bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of inclusive language in the Spanish of the Southeast
Authors: Michnowicz Jim , Ronquest Rebecca , Armbrister Bailey , Chisholm Nick , Green Rebecca , Bull Lindsey , Elkins Anne
Published: June 2023

This study examines the perceptions of inclusive language among first- and second-generation Spanish speakers residing in North Carolina, USA, based on survey data collected from 337 speakers by undergraduates. The survey examines familiarity with innovative inclusive language forms (including -@, -x, and -e), as well as opinions about different forms (including standard morphology forms such as masculine default and noun doubling – i.e., chicos y chicas), and reported use of inclusive forms. A majority of participants expressed negative opinions of innovative forms, and very few reported actually using them in their speech. Acceptance varied based not only on participant social characteristics, but also on the morphology and the context in which the form is used. Exceptions to these trends, as well as the possible future development of inclusive language forms, receive additional attention. Research methodologies with undergraduates are also discussed.
The impact of traditional and interactive post-editing on Machine Translation User Experience, quality, and productivity
Authors: Briva-Iglesias Vicent , O’Brien Sharon , Cowan Benjamin R.
Published: June 2023

This paper presents a user study with 15 professional translators in the English-Spanish combination. We present the concept of Machine Translation User Experience (MTUX) and compare the effects of traditional post-editing (TPE) and interactive post-editing (IPE) on MTUX, translation quality and productivity. Results suggest that translators prefer IPE to TPE because they are in control of the interaction in this new form of translator-computer interaction and feel more empowered in their interaction with Machine Translation. Productivity results also suggest that IPE may be an interesting alternative to TPE, given the fact that translators worked faster in IPE even though they had no experience in this new machine translation post-editing modality, but were already used to TPE.
Giant oral ulcers of Behçet's disease mimicking squamous cell carcinoma
Authors: Mansur AT , Kocaayan N , Serdar ZA , Alptekin F.
Published: June 2023

No abstract available
Treatment of protein contact dermatitis with topical tacrolimus
Authors: Mercader P , De La , Rodríguez-Serna M , Pitarch-Bort G , Fortea-Baixauli JM.
Published: June 2023

No abstract available
Oral challenge in patients with suspected cutaneous adverse drug reactions: findings in 784 patients during a 25-year-period
Authors: Lammintausta K , Kortekangas-Savolainen O.
Published: June 2023

The aim of this study was to analyse the usefulness of oral challenge test with different drugs in confirming cutaneous adverse drug reactions in routine clinical practice. During the years 1975-2000 a total of 1,001 challenges were carried out in 784 patients. Patients with serious drug reactions were excluded and those with positive skin test reactions were challenged only in dubious cases. Of 1,001 challenges, 136 (13%) patients developed a positive challenge reaction. Antimicrobial drugs were most commonly suspected, accounting for 67% of challenges and 66% of the positive reactions. Exanthema was the most common skin reaction (72%), followed by fixed drug eruption (16%) and urticaria (12%). One serious challenge reaction with salazosulfapyridine was seen. We conclude that the challenge test is most useful as a tolerance test or to exclude drug hypersensitivity. It may be useful to complete studies of adverse drug reactions in patients with a history of exanthema, if other diagnostic methods are not available or if other diagnostic tests yield negative results. Out-patient protocol can be used in most cases.
Photodynamic therapy for non-melanoma skin cancer
Authors: Szeimies RM , Morton CA , Sidoroff A , Braathen LR.
Published: June 2023

Photodynamic therapy is a treatment modality that has been shown to be effective mainly for the dermato-oncologic conditions: actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and basal cell carcinoma. Recent work has focused on the development and evaluation of topical photosensitizers like the haem precursor 5-aminolevulinic acid or its methyl ester, both inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization, unlike the systemically applied porphyrins or their derivatives. For dermatological purposes incoherent lamps or light-emitting diode arrays can be used for light activation. Cure rates reported for very superficial lesions (tumour thickness
Analysis of the virtual cathode and floating potential of a thermionic emissive probe operating in the space-charge-limited regime
Authors: Morales Crespo R , Muñoz-Serrano E , Tejero-del-Caz A
Published: June 2023

This paper analyses by this and characterizes a thermionic emissive probe operating in both the temperature-limited current regime (T-region) and the space-charge-limited current regime (S-region) characterized by the formation of a virtual cathode. For this last case, we obtain the potential profile, the emitted current that overcomes the virtual cathode, as well as the thickness and depth of the potential well in front of the probe for different probe temperatures, plasma electron temperatures and neutral gas pressures. From these results, we obtain the I–V curves and the floating potential. Depending on the probe radius, when the floating potential is reached in the S-region, its value saturates, becoming almost independent of the probe temperature and the electron temperature.
Analytical modeling and doping optimization for enhanced analog performance in a Ge/Si interfaced nanowire MOSFET
Authors: Das Amit , Rewari Sonam , Kanaujia Binod Kumar , Deswal S S , Gupta R S
Published: June 2023

This paper critically investigates the effect of doping on different device characteristics of a Ge/Si interfaced nanowire MOSFET (GSI-NWM) for analog performance enhancement. The doping of source, channel, and drain has a prominent effect on important device characteristics, which has been investigated through DC and AC analysis performed on the SILVACO TCAD simulator. A numerical computational-based simulation study has been used to investigate the modulation of various device characteristics, such as threshold voltage, cut-off frequency, subthreshold swing, MTPG, current ratio, channel resistance, and transconductance. The investigation revealed a strong dependence of most of these characteristics on the source, channel, and drain doping levels, providing valuable insights into device performance. Proper optimization in doping can significantly improve the performance of the device. A compact physics-based analytical model has been mathematically evaluated and proposed in this work, showing an excellent in-line agreement with the simulated results. This is a novel approach for improving the analog performance parameters of a nanowire MOSFET through doping optimization, which incorporates gate oxide stacking and germanium as a source material. In this work, the biosensing capability of the GSI-NWM has also been discussed and evaluated.
Sol-Gel growth of zinc oxide particles on graphene sheets for mode-locking in Thulium/Holmium-doped fiber laser
Authors: Ahmad Harith , Loganathan Kirubhashni , Yusoff Norazriena
Published: June 2023

This work used Graphene/Zinc Oxide (G/ZnO) nanocomposite to generate mode-locked pulses in Thulium/Holmium-doped fiber (THDF). The sol-gel method was used to synthesize the ZnO particles decorated graphene sheets. The G/ZnO nanocomposite solution was deposited onto the arc-shaped fiber that had been fabricated to act as the saturable absorber (SA) device. The nonlinear optical response of G/ZnO-based SA was investigated via the twin detection approach, in which it exhibits a modulation depth of 14.11% and a saturation intensity of 4.23 MW cm−2. After incorporating the fabricated SA into the THDF laser cavity, mode-locked pulses were produced at a threshold pump power of 274.3 mW with a center wavelength of 1895.11 nm, fundamental frequency of 11.82 MHz, and a pulse duration of 1.7 ps. The maximum average output power and single pulse energy were determined to be 1.39 mW and 117 pJ, respectively. The mode-locked pulses generated were exceptionally stable, giving a signal-to-noise ratio (SNR) of 58.2 dB. According to the findings of the current research, it is anticipated that the G/ZnO-arc-shaped fiber-based SA has the potential to produce stable mode-locked lasers in the 2.0 μm region.
Few-body model approach to the lowest bound S-state of non-symmetric exotic atoms and ions
Authors: Khan Md Abdul , Hasan Mahamadun
Published: June 2023

Lowest bound S-state energy of Coulombic three-body systems (N

Z+
μ
−
e
−) consisting of a positively charged nucleus of charge number Z (N

Z+), a negatively charged muon (μ
−) and an electron (e
−), is investigated in the framework of few-body (i.e., two- and three-body) cluster model approach. For the three-body cluster model, we adopted the hyperspherical harmonics expansion (HHE) method. An approximated two-body model calculation is also performed for all the three-body systems considered here. A Yukawa-type screened Coulomb potential with an arbitrary screening parameter (λ) is chosen for the two-body subsystems of the three-body system. In the resulting Schrödinger equation (SE), the three-body relative wave function is expanded in the complete set of hyperspherical harmonics (HH). The use of the orthonormality of HH in the SE leads to a set of coupled differential equations (CDEs) which are solved numerically for a manageable basis size to get the energy (E). The pattern of convergence in energy relative to increasing basis size is also investigated. Results are compared with some of those found in the literature.
Multi-channel terahertz focused beam generator based on shared-aperture metasurface
Authors: Li 李 Jiu-Sheng 九生 , Chen 陈 Yi 翊
Published: June 2023

Most of existing metasurfaces usually have limited channel behavior, which seriouslyhinders their development and application. In this paper, we propose a multi-channel terahertz focused beam generator based on shared-aperture metasurface, and the generator consists of a top square metal strip, a middle layer of silica and a metal bottom plate. By changing the position and size of the shared-aperture array, the designed metasurface can generate any number of multi-channel focusing beams at different predicted positions. In addition, the energy intensity of focusing beams can be controlled. The full-wave simulation results show that the metasurface achieves four-channel vortex focused beam generation with different topological charges, and five-, six-, eight-channel focused beam generation with different energy intensities at a frequency of 1 THz, which are in good agreement with the theoretically calculated predictions. This work can provide a new idea for designing the terahertz multichannel devices.
Strange quark mass (m

s
) dependent model of anisotropic strange quark star*
Authors: Hakim A. , Goswami K.B. , Chattopadhyay P.K.
Published: June 2023

This article presents the configuration of strange quark stars in hydrostatic equilibrium considering the Vaidya-Tikekar metric ansatz. The interior of such stars comprises strange quark matter (henceforth SQM), whose equation of state (

) is described by the MIT EoS

, where B is the difference between perturbative and non-perturbative vacuum. We have included the mass of the strange quark

into the EoS and studied its effect on the overall properties of the strange quark star in this work. It is observed that the maximum mass reaches its highest value when

. We have evaluated the range of the maximum mass of the strange quark star by solving the TOV equation for

necessary for stable strange quark matter at a zero external pressure condition with respect to neutrons. Maximum mass lies within the range of

to

when B ranges from

to

and

. It is noted that the maximum mass decreases with an increase in

. Our model is found suitable for describing the mass of pulsars such as PSR J1614-2230 and Vela X-1 and the secondary objects in the GW170817 event. The model is also useful in predicting the radius of the recently observed pulsars PSR J0030+0451, PSR J0740+6620, and PSR J0952-0607 and the secondary objects in the GW170817 and GW190814 events. Our model is found to be stable with respect to all stability criteria of the stellar configurations and is also stable with respect to small perturbations.
Effect of urbanization on gust wind speed in summer over an urban area in Eastern China
Authors: Liu Gang , Wang Xueyuan , Wu Qigang , Fang Dexian , Wu Zheng , Liu Hongnian , Lyu Mengyao
Published: June 2023

Previous studies have extensively examined effects of urbanization on mean wind speed, but few studies were aimed at gust wind speed, while large wind gust could cause safety and economic hazard to a variety of activities. In this study, the effect of urbanization on the gust wind speed in Nanjing, China is assessed using the Weather Research and Forecasting (WRF) model with a parameterization of the gust wind speed. The WRF simulations are run for the summer period of 2013 with the underlying surface before and after the urbanization. The results indicate that although the mean wind speed is reduced, the gust wind speed in the urban areas is increased significantly due to the enhanced friction velocity and less atmospheric stability induced by the urbanization, while the contribution of deep convection is relatively small. The gust wind speed increases more in the nighttime (0.6–0.9 m s−1) than in the daytime (less than 0.3 m s−1), since the turbulence is enhanced more in the nighttime than in the daytime after the urbanization. The probability distribution shows that the increase of gust wind speed is mainly between 0.0–0.5 m s−1 in the urban areas. In different urban land categories, the increase of the gust wind speed is larger in the commercial or industrial areas than in high-intensity and low-intensity residential urban areas. Averagely, the gust wind speed in the entire city after the urbanization increases by 0.02, 0.36 and 0.19 m s−1 for the daytime, nighttime and daily mean, respectively.
All-laser route for anti-fouling superhydrophobic albronze fabrication and non-contact microbial detection
Authors: Fan Lisha , Zhao Tianzhen , Qian Qiangqiang , Zhu Yuying , Wu Guolong , Wu Huaping , Guo Lianbo , Yao Jianhua
Published: June 2023

Biofouling leading to clog is one of the severe issues underwater valve components are facing today. Establishing a superhydrophobic barrier against microorganisms for underwater albronze components is hence of great significance. We demonstrate an all-laser route for superhydrophobic albronze surface fabrication and non-contact microbial diagnostics. Laser-textured albronze surfaces with well-defined periodic valleys and crests exhibit excellent superhydrophobicity with a contact angle up to 151 ± 1° and a contact angle hysteresis of 0.9 ± 0.1°, more than twice that of an original albronze surface (66 ± 2°). The theoretical wettability diagram of water droplets on laser-textured albronze surfaces shows that the surface wettability transits from hydrophilicity towards hydrophobicity as the surface undulation level elevated, matching well with the experimental observation. According to surface chemistry analysis, carbonyl groups on the albronze surfaces are extensively eliminated by laser texturing and vacuum heating treatment, which contributes to the wettability transformation. The anti-fouling performance of the laser-textured albronze surfaces was comparatively studied in chalk ash aqueous solution, starch solution, and microbial suspension, respectively. Laser-induced breakdown spectroscopy was applied for non-contact microbial diagnostics. Greatly enhanced resistance to biofouling on laser-textured albronze surfaces was confirmed. An all-laser route for anti-fouling superhydrophobic albronze surface fabrication and non-contact microbial diagnostics show great promise for next-generation underwater equipment upgrade and on-site monitoring.
Effect of environmental screening and strain on optoelectronic properties of two-dimensional quantum defects
Authors: Zhang Shimin , Li Kejun , Guo Chunhao , Ping Yuan
Published: June 2023

Point defects in hexagonal boron nitride (hBN) are promising candidates as single-photon emitters (SPEs) in nanophotonics and quantum information applications. The precise control of SPEs requires in-depth understanding of their optoelectronic properties. However, how the surrounding environment of host materials, including the number of layers, substrates, and strain, influences SPEs has not been fully understood. In this work, we study the dielectric screening effect due to the number of layers and substrates, and the strain effect on the optical properties of carbon dimer and nitrogen vacancy defects in hBN from first-principles many-body perturbation theory. We report that environmental screening causes a lowering of the quasiparticle gap and exciton binding energy, leading to nearly constant optical excitation energy and exciton radiative lifetime. We explain the results with an analytical model starting from the Bethe–Salpeter equation Hamiltonian with Wannier basis. We also show that optical properties of quantum defects are largely tunable by strain with highly anisotropic response, in good agreement with experimental measurements. Our work clarifies the effect of environmental screening and strain on optoelectronic properties of quantum defects in two-dimensional insulators, facilitating future applications of SPEs and spin qubits in low-dimensional systems.
Room-temperature degradation of o-xylene in simulated air using an online-regenerable plasma-catalysis reactor with low amounts of nanosized noble metals on Co3O4
Authors: DI Shucheng , XU Jiacheng , YAO Shuiliang , LI Jing , WU Zuliang , GAO Erhao , ZHU Jiali , DAI Lianxin , LIU Weihua , ZHANG Buhe , ZHANG Junwei
Published: June 2023

The plasma catalytic degradation of o-xylene in simulated air was improved by loading low amounts of Pt, Pd, or Au onto Co3O4. At room temperature, o-xylene conversion and CO
x
selectivity using a 0.1 wt% Pt/Co3O4 catalyst reached 98.9% and 80%, and the energy efficiency was at the top level in comparison with values in the literature. A stable o-xylene degradation performance could be obtained by online regenerating the heat-insulated reactor with a high energy density. After characterization, it was found that the loading of nanosized Pt not only increased the Co3+/Co2+ ratio, where the Co3+ benefitted the formation of reactive oxygen species, but also conduced Pt0 to oxygen activation, resulting in effective promotion of complete o-xylene oxidation. Operando plasma diffuse reflectance infrared Fourier transform spectroscopy demonstrated the complete o-xylene oxidation and proved that Pt played a key role in the complete oxidation of o-xylene.
Effect of different process conditions on the physicochemical and antimicrobial properties of plasma-activated water
Authors: CAI Zhicheng , WANG Jiamei , WANG Yuanyuan , SANG Xiaohan , ZENG Lixian , DENG Wentao , ZHANG Jianhao
Published: June 2023

The physicochemical properties of plasma-activated water (PAW) generated under different process conditions were investigated, and their changes under different storage conditions were also studied. The results showed that increasing the processing time and power, and decreasing generated water volume, could cause an increase in the redox potential, conductivity, and temperature of PAW, and a decrease in its pH. A slower dissipation of the reactive oxygen and nitrogen species in PAW was found on storage at 4 °C in a sealed conical flask than on storage at room temperature. The inactivation ability of plasma-activated lactic acid (LA) to Listeria monocytogenes (L. monocytogenes) and Pseudomonas aeruginosa (P. aeruginosa) was higher than that of PAW or LA alone under the same experimental conditions. The results of this study may provide theoretical information for the application of PAW as a potential antimicrobial agent in the future.
A new global coupled atmosphere-ocean wavenumber-4 pattern in Southern mid–latitudes during austral summer and its climate linkage
Authors: Yu Lejiang , Zhong Shiyuan , Sui Cuijuan , Sun Bo
Published: June 2023

A new pattern referred to as the coupled ocean-atmosphere wavenumber-4 (COAW4) pattern has been identified in the Southern mid-latitudes during austral summer. This pattern consists of a wavenumber-4 pattern in the anomalous 200-hPa meridional wind and a wavenumber-4 pattern of the anomalous sea surface temperature (SST). The SST component of the COAW4 pattern, which includes the Indian Ocean Subtropical Dipole (IOSD), the South Atlantic Subtropical Dipole (SASD) and the South Pacific Subtropical Dipole (SPSD), develops through air-sea interactions involving surface turbulent heat flux, surface wind, and ocean mixed-layer depth. The atmospheric component displays a barotropic structure. The sources for COAW4 pattern include not only the wavenumber-4 pattern of the anomalous SST over Southern oceans, but also the anomalous convective activities over Southern land areas. The COAW4 pattern is associated with increased precipitation over land in southern mid-latitudes, particularly in central Australia. Furthermore, the COAW4 pattern is linked to Antarctic sea ice cover in the Weddell, Amundsen, and northern Ross Seas. Plain language summary In the southern mid-latitudes, there exists a wavenumber 4 pattern in the anomalous 200-hPa meridional wind and a wavenumber-4 pattern of the anomalous sea surface temperature (SST). Previous studies have examined the two wavenumber-4 patterns separately, but their potential linkage remains largely unknown. Through statistical analyses of SST and atmospheric global data, we demonstrated that the two wavenumber 4 patterns could be integrated into a coupled ocean-atmosphere wavenumber-4 (COAW4) pattern in Southern mid-latitudes in austral summer. Additionally, we have investigated the sources of this pattern as well as its effect on precipitation over southern lands and on Antarctic sea ice.
Advances in 3D printing scaffolds for peripheral nerve and spinal cord injury repair
Authors: Song Juqing , Lv Baiheng , Chen Wencong , Ding Peng , He Yong
Published: June 2023

Because of the complex nerve anatomy and limited regeneration ability of natural tissue, the current treatment effect for long-distance peripheral nerve regeneration and spinal cord injury (SCI) repair is not satisfactory. As an alternative method, tissue engineering is a promising method to regenerate peripheral nerve and spinal cord, and can provide structures and functions similar to natural tissues through scaffold materials and seed cells. Recently, the rapid development of 3D printing technology enables researchers to create novel 3D constructs with sophisticated structures and diverse functions to achieve high bionics of structures and functions. In this review, we first outlined the anatomy of peripheral nerve and spinal cord, as well as the current treatment strategies for the peripheral nerve injury and SCI in clinical. After that, the design considerations of peripheral nerve and spinal cord tissue engineering were discussed, and various 3D printing technologies applicable to neural tissue engineering were elaborated, including inkjet, extrusion-based, stereolithography, projection-based, and emerging printing technologies. Finally, we focused on the application of 3D printing technology in peripheral nerve regeneration and spinal cord repair, as well as the challenges and prospects in this research field.
Unilingualism and Unibilingualism in Colombia
Authors: Roux Guillaume , Soler Millán Germana Carolina
Published: June 2023

In its language policy and planning (LPP), Colombia offers ethnoeducation for ethnic groups, with Spanish as a second language, and for the protection/revitalization of native languages. However, these LPP measures are insufficiently implemented. Meanwhile, with regard to foreign languages, LPP have specifically advocated a Spanish-English bilingualism emphasized since the early 2000s. What then favours English to the detriment of native languages? The objective of this research is to reveal what is hidden behind this LPP through a Critical Discourse Analysis of official documents. The elements brought to light show unilingualism and unibilingualism ideologies that discriminate against native languages, and value the linguistic imperialism of English.
The Effects of CLIL and Sources of Individual Differences on Receptive and Productive EFL Skills at the Onset of Primary School
Authors: Soto-Corominas Adriana , Roquet Helena , Segura Marta
Published: June 2023

Research on the implementation of CLIL at the onset of primary school is limited and has largely overlooked the role of other sources of individual differences. This study investigated the effects of the CLIL approach to English learning, together with the effects of out-of-school exposure to the language through media and other sources of individual differences, in a sample of Grade 1 students in Catalonia (Spain) using a longitudinal design. Participants (N = 176) from 14 different schools completed a test battery at the beginning and end of Grade 1 that assessed receptive and productive English skills. Results revealed that abilities at the onset of Grade 1 were the best predictor of abilities at the end of the year, and that CLIL was not associated with additional advantages in the students that followed the approach. In addition, certain characteristics of the linguistic and family background of participants predicted additional gains during the academic year: participants who engaged in more English extracurricular activities and participants with more educated mothers performed better at the end of Grade 1.
SPECK: an unsupervised learning approach for cell surface receptor abundance estimation for single-cell RNA-sequencing data
Authors: Javaid Azka , Frost H Robert
Published: June 2023

The rapid development of single-cell transcriptomics has revolutionized the study of complex tissues. Single-cell RNA-sequencing (scRNA-seq) can profile tens-of-thousands of dissociated cells from a tissue sample, enabling researchers to identify cell types, phenotypes and interactions that control tissue structure and function. A key requirement of these applications is the accurate estimation of cell surface protein abundance. Although technologies to directly quantify surface proteins are available, these data are uncommon and limited to proteins with available antibodies. While supervised methods that are trained on Cellular Indexing of Transcriptomes and Epitopes by Sequencing data can provide the best performance, these training data are limited by available antibodies and may not exist for the tissue under investigation. In the absence of protein measurements, researchers must estimate receptor abundance from scRNA-seq data. Therefore, we developed a new unsupervised method for receptor abundance estimation using scRNA-seq data called SPECK (Surface Protein abundance Estimation using CKmeans-based clustered thresholding) and primarily evaluated its performance against unsupervised approaches for at least 25 human receptors and multiple tissue types. This analysis reveals that techniques based on a thresholded reduced rank reconstruction of scRNA-seq data are effective for receptor abundance estimation, with SPECK providing the best overall performance.

Availability and implementation

SPECK is freely available at https://CRAN.R-project.org/package=SPECK.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
A New Synthesis among IR Theories? Moral Leadership in International Relations
Authors: Fang Yuanyuan
Published: June 2023

There is currently not only a retrogression of the global economy and governance in progress but also one of international morality, which the growth of populism has destructed. Moral retrogression has yet to arouse the same level of awareness among policymakers and the public as has economic retrogression. Scholars like Yan Xuetong, Joseph Nye, and Richard Ned Lebow, however, have discerned this problem and its significance. This article compares Yan and Nye, with respect to the gradual convergence of their views on leadership, along with that of Lebow’s perceptions of morality. But how can the research agendas of a moral realist, a neoliberalist, and a constructivist converge? It is argued that deep underlying similarities exist between their views on the nature of world politics and the perceptions of the current international order that may facilitate a much broader account of the international system. The relevance of this theoretical movement to real-world events is clear. Such convergence on moral leadership both reflects the reality of a moral leadership deficit and constitutes an antidote to the current global chaos.
Nanopore Third-Generation Sequencing for Comprehensive Analysis of Hemoglobinopathy Variants
Authors: Huang Weilun , Qu Shoufang , Qin Qiongzhen , Yang Xu , Han Wanqing , Lai Yongli , Chen Jiaqi , Zhou Shihao , Yang Xuexi , Zhou Wanjun
Published: June 2023

Background

Oxford Nanopore Technology (ONT) third-generation sequencing (TGS) is a versatile genetic diagnostic platform. However, it is nonetheless challenging to prepare long-template libraries for long-read TGS, particularly the ONT method for analysis of hemoglobinopathy variants involving complex structures and occurring in GC-rich and/or homologous regions.

Methods

A multiplex long PCR was designed to prepare library templates, including the whole-gene amplicons for HBA2/1, HBG2/1, HBD, and HBB, as well as the allelic amplicons for targeted deletions and special structural variations. Library construction was performed using long-PCR products, and sequencing was conducted on an Oxford Nanopore MinION instrument. Genotypes were identified based on integrative genomics viewer (IGV) plots.

Results

This novel long-read TGS method distinguished all single nucleotide variants and structural variants within HBA2/1, HBG2/1, HBD, and HBB based on the whole-gene sequence reads. Targeted deletions and special structural variations were also identified according to the specific allelic reads. The result of 158 α-/β-thalassemia samples showed 100% concordance with previously known genotypes.

Conclusions

This ONT TGS method is high-throughput, which can be used for molecular screening and genetic diagnosis of hemoglobinopathies. The strategy of multiplex long PCR is an efficient strategy for library preparation, providing a practical reference for TGS assay development.
Pre-emptive iron supplementation prevents myocardial iron deficiency and attenuates adverse remodelling after myocardial infarction
Authors: Chung Bomee , Wang Yong , Thiel Marleen , Rostami Fatemeh , Rogoll Anika , Hirsch Valentin G , Malik Zulaikha , Bührke Anne , Bär Christian , Klintschar Michael , Schmitto Jan D , Vogt Carla , Werlein Christopher , Jonigk Danny , Bauersachs Johann , Wollert Kai C , Kempf Tibor
Published: June 2023

Aims

Heart failure (HF) after myocardial infarction (MI) is a major cause of morbidity and mortality. We sought to investigate the functional importance of cardiac iron status after MI and the potential of pre-emptive iron supplementation in preventing cardiac iron deficiency (ID) and attenuating left ventricular (LV) remodelling.

Methods and results

MI was induced in C57BL/6J male mice by left anterior descending coronary artery ligation. Cardiac iron status in the non-infarcted LV myocardium was dynamically regulated after MI: non-haem iron and ferritin increased at 4 weeks but decreased at 24 weeks after MI. Cardiac ID at 24 weeks was associated with reduced expression of iron-dependent electron transport chain (ETC) Complex I compared with sham-operated mice. Hepcidin expression in the non-infarcted LV myocardium was elevated at 4 weeks and suppressed at 24 weeks. Hepcidin suppression at 24 weeks was accompanied by more abundant expression of membrane-localized ferroportin, the iron exporter, in the non-infarcted LV myocardium. Notably, similarly dysregulated iron homeostasis was observed in LV myocardium from failing human hearts, which displayed lower iron content, reduced hepcidin expression, and increased membrane-bound ferroportin. Injecting ferric carboxymaltose (15 µg/g body weight) intravenously at 12, 16, and 20 weeks after MI preserved cardiac iron content and attenuated LV remodelling and dysfunction at 24 weeks compared with saline-injected mice.

Conclusion

We demonstrate, for the first time, that dynamic changes in cardiac iron status after MI are associated with local hepcidin suppression, leading to cardiac ID long term after MI. Pre-emptive iron supplementation maintained cardiac iron content and attenuated adverse remodelling after MI. Our results identify the spontaneous development of cardiac ID as a novel disease mechanism and therapeutic target in post-infarction LV remodelling and HF.
Neodb: a comprehensive neoantigen database and discovery platform for cancer immunotherapy
Authors: Wu Tao , Chen Jing , Diao Kaixuan , Wang Guangshuai , Wang Jinyu , Yao Huizi , Liu Xue-Song
Published: June 2023

Neoantigens derived from somatic deoxyribonucleic acid alterations are ideal cancer-specific targets. However, integrated platform for neoantigen discovery is urgently needed. Recently, many scattered experimental evidences suggest that some neoantigens are immunogenic, and comprehensive collection of these experimentally validated neoantigens is still lacking. Here, we have integrated the commonly used tools in the current neoantigen discovery process to form a comprehensive web-based analysis platform. To identify experimental evidences supporting the immunogenicity of neoantigens, we performed comprehensive literature search and constructed the database. The collection of public neoantigens was obtained by using comprehensive features to filter the potential neoantigens from recurrent driver mutations. Importantly, we constructed a graph neural network (GNN) model (Immuno-GNN) using an attention mechanism to consider the spatial interactions between human leukocyte antigen and antigenic peptides for neoantigen immunogenicity prediction. The new easy-to-use R/Shiny web–based neoantigen database and discovery platform, Neodb, contains currently the largest number of experimentally validated neoantigens. In addition to validated neoantigen, Neodb also includes three additional modules for facilitating neoantigen prediction and analysis, including ‘Tools’ module (comprehensive neoantigen prediction tools); ‘Driver-Neo’ module (collection of public neoantigens derived from recurrent mutations) and ‘Immuno-GNN’ module (a novel immunogenicity prediction tool based on a GNN). Immuno-GNN shows improved performance compared with known methods and also represents the first application of GNN model in neoantigen immunogenicity prediction. The construction of Neodb will facilitate the study of neoantigen immunogenicity and the clinical application of neoantigen-based cancer immunotherapy.

Database URL https://liuxslab.com/Neodb/
Tumor size and presence of metastases in differentiated thyroid cancer: comparing cohorts from two countries
Authors: van Velsen Evert F S , Peeters Robin P , Stegenga Merel T , Mäder Uwe , Reiners Christoph , van Kemenade Folkert J , van Ginhoven Tessa M , Visser W Edward , Verburg Frederik A
Published: June 2023

Objective

Incidence of thyroid cancer varies widely, even across neighboring countries. Data on this phenomenon are largely lacking but are likely related to differences in health care systems. Therefore, we explored whether there are differences between populations from these 2 countries with respect to the relationship between tumor size and advanced disease.

Methods

We retrospectively studied 2 cohorts of adult differentiated thyroid cancer (DTC) patients from a Dutch and a German university hospital. We analyzed the presence of lymph node metastases with respect to tumor size for papillary thyroid cancer (PTC), and the presence of distant metastases for DTC, and PTC and follicular thyroid cancer (FTC) separately.

Results

We included 1771 DTC patients (80% PTC, 20% FTC; 24% lymph node and 8% distant metastases). For PTC, the proportion of patients with lymph node metastases was significantly higher in the Dutch than in the German population for tumors ≤ 1 cm (45% vs. 14%; P < .001). For DTC, distant metastases occurred particularly significantly more frequently in the Dutch than in the German population for tumors ≤ 2 cm (7% vs. 2%; P = .004).

Conclusion

The presence of lymph node and distant metastases is significantly higher in pT1 DTC cases in the Dutch compared to the German cohort, which might be caused by differences in the indication for and application of diagnostic procedures eventually leading to DTC diagnosis. Our results implicate that one should be cautious when extrapolating results and guidelines from 1 country to another.
Small regulatory RNAs in Vibrio cholerae
Authors: Ghandour Rabea , Papenfort Kai
Published: June 2023

Vibrio cholerae is a major human pathogen causing the diarrheal disease, cholera. Regulation of virulence in V. cholerae is a multifaceted process involving gene expression changes at the transcriptional and post-transcriptional level. Whereas various transcription factors have been reported to modulate virulence in V. cholerae, small regulatory RNAs (sRNAs) have now been established to also participate in virulence control and the regulation of virulence-associated processes, such as biofilm formation, quorum sensing, stress response, and metabolism. In most cases, these sRNAs act by base-pairing with multiple target transcripts and this process typically requires the aid of an RNA-binding protein, such as the widely conserved Hfq protein. This review article summarizes the functional roles of sRNAs in V. cholerae, their underlying mechanisms of gene expression control, and how sRNAs partner with transcription factors to modulate complex regulatory programs. In addition, we will discuss regulatory principles discovered in V. cholerae that not only apply to other Vibrio species, but further extend into the large field of RNA-mediated gene expression control in bacteria.
The molecular pathogenesis of achalasia: a paired lower esophageal sphincter muscle and serum 4D label-free proteomic study
Authors: Chen Songfeng , Xing Xiangbin , Hou Xun , Zhuang Qianjun , Tan Niandi , Cui Yi , Wang Jinhui , Zhang Mengyu , Hu Shixian , Xiao Yinglian
Published: June 2023

Background

Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain. This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia.

Methods

Paired lower esophageal sphincter (LES) muscle and serum samples from 24 achalasia patients were collected. We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients. The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia.

Results

Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls (both P < 0.05). Functional enrichment analysis suggested that these differentially expressed proteins were immunity-, infection-, inflammation-, and neurodegeneration-associated. The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix–receptor interaction increased sequentially between the control group, type III, type II, and type I achalasia. Only 26 proteins altered in the same directions in serum and muscle samples.

Conclusions

This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia, involving immunity, inflammation, infection, and neurodegeneration pathways. Distinct protein clusters between types I, II, and III revealed the potential molecular pathways associated with different disease stages. Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.
The Role of a Composite Fitness Score in the Association Between Low-Density Cholesterol and All-Cause Mortality in Older Adults: An Individual Patient Data Meta-Analysis
Authors: van der Ploeg Milly A , Poortvliet Rosalinde K E , Bogaerts Jonathan M K , van der Klei Veerle M G T H , Kerse Ngaire , Rolleston Anna , Teh Ruth , Robinson Louise , Jagger Carol , Arai Yasumichi , Shikimoto Ryo , Abe Yukiko , Blom Jeanet W , Drewes Yvonne M , Gussekloo Jacobijn
Published: June 2023

Background

In the general population, an increase in low-density lipoprotein cholesterol (LDL-C) predicts higher cardiovascular disease risk, and lowering LDL-C can prevent cardiovascular disease and reduces mortality risk. Interestingly, in cohort studies that include very old populations, no or inverse associations between LDL-C and mortality have been observed. This study aims to investigate whether the association between LDL-C and mortality in the very old is modified by a composite fitness score.

Methods

A 2-stage meta-analysis of individual participant data from the 5 observational cohort studies. The composite fitness score was operationalized by performance on a combination of 4 markers: functional ability, cognitive function, grip strength, and morbidity. We pooled hazard ratios (HR) from Cox proportional-hazards models for 5-year mortality risk for a 1 mmol/L increase in LDL-C. Models were stratified by high/low composite fitness score.

Results

Composite fitness scores were calculated for 2 317 participants (median 85 years, 60% females participants), of which 994 (42.9%) had a high composite fitness score, and 694 (30.0%) had a low-composite fitness score. There was an inverse association between LDL-C and 5-year mortality risk (HR 0.87 [95% CI: 0.80–0.94]; p < .01), most pronounced in participants with a low-composite fitness score (HR 0.85 [95% CI: 0.75–0.96]; p = .01), compared to those with a high composite fitness score (HR = 0.98 [95% CI: 0.83–1.15]; p = .78), the test for subgroups differences was not significant.

Conclusions

In this very old population, there was an inverse association between LDL-C and all-cause mortality, which was most pronounced in participants with a low-composite fitness scores.
Use of Caregiving Support Services Among Diverse Dementia Caregivers by Geographic Context
Authors: Yoshikawa Aya , Bouldin Erin D , López-Anuarbe Mónika , Kindratt Tiffany B , Sylvers Dominique L , Webster Noah J
Published: June 2023

Background and Objectives

Little is known about how race/ethnicity and geographic context relate to support service use among dementia caregivers. Our objectives were to investigate (a) whether the use of at least one formal caregiving service—support groups, respite care, and training—differed by race/ethnicity and across metro and nonmetro areas; and (b) whether predisposing, enabling, and need characteristics influenced support service use by race/ethnicity.

Research Design and Methods

Data were analyzed from a sample of primary caregivers of care recipients aged 65 years or older with probable dementia (n = 482) in the 2017 National Health and Aging Trends Study and National Study of Caregiving. We calculated weighted prevalence estimates and then used the Hosmer–Lemeshow goodness of fit statistic to find the best-fitting logistic regression models.

Results

Among minority dementia caregivers, support service use was higher in metro than nonmetro areas (35% and 15%); the trend was reversed for non-Hispanic White caregivers (47% nonmetro and 29% metro). The best-fitting regression models included predisposing, enabling, and need factors for both minority and non-Hispanic White caregivers. Younger age and more disagreement within the family were consistently associated with more service use in both groups. Among minority caregivers, better caregiver and care recipient health were associated with using support services. Among non-Hispanic White caregivers, nonmetro geographic context and caregiving interfering with valued activities were associated with using support services.

Discussion and Implications

Geographic context differently affected support service use and the influence of predisposing, enabling, and need factors varied by race/ethnicity.
Effect of Temperature on Mosquito Olfaction
Authors: Lahondère Chloé , Vinauger Clément , Liaw Jessica E , Tobin Kennedy K S , Joiner Jillian M , Riffell Jeffrey A
Published: June 2023

Synopsis

Mosquitoes use a wide range of cues to find a host to feed on, eventually leading to the transmission of pathogens. Among them, olfactory cues (e.g., host-emitted odors, including CO2, and skin volatiles) play a central role in mediating host-seeking behaviors. While mosquito olfaction can be impacted by many factors, such as the physiological state of the insect (e.g., age, reproductive state), the impact of environmental temperature on the olfactory system remains unknown. In this study, we quantified the behavioral responses of Aedes aegypti mosquitoes, vectors of dengue, yellow fever, and Zika viruses, among other pathogens, to host and plant-related odors under different environmental temperatures.
A fatal mono-intoxication with 4-fluoroisobutyrylfentanyl: Case report with postmortem concentrations
Authors: Roosendaal Jeroen , Oosting Roelof , Kloos Dick-Paul , de Boer Hans H , van den Berg Jorrit D.J , Oldenhof Sander , Bosman Ingrid J
Published: June 2023

We report on a case of a 35-year-old man who died suddenly and unexpectedly due to a 4-fluoroisobutyrylfentanyl (4-FIBF) mono-intoxication. Pathological, toxicological and chemical investigations were conducted at the Netherlands Forensic Institute. A full three-cavity forensic pathological examination was performed according to international guidelines. Biological samples obtained during autopsy were comprehensively investigated for the presence of toxic substances using headspace gas chromatography (GC) with flame ionization detection, liquid chromatography–time-of-flight mass spectrometry (LC–TOF-MS), GC–MS, high-performance LC with diode array detection and LC–tandem MS (LC–MS-MS). The seized crystalline substance found next to the body was investigated using a presumptive color test, GC–MS, Fourier-transform infrared spectroscopy and nuclear magnetic resonance. Pathological investigation identified minor lymphocytic infiltrates in the heart, considered irrelevant for the cause of death. Toxicological analysis of the victims’ blood indicated the presence of a fluorobutyrylfentanyl (FBF) isomer, with no other compounds detected. The FBF isomer was identified in the seized crystalline substance as 4-FIBF. 4-FIBF concentrations were quantified in femoral blood (0.030 mg/L), heart blood (0.12 mg/L), vitreous humor (0.067 mg/L), brain tissue (>0.081 mg/kg), liver tissue (0.44 mg/kg) and urine (approximately 0.01 mg/L). Based on the outcomes of the pathological, toxicological and chemical investigations, the cause of death of the deceased was attributed to a fatal 4-FIBF mono-intoxication. The presented case underlines the added value of a combined bioanalytical and chemical investigative approach to identify and subsequently quantify fentanyl isomers in postmortem cases. Furthermore, it demonstrates the importance of investigating the postmortem redistribution of novel fentanyl analogs to establish reference values and to subsequently allow for correct interpretation of cause of death analysis in future casework.