bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Hydrothermal Effect on Migration of Contaminants in Porous Media
Authors: GUO Zhi-guang , LIU Yong-Fu , AO Chang-jiang
Published: July 2021

This paper extends a one-dimensional model of adsorbed contaminants in saturated porous media to establish a three-dimensional case suitable for unsaturated porous media. The effects of hydrothermal influences on the distributions of temperature and moisture, evolution of the bulk strain and migration of nuclides are simulated and analysed, and the coupled thermo-hydro-mechanical governing equations determined by the author are presented. The results show that the saturation in the buffer layer gradually rises to 0.96 from the initial value of 0.5 after approximately 450 years, and increases slowly in the initial stage of the simulation. The nuclide concentration in the solidified body first increases and then decreases, reaching a maximum of 173.05 mol/m3 in approximately 110 years. Moreover, most of the radionuclides are released by buffer layer adsorption and the adsorbed concentration is almost 100 times the solute concentration. In addition, the calculation also shows that the nuclides penetrate the buffer and reach the surrounding rock approximately 400 years later.
A New WO3/FeVO4 Nanostructured Heterojunction for Solar-driven Water Oxidation
Authors: Naqvi Syeda Qurat-ul-Ain , Raza Syed Abbas , Soon Ying Woan , Liu Yeru , Jennings James Robert
Published: July 2021

We report the first application of a nanostructured WO3/FeVO4 heterojunction to photoelectrochemical (PEC) water oxidation. The heterojunction films were prepared by drop-casting a low bandgap (~2.1 eV) FeVO4 layer onto a wider bandgap (~2.8 eV) WO3 nanoporous film supported on a fluorine-doped tin oxide coated glass substrate. The structural, optical and PEC properties of the prepared heterojunction were analysed in detail, and it was found that the WO3/FeVO4 composite reached maximum photocurrent densities under simulated sunlight up to 3.3 and 12 times higher than those of pristine WO3 and FeVO4 photoanodes, respectively. A large and desirable ~400 mV cathodic shift in the photocurrent onset potential relative to pristine FeVO4 was also observed, which can be attributed to lower surface recombination and more efficient bulk separation of photogenerated electron–hole pairs compared with both pristine FeVO4 and WO3. These findings suggest that WO3/FeVO4 nanostructured heterojunctions may find applications in solar-driven water splitting cells.
Electron spin resonance studies of (La0.6Ln0.4)0.67Ca0.33MnO3 (Ln = La, Pr, Nd and Sm) nanoparticles at different temperatures
Authors: Leng Kai , Xia Weiren , Tang Qingkai , Yang Li , Wu Zhiwei , Yi Kang , Zhu Xinhua
Published: July 2021

In this work, (La0.6Ln0.4)0.67Ca0.33MnO3 (Ln = La, Pr, Nd and Sm) nanoparticles (NPs) synthesized by sol-gel process were investigated by electron spin resonance (ESR) in the temperature range 100–330 K. At the high temperature the ESR signals of La0.67Ca0.33MnO3 (LCMO) NPs only consist of a single peak with Landé g factor of 2.0. This signal is contributed from the paramagnetic (PM) Mn ions in the LCMO NPs. With decreasing the temperature the PM resonance line is split into two resonance lines, one is ferromagnetic (FM) resonance line shifting towards low field while the other is antiferromagnetic (AFM) resonance line moving to a high field. The resonance peak-to-peak spectra linewidth, increases monotonically with decreasing the temperature owing to the strong double exchange interactions below the Curie temperature (T
C). Resonance field is almost temperature independent in the PM phase whereas it drops fast at temperature below T
C. Consequently, the Landé g factor in the PM region is very close to 2.0 whereas in the range of 2.17–2.47 under FM state due to the strong FM interactions. For the Pr (Nd)-doped LCMO NPs below T
C, their g values are in the range of 2.04–2.18 due to the substantial reduction of the FM interactions caused by the Pr (Nd)-doping at La-site. The g values of the Sm-doped LCMO NPs exhibit a slight fluctuation around 1.88 (but smaller than 2.0) within the measured temperature due to the existence of weak magnetic interactions under the PM states.
Comparing Islamic and International Laws of War: Orthodoxy, “Heresy,” and Secularization in the Category of Civilians
Authors: Salaymeh Lena
Published: July 2021

This Article investigates how contemporary laws of war rationalize civilian deaths. I concentrate on two specific legal constructions in warfare: the definition of civilian/combatant and the principle of distinction. (The categories of civilian and combatant should be understood as dialogically constitutive and not entirely distinct. In addition, the category of “civilian” is a modern one and premodern legal sources often do not use one term to refer to noncombatants.) I focus on two significant parties in contemporary warfare: al-Qāʿidah (aka Al-Qaeda) and the U.S. military. Al-Qāʿidah diverges from orthodox Islamic law on these two legal issues, while remaining within the Islamic legal tradition. To scrutinize the nature of this divergence, I compare al-Qāʿidah’s legal reasoning to the legal reasoning of the U.S. military. I demonstrate that the U.S. military diverges from orthodox international law in ways that parallel how al-Qāʿidah diverges from orthodox Islamic law. Specifically, both the U.S. military and al-Qāʿidah elide orthodox categories of civilians and expand the category of combatant, primarily by rendering civilians as probable combatants. Based on this comparative analysis, I argue that the legal reasoning of al-Qāʿidah (and other militant Islamist groups) is as secular as it is Islamic; I call this fusion secularislamized law.
Interictal spikes with and without high-frequency oscillation have different single-neuron correlates
Authors: Guth Tim A , Kunz Lukas , Brandt Armin , Dümpelmann Matthias , Klotz Kerstin A , Reinacher Peter C , Schulze-Bonhage Andreas , Jacobs Julia , Schönberger Jan
Published: July 2021

Interictal epileptiform discharges (IEDs) are a widely used biomarker in patients with epilepsy but lack specificity. It has been proposed that there are truly epileptogenic and less pathological or even protective IEDs. Recent studies suggest that highly pathological IEDs are characterized by high-frequency oscillations (HFOs). Here, we aimed to dissect these ‘HFO-IEDs’ at the single-neuron level, hypothesizing that the underlying mechanisms are distinct from ‘non-HFO-IEDs’. Analysing hybrid depth electrode recordings from patients with temporal lobe epilepsy, we found that single-unit firing rates were higher in HFO- than in non-HFO-IEDs. HFO-IEDs were characterized by a pronounced pre-peak increase in firing, which coincided with the preferential occurrence of HFOs, whereas in non-HFO-IEDs, there was only a mild pre-peak increase followed by a post-peak suppression. Comparing each unit’s firing during HFO-IEDs to its baseline activity, we found many neurons with a significant increase during the HFO component or ascending part, but almost none with a decrease. No such imbalance was observed during non-HFO-IEDs. Finally, comparing each unit’s firing directly between HFO- and non-HFO-IEDs, we found that most cells had higher rates during HFO-IEDs and, moreover, identified a distinct subset of neurons with a significant preference for this IED subtype. In summary, our study reveals that HFO- and non-HFO-IEDs have different single-unit correlates. In HFO-IEDs, many neurons are moderately activated, and some participate selectively, suggesting that both types of increased firing contribute to highly pathological IEDs.
Stimulus Feature-Specific Control of Layer 2/3 Subthreshold Whisker Responses by Layer 4 in the Mouse Primary Somatosensory Cortex
Authors: Varani Stefano , Vecchia Dania , Zucca Stefano , Forli Angelo , Fellin Tommaso
Published: July 2021

In the barrel field of the rodent primary somatosensory cortex (S1bf), excitatory cells in layer 2/3 (L2/3) display sparse firing but reliable subthreshold response during whisker stimulation. Subthreshold responses encode specific features of the sensory stimulus, for example, the direction of whisker deflection. According to the canonical model for the flow of sensory information across cortical layers, activity in L2/3 is driven by layer 4 (L4). However, L2/3 cells receive excitatory inputs from other regions, raising the possibility that L4 partially drives L2/3 during whisker stimulation. To test this hypothesis, we combined patch-clamp recordings from L2/3 pyramidal neurons in S1bf with selective optogenetic inhibition of L4 during passive whisker stimulation in both anesthetized and awake head-restrained mice. We found that L4 optogenetic inhibition did not abolish the subthreshold whisker-evoked response nor it affected spontaneous membrane potential fluctuations of L2/3 neurons. However, L4 optogenetic inhibition decreased L2/3 subthreshold responses to whisker deflections in the preferred direction, and it increased L2/3 responses to stimuli in the nonpreferred direction, leading to a change in the direction tuning. Our results contribute to reveal the circuit mechanisms underlying the processing of sensory information in the rodent S1bf.
Causal Relationship between the Right Auditory Cortex and Speech-Evoked Envelope-Following Response: Evidence from Combined Transcranial Stimulation and Electroencephalography
Authors: Mai Guangting , Howell Peter
Published: July 2021

Speech-evoked envelope-following response (EFR) reflects brain encoding of speech periodicity that serves as a biomarker for pitch and speech perception and various auditory and language disorders. Although EFR is thought to originate from the subcortex, recent research illustrated a right-hemispheric cortical contribution to EFR. However, it is unclear whether this contribution is causal. This study aimed to establish this causality by combining transcranial direct current stimulation (tDCS) and measurement of EFR (pre- and post-tDCS) via scalp-recorded electroencephalography. We applied tDCS over the left and right auditory cortices in right-handed normal-hearing participants and examined whether altering cortical excitability via tDCS causes changes in EFR during monaural listening to speech syllables. We showed significant changes in EFR magnitude when tDCS was applied over the right auditory cortex compared with sham stimulation for the listening ear contralateral to the stimulation site. No such effect was found when tDCS was applied over the left auditory cortex. Crucially, we further observed a hemispheric laterality where aftereffect was significantly greater for tDCS applied over the right than the left auditory cortex in the contralateral ear condition. Our finding thus provides the first evidence that validates the causal relationship between the right auditory cortex and EFR.
De novo ARF3 variants cause neurodevelopmental disorder with brain abnormality
Authors: Sakamoto Masamune , Sasaki Kazunori , Sugie Atsushi , Nitta Yohei , Kimura Tetsuaki , Gürsoy Semra , Cinleti Tayfun , Iai Mizue , Sengoku Toru , Ogata Kazuhiro , Suzuki Atsushi , Okamoto Nobuhiko , Iwama Kazuhiro , Tsuchida Naomi , Uchiyama Yuri , Koshimizu Eriko , Fujita Atsushi , Hamanaka Kohei , Miyatake Satoko , Mizuguchi Takeshi , Taguri Masataka , Ito Shuuichi , Takahashi Hidehisa , Miyake Noriko , Matsumoto Naomichi
Published: July 2021

An optimal Golgi transport system is important for mammalian cells. The adenosine diphosphate (ADP) ribosylation factors (ARF) are key proteins for regulating cargo sorting at the Golgi network. In this family, ARF3 mainly works at the trans-Golgi network (TGN), and no ARF3-related phenotypes have yet been described in humans. We here report the clinical and genetic evaluations of two unrelated children with de novo pathogenic variants in the ARF3 gene: c.200A > T (p.Asp67Val) and c.296G > T (p.Arg99Leu). Although the affected individuals presented commonly with developmental delay, epilepsy and brain abnormalities, there were differences in severity, clinical course and brain lesions. In vitro subcellular localization assays revealed that the p.Arg99Leu mutant localized to Golgi apparatus, similar to the wild-type, whereas the p.Asp67Val mutant tended to show a disperse cytosolic pattern together with abnormally dispersed Golgi localization, similar to that observed in a known dominant negative variant (p.Thr31Asn). Pull-down assays revealed that the p.Asp67Val had a loss-of-function effect and the p.Arg99Leu variant had increased binding of the adaptor protein, Golgi-localized, γ-adaptin ear-containing, ARF-binding protein 1 (GGA1), supporting the gain of function. Furthermore, in vivo studies revealed that p.Asp67Val transfection led to lethality in flies. In contrast, flies expressing p.Arg99Leu had abnormal rough eye, as observed in the gain-of-function variant p.Gln71Leu. These data indicate that two ARF3 variants, the possibly loss-of-function p.Asp67Val and the gain-of-function p.Arg99Leu, both impair the Golgi transport system. Therefore, it may not be unreasonable that they showed different clinical features like diffuse brain atrophy (p.Asp67Val) and cerebellar hypoplasia (p.Arg99Leu).
Unscrambling the eggs: breaking up consummated mergers and dominant firms
Authors: Kwoka John , Valletti Tommaso
Published: July 2021

Entrenched dominant firms and anticompetitive consummated mergers pose growing problems for antitrust agencies throughout the world. A lot of thought is being given as to how to address these situations but perhaps the most obvious idea—breaking up such firms—is generally dismissed as impractical, the equivalent of trying to unscramble eggs. We disagree. We show that there have been a substantial number of successful breakups of firms, some in antitrust, more in regulated industries, and even more in the private sectors of the USA and UK as firms initiate their own restructuring. We believe that a policy of breakups can have a much greater chance at success compared to efforts to regulate such firms through rule-making conduct remedies. And we argue that breaking up such firms is facilitated by the fault lines that reveal the natural break points of these heavily merged firms. We recommend that breakups be on the policy menu for competition agencies.
Can self-regulation save digital platforms?
Authors: Cusumano Michael A , Gawer Annabelle , Yoffie David B
Published: July 2021

This article explores some of the critical challenges facing self-regulation and the regulatory environment for digital platforms. We examine several historical examples of firms and industries that attempted self-regulation before the Internet. All dealt with similar challenges involving multiple market actors and potentially harmful content or bias in search results: movies and video games, radio and television advertising, and computerized airline reservation systems. We follow this historical discussion with examples of digital platforms in the Internet era that have proven problematic in similar ways, with growing calls for government intervention through sectoral regulation and content controls. We end with some general guidelines for when and how specific types of platform businesses might self-regulate more effectively. Although our sample is small and exploratory, the research suggests that a combination of self-regulation and credible threats of government regulation may yield the best results. We also note that effective self-regulation need not happen exclusively at the level of the firm. When it is in their collective self-interest, as occurred before the Internet era, coalitions of firms within the same market and with similar business models may agree to abide by a jointly accepted set of rules or codes of conduct.
Regulating digital ecosystems: bridging the gap between competition policy and data protection
Authors: Kira Beatriz , Sinha Vikram , Srinivasan Sharmadha
Published: July 2021

Data collection and processing are at the core of rapidly growing business models, underpinning the activities of technology companies and acting as a source of market power. The key role played by data in the competitive dynamics of digital ecosystems has brought competition policy and data protection regulation closer together and raised important questions about the substantive relationship between these two branches of law. After identifying the specific ways in which data create and power digital ecosystems and examining the effects of digital privacy (or lack thereof) on consumer welfare, we compare the legal obligations imposed by competition policy and data protection regulation. We then map the interfaces between these two branches of law and critically assess the areas of substantive overlap between them. We show that while in the majority of situations there is an alignment of these two frameworks, opposite outcomes can sometimes be reached when competition and data protection rules are applied separately. We suggest that these two legal instruments should be considered as overlapping areas in a regulatory continuum to facilitate positive synergies and neutralize potential conflicts. We show that there is a significant scope for competition policy actors and institutions to substantially incorporate data protection considerations into their decisional practice and that this integration can inform and enhance the enforcement of competition law. We propose an integrated approach to more effectively regulate digital platform ecosystems, to support innovation, and to protect consumers and the competitive process.
In patients with thoracic aortic graft infection, is graft explantation and replacement superior toin situgraft preservation?
Authors: Poon Shi Sum , George Joseph , Kumar Pankaj , Field Mark
Published: July 2021

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether graft explantation and replacement are superior to graft preservation in patients with thoracic aortic graft infections. Altogether, more than 487 papers were found using the reported search; of these, 7 comparative studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Although thoracic aortic graft infection is uncommon following cardiac surgery, it still carries a significant risk of in-hospital mortality and poor long-term survival. Current findings in the literature are limited to retrospective cohort studies with relatively small sample sizes; also, there is a lack of randomized controlled trials on this topic. There was significant heterogeneity in patient groups and variation in surgical techniques across centres. In this context, a graft-sparing approach may be a safe therapy with comparable early mortality and late survival outcomes in carefully selected patients. The selection may include the absence of graft pseudoaneurysm, anastomotic leak and fistula; the presence of indolent infection in patients with poor clinical conditions; and significant frailty and comorbidities where the risks of surgical explantation exceed the benefits. The rate of reinfection is low following both graft replacement and the graft-sparing approach. Moreover, the use of a tissue flap improves the surgical outcomes.
Noncommutative Tensor Triangular Geometry and the Tensor Product Property for Support Maps
Authors: Nakano Daniel K , Vashaw Kent B , Yakimov Milen T
Published: July 2021

The problem of whether the cohomological support map of a finite dimensional Hopf algebra has the tensor product property has attracted a lot of attention following the earlier developments on representations of finite group schemes. Many authors have focused on concrete situations where positive and negative results have been obtained by direct arguments. In this paper we demonstrate that it is natural to study questions involving the tensor product property in the broader setting of a monoidal triangulated category. We give an intrinsic characterization by proving that the tensor product property for the universal support datum is equivalent to complete primeness of the categorical spectrum. From these results one obtains information for other support data, including the cohomological one. Two theorems are proved giving compete primeness and non-complete primeness in certain general settings. As an illustration of the methods, we give a proof of a recent conjecture of Negron and Pevtsova on the tensor product property for the cohomological support maps for the small quantum Borel algebras for all complex simple Lie algebras.
Evaluating Real-World National and Regional Trends in Definitive Closure in U.S. Burn Care: A Survey of U.S. Burn Centers
Authors: Carter Jeffrey E , Amani Hamed , Carter Damien , Foster Kevin N , Griswold John A , Hickerson William L , Holmes James H , Jones Samuel , Khandelwal Anjay , Kopari Nicole , Litt Jeffrey S , Savetamal Alisa , Shupp Jeffrey W , Sood Rajiv , Ferrufino Cheryl P , Vadagam Pratyusha , Kowal Stacey , Walsh Tom , Sparks Jeremiah
Published: July 2021

To better understand trends in burn treatment patterns related to definitive closure, this study sought to benchmark real-world survey data with national data contained within the National Burn Repository version 8.0 (NBR v8.0) across key burn center practice patterns, resource utilization, and clinical outcomes. A survey, administered to a representative sample of U.S. burn surgeons, collected information across several domains: burn center characteristics, patient characteristics including number of patients and burn size and depth, aggregate number of procedures, resource use such as autograft procedure time and dressing changes, and costs. Survey findings were aggregated by key outcomes (number of procedures, costs) nationally and regionally. Aggregated burn center data were also compared to the NBR to identify trends relative to current treatment patterns. Benchmarking survey results against the NBR v8.0 demonstrated shifts in burn center patient mix, with more severe cases being seen in the inpatient setting and less severe burns moving to the outpatient setting. An overall reduction in the number of autograft procedures was observed compared to NBR v8.0, and time efficiencies improved as the intervention time per TBSA decreases as TBSA increases. Both nationally and regionally, an increase in costs was observed. The results suggest resource use estimates from NBR v8.0 may be higher than current practices, thus highlighting the importance of improved and timely NBR reporting and further research on burn center standard of care practices. This study demonstrates significant variations in burn center characteristics, practice patterns, and resource utilization, thus increasing our understanding of burn center operations and behavior.
The Effect of a Recreational Therapy Program on the Pain Anxiety and Quality of Life of Patients With Burn Injuries: A Randomized Clinical Trial
Authors: Froutan Razieh , Saberi Abolfazl , Ahmadabadi Ali , Mazlom Seyed Reza
Published: July 2021

Pain anxiety and dysfunction are among the most prevalent complications of burns, impacting the quality of life (QOL) of patients with burn injuries. As a nonpharmaceutical approach, recreational therapy can be effective in reducing the complications of burns. This study aimed to examine the effect of a recreational therapy program on the pain anxiety and QOL of patients with burn injuries. This controlled randomized clinical trial was conducted on 58 patients admitted to the burn center of Imam Reza Hospital in Mashhad, Iran. These patients were randomly allocated to the intervention and control group. The intervention group received a recreational therapy program three sessions a week, for 2 weeks. The control group performed routine daily activities. As the main variable of the study, the Burn Specific Pain Anxiety Scale and Burn Specific Health Scale-Brief were completed for both groups before and 2 weeks after the intervention. After controlling confounders, the pain anxiety score in the intervention group was significantly lower than in the control group (P = .002). The total QOL score was significantly higher in the intervention group than the control group (P = .001). In addition, the intervention significantly increased the scores of QOL in the physical (P < .001), emotional (P = .009), and social (P < .001) dimensions. As it reduces pain anxiety and promotes the QOL of patients with burn injuries, this recreational therapy program is recommended for promoting the mental health and QOL of these patients.
Human-Mediated Admixture and Selection Shape the Diversity on the Modern Swine (Sus scrofa) Y Chromosomes
Authors: Ai Huashui , Zhang Mingpeng , Yang Bin , Goldberg Amy , Li Wanbo , Ma Junwu , Brandt Debora , Zhang Zhiyan , Nielsen Rasmus , Huang Lusheng
Published: July 2021

Throughout its distribution across Eurasia, domestic pig (Sus scrofa) populations have acquired differences through natural and artificial selection, and have often interbred. We resequenced 80 Eurasian pigs from nine different Asian and European breeds; we identify 42,288 reliable SNPs on the Y chromosome in a panel of 103 males, among which 96.1% are newly detected. Based on these new data, we elucidate the evolutionary history of pigs through the lens of the Y chromosome. We identify two highly divergent haplogroups: one present only in Asia and one fixed in Europe but present in some Asian populations. Analyzing the European haplotypes present in Asian populations, we find evidence of three independent waves of introgression from Europe to Asia in last 200 years, agreeing well with the literature and historical records. The diverse European lineages were brought in China by humans and left significant imprints not only on the autosomes but also on the Y chromosome of geographically and genetically distinct Chinese pig breeds. We also find a general excess of European ancestry on Y chromosomes relative to autosomes in Chinese pigs, an observation that cannot be explained solely by sex-biased migration and genetic drift. The European Y haplotype is associated with leaner meat production, and we hypothesize that the European Y chromosome increased in frequency in Chinese populations due to artificial selection. We find evidence of Y chromosomal gene flow between Sumatran wild boar and Chinese pigs. Our results demonstrate how human-mediated admixture and selection shaped the distribution of modern swine Y chromosomes.
Under attack: Terrorism and international trade in France, 2014–2016
Authors: Nitsch Volker , Rabaud Isabelle
Published: July 2021

Terrorist events typically vary along many dimensions, making it difficult to identify their economic effects. This paper analyses the impact of terrorism on international trade by examining a series of three large-scale terrorist incidents in France over the period from January 2015 to July 2016. Using firm-level data at monthly frequency, we document an immediate and lasting decline in cross-border trade after a mass terrorist attack. According to our estimates, France’s trade in goods, which accounts for about 70% of the country’s trade in goods and services, is reduced by more than 6 billion euros in the first 6 months after an attack. The reduction in trade mainly takes place along the intensive margin, with particularly strong effects for partner countries with low border barriers to France, for firms with less frequent trade activities and for homogeneous products. A possible explanation for these patterns is an increase in trade costs due to stricter security measures.
Fixing capitalism’s good jobs problem
Authors: Rodrik Dani , Stantcheva Stefanie
Published: July 2021

Conventional welfare state policies that centre on education, training, progressive taxation, and social insurance are inadequate to address labour market polarization, which is capitalism’s most pressing inclusion challenge at present. We propose a strategy aimed directly at the productive sphere of the economy and targeting an increase in the supply of ‘good jobs’. The main elements of this strategy are: (i) active labour market policies linked to employers; (ii) industrial and regional policies directly targeting the creation of good jobs; (iii) innovation policies that incentivize labour-friendly technologies; (iv) international economic policies that facilitate the maintenance of high domestic labour/social standards. These elements are connected both by their objective—expanding the number of good jobs—and by a new approach to regulation that is collaborative and iterative rather than top-down and prescriptive. We emphasize the importance of new institutional arrangements that enable strategic long-term information exchange and cooperation between governments and firms.
Communities, the state, and markets: the case for inclusive localism
Authors: Rajan Raghuram
Published: July 2021

Opportunities are maximized for all when society’s three pillars, the market, the state, and the community, are balanced. In recent years, technological change and globalization have led to an expansion of the market and the state at the expense of certain communities. The resulting disparities in opportunities have led to widespread dissatisfaction, which can be addressed effectively only by strengthening left-behind communities. New technological solutions combined with policies that encourage inclusive localism are needed to restore the balance to society.
The Small GTPase OsRac1 Forms Two Distinct Immune Receptor Complexes Containing the PRR OsCERK1 and the NLR Pit
Authors: Akamatsu Akira , Fujiwara Masayuki , Hamada Satoshi , Wakabayashi Megumi , Yao Ai , Wang Qiong , Kosami Ken-ichi , Dang Thu Thi , Kaneko-Kawano Takako , Fukada Fumi , Shimamoto Ko , Kawano Yoji
Published: July 2021

Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. In this study, using biochemical and bioimaging approaches, we revealed that OsRac1 formed two distinct receptor complexes with OsCERK1 and with Pit. Supporting this result, OsCERK1 and Pit utilized different transport systems for anchorage to the plasma membrane (PM). Activation of OsCERK1 and Pit led to OsRac1 activation and, concomitantly, OsRac1 shifted from a small to a large protein complex fraction. We also found that the chaperone Hsp90 contributed to the proper transport of Pit to the PM and the immune induction of Pit. These findings illuminate how the PRR OsCERK1 and the NLR Pit orchestrate rice immunity through the small GTPase OsRac1.
Brain Asymmetry in Pain Affective Modulation
Authors: Toutain Thaise Graziele L de O , Alba Guzmán , Miranda José Garcia Vivas , Silva do Rosário Raphael , Muñoz Miguel , de Sena Eduardo Pondé
Published: July 2021

Objective

The aim of this study was to characterize the dynamic brain networks underlying the affective modulation of pleasant, unpleasant, and neutral image perception due to painful stimulations in healthy subjects.

Methods

Forty volunteers, 20 men and 20 women, participated in this study. Brain activity was recorded by 64-channel electroencephalography. After data cleaning, brain functional networks were built through the use of the motif synchronization method.

Results

We found that increased cerebral connectivity in the left hemisphere under the pain condition broke the connection symmetry. Both women and men showed homophilic connections (intrahemispheric), but women were more homophilic than men. The pain condition increased homophily in the left hemisphere, and emotions could modulate pain. The frontal, central, and left temporal regions showed homophilic variation, depending on the emotional stimulus.

Conclusions

Pain and emotions altered brain activity. There was increased connectivity and homophily in the left brain hemisphere for the painful experience. The emotions modulated brain activity in the pain condition. Overall, the brain presented homophilic characteristics; homophily changed, depending on emotion or pain. The left brain hemisphere seems to be related to pain processing.
Patients with Clinically Elevated Depressive Symptoms Report Improvements in Mood, Pain, and Functioning Following Participation in Interdisciplinary Pain Rehabilitation
Authors: Craner Julia R , Flegge Lindsay G , Lake Eric S , Perra Arianna E A
Published: July 2021

Objective

Chronic pain and depression frequently co-occur and exacerbate one another; therefore, it is important to treat both conditions to improve patient outcomes. The current study evaluates an interdisciplinary pain rehabilitation program (IPRP) with respect to the following questions: 1) How do clinically elevated depressive symptoms impact pain-related treatment outcomes? and 2) To what extent does IPRP participation yield reliable and clinically significant change in depressed mood?

Methods

Participants in this study included 425 adults who engaged in a 10-week IPRP and completed self-report measures of pain, mood, and functioning at intake and discharge. Participants were categorized into 4 groups based on self-reported depressive symptoms (PROMIS Depression): within normal limits (WNL; n = 121), Mild (n = 115), Moderate (n = 153), and Severe (n = 36).

Results

Participants reported significant improvement in pain, pain-related life interference, health-related quality of life, pain catastrophizing, and depressed mood regardless of initial symptom level. In addition, 43.4% of patients with Mild, Moderate, or Severe depressed mood reported reliable and clinically significant improvement in depressive symptoms and 30.3% were in remission at the end of treatment.

Conclusions

These findings support the assertion that IPRPs represent an effective treatment for patients with comorbid chronic pain and depression and that participation is associated with improvement in both conditions.
Prenatal acetaminophen use in women with autoimmune disorders and adverse pregnancy and birth outcomes
Authors: Killion Jordan A , Chambers Christina , Smith Chelsey J F , Bandoli Gretchen
Published: July 2021

Objectives

Most women may have temporary pain for which they use analgesics, but those with autoimmune disorders have chronic pain that may be exacerbated for some during pregnancy. This study aimed to determine whether prenatal acetaminophen use was associated with an increased risk of adverse pregnancy and birth outcomes in women with autoimmune disorders.

Methods

Participants were enrolled between 2004 and 2018 in the MotherToBaby cohort study and limited to women with an autoimmune disorder (n = 1821). Self-reported acetaminophen use was characterized over gestation for indication, timing of use and duration. Cumulative acetaminophen use through 20 and 32 weeks was categorized into quintiles, with no acetaminophen use as the reference category. The association between acetaminophen quintile and preeclampsia or pregnancy-induced hypertension, small for gestational age and preterm birth was examined using adjusted multiple log-linear regression.

Results

Overall, 74% of women reported acetaminophen use during pregnancy. The most often reported indication for using acetaminophen was headache/migraines, followed by pain and injury. Risk of preeclampsia was 1.62 (95% CI: 1.10, 2.40) times greater for those in the fifth quintile of cumulative acetaminophen use through 20 weeks compared with those with no acetaminophen use. There were no associations with lower use quintiles, nor for the other outcomes.

Conclusion

The highest quintile of cumulative acetaminophen was associated with a modestly increased risk for preeclampsia. Some women with autoimmune conditions have pain throughout pregnancy; clinicians and patients should discuss approaches to best avoid high levels of acetaminophen in their pain management strategies.
Developmental differences in affective representation between prefrontal and subcortical structures
Authors: Mitchell William J , Tepfer Lindsey J , Henninger Nicole M , Perlman Susan B , Murty Vishnu P , Helion Chelsea
Published: July 2021

Developmental studies have identified differences in prefrontal and subcortical affective structures between children and adults, which correspond with observed cognitive and behavioral maturations from relatively simplistic emotional experiences and expressions to more nuanced, complex ones. However, developmental changes in the neural representation of emotions have not yet been well explored. It stands to reason that adults and children may demonstrate observable differences in the representation of affect within key neurological structures implicated in affective cognition. Forty-five participants (25 children and 20 adults) passively viewed positive, negative and neutral clips from popular films while undergoing functional magnetic resonance imaging. Using representational similarity analysis to measure variability in neural pattern similarity, we found developmental differences between children and adults in the amygdala, nucleus accumbens and ventromedial prefrontal cortex (vmPFC): children generated less pattern similarity within subcortical structures relative to the vmPFC—a phenomenon not replicated among their older counterparts. Furthermore, children generated valence-specific differences in representational patterns across regions; these valence-specific patterns were not found in adults. These results may suggest that affective representations grow increasingly dissimilar over the course of development as individuals mature from visceral affective responses to more evaluative analyses.
Noninvasive Urine Oxygen Monitoring and the Risk of Acute Kidney Injury in Cardiac Surgery
Authors: Silverton Natalie A. , Lofgren Lars R. , Hall Isaac E. , Stoddard Gregory J. , Melendez Natalia P. , Van Tienderen Michael , Shumway Spencer , Stringer Bradley J. , Kang Woon-seok , Lybbert Carter , Kuck Kai
Published: July 2021

Background

Acute kidney injury (AKI) is a common complication of cardiac surgery. An intraoperative monitor of kidney perfusion is needed to identify patients at risk for AKI. The authors created a noninvasive urinary oximeter that provides continuous measurements of urinary oxygen partial pressure and instantaneous urine flow. They hypothesized that intraoperative urinary oxygen partial pressure measurements are feasible with this prototype device and that low urinary oxygen partial pressure during cardiac surgery is associated with the subsequent development of AKI.

Methods

This was a prospective observational pilot study. Continuous urinary oxygen partial pressure and instantaneous urine flow were measured in 91 patients undergoing cardiac surgery using a novel device placed between the urinary catheter and collecting bag. Data were collected throughout the surgery and for 24 h postoperatively. Clinicians were blinded to the intraoperative urinary oxygen partial pressure and instantaneous flow data. Patients were then followed postoperatively, and the incidence of AKI was compared to urinary oxygen partial pressure measurements.

Results

Intraoperative urinary oxygen partial pressure measurements were feasible in 86/91 (95%) of patients. When urinary oxygen partial pressure data were filtered for valid urine flows greater than 0.5 ml · kg–1 · h–1, then 70/86 (81%) and 77/86 (90%) of patients in the cardiopulmonary bypass (CPB) and post-CPB periods, respectively, were included in the analysis. Mean urinary oxygen partial pressure in the post-CPB period was significantly lower in patients who subsequently developed AKI than in those who did not (mean difference, 6 mmHg; 95% CI, 0 to 11; P = 0.038). In a multivariable analysis, mean urinary oxygen partial pressure during the post-CPB period remained an independent risk factor for AKI (relative risk, 0.82; 95% CI, 0.71 to 0.95; P = 0.009 for every 10-mmHg increase in mean urinary oxygen partial pressure).

Conclusions

Low urinary oxygen partial pressures after CPB may be associated with the subsequent development of AKI after cardiac surgery.

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Dietary sodium and cardiovascular morbidity/mortality: a brief commentary on the ‘J-shape hypothesis’
Authors: Tsirimiagkou Christiana , Karatzi Kalliopi , Argyris Antonios , Basdeki Eirini D. , Kaloudi Panagiota , Yannakoulia Mary , Protogerou Athanase D.
Published: July 2021

The last decade, a growing number of evidence support J-shape or inverse – instead of positive linear -- associations between dietary sodium intake and cardiovascular morbidity/mortality. A careful evaluation of these studies leads to the following observations: less accurate methods for dietary sodium assessment are usually used; most studies included high-risk participants, enhancing the possibility of a ‘reverse causality’ phenomenon. However, these limitations do not explain all the findings. Few carefully designed randomized clinical trials comparing different levels of sodium intake that address the issue of the optimal and safe range exist; therefore, current guidelines recommend a higher cut-off instead of a safe range of intake. Given the demonstrated harmful effects of very low sodium diets leading to subclinical vascular damage in animal studies, the ‘J-shape hypothesis’ cannot yet be either neglected or verified. There is a great need of well-designed general population-based prospective randomized clinical trials to address the issue.
Accuracy of OCT–derived net corneal astigmatism measurement
Authors: Llorens-Quintana Clara , Pavlatos Elias , Thaware Omkar , Gupta Seema , Gradin Daniel , Romfh Denzil , Li Yan , Huang David
Published: July 2021

Purpose:

To assess the repeatability and accuracy of corneal astigmatism measurement with a spectral-domain optical coherence tomography (OCT) system (Avanti, Optovue) and compare them with Scheimpflug imaging (Pentacam HR, Oculus) and swept-source optical biometry (IOLMaster 700, Carl Zeiss Meditec AG).

Setting:

Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.

Design:

Prospective cross-sectional observational study.

Methods:

60 pseudophakic eyes with monofocal nontoric intraocular lens that previously had refractive surgery were analyzed. To assess accuracy, simulated keratometry (SimK) and net corneal astigmatism, obtained from each device, were compared with subjective manifest refraction astigmatism. Repeatability for corneal astigmatism was assessed for OCT and Pentacam HR by the coefficient of repeatability from 3 repeated measures.

Results:

Compared with manifest refraction, SimK readings produced with-the-rule astigmatic bias that was reduced for net astigmatism for the 3 devices. Except for OCT net astigmatism, all instruments significantly overestimated the magnitude of the astigmatism (linear mixed-effects model [LMM], P < .05). OCT net astigmatism showed the highest accuracy for manifest astigmatism prediction with the smaller 95% confidence ellipse for the mean difference vector. OCT net mean absolute difference was 0.57 diopters (D), significantly smaller than that of the other modalities (LMM, P < .05). Net corneal astigmatism measured with OCT showed the best repeatability (coefficient of repeatability = 0.29 D).

Conclusions:

OCT has the capability to measure net corneal astigmatism with higher precision and accuracy than Pentacam HR Scheimpflug imaging and IOLMaster 700 swept-source optical biometry in postrefractive subjects.
Protein arginine methyltransferase 7 modulates neuronal excitability by interacting with NaV1.9
Authors: Ma Tingbin , Li Lulu , Chen Rui , Yang Luyao , Sun Hao , Du Shiyue , Xu Xuan , Cao Zhijian , Zhang Xianwei , Zhang Luoying , Shi Xiaoliu , Liu Jing Yu
Published: July 2021

Human NaV1.9 (hNaV1.9), encoded by SCN11A, is preferentially expressed in nociceptors, and its mutations have been linked to pain disorders. NaV1.9 could be a promising drug target for pain relief. However, the modulation of NaV1.9 activity has remained elusive. Here, we identified a new candidate NaV1.9-interacting partner, protein arginine methyltransferase 7 (PRMT7). Whole-cell voltage-clamp recordings showed that coelectroporation of human SCN11A and PRMT7 in dorsal root ganglion (DRG) neurons of Scn11a
−/− mice increased the hNaV1.9 current density. By contrast, a PRMT7 inhibitor (DS-437) reduced mNaV1.9 currents in Scn11a
+/+ mice. Using the reporter molecule CD4, we observed an increased distribution of hLoop1 on the cell surface of PRMT7-overexpressing HKE293T cells. Furthermore, we found that PRMT7 mainly binds to residues 563 to 566 within the first intracellular loop of hNaV1.9 (hLoop1) and methylates hLoop1 at arginine residue 519. Moreover, overexpression of PRMT7 increased the number of action potential fired in DRG neurons of Scn11a
+/+ mice but not Scn11a
−/− mice. However, DS-437 significantly inhibited the action potential frequency of DRG neurons and relieved pain hypersensitivity in Scn11a
A796G/A796G mice. In summary, our observations revealed that PRMT7 modulates neuronal excitability by regulating NaV1.9 currents, which may provide a potential method for pain treatment.
Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn
Authors: Gradwell Mark A. , Boyle Kieran A. , Browne Tyler J. , Bell Andrew M. , Leonardo Jacklyn , Peralta Reyes Fernanda S. , Dickie Allen C. , Smith Kelly M. , Callister Robert J. , Dayas Christopher V. , Hughes David I. , Graham Brett A.
Published: July 2021

Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here, we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported and that both ePVIN and inhibitory PVIN populations form synaptic connections among (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity.