided into overt HE and minimal hepatic encephalopathy (MHE) (HE OR = 2.66, 95% CI: 2.01–3.51, MHE OR = 1.74, 95% CI: 1.10–2.76). After H. pylori eradication, the risk of HE was reduced by 64%.

Conclusions

H. pylori infection is significantly associated with HE, and the infection rate of H. pylori also increases with the severity of HE. Eradication of H. pylori has a protective effect on HE. Therefore, it is necessary to eradicate H. pylori in HE treatments.
Competition for Attention in the ETF Space
Authors: Ben-David Itzhak , Franzoni Francesco , Kim Byungwook , Moussawi Rabih
Published: August 2022

The interplay between investors’ demand and providers’ incentives has shaped the evolution of exchange-traded funds (ETFs). While early ETFs invested in broad-based indexes and therefore offered diversification at low cost, more recent products track niche portfolios and charge high fees. Strikingly, over their first 5 years, specialized ETFs lose about 30$\%$ (risk-adjusted). This underperformance cannot be explained by high fees or hedging demand. Rather, it is driven by the overvaluation of the underlying stocks at the time of the launch. Our results are consistent with providers catering to investors’ extrapolative beliefs by issuing specialized ETFs that track attention-grabbing themes.
Vulvar Aphthous Ulcers in an Adolescent After Coronavirus Disease 2019 (COVID-19) Vaccination
Authors: Scott Stephen M. , Alaniz Veronica , Appiah Leslie , Buyers Eliza , Holton Carri , Huguelet Patricia
Published: August 2022

BACKGROUND:

Nonsexually acquired genital ulcers have been described among girls who are prepubertal after various viral illnesses due to mucosal inflammation from an immunologic response. Until recently, nonsexually acquired genital ulcers have only been associated with viral infections.

CASE:

We present a case of an adolescent girl developing nonsexually acquired genital ulcers after both her first and second coronavirus disease 2019 (COVID-19) vaccine doses. Her course followed an expected timeline for severity and resolution of ulcers.

CONCLUSIONS:

Aphthous ulcers may arise from inflammatory effects of COVID-19 vaccination. Clinical monitoring after COVID-19 vaccination from all formulations should include assessment for nonsexually acquired genital ulcers if vaginal pain is reported.
Valproate Teratogenicity
Authors: Gruppuso Philip A. , Ahmed Rashid , Adashi Eli Y.
Published: August 2022

Within several years after receiving U.S. Food and Drug Administration (FDA) approval in the late 1970s, valproate was shown to increase the risk for major congenital malformations and learning disabilities in the offspring of women who used the drug during pregnancy. Nonetheless, its use in pregnant women has persisted for more than four decades, recently resulting in numerous lawsuits and, in countries other than the United States, criminal indictments of the manufacturers of valproate. The use of valproate in pregnancy persisted and extended beyond its original indication for the treatment of epilepsy. Several recent studies indicate that the drug is more often prescribed to treat pregnant women with bipolar depression and migraine than for seizure control. Especially concerning is the absence of valproate from the list of more than 60 drugs for which the FDA has implemented Risk Evaluation and Mitigation Strategies to prevent or limit untoward consequences associated with specific drugs. Until this step is taken, avoidance of the teratogenic effects of valproate will rely on the vigilance of those caring for women and people with the potential to get pregnant.
Ketamine Compared With Fentanyl for Surgical Abortion
Authors: Chin Jennifer , McGrath Madeline , Lokken Erica , Upegui Carlos Delgado , Prager Sarah , Micks Elizabeth
Published: August 2022

OBJECTIVE:

To compare patient satisfaction with anesthesia after first-trimester surgical abortion among patients receiving intravenous (IV) ketamine compared with IV fentanyl for procedural sedation.

METHODS:

This was a randomized noninferiority trial comparing IV ketamine to IV fentanyl for first-trimester surgical abortion up to 13 6/7 weeks of gestation. Patients were randomized to receive either ketamine 200–500 micrograms/kg IV over 2 minutes, repeated every 5 minutes until appropriate analgesia was achieved, or fentanyl 0.5–1 micrograms/kg IV over 2 minutes, repeated every 5 minutes until appropriate analgesia was achieved. All patients received midazolam 2 mg IV. The primary outcome, patient satisfaction, was measured using the Iowa Satisfaction with Anesthesia Scale immediately postprocedure. Secondary outcomes included postoperative pain, additional pain medication necessary during the procedure and on discharge, physician satisfaction, and time to discharge. We calculated a sample size of 84 with a noninferiority margin of 0.6 on the Iowa Satisfaction with Anesthesia Scale with 80% power, one-sided type 1 error of 0.025, and further increased this number to 110 to account for potential dropout.

RESULTS:

From April to October 2021, 184 patients were screened and 110 were randomized (57 to ketamine and 53 to fentanyl). Demographics were similar between groups. The primary outcome, patient satisfaction with anesthesia, was noninferior in the ketamine group (mean score 2.4, SD 0.8) as compared with the fentanyl group (mean score 2.2, SD 0.9) with a risk difference of 0.20 (95% CI 0.11–0.52). More hallucinations were reported in the ketamine group. Otherwise, secondary outcomes were similar between the groups.

CONCLUSION:

Compared with IV fentanyl, IV ketamine is noninferior for patient satisfaction with anesthesia when used for procedural sedation for first-trimester outpatient surgical abortion.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04871425.
The Effect of Pulse Shape and Interphase Gaps on Speech Perception and Perceived Sound Quality in Electrical Hearing
Authors: Liepins Rudolfs , Kaider Alexandra , Auinger Alice Barbara , Dahm Valerie , Honeder Clemens , Riss Dominik , Arnoldner Christoph
Published: August 2022

Background:

Stimulation with triphasic pulses has been shown to reduce the occurrence of unwanted facial nerve stimulation (FNS) with cochlear implants (CIs). However, there is little data available on how different pulse shapes affect the hearing outcome with electrical hearing in general. The aim of the study was to evaluate the effects of different stimulation pulse shapes on speech perception in noise, as well as loudness perception and subjective sound quality.

Methods:

Twenty experienced cochlear-implant users not suffering from FNS participated in a prospective single-visit study. Based on the subjects’ current clinical fitting, six fitting maps with different pulse shapes (biphasic and triphasic) and different interphase gap (IPG) durations (2.1 µs, 10 µs, and 20 µs) were created. First, the loudness was balanced for each configuration by adjusting the stimulation charge amount. Then, speech perception in noise was measured with a German matrix sentence test (Oldenburg Sentence test). The perception of particular sound attributes of speech and music, as well as overall preference, was evaluated with visual analog scales.

Results:

Similar levels of speech perception were obtained with triphasic stimulation (P = 0.891) and longer IPGs (P = 0.361) compared to the subjects’ clinical map settings. The stimulation amplitudes for equal loudness were significantly higher with triphasic stimulation compared to biphasic stimulation when keeping the IPG constant. Increasing the IPG had a significantly larger effect on perceived loudness (P < 0.0001) and charge reduction for equal loudness with triphasic pulses compared to biphasic pulses. Triphasic configuration showed lower overall subjective sound quality ratings than biphasic for speech intelligibility, clarity, naturalness, and overall preference, as well as for music naturalness, and overall preference in the acute setting without adaptation time. Post-hoc pairwise comparisons against the clinical map revealed significantly lower speech naturalness ratings for triphasic with 2.1 µs IPG and for triphasic with 20 µs IPG only.

Conclusion:

Although some sound quality attributes were rated lower compared to the clinical map in the acute test setting, stimulation with triphasic pulses does not affect speech perception in noise and can be considered as a valuable option in CI fitting.
A multicenter retrospective analysis of risk factors for poor outcomes after tibial pilon fractures
Authors: Ashworth Timothy J. , Alvarez Paul M. , Laux Jeffrey P. , Ganga Sarat , Ostrum Robert F.
Published: August 2022

Background:

Despite the high rate of complications associated with tibial pilon fractures, treatment often remains fairly algorithmic. This study highlights risk factors for poor outcomes to guide individualized treatment in an effort to minimize complications.

Methods:

One hundred and fifty-seven surgically treated pilon fractures in 151 patients over 6 yr were included. The following factors were studied: age, gender, presence of diabetes, smoking status, presence of an open fracture, Association for Osteosynthesis-Orthopaedic Trauma Association (AO/OTA) fracture classification, number of plates and incisions, time to external fixator placement, time to definitive treatment, and incisions used. The two primary outcomes were nonunion and infection/wound complications requiring re-operation. Univariate tests were used for each variable in isolation. Multiple regression models were used to control important covariates. Interactions between the number of incisions, patient history of smoking, the number of plates utilized, and patient history of diabetes were analyzed.

Results:

Male gender, open fracture, history of diabetes and increasing time to fixation were associated with infection/wound complications. Open fractures were strongly associated with the development of nonunion. The interaction model for diabetes and increasing number of plates showed that each additional plate used when treating patients with a history of diabetes was associated with 6.08 times higher odds of developing an infection, a marginally significant result (P=0.065).

Conclusions:

Increased caution may be warranted when treating tibial pilon fractures in patients with certain risk factors. In patients with a history of diabetes, the additional dissection needed to place more implants may contribute to higher rates of infection.

Level of Evidence:

Prognostic Level III.
Pelagibacterium xiamenense sp. nov., isolated from intertidal sediment
Authors: He Yufei , Lyu Lina , Dong Chunming , Wang Wanpeng , Yu Zhiqiang , Shao Zongze
Published: August 2022

A Gram-stain-negative, obligately aerobic bacterium, designated as HS1C4-1T, was isolated from a sediment sample from the tidal zone of the Haicang Coast, Xiamen, Fujian Province, PR China. The strain was yellowish-coloured, non-gliding, rod-shaped and motile, with a single polar flagellum. Cells of HS1C4-1T were oxidase- and catalase-positive. The strain could grow at 15–55 °C (optimum 37 °C), pH 6.0–10.0 (optimum, pH 7.0–9.0), in the presence of 0–12 % (optimum, 1 %) NaCl (w/v). Phylogenetic analysis based on the 16S rRNA gene sequences indicated that HS1C4-1T represented a member of the genus

Pelagibacterium

, and shared the highest similarity to

Pelagibacterium luteolum

CGMCC 1.10267T (97.6 %). Digital DNA–DNA hybridization values and average nucleotide identity between HS1C4-1T and all the species of genus

Pelagibacterium

were 18.7–20.2 % and 77.3–78.4 %, respectively. The principal fatty acids (>10 %) were C19 : 0 cyclo ω8c (50.5 %) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 29.1%). Q-10 was the sole respiratory quinone. The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids and six unidentified lipids. The G+C content of the chromosomal DNA was 62.9 %. On the basis of phylogenetic, phenotypic, chemotaxonomic and genomic characteristics, HS1C4-1T represents a novel species within the genus

Pelagibacterium

, for which the name Pelagibacterium xiamenense sp. nov. is proposed. The type strain is HS1C4-1T (=MCCC 1A18759T=KCTC 92097T).
Quadrisphaera setariae sp. nov., polyphosphate-accumulating bacterium occurring as tetrad or aggregate cocci and isolated from Setaria viridis
Authors: Kim Inhyup , Chhetri Geeta , Kim Jiyoun , So Yoonseop , Seo Taegun
Published: August 2022

A Gram-stain-positive, orange-pigmented, aerobic, cocci (occurring in tetrads), non-spore-forming, non-motile bacterium, designated as DD2AT, was isolated from Setaria viridis collected at Dongguk University, Republic of Korea. Phylogenetic analysis based on the 16S rRNA gene revealed that strain DD2AT was most closely related to type strains of the genus

Quadrisphaera

. Strain DD2AT showed the highest 16S rRNA gene sequence similarities to

Quadrisphaera oryzae

TBRC 8486T (99.4 %) and

Quadrisphaera granulorum

JCM 16010T (98.8 %). Strain DD2AT also showed auto-aggregation ability. The digital DNA–DNA hybridization values between strain DD2AT and the reference strains,

Q. oryzae

TBRC 8486T and

Q. granulorum

JCM 16010T were 31.1 and 27.4 %, respectively. The average nucleotide identity values between strain DD2AT and

Q. oryzae

TBRC 8486T and

Q. granulorum

JCM 16010T were 86.3 and 84.1 %, respectively. The major polar lipids of strain DD2AT were diphosphatidylglycerol and phosphatidylglycerol. The major cellular fatty acid of strain DD2AT was anteiso-C15 : 0. The cell-wall peptidoglycan contained meso-diaminopimelic acid (which is a diagnostic cell-wall diamino acid), alanine and glutamic acid. The respiratory quinones was found to be menaquinone-8. The DNA G+C content of strain DD2AT was 74.8 mol%. On the basis of the findings of genotypic, phenotypic, chemotaxonomic and phylogenetic analyses, strain DD2AT was considered to represent a novel member in the genus

Quadrisphaera

, for which the name Quadrisphaera setariae sp. nov. is proposed. The type strain of Quadrisphaera setariae is DD2AT (=KACC 21165T=NBRC 113770T).
Microglia Depletion Selectively Eliminates a Singular Form of Hippocampal Long-Term Potentiation
Authors: Chavez Jasmine , Le Aliza A. , Quintanilla Julian , Tagne Alex Mabou , Piomelli Daniele , Lynch Gary , Gall Christine M.
Published: August 2022

There has been considerable recent interest in the possibility that microglia contribute to synaptic plasticity and some forms of learning. We report here that elimination of the cells in young adult male mice with a 7-12 day treatment with an antagonist (PLX5622) of the colony stimulating factor 1 receptor causes a profound but highly selective impairment to long-term potentiation (LTP) expressed by lateral perforant path (LPP) synapses with the dentate gyrus. Input/output functions and frequency facilitation to repetitive stimulation were not measurably affected. Direct infusion of PLX5622 into slices from naiive mice did not reduce the magnitude of LPP-LTP. Microglial depletion had no detectable effect on LTP in either the medial perforant path input to the dentate gyrus or the Schaffer-commissural projections between fields CA3 and CA1. We conclude that microglia discretely regulate the unusual form of LTP expressed by the LPP and thus exert region-specific effects on circuit function within hippocampus.
Choice of spatial discretisation influences the progression of viral infection within multicellular tissues
Authors: Williams Thomas , McCaw James , Osborne James
Published: August 2022

There has been an increasing recognition of the utility of models of the spatial dynamics of viral spread within tissues. Multicellular models, where cells are represented as discrete regions of space coupled to a virus density surface, are a popular approach to capture these dynamics. Conventionally, such models are simulated by discretising the viral surface and depending on the rate of viral diffusion and other considerations, a finer or coarser discretisation may be used. The impact that this choice may have on the behaviour of the system has not been studied. Here we demonstrate that, if rates of viral diffusion are small, then the choice of spatial discretisation of the viral surface can have quantitative and even qualitative influence on model outputs. We investigate in detail the mechanisms driving these phenomena and discuss the constraints on the design and implementation of multicellular viral dynamics models for different parameter configurations.

Author summary

Here we analyse the impact that the resolution of spatial discretisation has on the behaviour of spatial models of viral dynamics. We show that the extent of this influence depends on the size of the diffusion coefficient, and that, if the diffusion coefficient is sufficiently small - for example, small enough to describe tight plaque-forming dynamics - the choice of discretisation of the viral surface relative to the cell grid can appreciably change key predictions of the model. We show that the resolution of spatial discretisation modulates the timescale of infection, and identify the mechanisms by which this occurs. This work provides theory to inform the development of multicellular models of viral dynamics, which is in short supply in the literature.
Bacterial droplet-based single-cell RNA-seq reveals heterogeneity in bacterial populations and in response to antibiotic perturbation
Authors: Ma Peijun , Amemiya Haley M. , He Lorrie L. , Gandhi Shivam J. , Nicol Robert , Bhattacharyya Roby P. , Smillie Christopher S. , Hung Deborah T.
Published: August 2022

We introduce BacDrop, a highly scalable technology for bacterial single-cell RNA sequencing that has overcome many challenges hindering the development of scRNA-seq in bacteria. BacDrop can be applied to thousands or millions of cells from both gram-negative and gram-positive species. It features universal ribosomal RNA depletion and combinatorial barcodes that enable multiplexing and massively parallel sequencing. We applied BacDrop to study Klebsiella pneumoniae clinical isolates and to elucidate their heterogeneous responses to antibiotic stress. In an unperturbed population presumed to be homogenous, we find within- population heterogeneity largely driven by the expression of mobile genetic elements that promote the evolution of antibiotic resistance. Under antibiotic perturbation, BacDrop revealed transcriptionally distinct subpopulations associated with different phenotypic outcomes including antibiotic persistence. BacDrop thus can capture cellular states that cannot be detected by bulk RNA-seq, which will unlock new microbiological insights into bacterial responses to perturbations and larger bacterial communities such as the microbiome.