bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the effect of double mineral admixtures on the properties of high water materials
Authors: Zheng Yuying , Wang Qiufeng , Zhao Yuanyuan
Published: March 2024

In this paper, different contents of fly ash, silica fume, slag, and Nano-SiO2 were added to the high water material. Then, fly ash-silica fume, slag-silica fume, and Nano SiO2-silica fume are mixed into the high water material. Through the strength test of two groups of specimens, the influence of different types of mineral admixtures and blending ratios on the physical and mechanical properties of high-water materials was studied. The mechanical parameters of high water doped materials were measured by ultrasonic method, and the internal pore structure of high water doped materials was analyzed. In the case of double mixing, the optimal mixing amount is 4% fly ash and 6% silica fume, and the 7 d compressive strength of this group of specimens is increased by 15.85% compared with the original high water material. Through ultrasonic detection, the first wave is smooth and stable, the longitudinal wave amplitude curve is flat, the peak difference is slight, and the periodic amplitude is uniform, indicating that the structure of this group of specimens is dense. The shear modulus is increased by 20.31%, Young’s modulus is 1.3 times, and the volume modulus is 8.9 times that of the original high water material. The research findings suggest that high water materials can be modified by double mixing.
Crystallization, thermal properties, rheological properties, mechanical properties, and morphology of thermoplastic polyurethanes/calcium sulfate whiskers composites
Authors: Zhang Daohai , Zhan Xiao , Liu Guilan , Tan Yanyan , Shi Lianjun , Chen Qianlin , Xie Tian
Published: March 2024

The research shows that thermoplastic polyurethane (TPU) which is easy to process has great application potential in practical application. In this study, a calcium sulfate whisker (CSW) with high strength and stability was used as a reinforcing filler to improve the processability of flexible TPU. In this paper, TPU/CSW composites were prepared by the melt blending method, and the effects of modified CSW on the thermal, crystalline, and melt properties, as well as the rheological and mechanical properties of TPU composites were investigated. The results showed that when the mass content of modified CSW was 10%, the maximum values of ΔH
c and ΔH
m were 222.81°C and 9.24 J/g, respectively, and the thermal properties of the composites were the most stable. When the content of modified CSW is 5%, the maximum impact strength, bending strength, and tensile strength are 50.5 KJ/m2, 38.8 MPa, and 927.7 MPa, respectively, and the mechanical properties of the composites are the best. The excellent stability and high strength of TPU/CSW composites show great promise for various applications in transportation and building materials.
Precision cutting mechanics and mechanical performance testing on the spindle of machine tool
Authors: Yang Hongping , Guo Zhongwen , Xia Yingjie
Published: March 2024

The manufacturing industry is the foundation of national development. With science and technology developing, precision turning technology has gradually become one of the cutting-edge technologies of advanced manufacturing technology. In the paper, the turning mechanics model is established based on the principle of metal cutting, and the corresponding cutting force is calculated. Considering the cutting force, material weight, flange weight, and other loads, the analysis model of the CK61125 machine tool spindle is constructed based on the finite element method, and the corresponding maximum strain and modal solution are calculated. The results are that when the 30, 000 N load is applied, the largest strain of the spindle is 0.0013 mm/mm, and the largest stress is 265 MPa. When the 100, 000 N load is applied, the strain of the spindle largest is 0.0015 mm/mm, and the stress is 290 MPa. The four orders of vibration modes of the spindle are obtained, which are 215.3 Hz, 256.2 Hz, 436.33 Hz, and 974.5 Hz. By comparison with the experiment, the spindle vibration frequencies are 87.8 Hz and 625 Hz, while the spindle rotating testing speeds are 100 rpm, 500 rpm, and 800 rpm.
Design and implementation of facility intelligent carbon dioxide incubator control system based on POA optimized fuzzy PID
Authors: Luo Qiangke , Zhao Zeneng , Chen Xingjiang , Zhang Huanbo , Liu Yong
Published: March 2024

To solve the problem that traditional carbon dioxide incubators are difficult to accurately control the required carbon dioxide environment to the detriment of experimental cultivation, and given the difficulties of time lag, nonlinearity, time-varying, and poor adaptive ability of the incubator control system, this study designs a set of intelligent carbon dioxide incubator control system suitable for laboratory cultivation. The system is based on the POA (Pelican optimization algorithm) to optimize the fuzzy PID (Proportional Integral Derivative) control to regulate the opening degree of the solenoid valve to accurately control the carbon dioxide concentration in the incubator to the set range. In this study, the simulation and comparison tests of POA-based optimized fuzzy PID control, PID control, and fuzzy PID control are carried out by MATLAB/Simulink, and it is found that the overshooting amount of the system is reduced by 11.6%, the regulating time is shortened by 69.3 s, and the steady state error is reduced by 0.1% compared with that of the traditional fuzzy PID control. It can be obtained through practical tests that the accuracy, response, and stability of the optimized fuzzy PID control of the pelican algorithm are better than those of the fuzzy PID control method, and it has better robustness. Therefore, the carbon dioxide incubator control system has high practical application value.
Study on the microstructure and mechanical properties of VW73B alloy at high extrusion ratio
Authors: Wei Xiaowei , Li Yongjun , Ma Minglong , Li Xinggang , Shi Guoliang , Yuan Jiawei , Sun Zhaoqian , Zhang Kui
Published: March 2024

The microstructure and mechanical characteristics of VW73B prepared by a high extrusion ratio (70:1) were studied. High-strength plastic VW73B alloy containing long-period structural phase (LPSO) was obtained by extrusion process. OM, SEM, TEM, and EBSD were used to investigate the relationship between microstructure and mechanical characteristics of VW73B. The findings indicate that VW73B presents complete dynamic recrystallization after deformation, and there are 14H-LPSO phases, SFs, and a large amount of β´ phase, which are precipitated after aging treatment. The UTS, YS, and EL of VW73B in peak aging state are 406 MPa, 339 MPa, and 9%, respectively. The β´ phase, LPSO phase, poor texture, and fine grain strengthening of VW73B contribute to its exceptional characteristics.
Experimental study on shock isolation of metal rubber-disc spring composite shock absorber under different shock excitation
Authors: Liu Guoqiang , Wang Xuebao , Guo Zhirong , Zhang Yiqun
Published: March 2024

Due to the instability and aiming accuracy of the onboard laser emission system cannot meet the requirements of its work tasks, it is necessary to carry out vibration isolation optimization design for the laser emission system. This paper designs a metal rubber-disc spring composite shock absorber and conducts relevant experimental research on the shock isolation performance of the metal rubber-disc spring composite shock absorber. The shock isolation performance tests of the shock absorber under different shock excitation conditions with pendulum heights of 300 mm, 600 mm, 900 mm, and 1200 mm were carried out respectively. Through the experiments, it was found that when the pendulum height is 300 mm, the shock isolation effect of the metal rubber-disc spring composite shock absorber is the best, and the shock isolation rate is above 95%.
Low-cost porous silicon material based on fenton process assisted chemical etching and its application as anode for lithium-ion battery
Authors: Li Junpeng , Wen Yihao , Wang Zi
Published: March 2024

Nanostructured silicon-based materials are considered as one of the most promising alternatives for anode electrodes of lithium-ion batteries. Nevertheless, the relatively high cost and complexity of most present processes make them difficult to scale up. In this manuscript, we would like to introduce a porous anode prepared by Fenton reaction-assisted chemical etching of low-cost ferrosilicon in the mixed solution of hydrogen fluoride and hydrogen peroxide. The experimental results show that hierarchical structures containing both mesopores and micropores can be formed by this convenient room-temperature etching process and its electrochemical performance as the anode is comparable to that of commercial product. Furthermore, the low cost of ferrosilicon ($1200~1500/ton) compared with the silicon powder of industrial grade (~$3000/ton) traditionally used in Li-ion battery anode preparation also renders this method potential and feasible for large-scale production of Si-based anode materials.
Investigation on the improvement of microwave dielectric properties of plasma-prepared fluoropolymer-coated CaTiO3-filled PTFE composites
Authors: Zheng Xiaolei , Wang Qun , Li Xiaoqiang , Shen Chenjie , Zheng Changkuan
Published: March 2024

High-performance polymer matrix composites preparation has been urgently hampered by poor interfacial adhesion between two phases. In this article, a thorough analysis of the microstructure and overall properties of composites made of polytetrafluoroethylene filled with fluorocarbon polymer film-coated CaTiO3 was conducted. The similar fluorocarbon molecular structure of CaTiO3 surface and PTFE provides a bridge between the two, significantly improving and promoting the microstructure and interface adhesion of the composite. The comprehensive properties of modified composites are obviously superior to those of untreated composites. Composites filled with 30 wt% CaTiO3 have an excellent dielectric constant at 5.53, acceptable dielectric loss at 0.0047, an outstanding heat resistance index of 281.1°C, and relatively low hygroscopicity of 0.10%. At the same time, the mechanical properties are maintained at a high application level, which makes them promising for microwave devices.
Risk assessment of fire and explosion accidents in oil-hydrogen fueling station based on fault tree analysis
Authors: Du Lianming , Liao Guangrong , Zhang Tong , Deng Qian , Li Aijun , Mao Ning
Published: March 2024

Owing to the coexistence of gasoline, diesel, and hydrogen, a specific and thorough risk assessment approach must be promptly implemented for oil-hydrogen fueling stations. Consequently, this study makes innovations in considering the safety issues of the joint construction of gas station and hydrogen refueling station, and undertaking the modeling and analysis of fire and explosion incidents at oil-hydrogen fueling stations based on fault tree analysis. The findings reveal that the risk level for fire and explosion at oil-hydrogen fueling stations is categorized as grade III. In our fault tree analysis model, there are 3240 minimum cut sets and 194 minimum path sets. The probability of fire and explosion incidents occurring at oil-hydrogen fueling stations is calculated to be 0.000265. This indicates that while the possibility of such accidents is low, their potential severity is exceedingly high. Ultimately, it is recommended that the safety of oil-hydrogen fueling stations be enhanced through the reinforcement of emergency management, customer safety education, and electrostatic discharge devices.
Comparison Study by using Pyrolysis of Kenna Sugarcane Bagasse and Sawdust in Sudan
Authors: Abuelnuor Abuelnuor A.A.
Published: March 2024

Today the request for save energy and addressing emissions has become a primary concern for every country aiming to achieve sustainable development while preserving its environment. The demand for energy is steadily rising, driven by rapid population growth and industrial development. Fossil fuels continue to play a major role in fulfilling these energy needs., but their combustion is linked to rising environmental issues. There are many sources of energy use to solve the environmental problems and fossil fuel shorted such as biomass. This paper aims to explore the potential of biomass to provide significantly higher amounts of useful energy while reducing pollutant emissions compared to fossil fuels. In this research the two samples of sugar cane bagasse and sawdust is study by slow pyrolysis. Two samples are presented—one from Kenana bagasse and the other from sawdust. Bio-oil is a product of the slow pyrolysis process, and its calorific value, determined through laboratory analysis, is significantly high compared to previous studies. This indicates that bio-oil emits fewer pollutants than fossil fuels, making it suitable for use in transportation and various industrial sectors.
Compact super-Gaussian evanescent beam expanders for integrated photonics
Authors: Kouznetsov Dmitry , Deng Qingzhong , Yurtsever Günay , Neutens Pieter , Garcia-Munoz Victor , Matos Manuel , Stassen Andim , Van Dorpe Pol , Verellen Niels
Published: March 2024

This paper presents the modeling, design and experimental validation of integrated optical super-Gaussian evanescent beam expanders. A general analytical model for converting the mode of a single mode waveguide into a wide super-Gaussian slab mode is derived and the design procedure is described. Several structures have been experimentally verified on wafer scale and the results are in good correspondence with the design. Applications where wide flat-top beams would prove their superiority are, for instance, bio-sensing applications, flow cytometry and on-chip microscopy.
Inverse-designed metasurfaces with facile fabrication parameters
Authors: Zhou You , Shao Yixuan , Mao Chenkai , Fan Jonathan A
Published: March 2024

Optical metasurfaces are planar nanostructured devices that are industrially attractive in part because they utilize high-throughput microelectronic fabrication techniques for implementation. It is therefore critical to develop design paradigms that can balance the realization of highly efficient wavefront responses together with device manufacturability. We introduce a gradient-based design framework for freeform metasurfaces in which nanoscale elements are explicitly constrained to feature basic shapes, nearly uniform feature sizes, and exceptionally low aspect ratios. In spite of the apparent uniformity of the metasurface geometric features, the devices are able to utilize nonlocal near-field optical coupling to achieve highly efficient and extreme wavefront scattering beyond conventional design methodologies. Utilizing this approach, we design facile high-numerical-aperture devices such as beam deflectors and large-area metalenses capable of diffraction-limited focusing. We anticipate that these concepts can facilitate the design and integration of metasurfaces into monolithic optical systems.
On the Iwasawa main conjecture for the double product
Authors: Delbourgo Daniel
Published: March 2024

Let

σ
\sigma

and

τ
\tau

denote a pair of absolutely irreducible

p
p

-ordinary and

p
p

-distinguished Galois representations into

GL
2

⁡
(

F

¯

p

)

\operatorname {GL}_2(\overline {\mathbb {F}}_p)

. Given two primitive forms

(
f
,
g
)

(f,g)

such that

wt
⁡
(
f
)
>
wt
⁡
(
g
)
>
1

\operatorname {wt}(f)>\operatorname {wt}(g)> 1

and where

ρ
¯

f

≅
σ

\overline {\rho }_f\cong \sigma

and

ρ
¯

g

≅
τ

\overline {\rho }_g\cong \tau

, we show that the Iwasawa Main Conjecture for the double product

ρ
f

⊗

ρ
g

\rho _f\otimes \rho _g

depends only on the residual Galois representation

σ
⊗
τ
:

G

Q

→

GL
4

⁡
(

F

¯

p

)

\sigma \otimes \tau : G_{\mathbb {Q}}\rightarrow \operatorname {GL}_4(\overline {\mathbb {F}}_p)

. More precisely, if IMC(

f
⊗
g

f\otimes g

) is true for one pair

(
f
,
g
)

(f,g)

with

ρ
¯

f

≅
σ

\overline {\rho }_f \cong \sigma

and

ρ
¯

g

≅
τ

\overline {\rho }_g\cong \tau

and whose

μ
\mu

-invariant equals zero, then it is true for every congruent pair too.
The Human Factor
Authors: Sinner Alejandro , Carreras Cèsar , Houten Pieter
Published: March 2024

This book establishes a foundation for the study of ancient demography in the Iberian peninsula, focusing on its largest province, Hispania Citerior (renamed as Tarraconensis in the Early Empire). The authors follow a multidisciplinary approach that includes compiled archaeological, epigraphic, architectonic, osteological, and genetic datasets. Their integration and interpretation provide cutting-edge research and methodology in this area, and fills a gap in the scholarly literature, as no comprehensive work currently exists on the topic in English, Spanish, or any other language. This comprehensive and detailed study of a single province is necessary to generate accurate demographic estimates and to compare it with datasets from other regions and historical periods. By examining the province of Hispania Citerior/Tarraconensis in depth, the authors provide a detailed understanding of demographic patterns, urbanism, and urbanization rates over time, and link them with the social, cultural, and economic factors that affected the Iberian peninsula and the western Mediterranean from the fourth century BCE until the end of the Roman period. For instance, population size was a significant indicator of economic growth and performance, and the distribution of people between urban and rural areas played a vital role in the negotiation and construction of collective identities. Additionally, human mobility promoted cultural change and mediated information and technological flows. The volume provides the first comprehensive, state-of-the-art demographic analysis of the Iberian peninsula from the late Iron Age down to the end of the Roman period, including diachronic comparisons between different cultures and a significant number of case studies. By doing so, the authors provide new methodological approaches and insights into demographic patterns and their impact on ancient societies, allowing for a more nuanced understanding of the ancient Mediterranean.
Introduction
Authors: Sinner Alejandro , Carreras Cèsar , Houten Pieter
Published: March 2024

The chapter introduces the volume and its contents from a historiographic, methodological, and theoretical perspective. It first reflects on the recent interest that the field of ancient demography in general and the demography of the Roman world in particular have experienced in the last few decades, but also discusses how this interest either still focuses on specific areas (e.g. Egypt, Italy, and Britain) or just considers the Roman Empire as a whole. The chapter then explains why a book devoted to the province of Hispania Citerior/Tarraconensis is necessary and introduces the new and diverse datasets and the methodological and theoretical approaches that lie at the core of the present study. The final section presents the main topics covered by each individual chapter as well as some of the themes that are treated across several chapters.
Economics
Authors: Deaves Richard
Published: March 2024

This chapter provides some important background material from modern economics that will be useful for household finance. Front and center are preferences, utility (reflecting preferences), and the maximization of utility subject to constraints. Another important concept is valuation, namely ascertaining the intrinsic value of any asset. In markets, equilibrium prices are determined by the interaction of demanders and suppliers. Whenever risk (appropriately defined) is present, it is natural for investors to require a risk premium in compensation for the risk borne. Potentially subverting this rational ideal is the possibility of market inefficiency, which exists when intrinsic value and market price are too far apart.
Time
Authors: Deaves Richard
Published: March 2024

This chapter presents time preference, both rational and behavioral. Rational time preference implies exponential discounting. This means that one’s rate of time preference in comparing near and far consumption does not change as the near focal point moves farther into the future. The major problem with exponential discounting is that many people exhibit present bias. This means that one’s rate of time preference is high if the near focal point is the present. Quasi-hyperbolic utility can explain choices characterized by present bias. Some demographic determinants, such as cognitive skills. and psychological factors, such as emotion, behind time preference are also discussed.
Hedgers
Authors: Deaves Richard
Published: March 2024

This chapter focuses on insurance, an important risk management tool used by households for hedging. The major types of insurance are life, health, auto and home. I begin by considering what risks should be insured against and different insurance types. How an insurance market ideally works is next addressed. Whether policies are purchased often comes down to an interplay between risk aversion and wealth, with prospect theory preferences sometimes playing a role. Poor insurance decisions are not uncommon. Three important mistakes that are not uncommon are overpaying for modest-payoff insurance, overestimating probability loss because of availability (and so overpaying for insurance), and not insuring when advisable.
Investors
Authors: Deaves Richard
Published: March 2024

This chapter focuses on errors made by individual investors. The preference for skewness is evidenced by the popularity of lottery stocks. Firms with high availability, perhaps because they are in the news or have recently experienced price swings, attract investors. Zeroing in by many investors on stocks with these and other characteristics may lead to buying pressure and inflated prices. Local bias occurs when people favor geographically close investments, but the existence of a payoff is dubious. Path-dependent investment behaviors such as repurchase effects and the disposition effect are displayed by many investors. Which investors are most susceptible to various biases is discussed.
Followers
Authors: Deaves Richard
Published: March 2024

This chapter focuses on intervention designed to ameliorate outcomes for individual financial decision makers. Intervention can come from different sources: from industry (to better serve customers or in response to government pressures or mandates), from government via rules (whether direct legislation or regulation), or by individuals themselves (through commitment devices). Nudges have proved useful in getting people to save enough while taking on an appropriate amount of risk. A good nudge is a default. Various defaults have proved to be very useful in the context of pension design. For example, auto-enrollment nudges people to save, and auto-escalation nudges people to save an appropriate amount.
Cost-effectiveness of proactive health support—telephone-based self-management support compared with standard care for persons at risk of hospital admission
Authors: Rasmussen Maja Kjær , Benthien Kirstine Skov , Nielsen Camilla Palmhøj , Rasmussen Knud , Grønkjær Mette , Toft Ulla , Kidholm Kristian
Published: March 2024

Background

A small share of patients account for a large proportion of costs to the healthcare system in Denmark as in many Western countries. A telephone-based self-management support, proactive health support (PaHS), was suggested for prevention of hospitalisations for persons at risk of hospital admission. These persons have chronic diseases, unplanned hospitalisations and age ≥ 65 years. However, evidence is limited on whether this type of intervention is cost-effective.

Aim

The aim of this study was to assess the incremental cost-utility ratio (ICER) of PaHS, compared with standard care.

Methods

The economic evaluation was nested within a randomised controlled trial, and was based on a health system perspective, with follow-up and time horizon of 12 months. We measured incremental costs per quality-adjusted life years (QALY) gained. Total average costs per patient included PaHS programme costs, and costs in hospitals, primary care and municipalities. We analysed differences by generalised linear models with Gamma distribution for costs and mixed models for QALY.

Results

We analysed data on 6,139 patients, where 3,041 received PaHS and 3,098 received usual care. We found no difference in healthcare costs, and programme costs were on average €1,762 per patient, providing incremental costs of €2,075. Incremental effects on QALY were 0.007, resulting in an ICER of €296,389 per QALY gained.

Conclusion

We found no evidence of PaHS being cost-effective in this study, but the results will be used to identify new ways to organise similar interventions and identify patients with the objective to reduce health system costs per patient.
Sexual selection: competition for resources provided by mating partners
Authors: Janicke Tim
Published: March 2024

Ever since Darwin’s pioneering work, the definition of sexual selection has been subject to recurrent controversies. The main focus of a more recent debate centers on whether or not sexual selection encompasses intra-sexual competition for resources other than gametes. Specifically, it has been proposed to define sexual selection as competition for access to gametes and to consider competition for any other resources provided by mates as forms of natural selection. In this review, I elaborate on several drawbacks of this gamete-centered approach arguing that it (1) implies an artificial split of pre-copulatory competition for mates into two indistinguishable processes, (2) hinders the identification and quantification of sexual selection and, therefore, its distinction from other forms of natural selection, (3) gives rise to an overly male-biased perception on sexual selection, and (4) does not conform to Darwin’s original conception. In an attempt to provide a definition, which is explicit regarding the ultimate target of intra-sexual competition, I propose to define sexual selection as competition for access to reproductive resources provided by potential mating partners. I specify the main characteristics of this alternative definition in the context of previous ones and discuss potential limitations.
4D label-free quantitative proteomic analysis identifies CRABP1 as a novel candidate gene for litter size in rabbits
Authors: Bao Zhiyuan , Chen Yang , Li Jiali , Cai Jiawei , Yang Jie , Zhai Pin , Zhao Bohao , Wu Xinsheng
Published: March 2024

In commercial rabbit breeding, litter size is a crucial reproductive trait. This trait directly determines the reproductive ability of female rabbits and is crucial for evaluating the production efficiency. We here compared differentially expressed proteins of in the ovary tissue from New Zealand female rabbits with high (H) and low (L) litter sizes by using 4D label-free quantitative proteomic technology and identified 92 differential proteins. The biological functions of these proteins were revealed through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Most distributions of GO and KEGG were related to reproduction, growth development, and metabolism. Furthermore, a novel candidate gene cellular retinoic acid binding protein-1 (CRABP1), which was highly expressed in the L group, was selected for further biological function verification. The Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis revealed that CRABP1 can promote granulosa cell (GC) apoptosis and inhibit GC proliferation. Furthermore, qRT-PCR and western blotting analysis revealed that CRABP1 regulates the genes (HSD17B1, Wnt-10b, FSHR, TAF4B, BMP15, and BMP6) and protein (Wnt-10b) associated with steroid hormone synthesis and follicle development. The PCR product direct sequencing method revealed single nucleotide polymorphisms in the core promoter region of CRABP1. Luciferase activity assays revealed that the transcriptional activity of the GG genotype was significantly higher than that of the TT or TG genotype. Different genotypes are accompanied by changes in transcription factors, which indicates that T-359G polymorphism can regulate CRABP1 expression. In general, we identified litter size-related genes and revealed the mechanism underlying the effect of CRABP1 on litter size. CRABP1 serves as a key factor in the reproductive capacity of rabbits and can act as a molecular biomarker for the breeding of New Zealand rabbits.
Dominant dystrophic epidermolysis bullosa is associated with glycolytically active GATA3+ T helper 2 cells which may contribute to pruritus in lesional skin
Authors: Aala Wilson Jr F , Hou Ping-Chen , Hong Yi-Kai , Lin Yu-Chen , Lee Yu-Rong , Tu Wei-Ting , Papanikolaou Marieta , Benzian-Olsson Natashia , Onoufriadis Alexandros , I Chen Harn Hans , Hwang Daw-Yang , Cheng Siao Muk , Lu Kurt , Chen Peng-Chieh , McGrath John A , Hsu Chao-Kai
Published: March 2024

Background

Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined.

Objectives

To characterize DDEB skin transcriptomes to identify therapeutic targets to reduce pruritus in patients.

Methods

Using bulk RNA sequencing, we evaluated affected and unaffected skin biopsy samples from six patients with DDEB (all with the very itchy pruriginosa subtype) and four healthy individuals. Single-cell transcriptomes of affected (n = 2) and unaffected (n = 1) DDEB skin and healthy skin (n = 2) were obtained. Dupilumab treatment was provided for three patients.

Results

The skin bulk transcriptome showed significant enrichment of T helper (Th)1/2 and Th17 pathways in affected DDEB skin compared with nonlesional DDEB skin and healthy skin. Single-cell transcriptomics showed an association of glycolytically active GATA3+ Th2 cells in affected DDEB skin. Treatment with dupilumab in three people with DDEB led to significantly reduced visual analogue scale (VAS) itch scores after 12 weeks (mean VAS 3.83) compared with pretreatment (mean VAS 7.83). Bulk RNAseq and quantitative polymerase chain reaction showed that healthy skin and dupilumab-treated epidermolysis bullosa (EB) pruriginosa skin have similar transcriptomic profiles and reduced Th1/Th2 and Th17 pathway enrichment.

Conclusions

Single-cell RNAseq helps define an enhanced DDEB-associated Th2 profile and rationalizes drug repurposing of anti-Th2 drugs in treating DDEB pruritus.
Digenic Leigh syndrome on the background of the m.11778G>A Leber hereditary optic neuropathy variant
Authors: Blickhäuser Beryll , Stenton Sarah L , Neuhofer Christiane M , Floride Elisa , Nesbitt Victoria , Fratter Carl , Koch Johannes , Kauffmann Birgit , Catarino Claudia , Schlieben Lea Dewi , Kopajtich Robert , Carelli Valerio , Sadun Alfredo A , McFarland Robert , Fang Fang , La Morgia Chiara , Paquay Stéphanie , Nassogne Marie Cécile , Ghezzi Daniele , Lamperti Costanza , Wortmann Saskia , Poulton Jo , Klopstock Thomas , Prokisch Holger
Published: March 2024

Leigh syndrome spectrum (LSS) is a primary mitochondrial disorder defined neuropathologically by a subacute necrotizing encephalomyelopathy and characterized by bilateral basal ganglia and/or brainstem lesions. LSS is associated with variants in several mitochondrial DNA genes and more than 100 nuclear genes, most often related to mitochondrial complex I (CI) dysfunction. Rarely, LSS has been reported in association with primary Leber hereditary optic neuropathy (LHON) variants of the mitochondrial DNA, coding for CI subunits (m.3460G>A in MT-ND1, m.11778G>A in MT-ND4 and m.14484T>C in MT-ND6). The underlying mechanism by which these variants manifest as LSS, a severe neurodegenerative disease, as opposed to the LHON phenotype of isolated optic neuropathy, remains an open question. Here, we analyse the exome sequencing of six probands with LSS carrying primary LHON variants, and report digenic co-occurrence of the m.11778G > A variant with damaging heterozygous variants in nuclear disease genes encoding CI subunits as a plausible explanation.

Our findings suggest a digenic mechanism of disease for m.11778G>A-associated LSS, consistent with recent reports of digenic disease in individuals manifesting with LSS due to biallelic variants in the recessive LHON-associated disease gene DNAJC30 in combination with heterozygous variants in CI subunits.
Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease
Authors: Record Christopher J , Pipis Menelaos , Skorupinska Mariola , Blake Julian , Poh Roy , Polke James M , Eggleton Kelly , Nanji Tina , Zuchner Stephan , Cortese Andrea , Houlden Henry , Rossor Alexander M , Laura Matilde , Reilly Mary M
Published: March 2024

Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes. Whole genome sequencing (WGS) has improved diagnosis across genetic diseases, but the diagnostic impact in CMT is yet to be fully reported. We present the diagnostic results from a single specialist inherited neuropathy centre, including the impact of WGS diagnostic testing.

Patients were assessed at our specialist inherited neuropathy centre from 2009 to 2023. Genetic testing was performed using single gene testing, next-generation sequencing targeted panels, research whole exome sequencing and WGS and, latterly, WGS through the UK National Health Service. Variants were assessed using the American College of Medical Genetics and Genomics and Association for Clinical Genomic Science criteria.

Excluding patients with hereditary ATTR amyloidosis, 1515 patients with a clinical diagnosis of CMT and related disorders were recruited. In summary, 621 patients had CMT1 (41.0%), 294 CMT2 (19.4%), 205 intermediate CMT (CMTi, 13.5%), 139 hereditary motor neuropathy (HMN, 9.2%), 93 hereditary sensory neuropathy (HSN, 6.1%), 38 sensory ataxic neuropathy (2.5%), 72 hereditary neuropathy with liability to pressure palsies (HNPP, 4.8%) and 53 ‘complex’ neuropathy (3.5%). Overall, a genetic diagnosis was reached in 76.9% (1165/1515). A diagnosis was most likely in CMT1 (96.8%, 601/621), followed by CMTi (81.0%, 166/205) and then HSN (69.9%, 65/93). Diagnostic rates remained less than 50% in CMT2, HMN and complex neuropathies. The most common genetic diagnosis was PMP22 duplication (CMT1A; 505/1165, 43.3%), then GJB1 (CMTX1; 151/1165, 13.0%), PMP22 deletion (HNPP; 72/1165, 6.2%) and MFN2 (CMT2A; 46/1165, 3.9%). We recruited 233 cases to the UK 100 000 Genomes Project (100KGP), of which 74 (31.8%) achieved a diagnosis; 28 had been otherwise diagnosed since recruitment, leaving a true diagnostic rate of WGS through the 100KGP of 19.7% (46/233). However, almost half of the solved cases (35/74) received a negative report from the study, and the diagnosis was made through our research access to the WGS data. The overall diagnostic uplift of WGS for the entire cohort was 3.5%.

Our diagnostic rate is the highest reported from a single centre and has benefitted from the use of WGS, particularly access to the raw data. However, almost one-quarter of all cases remain unsolved, and a new reference genome and novel technologies will be important to narrow the ‘diagnostic gap’.
Characterizing Patients Presenting on Hospital Admission With Central Line–Associated Bloodstream Infections: A Multicenter Study
Authors: Oladapo-Shittu Opeyemi , Cosgrove Sara E , Rock Clare , Hsu Yea-Jen , Klein Eili , Harris Anthony D , Mejia-Chew Carlos , Saunders Heather , Ching Patrick R , Gadala Avi , Mayoryk Stephanie , Pineles Lisa , Maragakis Lisa , Salinas Alejandra , Helsel Taylor , Keller Sara C
Published: March 2024

Background

There are no systematic measures of central line–associated bloodstream infections (CLABSIs) in patients maintaining central venous catheters (CVCs) outside acute care hospitals. To clarify the burden of CLABSIs in these patients, we characterized patients with CLABSI present on hospital admission (POA).

Methods

Retrospective cross-sectional analysis of patients with CLABSI-POA in 3 health systems covering 11 hospitals across Maryland, Washington DC, and Missouri from November 2020 to October 2021. CLABSI-POA was defined using an adaptation of the acute care CLABSI definition. Patient demographics, clinical characteristics, and outcomes were collected via record review. Cox proportional hazard analysis was used to assess factors associated with the all-cause mortality rate within 30 days.

Results

A total of 461 patients were identified as having CLABSI-POA. CVCs were most commonly maintained in home infusion therapy (32.8%) or oncology clinics (31.2%). Enterobacterales were the most common etiologic agent (29.2%). Recurrent CLABSIs occurred in a quarter of patients (25%). Eleven percent of patients died during the hospital admission. Among patients with CLABSI-POA, mortality risk increased with age (hazard ratio vs age <20 years by age group: 20–44 years, 11.2 [95% confidence interval, 1.46–86.22]; 45–64 years, 20.88 [2.84–153.58]; ≥65 years, 22.50 [2.98–169.93]) and lack of insurance (2.46 [1.08–5.59]), and it decreased with CVC removal (0.57 [.39–.84]).

Conclusions

CLABSI-POA is associated with significant in-hospital mortality risk. Surveillance is required to understand the burden of CLABSI in the community to identify targets for CLABSI prevention initiatives outside acute care settings.
Profits and capital accumulation in the Mexican economy
Authors: Ibarra Carlos A
Published: March 2024

The paper studies the long-run disconnection between a rising profit share of income and a constant rate of capital accumulation in Mexico since the early 1990s. According to stylized facts based on the Cambridge accumulation equation, the disconnection reflects two factors: first, a flat trajectory of the investment share of profits, and second, a gap between a rising profit share and a constant or even falling profit rate due to a decline in the output/capital ratio. In manufacturing—where the disconnection was particularly sharp—econometric estimates show that the accumulation rate was negatively affected not only by the decline in the output/capital ratio but also by a fall in the relative Mexican/US profit rate. The estimates show in addition that, among financialization indicators, a rise in interest payments as a share of profits may have contributed to the low accumulation rate.
Disease-specific quality of life as part of the long-term follow-up for children born with esophageal atresia in an academic unit in South Africa—a pilot study
Authors: de Vos C , Dellenmark-Blom M , Sikwete F M , Sidler D , van Wyk L , Goussard P
Published: March 2024

As neonatal mortality rates have decreased in esophageal atresia (EA), there is a growing focus on quality of life (QoL) in these children. No study from Africa has reported on this topic. This pilot study aimed to describe disease-specific QoL in EA children and its applicability as part of long-term follow-up in an academic facility in South Africa. Disease-specific QoL in children born with EA was assessed utilizing the EA-QoL questionnaire for children aged 2–17 years during a patient-encounter. The parent-report for children aged 2–7 years compromised 17 items categorized into three domains: eating, physical health and treatment, and social isolation/stress. The 24-item EA-QL questionnaire for children aged 8–18 (child- and parent-report) explored four domains: eating, body perception, social relationships, and health and well-being. A total of 13 questionnaires for children aged 2–7 years were completed by five parents. A negative perceived impact on their child’s eating was reported by 46–92% of parents, and less impact in the other two domains. A total of 27 questionnaires were completed by eight children aged 8–17 years and 10 parents. Similar percentages children and parents reported a negative impact in the eating, social relationships, and body perception domains. More than half reported a negative impact on the child’s health and well-being. This study supports the concept that assessment of disease-specific QoL should play a vital role in the comprehensive follow-up approach for children born with EA. We identified that parents of younger children were more likely to report eating disorders, whereas parents of older children were more likely to report health difficulties with different perceptions when it came to the child’s scar.
Configuration of the neoaortic root after chimney reconstruction in the Norwood procedure
Authors: Asada Satoshi , Oda Shinichiro , Maeda Yoshinobu , Fujita Shuhei , Hongu Hisayuki , Yamashita Eijiro , Nakatsuji Hiroki , Nagase Takashi , Nakai Rie , Hayashi Takaaki , Ikarashi Jin , Goto Yasutaka , Yamagishi Masaaki
Published: March 2024

OBJECTIVES

After staged reconstruction for hypoplastic left heart syndrome, the neoaortic root tends to dilate, and the incidence of significant neoaortic valve insufficiency increases with time. This study aimed to evaluate the mid-term outcomes of the neoaortic root geometries and valve function after chimney reconstruction in the Norwood procedure.

METHODS

Between 2013 and 2021, 20 consecutive patients who underwent chimney reconstruction during the Norwood procedure for hypoplastic left heart syndrome and its variants in our institution were enrolled. The actual diameters of the following points were measured, and Z-scores were calculated based on the normal aortic root geometries using the long axis view of echocardiography at the pre-Norwood stage and the lateral view of angiography at pre-Glenn, pre-Fontan, post-Fontan and follow-up (age 5–6 years) stages: neoaortic valve annulus; sinus of Valsalva; sinotubular junction; and ascending aorta just proximal to the anastomosis to the aortic arch. The degree of neoaortic valve regurgitation was evaluated by echocardiography at each stage.

RESULTS

The median follow-up period was 3.9 years. Neoaortic roots after chimney reconstruction were spared from progressive dilation over time. With growth, the conical configuration of the neoaortic roots was preserved without geometrical distortion. The Z-scores of the annulus, sinus of Valsalva, sinotubular junction and ascending aorta ranged roughly from 4 to 6, 4 to 6, 2 to 4 and 0 to 2, respectively. All neoaortic valves at each stage had mild or no regurgitation.

CONCLUSIONS

Chimney reconstruction prevented neoaortic root dilation and avoided significant neoaortic valve regurgitation in the mid-term. These neoaortic dimensions with smooth flow profiles in the neoaorta after chimney reconstruction may have contributed to the current results. Further studies are needed to clarify the long-term outcomes.
Fungal traits help to understand the decomposition of simple and complex plant litter
Authors: Leifheit Eva F , Camenzind Tessa , Lehmann Anika , Andrade-Linares Diana R , Fussan Max , Westhusen Sophia , Wineberger Till M , Rillig Matthias C
Published: March 2024

Litter decomposition is a key ecosystem process, relevant for the release and storage of nutrients and carbon in soil. Soil fungi are one of the dominant drivers of organic matter decomposition, but fungal taxa differ substantially in their functional ability to decompose plant litter. Knowledge is mostly based on observational data and subsequent molecular analyses and in vitro studies have been limited to forest ecosystems. In order to better understand functional traits of saprotrophic soil fungi in grassland ecosystems, we isolated 31 fungi from a natural grassland and performed several in vitro studies testing for i) leaf and wood litter decomposition, ii) the ability to use carbon sources of differing complexity, iii) the enzyme repertoire. Decomposition strongly varied among phyla and isolates, with Ascomycota decomposing the most and Mucoromycota decomposing the least. The phylogeny of the fungi and their ability to use complex carbon were the most important predictors for decomposition. Our findings show that it is crucial to understand the role of individual members and functional groups within the microbial community. This is an important way forward to understand the role of microbial community composition for the prediction of litter decomposition and subsequent potential carbon storage in grassland soils.
A novel fully distributed discrete-time min–max consensus seeking algorithm with high convergence speed
Authors: Rezaei Vahid , Khanmirza Esmaeel
Published: March 2024

In this paper, we propose a novel discrete-time consensus algorithm based on the new min–max criterion for the discrete-time second-order linear agents. To boost the convergence speed, the proposed algorithm allocates three different operating modes to the network agents. Unlike most of the existing consensus algorithms in which the links of the communication graph have specific weights and these weights are required to have positive lower bounds to achieve asymptotic convergence, the communication graph in this paper has unspecific link weights. Accordingly, because of data transmission errors and faults, the weights of the communication links can even go from a positive to a negative value. Thus, the proposed algorithm can bring the agents to consensus under more general conditions. To demonstrate the efficacy of the proposed algorithm, numerical simulations are performed, and their results are compared with those of the minimum consensus algorithm, which shows a significantly faster convergence speed.
Safety and Immunogenicity of a Messenger RNA–Based Cytomegalovirus Vaccine in Healthy Adults: Results From a Phase 1 Randomized Clinical Trial
Authors: Fierro Carlos , Brune Daniel , Shaw Marian , Schwartz Howard , Knightly Conor , Lin Jiang , Carfi Andrea , Natenshon Andrew , Kalidindi Shiva , Reuter Caroline , Miller Jacqueline , Panther Lori
Published: March 2024

Background

This phase 1 trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1647, a messenger RNA (mRNA)–based cytomegalovirus (CMV) vaccine, in CMV-seronegative and -seropositive adults.

Methods

Participants were randomly assigned to receive 30, 90, 180, or 300 µg of mRNA-1647 or placebo on a 0-, 2-, and 6-month schedule and followed for 12 months after the last dose.

Results

A total of 154 (80 CMV-seronegative and 74 CMV-seropositive) participants were enrolled; 118 participants were randomized to mRNA-1647 and 36 to placebo. Mean (standard deviation) age was 32.5 (8.6) and 35.1 (8.9) years in the placebo and mRNA-1647 groups, respectively, in phase B (63% and 64% female) and 42.5 (6.2) and 33.3 (8.7) years, respectively, in phase C (2% and 16% female). No deaths, related serious adverse events, or adverse events of special interest were reported. Most adverse reactions were grade ≤2 severity. Increased neutralizing antibody, binding antibody, and antigen-specific cell-mediated responses were observed across mRNA-1647 treatment groups, regardless of CMV serostatus.

Conclusions

This phase 1, first-in-human trial demonstrated that mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses.

Clinical Trials Registration.  NCT03382405.