bluuebunny/crossref_metadata_2025 huggingface dataset:
Is ‘white nationalism’, nationalism?
Authors: Rigney Maeve , Holmes Carolyn E
Published: September 2022

Are ‘white nationalists’ really nationalists? This label is one that right‐wing, white activists themselves have chosen, and as such, compels rigorous investigation to avoid simply adopting the preferred nomenclature of these activists and their ambitions. The nation and nationalism are concepts with rich scholarly histories, and this paper seeks to examine the discussion, activities and statements of so‐called white nationalists in light of this literature. We argue through a three‐fold concept of the nation—based on territoriality, population and symbolic and/or cultural content—that the vision of the political community and ambitions of these activists falls short of the standard of a nation and that their aspirations do not conform to what the literature lays out as nationalism. We argue, therefore, that using the language of ‘white nationalism’ to describe these groups obfuscates and sanitises their motives and lends undue legitimacy to their standing in public discourse.
A critical ethnographic perspective on risk and dangerousness in forensic psychiatry
Authors: Domingue Jean‐Laurent , Jacob Jean‐Daniel , Perron Amélie , Pariseau‐Legault Pierre , Foth Thomas
Published: September 2022

In the Canadian forensic psychiatric context, the concepts of risk and dangerousness interact, intersect, and morph into the notion of significant threat to the safety of the public. Stemming from the results of a critical ethnography of the Ontario Review Board, this article unpacks the central role of forensic psychiatric nursing, as an example of a 'psych' discipline (e.g., psychiatry and psychology), in a system that is built to produce risky persons and to legitimize their detention and supervision. By using excerpt of interviews conducted with nurses, ethnographic observations of Review Board hearings, and other documentary artifacts, the findings illustrate how rationalizations of risk and dangerousness are contingent on space, time, and observer. Depending on the time of the assessment or on the health‐care professional who performs it, different elements including, but not limited to, mental illness, interpersonal relationships, financial instability, and sexual vulnerability, are relied upon in very fluid, interchangeable, and discretionary ways to justify findings of dangerousness. Such a dynamic expands the reach of psychiatry's legitimacy at identifying risky conduct and controlling risky persons to domains very loosely associated with the notion of dangerousness. The work of Foucault and Castel provides the theoretical backdrop on which rests the discussion and the implications for nursing.
Overcoming legal barriers to coastal wetland restoration: lessons from Australia's Blue Carbon methodology
Authors: Bell‐James Justine
Published: September 2022

Globally, there is a recognized need for widespread restoration of coastal wetlands. Despite this recognition, progress in many places has been slow, for reasons including legal and policy barriers. In Australia many of these legal barriers have been overcome in the development of the Carbon Credits (Carbon Farming Initiative ‐ Tidal Restoration of Blue Carbon Ecosystems) Methodology Determination 2022, which allows for certain coastal restoration projects to be accredited and ultimately receive Australian Carbon Credit Units. This paper describes the new methodology, outlines the key legal barriers which had to be addressed in its development, and analyzes the legal solutions utilized. It concludes with some general observations for fucoastal wetland restoration projects. Despite the jurisdictional focus on Australia, it is anticipated that these lessons will be of broader relevance to other countries grappling with restoration projects in the intertidal zone.
Ecological impacts of coral gardening outplanting in the Maldives
Authors: Dehnert Inga , Galli Paolo , Montano Simone
Published: September 2022

As coral reefs continue to degrade at an alarming rate, coral restoration efforts are increasing worldwide in an attempt to keep up with the global challenge of preserving these iconic ecosystems and the many services they provide. Coral gardening, the farming and outplanting of coral fragments, is a commonly applied practice; however, regional validation is required before upscaling can be considered. This study follows up from the successful farming of fragments in mid‐water rope nurseries, by reporting on the successive outplanting of these corals. Specifically, 60 Pocillopora verrucosa colonies were outplanted to a degraded reef at different depths (1–12 m), applying three arrangement patterns (equal, clustered, random). After 1 year, 72% were considered successfully outplanted (alive and still attached), with detachment being the main challenge at wave‐impacted shallow depths, while loose coral rubble caused more partial mortality at depth. Outplanting stress was observed at 1–6 m depth, but had no impact on survival or growth. Drupella sp. predation was most common at 3 m and 79% of colonies hosted mutualistic fauna after 1 year. Outplanting significantly benefitted the reef environment with a higher fish abundance and diversity along with a higher increase in natural coral cover (H = 2.7; 6.2% increase) in comparison with the control sites. These are promising results, considering that the restoration site has shown little natural recovery in the last few years (coral cover <4%). We hope that our findings provide useful initial insights and help to guide effective restoration practices in the Maldives.
The Taylor Rule in Egypt: Is it Optimal? Is there Equilibrium Determinacy?
Authors: Maher Mohamed , Zhao Yanzhi , Tang Chuanzhong
Published: September 2022

We investigate Egypt's Taylor rule (interest rate targeting) between 1976 and 2019 by including the main economic variables in its reaction function. Using the Taylor principle, we investigate Egypt’s monetary policy optimality. To this end, we conduct the generalized method of moments (GMM) estimation procedure with different Taylor rule specifications to deal with potential endogeneity among variables. Our GMM estimates reveal that the partial adjustment coefficient is of considerable magnitude, indicating the explanatory power of policy inertia on many total variations in the current values of the nominal interest rate in Egypt. Furthermore, the inflation gap coefficient violates the Taylor principle, making the policy procyclical and inflation "spiral" and inducing divergence from the long-run equilibrium. Therefore, Egypt's Taylor rule, and thus monetary policy, reflects the indeterminacy of equilibrium and is a passive and destabilizing policy. Besides, the output gap coefficient was unexpectedly found to be insignificant.
Institutional Quality and Labour Productivity: Evidence from the Economic Community of West African States Countries
Authors: Sanga Dimitri , Ahouakan Ehouman Williams Venance , Adje N'goran Assigno Frejus
Published: September 2022

This study investigates how institutional quality influences labor productivity in West Africa. Thus, a panel of 15 Economic Community of West African States (ECOWAS) member states over the period 2005-2017 was considered. The panel was analyzed for the primary, secondary, and tertiary sectors. For the empirical analysis, a panel fixed effect regression was conducted based on a neoclassical framework. Results show that institutional quality improvement is overall associated with higher levels of productivity, regardless of the sector. Some specificities were also observed at the sectoral levels. Furthermore, the econometric analysis reconfirms a positive effect of investment and human capital on productivity. Therefore, improving institutional quality would be helpful for productivity growth in this sub-region. This event could enable ECOWAS member states to reap greater benefits from the implementation of the African Continental Free Trade Area agreement.
Effects of Cooled Exhaust Gas Recirculation Combined With Prechamber Jet Ignition on the Combustion Characteristics in a Kerosene-Fueled Spark Ignition Engine
Authors: Liu Fengnian , Zhou Lei , Zhang Yusheng , Liu Changwen , Wei Haiqiao
Published: September 2022

For security and logistical convenience, the single fuel forward policy hopes to use a single kerosene fuel to replace a variety of military fuels, especially the unsafe gasoline. However, the performance of kerosene-fueled spark ignition (SI) engines is severely restricted by knock, slow combustion rate, and poor combustion stability. This work innovatively applies cooled exhaust gas recirculation (EGR) combined with prechamber jet ignition (PJI) to a kerosene-fueled engine to suppress knock and improve performance. The results show that applying cooled EGR at a fixed throttle opening can suppress knock and improve fuel economy. However, the power decreased due to the decreased intake of energy. While applying EGR with constant fresh air mass flow makes the knock more prominent because of the microboosting effect caused by the increased throttle opening. This indicates that cooled EGR alone cannot improve the power output. Moreover, combustion instability was also caused due to the slower combustion rate. Therefore, PJI was introduced to compensate for the negative impact of EGR. As a result, a synergistic effect of cooled EGR and PJI was discovered, improving the IMEP by 5% and reducing the ISFC by 4.9% compared to the baseline. The PJI can shorten the combustion duration and improve the combustion stability because of the high kinetic energy jet and high turbulence flame. In addition, a novel two-stage heat release process which includes the unusual first-stage low-temperature heat release was discovered. Overall, EGR dominates the knock suppression, and PJI contributes to the combustion rate improvement.
The Ignition of C1–C7 Natural Gas Blends and the Effect of Hydrogen Addition in the Low and High Temperature Regimes
Authors: Mohamed A. Abd El-Sabor , Bikram Sahu Amrit , Panigrahy Snehasish , Bourque Gilles , Curran Henry
Published: September 2022

New ignition delay time (IDT) measurements for two natural gas (NG) blends composed of C1–C7n-alkanes, NG6 (C1:60.625%, C2:20%, C3:10%, C4:5%, nC5:2.5%, nC6:1.25%, nC7:0.625%) and NG7 (C1:72.635%, C2:10%, C3:6.667%, C4:4.444%, nC5:2.965%, nC6:1.976%, nC7:1.317%) by volume with methane as the major component are presented. The measurements were recorded using a high-pressure shock tube (HPST) for stoichiometric fuel in air mixtures at reflected shock pressures (p5) of 20–30 bar and at temperatures (T5) of 987–1420 K. The current results together with rapid compression machine (RCM) measurements in the literature show that higher concentrations of the higher n-alkanes (C4–C7) ∼1.327% in the NG7 blend compared to the NG6 blend result in the ignition times for NG7 being almost a factor of two faster than those for NG6 at compressed temperatures of (TC) ≤ 1000 K. This is due to the low temperature chain branching reactions that occur for higher alkane oxidation kinetics in this temperature range. On the contrary, at TC > 1000 K, NG6 exhibits ∼20% faster ignition than NG7, primarily because about 12% of the methane in the NG7 blend is primarily replaced by ethane (∼10%) in NG6, which is significantly more reactive than methane at these higher temperatures. The performance of NUIGMech1.2 in simulating these data is assessed, and it can reproduce the experiments within 20% for all the conditions considered in the study. We also investigate the effect of hydrogen addition to the auto-ignition of these NG blends using NUIGMech1.2, which has been validated against the existing literature for natural gas/hydrogen blends. The results demonstrate that hydrogen addition has both an inhibiting and a promoting effect in the low- and high-temperature regimes, respectively. Sensitivity analyses of the hydrogen/NG mixtures are performed to understand the underlying kinetics controlling these opposite ignition effects. At low temperatures, H-atom abstraction byO˙H radicals from C3 and larger fuels are the key chain-branching reactions consuming the fuel and providing the necessary fuel radicals, which undergo low temperature chemistry (LTC) leading to ignition. However, with the addition of hydrogen to the fuel mixture, the competition by H2 for O˙H radicals via the reaction H2 +  O˙H ↔ H˙ + H2O reduces the progress of the LTC of the higher hydrocarbon fuels thereby inhibiting ignition. At higher temperatures, since H˙ + O2 ↔ Ö + O˙H is the most sensitive reaction promoting reactivity, the higher concentrations of H2 in the fuel mixture lead to higher H˙ atom concentrations leading to faster ignition due to an enhanced rate of the H˙ + O2 ↔ Ö + O˙H reaction.
X-ray absorption measurements at a bending magnet beamline with an Everhart–Thornley detector: A monolayer of Ho3N@C80 on graphene
Authors: Lee Wei Chuang , Sagehashi Ryunosuke , Zhang Yang , Popov Alexey A. , Muntwiler Matthias , Greber Thomas
Published: September 2022

X-ray Absorption Spectroscopy (XAS) is used for measuring monolayer quantities of Ho3N@C80 endofullerene molecules on graphene at a low flux bending magnet beamline. The total electron yield is measured with an Everhart–Thornley detector. In comparison to sample current measurements with the same noise level, our approach reduces data acquisition time and radiation dose by a factor of 25. As the first application of this setup, we report temperature-dependent measurements of the Ho M45 edge with per mille accuracy. This documents the advantages and capabilities of an Everhart–Thornely detector for XAS measurements under low x-ray flux.
Dependence of film structure on the film structure-independent equivalent film thickness in magnetron sputtering deposition of Ag thin films
Authors: Kusano Eiji
Published: September 2022

In this work, I have investigated the structures and properties of Ag thin films deposited by magnetron sputtering onto glass substrates with temperatures of 150 and 600 °C for film structure-independent equivalent film thicknesses in the range of 20–400 nm. The Ag thin film morphologies observed using scanning electron microscopy and atomic force microscopy showed the following distinguishable changes: an Ag thin film with an equivalent film thickness of 20 nm deposited at a substrate temperature of 150 °C displayed a film microstructure of oblate grains separated by voids, while those with equivalent film thicknesses of 50 nm or more displayed microstructures consisting of flat-topped grains without any obvious voids between them. In comparison, an Ag thin film with an equivalent film thickness of 20 nm deposited at a substrate temperature of 600 °C displayed a microstructure consisting of isolated spherically shaped grains with a uniform diameter of approximately 40 nm and spaced at uniform intervals; an Ag thin film with an equivalent film thickness of 50 nm displayed a microstructure of more oblate grains; Ag thin films with equivalent film thicknesses of 100 and 200 nm displayed microstructures of highly isolated, flat-topped, mound-shaped grains; and an Ag thin film with an equivalent film thickness of 400 nm displayed a microstructure of continuous flat-topped, mound-shaped grains. In addition, the Ag thin films with equivalent film thicknesses of 20 and 50 nm deposited at 600 °C exhibited higher compressive stresses. The quantitative results of optical-transmittance and electrical resistivity measurements were consistent with the changes in thin film morphology. The morphological structures of the Ag thin films deposited at 600 °C result from the high surface diffusivity of the Ag atoms, which do not wet the glass substrate, whereas the morphologies of the Ag thin films deposited at 150 °C result from in-place grain growth following the formation of multiple nuclei because of the low surface diffusivity of the Ag atoms at this temperature. The observed thin film microstructures are unexplained by the classical structure model for sputter-deposited metal thin films, which does not consider either the high surface diffusivity of adatoms that do not wet the substrate or the increase in surface area required to dissipate the energy accumulating in grains during film deposition. The results obtained in this study provide a fundamental description and explanation of the grain structure of metal thin films with thicknesses of a few tens of nanometers or less.
Comparison of glancing-angle scatterings on different materials in a high aspect ratio plasma etching process using molecular dynamics simulation
Authors: Du Yao , Krüger Florian , Nam Sang Ki , Lee Hoki , Yoo Suyoung , Eapen Jacob , Kushner Mark J. , Shannon Steven
Published: September 2022

In plasma etching for microelectronics fabrication, one of the objectives is to produce a high aspect ratio (HAR) via and trench structures. A principal contributor to the HAR feature shape is the manner in which energetic ions interact with sidewalls inside the feature. The scattering angle and energy loss of ions reflecting from sidewalls determine the sidewall slope and can lead to defects such as microtrenching and bowing. Understanding how ions interact with sidewalls can improve our control of the critical dimensions of HAR features. Ions accelerated in the plasma sheath arrive in the feature with energies as large as a few keV and initially strike the sidewalls at glancing angles. These scattering events extend to the photolithographic mask. Scattering from the mask at glancing angles can produce ions incident into the underlying feature with a broader angular distribution, leading to less desirable feature properties. In this work, results are discussed from Molecular Dynamics (MD) simulations of glancing-angle scattering of argon ions from three materials common to HAR etch: polystyrene (as a photoresist surrogate), amorphous carbon (a hard mask material), and SiO2 (a common insulating material used in microelectronics devices). Results from simulations reveal a transition from specular scattering to diffuse scattering as the angle of the incident ion decreases (90° being glancing incidence) and incident energy increases. Scattering from polystyrene is more diffuse compared to amorphous carbon and SiO2 for identical incident ion conditions.
Elaboration and characterization of porous ultrathin gold films grown by ion beam assisted deposition
Authors: Aassime A. , Duquennoy M. , Hamouda F. , Kadi T. , Mahut F. , Ouaftouh M.
Published: September 2022

The growth of ultrathin gold layers on a silicon substrate is performed with an unconventional ion beam assisted deposition. In this setup, evaporated gold flow and ion beam flux are perpendicular. 5 and 10 nm thick gold were deposited on tilted samples with the assistance of an argon ion beam at energies of 70 and 150 eV. We explored the evolution of surface morphology, mainly roughness and porosity, with ion bombardment for two gold thicknesses. We have also extrapolated Young’s modulus of these ultrathin layers by means of high-frequency acoustic measurements in the 90–260 MHz range. We also investigated the evolution of wettability of our structures with ion bombardment as well as their electrical and optical responses.
The application of acoustics to heat engines and refrigerators
Authors: Garrett Steven
Published: September 2022

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.
Shallow-water waveguide acoustic analysis in a fluctuating environment
Authors: Pinson Samuel , Quilfen Victor , Le Courtois Florent , Real Gaultier , Fattaccioli Dominique
Published: September 2022

The Acoustic Laboratory for Marine Applications (ALMA) is a deployable and autonomous acoustic system, designed by DGA Naval Systems, to address problems in underwater acoustics, such as sound propagation in fluctuating environments. In this article, data from the ALMA-2016 at-sea campaign are used to analyze the ocean fluctuation's influence on sound propagation in a shallow-water waveguide. The experiment took place on the continental shelf of the island of Corsica in November 2016. A source and a receiver array were 9.3 km apart in a nearly constant water depth of 100 m. The source emitted a variety of signals from which the chirp (1–13 kHz) is used to extract the waveguide eigenrays. To do so, a time-domain beamforming is performed on the match-filtered received signals with an automatic detection of local maxima in the time of arrival/direction of arrival (TOA/DOA) domain. A 2 min acquisition period of more than 13 h duration shows significant fluctuations in eigenray TOAs/DOAs. Qualitative comparisons with synthetic signals obtained from simulations in two and three dimensions permit reproduction of the observed eigenray fluctuations without including range dependence of the sound-speed profile.
An experimental investigation into a dual taper acoustic black hole termination
Authors: Hook K. , Cheer J. , Karlos A.
Published: September 2022

Acoustic black holes (ABHs) can provide effective damping of the reflected wave component when used to terminate a beam. The behaviour of an ABH is characterised by its local modes, which produce narrow frequency bands of high absorption. To enhance the performance of ABH terminations, a multi-taper ABH has previously been proposed and analytical results demonstrate that the use of two or more tapers produces a compound effect on the reflection coefficient, resulting in more bands of low reflection. This paper extends this work and presents an experimental realisation of a multi-taper ABH confirming the previous analytical results.
Association of Proximal and Distal Factors With Lower Limb Kinematics During a Classical Ballet Jump
Authors: Cabral Anelise Moreti , Martinez Adalberto Felipe , Leme Vitor , Luz Bruna Calazans , Serrão Fábio Viadanna
Published: September 2022

Context: Excessive dynamic lower limb misalignment may predispose ballet dancers to jump-related injuries. However, it is unknown whether proximal and distal factors influence this movement pattern. The aim of this study was to investigate whether hip abduction strength, foot alignment, and ankle dorsiflexion range of motion (ROM) are associated with peak angles of hip adduction and internal rotation and knee abduction during the preparation and landing phases of a classical ballet jump. Design: Cross-sectional study. Methods: Forty-one healthy amateur ballet dancers were included. Hip abduction strength was evaluated isometrically using a handheld dynamometer, foot alignment was determined by the shank-forefoot alignment, and weight-bearing ankle dorsiflexion ROM was measured by performing the lunge test. Peak hip and knee angles were analyzed 3-dimensionally during the preparation and landing phases of a single-leg jump. A Pearson correlation matrix was used to investigate the association of hip abduction strength, shank-forefoot alignment, and ankle dorsiflexion ROM with peak angles of hip adduction and internal rotation and knee abduction during the preparation and landing phases of the jump. Results: Greater hip abduction strength was associated with greater peak hip internal rotation angle (r = .43, P < .05), but not with peak hip adduction and knee abduction angles during the preparation phase of the jump. There were no associations of shank-forefoot alignment and ankle dorsiflexion ROM with peak hip and knee angles during the preparation (r = −.23 to .36, P > .05) and landing (r = −.20 to .24, P > .05) phases of the jump. There was no association of hip abduction strength with peak hip and knee angles during the landing phase of the jump (r = −.28 to .16, P > .05). Conclusion: Hip abductors strengthening, correction of foot misalignments, and increasing ankle dorsiflexion ROM may not prevent excessive hip and knee movements during a classical ballet single-leg jump in amateur dancers.
What Kind of Interpersonal Need-Supportive or Need-Thwarting Teaching Style Is More Associated With Positive Consequences in Physical Education?
Authors: Leo Francisco M. , Behzadnia Behzad , López-Gajardo Miguel A. , Batista Marco , Pulido Juan J.
Published: September 2022

Purpose: Based on a multilevel approach (individual and class level), this study aimed to test which need-supportive/thwarting teaching styles were more closely associated with students’ motivation and other positive physical education (PE) out-of-school consequences. Method: Participants were 654 primary (n = 385) and secondary (n = 269) PE students (Mage = 11.96 ± 1.95; boys = 317 and girls = 337). Results: The three need-supportive teaching behaviors were related to autonomous motivation, PE importance and usefulness, and the intentions to practice physical activity at the individual level; the role of competence support at both individual and class levels is highlighted. Competence-thwarting style was also negatively related to autonomous motivation at both levels, and jointly to relatedness-thwarting behaviors positively to a motivation at the individual level. Conclusion: Our results provide insight into how the specific type of interpersonal styles adopted by teachers can be decisive to achieve positive PE outcomes in and out of school.
3D-printing nanocrystals with light
Authors: Pan Jia-Ahn , Talapin Dmitri V.
Published: September 2022

Nanocrystals are connected to form complex 3D structures by means of two-photon lithography
Strongly Bactericidal All-Oral β-Lactam Combinations for the Treatment of Mycobacterium abscessus Lung Disease
Authors: Negatu Dereje A. , Zimmerman Matthew D. , Dartois Véronique , Dick Thomas
Published: September 2022

Bioactive forms of oral β-lactams were screened
in vitro
against
Mycobacterium abscessus
with and without the bioactive form of the oral β-lactamase inhibitor avibactam ARX1796. Sulopenem was equally active without avibactam, while tebipenem, cefuroxime, and amoxicillin required avibactam for optimal activity.
A Multiscale Spatiotemporal Model Including a Switch from Aerobic to Anaerobic Metabolism Reproduces Succession in the Early Infant Gut Microbiota
Authors: Versluis David M. , Schoemaker Ruud , Looijesteijn Ellen , Muysken Daniël , Jeurink Prescilla V. , Paques Marcel , Geurts Jan M. W. , Merks Roeland M. H.
Published: September 2022

The composition of the infant microbiota has a great impact on infant health, but its controlling factors are still incompletely understood. The frequently dominant anaerobic
Bifidobacterium
species benefit health, e.g., they can keep harmful competitors under control and modulate the intestinal immune response.
Control of myopia using diffusion optics spectacle lenses: 12-month results of a randomised controlled, efficacy and safety study (CYPRESS)
Authors: Rappon Joe , Chung Carol , Young Graeme , Hunt Christopher , Neitz Jay , Neitz Maureen , Chalberg Thomas
Published: September 2022

Background

Mutations in the L/M cone opsin gene array cause abnormally high perceived retinal contrast and the development of myopia. Environmental factors may also lead to high visual contrast and cause myopia. Diffusion optics technology (DOT) lenses are designed to reduce contrast signalling in the retina and slow myopia progression.

Methods

TheControl of Myopia UsingPeripheral Diffusion LensesEfficacy andSafetyStudy (CYPRESS,NCT03623074) is a 36-month, multicentre, randomised, controlled, double-masked trial evaluating two investigational spectacle lenses versus control lenses in myopic children aged 6–10, with a planned interim analysis at 12 months. The primary endpoints are change from baseline in axial length (AL) and spherical equivalent refraction (SER).

Results

256 children (58% female; mean age at screening, 8.1 years) were dispensed spectacles. Across all groups, baseline averages were AL 24.02 mm (SD±0.77 mm), SER −2.01 D (SD±0.9 D) using manifest refraction, and SER −1.94 D (SD±1.0 D) using cycloplegic autorefraction. At 12 months, mean difference in SER progression for test 1 versus control was −0.40 D (p<0.0001), representing a 74% reduction and −0.32 D for Test 2 (p<0.0001), representing a 59% reduction. The difference in AL progression for test 1 versus control was 0.15 mm (p<0.0001) and test 2 versus control was 0.10 mm (p=0.0018).

Conclusion

12-month results from this ongoing trial demonstrate the safety and effectiveness of DOT spectacles for reducing myopic progression.
Heteromeric formation with βA3 protects the low thermal stability of βB1-L116P
Authors: Xu Jingjie , Zhang Ying , Liu Jian , Hu Lidan , Luo Chenqi , Yao Ke , Chen Xiangjun
Published: September 2022

Background/aims

Congenital cataract is the leading cause of visual disability and blindness in childhood. βB1-crystallin (CRYBB1) comprises about 1/10th of crystallin structural proteins, forming heteromers to maintain lens transparency. We previously reported a CRYBB1 mutation (c.347T>C, p.L116P) affecting 16 patients in a congenital nuclear cataract family. In this study, we investigate the underlying pathogenic mechanism of βB1-L116P.

Methods

Protein isolation, size-exclusion chromatography, spectroscopy, Uncle stability screens and molecular dynamics simulations were used to assess βA3- and βB1-crystallin thermal stability, structural properties and heteromer formation.

Results

Cells that overexpressed βB1-L116P tended to form aggregates and precipitations under heat-shock stress. Thermal denaturation and time-dependent turbidity experiments showed that thermal stability was significantly impaired. Moreover, protein instability appeared to increase with elevated concentrations detected by the Uncle system. Additionally, βA3 had a relative protective effect on βB1-L116P after heteromers were formed, although βA3 was relatively unstable and was usually protected by basic β-crystallins. Molecular dynamic simulations revealed that L116P mutation altered the hydrophobic residues at the surface around the mutant site, providing solvents more access to the internal and hydrophobic parts of the protein.

Conclusions

Decreased βB1-crystallin thermal stability in the presence of the cataract-related L116P mutation contributes significantly to congenital cataract formation. Moreover, its formation of heteromers with βA3 protects against the low thermal stability of βB1-L116P.
Effect of age, sex, and morbidity count on trial attrition: meta-analysis of individual participant level data from phase 3/4 industry funded clinical trials
Authors: Lees Jennifer S , Hanlon Peter , Butterly Elaine W , Wild Sarah H , Mair Frances S , Taylor Rod S , Guthrie Bruce , Gillies Katie , Dias Sofia , Welton Nicky J , McAllister David A
Published: September 2022

Objectives

To estimate the association between individual participant characteristics and attrition from randomised controlled trials.

Design

Meta-analysis of individual participant level data (IPD).

Data sources

Clinical trial repositories (Clinical Study Data Request and Yale University Open Data Access).

Eligibility criteria for selecting studies

Eligible phase 3 or 4 trials identified according to prespecified criteria (PROSPERO CRD42018048202).

Main outcome measures

Association between comorbidity count (identified using medical history or concomitant drug treatment data) and trial attrition (failure for any reason to complete the final trial visit), estimated in logistic regression models and adjusted for age and sex. Estimates were meta-analysed in bayesian linear models, with partial pooling across index conditions and drug classes.

Results

In 92 trials across 20 index conditions and 17 drug classes, the mean comorbidity count ranged from 0.3 to 2.7. Neither age nor sex was clearly associated with attrition (odds ratio 1.04, 95% credible interval 0.98 to 1.11; and 0.99, 0.93 to 1.05, respectively). However, comorbidity count was associated with trial attrition (odds ratio per additional comorbidity 1.11, 95% credible interval 1.07 to 1.14). No evidence of non-linearity (assessed via a second order polynomial) was seen in the association between comorbidity count and trial attrition, with minimal variation across drug classes and index conditions. At a trial level, an increase in participant comorbidity count has a minor impact on attrition: for a notional trial with high level of attrition in individuals without comorbidity, doubling the mean comorbidity count from 1 to 2 translates to an increase in trial attrition from 29% to 31%.

Conclusions

Increased comorbidity count, irrespective of age and sex, is associated with a modest increased odds of participant attrition. The benefit of increased generalisability of including participants with multimorbidity seems likely to outweigh the disadvantages of increased attrition.
SK2 channels set a signalling hub bolstering CAF-triggered tumourigenic processes in pancreatic cancer
Authors: Rapetti-Mauss Raphael , Nigri Jérémy , Berenguier Camille , Finetti Pascal , Tubiana Sarah Simha , Labrum Bonnie , Allegrini Benoit , Pellissier Bernard , Efthymiou Georgios , Hussain Zainab , Bousquet Corinne , Dusetti Nelson , Bertucci François , Guizouarn Hélène , Melnyk Patricia , Borgese Franck , Tomasini Richard , Soriani Olivier
Published: September 2022

Objective

Intercellular communication within pancreatic ductal adenocarcinoma (PDAC) dramatically contributes to metastatic processes. The underlying mechanisms are poorly understood, resulting in a lack of targeted therapy to counteract stromal-induced cancer cell aggressiveness. Here, we investigated whether ion channels, which remain understudied in cancer biology, contribute to intercellular communication in PDAC.

Design

We evaluated the effects of conditioned media from patient-derived cancer-associated fibroblasts (CAFs) on electrical features of pancreatic cancer cells (PCC). The molecular mechanisms were deciphered using a combination of electrophysiology, bioinformatics, molecular and biochemistry techniques in cell lines and human samples. An orthotropic mouse model where CAF and PCC were co-injected was used to evaluate tumour growth and metastasis dissemination. Pharmacological studies were carried out in the Pdx1-Cre, Ink4afl/flLSL-KrasG12D(KICpdx1) mouse model.

Results

We report that the K+channel SK2 expressed in PCC is stimulated by CAF-secreted cues (8.84 vs 2.49 pA/pF) promoting the phosphorylation of the channel through an integrin–epidermal growth factor receptor (EGFR)–AKT (Protein kinase B) axis. SK2 stimulation sets a positive feedback on the signalling pathway, increasing invasiveness in vitro (threefold) and metastasis formation in vivo. The CAF-dependent formation of the signalling hub associating SK2 and AKT requires the sigma-1 receptor chaperone. The pharmacological targeting of Sig-1R abolished CAF-induced activation of SK2, reduced tumour progression and extended the overall survival in mice (11.7 weeks vs 9.5 weeks).

Conclusion

We establish a new paradigm in which an ion channel shifts the activation level of a signalling pathway in response to stromal cues, opening a new therapeutic window targeting the formation of ion channel-dependent signalling hubs.
Genomic landscape of colorectal carcinoma in sub-Saharan Africa
Authors: Aldera Alessandro Pietro , Pillay Komala , Robertson Barbara , Boutall Adam , Ramesar Rajkumar
Published: September 2022

Our understanding of the molecular classification of colorectal carcinoma (CRC) has evolved significantly over the past two decades. Tumours can be broadly categorised as microsatellite stable (MSS), microsatellite instability (MSI) or CpG island-methylator phenotype. Prognostic and predictive information is provided by these categories. The overwhelming majority of the data on which these categories are based have originated from Europe and North America. There is a dearth of information represented from Africa and indigenous African patients. However, some small studies and preliminary data have shown significant differences in all of these groups. The prevalence of MSI in Africa is consistently reported as almost double that of European and North American data. Interestingly,BRAFV600E mutations andMLH1promotor hypermethylation seem to be uncommon in Africa. The high proportion of MSI tumours is only partly accounted for by germline mutations in mismatch repair genes (Lynch syndrome), suggesting that there are likely to be other mechanisms at play. Within the MSS group, preliminary data suggest that the typical molecular pathways (Wingless/Integrated pathway activation) may not be as dominant in Africa. The purpose of this review is to summarise the current state of the molecular genetic landscape of CRC in Africa and provide insights into areas for further study.
IL1R2 increases regulatory T cell population in the tumor microenvironment by enhancing MHC-II expression on cancer-associated fibroblasts
Authors: Chen Lujun , Huang Hao , Zheng Xiao , Li Yuan , Chen Junjun , Tan Bo , Liu Yingting , Sun Runzi , Xu Bin , Yang Min , Li Bin , Wu Changping , Lu Binfeng , Jiang Jingting
Published: September 2022

Background

Regulatory T cells (Treg) are an integral part of the tumor immune tolerance. Carcinoma-associated fibroblasts (CAFs) is a pivotal driver for accumulation of Treg cells in the tumor microenvironment (TME). The molecular nature underpinning Treg cells and CAFs coupling needs to be further defined.

Methods

The Il1r2flox/floxFoxp3Cremice were generated to establish the conditional knock-out ofIl1r2in Foxp3+Tregs in vivo. Using the MC38 tumor model, we evaluated the antitumor efficacy of immune checkpoint inhibitors (ICIs) and further analyzed the immune profiling of the TME by multicolor flow cytometry. Single-cell RNA sequencing of the whole tumor tissues, TCR repertoire analysis of sorted CD3+TILs were also performed.

Results

We showed that IL1 receptor 2 (IL1R2), a decoy receptor that neutralizes IL1, was highly expressed in Treg cells in the TME. In addition, we found thatIl1r1was largely expressed in the CAFs, suggesting IL1R2 plays a role in modulating crosstalk between Tregs and CAFs. We further demonstrated thatIl1r2deficiency in Treg cells led to greater antitumor efficacy of ICI, decreased Tregs and increased CD8+T cells in the TME, as well as reduced levels of T cell dysfunction. Mechanistically, we showed that IL1 inhibited major histocompatibility complex class II (MHC-II) expression on fibroblasts and Treg-specificIl1r2deletion led to a decrease in genes associated with MHC-II antigen presentation in CAFs.

Conclusions

Our study established a critical role of IL1 signaling in inhibiting Treg-mediated tumor immune suppression through downregulating MHC-II antigen presentation in CAFs.
Efficacy of pulse intravenous methylprednisolone in epileptic encephalopathy: a randomised controlled trial
Authors: Rangarajan Anush , Mundlamuri Ravindranadh Chowdary , Kenchaiah Raghavendra , Prathyusha Parthipulli Vasuki , Viswanathan Lakshminarayanapuram Gopal , Asranna Ajay , Chatterjee Aparajita , Nagappa Madhu , Seshagiri Doniparthi Venkata , Kulanthaivelu Karthik , Bharath Rose Dawn , Jitender Saini , Thennarasu Kandavel , Sinha Sanjib
Published: September 2022

Background

High-level evidence for using steroids in epileptic encephalopathy (EE), other than West syndrome (WS), is lacking. This study investigated the efficacy and safety of pulse intravenous methylprednisolone (IVMP) in EE other than WS.

Methods

This is an open-label evaluator-blinded randomised controlled study. Children aged 6 months or more with EE other than WS were included. Eighty children were randomised into intervention and non-intervention groups with 40 in each group. At the first visit (T1) seizure frequency, electroencephalographic (EEG) and Vineland Social Maturity Scale (VSMS) were obtained, and antiseizure medication (ASM) were optimised. After 1 month (T2), subjects were randomised to intervention (ASM+3 months IVMP pulse) or non-intervention group (only ASM) with 40 subjects in each group. They were followed up for 4 months (T3) and assessed.

Results

After 4 months of follow-up, 75% of patients receiving IVMP had >50% seizure reduction versus 15.4% in control group (χ2=28.29, p<0.001) (RR 4.88, 95% CI 2.29 to 10.40), median percentage change in seizure frequency (91.41% vs 10%, p<0.001), improvement in EEG (45.5% vs 9.4%, χ2=10.866, p=0.001) and social age domain of VSMS scores (Z=−3.62, p<0.001) compared with baseline. None of the patients in the intervention group had any serious side-effects.

Discussion

Three-month pulse IVMP therapy showed significant improvement in seizure frequency, EEG parameters and VSMS scores, with no steroid-related serious adverse effects. It can be considered as a safe and effective add on treatment in children with EE other than WS.

Trial registration number

CTRI/2019/02/017807.
Clinical and genetic analysis of familial neuromyelitis optica spectrum disorder in Chinese: associated with ubiquitin-specific peptidase USP18 gene variants
Authors: Chang Yanyu , Zhou Luyao , Zhong Xiaonan , Shi Ziyan , Sun Xiaobo , Wang Yuge , Li Rui , Long Youming , Zhou Hongyu , Quan Chao , Kermode Allan G , Yu Qingfen , Qiu Wei
Published: September 2022

Background

Familial clustering of neuromyelitis optica spectrum disorder (NMOSD) was present in Chinese. This study was to investigate the clinical characteristics and genetic background of familial NMOSD.

Methods

Through questionnaires in four medical centres in 2016–2020, we identified 10 families with NMOSD aggregation. The statistical differences of clinical characteristics between familial and sporadic NMOSD (22 cases and 459 cases) were summarised. The whole-exome sequencing (WES) for seven families (13 cases and 13 controls) was analysed, compared with our previous WES data for sporadic NMOSD (228 cases and 1 400 controls). The family-based and population-based association and linkage analysis were conducted to identify the pathogenetic genes, the variant impacts were predicted.

Results

The familial occurrence was 0.87% in Chinese. Familial patients had higher expanded disability status scale score than sporadic patients (p=0.03). The single-nucleotide polymorphism (SNP) rs2252257 in the promoter and enhancer of ubiquitin-specific peptidase USP18 was linked to familial NMOSD (p=7.8E-05, logarithm of the odds (LOD)=3.1), SNPs rs361553, rs2252257 and rs5746523 were related to sporadic NMOSD (p=1.29E-10, 3.45E-07 and 2.01E-09, respectively). Patients with the SNP rs361553 T/T genotype had higher recurrence rate than C/T or C/C genotype (1.22±0.85 vs 0.69±0.57 and 0.81±0.65, p=0.003 and 0.001, respectively). SNPs rs361553 and rs2252257 altered USP18 expression in brain and nerve tissues.

Conclusion

Most clinical characteristics of familial NMOSD were indistinguishable from sporadic NMOSD except for the worst episodes severity. USP18 with impaired intronic regulatory function contributed to the pathogenesis of NMOSD.
Endovascular treatment for acute ischaemic stroke due to medium vessel occlusion: data from ANGEL-ACT registry
Authors: Sun Dapeng , ­ Raynald , Huo Xiaochuan , Jia Baixue , Tong Xu , Wang Anxin , Ma Gaoting , Ma Ning , Gao Feng , Mo Dapeng , Miao Zhongrong
Published: September 2022

Objectives

To investigate the safety and efficacy of endovascular treatment (EVT) for acute medium vessel occlusion (MeVO) in the anterior circulation and to explore the independent predictors of the 90-day good outcome for such patients.

Methods

Data from ANGEL-ACT Registry were analysed in our study. The outcomes, such as the modified Rankin Scale (mRS) at 90 days, successful recanalisation rate and symptomatic intracranial haemorrhage (SICH) rate, were compared between MeVO and acute large vessel occlusions (LVO). Then, the independent predictors of the good outcome at 90 days in MeVO patients were determined by the logistic regression analyses.

Results

We included 1032 subjects in the analysis, of which, 147 were MeVO and 885 were LVO. mRS at 90 days distribution (3 (0–4) vs 3 (0–5), common odds ratio (OR) =1.00, 95% confidence interval (CI) 0.73 to 1.38, p=0.994), SICH rate (4.8% vs 8.9%; OR=0.59, 95% CI 0.26 to 1.34, p=0.205) and successful recanalisation rate (89.8% vs 89.7%; OR=1.00 95% CI 0.51 to 1.93, p=0.992) were similar between the MeVO and LVO groups after adjusting for the confounders. We identified that baseline neutrophil-to-lymphocyte ratio ≤4.1 (OR=2.13, 95% CI 1.14 to 3.99, p=0.019), baseline National Institutes of Health Stroke Scale ≤14 (OR=1.96, 95% CI 1.02 to 3.80, p=0.045) and mechanical thrombectomy passes ≤1 (OR=2.16, 95% CI 1.14 to 4.11, p=0.021) were independent predictors of the 90-day good outcome in MeVO patients undergoing EVT.

Conclusions

Patients with MeVO achieved similar 90-day mRS, SICH rate and successful recanalisation rate after EVT compared with patients with LVO. Several independent predictors of 90-day good outcome in MeVO patients undergoing EVT were determined, which should be highly considered in MeVO stroke management.
Regioselectivity in Wacker oxidations of internal alkenes: antiperiplanar effects?
Authors: Usama W.O. , Markewich D.J. , East A.L.L.
Published: September 2022

Computational chemistry, with considerable effort, was used to elucidate the reason for regioselectivity (12:1 distal:proximal product distribution) in a published Wacker oxidation of internal alkenes with a homoallylic lactam ring. Such a distribution is reproduced by a non-chelating reaction pathway; chelated intermediates are found to be too high in energy. Despite much speculation of chelation effects in the literature, this particular result is most probably an antiperiplanar field effect with no chelation. Partial charge data are provided to support the proposed antiperiplanar effect. The great care needed in modelling Wacker oxidations is emphasized, but optimism is offered that its various product mysteries can be elucidated on a case-by-case basis.
Thermodynamics of the Reissner–Nordström-de Sitter spacetime with quintessence
Authors: Zhang Yang , Ma Yu-Bo , Du Yun-Zhi , Li Huai-Fan , Zhang Li-Chun
Published: September 2022

For Anti-de Sitte (AdS) black holes, the isochoric heat capacity of system is vanished, while the isobaric heat capacity is not. However, this situation does not hold on for de Sitter (dS) black holes. In this work, by introducing the interaction between the black hole horizon and the cosmological horizon of the Reissner–Nordström-de Sitter (RNdS) spacetime with quintessence, we discuss the phase transition of this system. The results show that the spacetime not only has the similar phase transition behavior to that of Van der Waals (VdW) system, and the non-vanishing isochoric heat capacity fulfills the whole thermodynamics system. Through the discussion of the entropic force between two horizons, we find out the role of entropic force in the evolution of spacetime. In addition, we also study the influence of various parameters on the phase transition and entropic force, which will provide a new method for exploring the interaction among black hole molecules from a micro perspective.
Analyses of Past Extremes Precipitation–Evapotranspiration Indices Over Sub-Saharan Countries
Authors: Mbaye Mamadou Lamine , Bodian Amy , Kimambo Offoro Neema , Rouamba Fabienne Inès , Gaveta Elias
Published: September 2022

Extreme weather and climate events including extreme precipitation have increased in frequency, intensity, and severity due to climate change and hit vulnerable communities disproportionately hard. However, there is a gap in the understanding of the characteristics of extreme precipitation and their effects on socio-economic activities in sub-Saharan Africa societies. The study utilized climate hazards group infrared precipitation with station data (CHIRPS) to analyze the climate characteristics from 1981 to 2019 over Senegal, Burkina Faso, Tanzania, and Malawi. Standardized precipitation evapotranspiration index (SPEI) and standardized precipitation index (SPI) were used to classify the precipitation and water balance anomalies with respect to the long-term observations. It was found that Burkina Faso and Senegal have a similar climate signal with more rainfall in Burkina Faso. Malawi recorded more rainfall than Tanzania. All the four countries recorded a high rainfall variability of extreme events. Standardized hydro climatic indices have shown that these sub-Saharan countries have suffered severe droughts which have negatively affected the socio-economic activities among the rural populations.