bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous measurements for fast neutron flux and tritium production rate using pulse shape discrimination and single crystal CVD diamond detector
Authors: Kobayashi M.I. , Yoshihashi S. , Ogawa K. , Isobe M. , Aso T. , Hara M. , Sangaroon S. , Tamaki S. , Murata I. , Toyama S. , Miwa M. , Matsuyama S. , Osakabe M.
Published: April 2024

This paper presents the development of a simultaneous measurement method for fast neutron energy spectra and tritium production rates within mixed radiation fields using a single crystal chemical vapour deposition diamond detector combined with a lithium fluoride (LiF) foil. The method involves the separation of pulses with rectangular shapes and the determination of the depth position within the single crystal diamond (SCD) struck by fast neutrons or nuclear reaction products including recoil tritons from the LiF foil based on pulse width, extracting pulse events occurred at the specific bulk region and the surface region of the SCD. Subsequently, unfolding techniques were employed to analyse the energy deposition spectrum of pulses at the specific bulk region which are induced only by fast neutrons, allowing the deduction of the fast neutron energy spectrum. To evaluate the tritium production rate, the energy deposition spectrum of pulses from events occurring at the SCD surface facing the LiF foil was analysed. By estimating the energy deposition spectrum solely induced by fast neutrons striking the SCD surface and subtracting it from the energy deposition spectrum of events at the SCD surface, the contribution of energetic ions, such as recoil tritons generated by the 6Li(n,α)3H reaction in the LiF foil, was determined. The fast neutron flux and tritium production rate obtained through this study were consistent with particle transport calculations, demonstrating the successful development of a method suitable for performance testing of fusion reactor blankets.
Investigation of fast ion effects on core turbulence in FIRE mode plasmas
Authors: Kim D. , Park S.J. , Choi G.J. , Cho Y.W. , Kang J. , Han H. , Candy J. , Belli E.A. , Na Y.-S. , Hahm T.S. , Sung C.
Published: April 2024

Further investigation of fast ion effects on turbulence and transport in the fast ion regulated enhancement (FIRE) mode discharge (Han et al 2022 Nature
609 269–275) was performed in this work as a continuation of a previous study (Kim et al 2023 Nucl. Fusion
63 124001) that showed that the dominant turbulence suppression mechanism by fast ions is the dilution effect in the FIRE mode discharge. The current study includes (i) the impact of the fast ion relevant mode observed in the simulation of thermal energy flux, (ii) dilution effects by fast ions compared to dilution effects by other species, and (iii) fast ion effects on electron-scale turbulence. First, nonlinear gyrokinetic simulation results show that turbulence is significantly suppressed even without the fast ion relevant mode, indicating that the impact of this mode on thermal transport is not significant in this discharge. Second, further analysis on the dilution effects shows the three following results: Turbulence is not completely suppressed by the reduced main ion density fraction effect due to impurities; the reduction in energy flux can be limited by a certain impurity mode that is destabilized by a high impurity density gradient from adjusting the main ion density gradient; electrons can contribute to turbulence suppression through the main ion density gradient change, although this effect is less significant compared to other species. Third, we observe that two fast ion effects can influence the linear growth rate of the electron-scale turbulence mode. The growth rate decreases by an increase in

β
∗

(

≡

(

−
8
π

/

B
2

)

d

p

/

d

r

)

and increases by dilution effects, suggesting that fast ion effects on electron-scale turbulence can differ depending on the operation scenario, such as the fast ion fraction. The comprehensive analysis performed in this study can enhance our understanding of fast ion physics, required for burning plasma operation in the future.
Prediction of pellet mass thresholds for ELM triggering in low-collisionality, ITER-like discharges
Authors: Wingen A. , Wilcox R.S. , Lyons B.C. , Baylor L.R. , Ferraro N.M.
Published: April 2024

In ITER, pellets are calculated to require more than 8 times the mass than currently planned to reliably trigger edge-localized modes (ELMs). Unmitigated heat flux impulses from ELMs are intolerable in ITER at full power and current. Therefore, ITER operation relies on multiple approaches to control ELM heat fluxes. One method is pellet ELM pacing to instigate small rapid ELMs with low heat flux. Predicting the performance of pellet pacing is critical for ITER, which is expected to operate in a regime with a low-collisionality, peeling-limited pedestal. However, to trigger ELMs the local pressure increase in the expanding pellet cloud pushes the equilibrium over the ballooning stability limit. In this work, linear and nonlinear M3D-C1 simulations are used to predict pellet mass thresholds in DIII-D discharges and ITER scenarios with peeling-limited pedestals. It is found that the distance of the equilibrium’s operational point from the ballooning branch of the pedestal stability boundary strongly changes thresholds. Linear M3D-C1 simulations find a strong dependence of the pellet mass threshold on the poloidal injection location for ITER’s 15 MA, Q = 10 scenario. The required pellet mass at the planned injection locations is 8 to 17 times larger than currently considered. However, such linear simulations do not include pellet ablation physics or time evolution of density and temperature. A new scheme of 2D nonlinear simulations, coupled with linear stability analysis at various steps throughout the nonlinear time evolution, was developed to include such physics and improve on the linear results. These new nonlinear-to-linear simulations confirm previous findings. This result suggests that pellet ELM triggering in ITER could require pellets much larger than those currently planned, which makes ELM-pacing operationally challenging. On the other hand, fueling pellets injected from the high-field side will likely not unintentionally trigger ELMs in an otherwise ELM-stable plasma.
Integration of EDWARD readout architecture in full-field fluorescence imaging detector
Authors: Gorni D.S. , Carini G.A. , Deptuch G.W. , Kuczewski A. , Maj P. , Mandal S. , Pinaroli G. , Rumaiz A. , Siddons D.P. , John N.St.
Published: April 2024

Data bandwidth, timing resolution and resource utilization in readouts of radiation detectors are a constant challenge. Event driven solutions are pushing against well-trenched framed solutions. The idea for an asynchronous readout architecture called EDWARD (Event-Driven With Access and Reset Decoder) was presented at the TWEPP 2021 conference. Here we show the progress of our work which resulted in two chip prototypes. The first one, named 3FI65P1, is a full device with the analog pixel circuitry suited for full-field fluorescence imaging. It is already manufactured, and preliminary results are presented. The second chip, named EDWARD65P1, contains digital pulse generators with Poisson-exponential distribution in each pixel for extraction of the performance matrix of the EDWARD architecture alone.
A novel silicon pixel sensor for beam monitoring applications at heavy-ion accelerators
Authors: Tian Y. , Zhou W. , Wang Q. , Niu X. , Han W. , Yang H. , Zhang H. , Liao S. , Li X. , Zhao C.
Published: April 2024

This paper describes a silicon pixel sensor for non-interceptive real-time beam monitoring at heavy-ion accelerators. The total size of the sensor is 4 mm × 5 mm. It has 64 (row) × 120 (column) square pixels, each single of which is in the size of 40 μm × 40 μm. With the exposed sensing pad, this sensor can directly collect the charge in the media over the pixels. The in-pixel circuit mainly consists of a low-noise Charge Sensitive Amplifier (CSA) to establish the signal for the energy reconstruction and a discriminator with a Time-to-Amplitude Converter (TAC) for the Time of Arrival (TOA) measurement. The analog signal from each pixel is accessible through time-shared multiplexing over the entire pixel array. This paper will discuss the design of this IMPix-S1 sensor.
Fully synthetic, tunable poly(α-amino acids) as the base of bioinks curable by visible light
Authors: Golunova Anna , Dvořáková Jana , Velychkivska Nadiia , Strachota Beata , Dydowiczová Aneta , Trousil Jiří , Proks Vladimír
Published: April 2024

Bioinks play a crucial role in tissue engineering, influencing mechanical and chemical properties of the printed scaffold as well as the behavior of encapsulated cells. Recently, there has been a shift from animal origin materials to their synthetic alternatives. In this context, we present here bioinks based on fully synthetic and biodegradable poly(α,L-amino acids) (PolyAA) as an alternative to animal-based gelatin methacrylate (Gel-Ma) bioinks. Additionally, we first reported the possibility of the visible light photoinitiated incorporation of the bifunctional cell adhesive RGD peptide into the PolyAA hydrogel matrix. The obtained hydrogels are shown to be cytocompatible, and their mechanical properties closely resemble those of gelatin methacrylate-based scaffolds. Moreover, combining the unique properties of PolyAA-based bioinks, the photocrosslinking strategy, and the use of droplet-based printing allows the printing of constructs with high shape fidelity and structural integrity from low-viscosity bioinks without using any sacrificial components. Overall, presented PolyAA-based materials are a promising and versatile toolbox that extends the range of bioinks for droplet bioprinting.
Operational Markovianization in randomized benchmarking
Authors: Figueroa-Romero P , Papič M , Auer A , Hsieh M-H , Modi K , de Vega I
Published: April 2024

A crucial task to obtain optimal and reliable quantum devices is to quantify their overall performance. The average fidelity of quantum gates is a particular figure of merit that can be estimated efficiently by randomized benchmarking (RB). However, the concept of gate-fidelity itself relies on the crucial assumption that noise behaves in a predictable, time-local, or so-called Markovian manner, whose breakdown can naturally become the leading source of errors as quantum devices scale in size and depth. We analytically show that error suppression techniques such as dynamical decoupling (DD) and Pauli-twirling can operationally Markovianize RB: (i) fast DD reduces non-Markovian RB to an exponential decay plus longer-time corrections, while on the other hand, (ii) Pauli-twirling generally does not affect the average, but (iii) it always suppresses the variance of such RB outputs. We demonstrate these effects numerically with a qubit noise model. Our results show that simple and efficient error suppression methods can simultaneously tame non-Markovian noise and allow for standard and reliable gate quality estimation, a fundamentally important task in the path toward fully functional quantum devices.
Laser-based bionic manufacturing
Authors: Li Xingran , Zhang Baoyu , Jakobi Timothy , Yu Zhenglei , Ren Luquan , Zhang Zhihui
Published: April 2024

Over millions of years of natural evolution, organisms have developed nearly perfect structures and functions. The self-fabrication of organisms serves as a valuable source of inspiration for designing the next-generation of structural materials, and is driving the future paradigm shift of modern materials science and engineering. However, the complex structures and multifunctional integrated optimization of organisms far exceed the capability of artificial design and fabrication technology, and new manufacturing methods are urgently needed to achieve efficient reproduction of biological functions. As one of the most valuable advanced manufacturing technologies of the 21st century, laser processing technology provides an efficient solution to the critical challenges of bionic manufacturing. This review outlines the processing principles, manufacturing strategies, potential applications, challenges, and future development outlook of laser processing in bionic manufacturing domains. Three primary manufacturing strategies for laser-based bionic manufacturing are elucidated: subtractive manufacturing, equivalent manufacturing, and additive manufacturing. The progress and trends in bionic subtractive manufacturing applied to micro/nano structural surfaces, bionic equivalent manufacturing for surface strengthening, and bionic additive manufacturing aiming to achieve bionic spatial structures, are reported. Finally, the key problems faced by laser-based bionic manufacturing, its limitations, and the development trends of its existing technologies are discussed.
Self-cascode and self-biased Dickson charge pump for fast locking wide lock range PLL with reduced phase noise
Authors: Buddha Dharani , Jena Biswajit , Pandey Chandan Kumar , Nanda Umakanta , Hsu Chih-Chieh
Published: April 2024

The charge pump is a fundamental component in phase-locked loop (PLL) circuits, essential for generating a control voltage that adjusts the frequency and phase of the voltage-controlled oscillator (VCO) to match the input reference signal. The self-cascode and self-biased Dickson charge pump architecture presented in this work addresses several key challenges encountered in conventional PLL designs. By integrating self-cascode techniques, the charge pump exhibits enhanced charging and discharging capabilities, enabling faster locking times essential for wide lock range PLLs. This comprehensive approach offers a compact and integrated solution that simultaneously enhances locking speed, widens the lock range, reduces phase noise, and simplifies design complexity, making it highly suitable for demanding applications in communication systems, radar, and wireless technologies. The novel CP is implemented in 90-nm CMOS technology with a 1.0-V supply voltage. It is integrated with a phase-locked loop (PLL) that has a lock time of 1.0 us, a negligible reference spur, and an average power consumption of 34.7 mW. The PLL is having a wide lock range of 0.98 GHz to 2.98 GHz with a center frequency of 1.54 GHz where the phase noise is calculated to be −100.9 dBc/Hz at 1 MHz offset frequency. This makes the PLL compatible with both GSM having 1.8 GHz and Wi-Fi having 2.8 GHz frequency bands. The proposed PLL is also capable of operating at a wide range of temperatures (−27 °C, 0 °C, 27 °C, 84 °C) and at various corners (NN, FS, SF, SS, FF) making it reliable in adverse circumstances.
Interchangeability of multi-decade skin and surface air temperature trends over land in models
Authors: Richardson Mark T
Published: April 2024

Satellite land surface temperature (Ts
) records have now reached 20+ year length, but their trends may differ from historical records built from in-situ measurements of near-surface air temperature (Tas
). In the ERA5 reanalysis, 60° S–60° N land Ts
and Tas
trends can differ by up to ±0.06 °C decade−1 over 20 years, depending on the period, or more on smaller spatial scales. Here I use 1979–1998 outputs from ACCESS1-0 climate model simulations with prescribed land Ts
to understand changes in Ts
and Tas
. CO2’s effective radiative forcing causes adjustments that warm Tas
relative to Ts
. In ACCESS1-0, vegetation enhances the adjustments to CO2 over land. Meanwhile, feedbacks in ACCESS1-0 oppose the adjustments, resulting in small long-term net effects on global temperature estimates. In coupled simulations from other models, there is no agreement on whether Ts
or Tas
warms more and the most extreme case shows global long-term differences of just 5% between land Ts
or land Tas
trends. The results contrast with over-ocean behavior where adjustments and feedbacks reinforce each other, and drive larger long-term Tas
warming relative to Ts
across all models.
Maternal Emotions and Childrearing in China
Authors: Li Meng
Published: April 2024

Psychological research on maternal emotions often examines how mothers’ emotional expression or regulation may affect children’s development. This perpetual interest in the benefit and harm of mothers’ emotions reflects popular beliefs that women are inherently emotional and, as the primary caregiver of children, mothers must restrain and regulate their emotions in order to raise well-balanced children. Rather than treating maternal emotions as private, intrapersonal feelings, scholars from various disciplines (e.g., sociology, anthropology, communication, women’s and gender studies, etc.) have recognized that many sociocultural forces contribute to the formation and interpretation of emotions. Emotions are not just a primary means through which humans experience the world but are also an avenue for understanding both the individual and the society. The interaction between the psychological and the social is especially salient in societies undergoing radical social transformations, such as China.

In the postsocialist era (1978–present), a mother-responsible, child-centered, and education-oriented childrearing culture has emerged in China, presenting unforeseen challenges to parents. Unlike their parents’ generation who mostly adopted traditional authoritarian styles of childrearing, parents who raise children in the new cultural environment are expected to meet the multifaceted needs of their children while also cultivating intimate bonds with them. Mothers in particular carry the greatest emotional burden of childrearing. To be good mothers, they are told that they must learn how to express their emotions appropriately. Proper expressions of love and intimacy keep the channels of communication open and foster trust between generations. Expressions of negative emotions, conversely, are described by childcare experts as a potential threat to children’s psychological development. But when mothers are confronting a highly competitive education system and an increasingly narrower path for social mobility, negative emotions, such as anger and ambivalence, are inevitable and justified. Mothers from different socioeconomic backgrounds also have different emotional experiences when raising children. While urban middle-class mothers are anxious about food safety, environmental pollution, and their children’s educational achievements, rural–urban migrant mothers feel guilty for leaving their children behind in the countryside to pursue a dependable income. Overall, the Chinese case illustrates how maternal emotions can provide a unique window through which a society’s childrearing culture, intergenerational dynamics, and structural inequalities can be observed.
The North Korean Nuclear Crisis: A Non-Compensatory Explanation
Authors: Heo Uk , Welch Cassidy
Published: April 2024

Since the North Korean nuclear crisis began in the early 1990s, various efforts have been made to induce North Korea’s nuclear disarmament. Both engagement approaches as well as pressure tactics have been employed, yet nothing has worked, and North Korea is essentially a nuclear power considering that it has conducted six nuclear tests. Why do North Korea want nuclear weapons, and why have previous denuclearization efforts failed? It could be argued that the reason for the failures of previous efforts is that these strategies did not address the underlying basis for North Korea’s nuclear pursuit, regime security. Utilizing the poliheuristic theory, the motive of North Korea’s nuclear development and why previous policies have failed may be theoretically and empirically explained.
Combat Games in the Black Atlantic, 17th–19th Centuries
Authors: Assunção Matthias Röhrig
Published: April 2024

Combat games are attested in Africa from the time of the transatlantic slave trade and throughout the 19th century. In the agricultural societies in the rainforest of West and West Central Africa, wrestling was the most common form, while pastoral societies in the savannahs of central and southern Africa excelled in stick fighting. Fist fighting, slap boxing, and kicking also constituted the base of combat games in some locations.

The enslaved Africans and their descendants made use of these bodily techniques in the plantation societies of the Americas and the Indian Ocean. The new oppressive context of slavery led to adjustments of techniques and practice. Stick fighting was widespread in Brazil and the Caribbean, whereas wrestling only became important in the United States. The previously rather marginal techniques of kicking and head butting became central to capoeira, ladja, and moring, even though it is difficult to establish precise genealogies.

Bodily techniques were onlys one aspect of the complex cultural reinvention of combat games in the Atlantic world. African religious practices such as protections from supernatural forces and broader cultural meanings were incorporated into African-derived and creole combat games. While keeping some of their former social function, combat games in the “New World” also acquired new, contradictory meanings as either tools of resistance, spectacle for monetary gains, or even instruments of oppression. They provided an early example of globalization of bodily techniques and cultural meanings, and the most successful ones, such as capoeira, continue to expand worldwide to this day.
Labor Market Returns to Higher Education
Authors: Azmat Ghazala , Britton Jack
Published: April 2024

The persistent high wage premium associated with college education, despite increasing participation rates, continues to generate a great deal of academic and policy interest. While it is widely agreed that the financial benefits associated with college completion outweigh the costs, modeling and empirically estimating the returns are complicated. A simple theoretical framework on educational investment illustrates the decision-making processes and key factors, such as expected returns, that guide the choice of an individual to engage in higher education and to achieve an optimal level of educational investment. Broadening the investment model, however, is instrumental to account for potential heterogeneous returns to higher education—the variation in returns by institution, field of study, and students’ background characteristics, among others—and to recognize the wider societal benefits of higher education, beyond private returns.

The challenges involved in estimating the returns to higher education and the heterogeneity in returns are central in the discussion. Interpreting a naive correlation between education and wages is complicated by the nonrandom selection of individuals into higher education, such that individuals who are most likely to benefit from higher education are also those most likely to attend. Advancements in data collection, the ability to track individuals from compulsory education to the labor market, and improvements in econometric methodologies have enabled researchers to causally estimate the impact of higher education on earnings and allow for an improved insight into the disparities in returns to higher education. Recognizing the links between students’ characteristics (or backgrounds) and associated constraints helps to understand differences in higher education choices. Similarly, identifying differences in labor market returns associated with attending certain colleges or pursuing particular academic disciplines is as important in shedding light on the complex nature of human capital disparities and the signaling effect of higher education.

As the costs of higher education provision constitute an increasingly large share of government spending all over the world, the high returns to college raise questions associated with who should pay for attending college and the role of the state. Internalizing the social returns to education and their broader implications on the growth and the persistence of inequality complicates this discussion. Higher education funding is one potential policy instrument to influence college attendance and returns. It is not, however, the only one. Better information on returns to education or access to policies that target members of certain social groups might be other potential tools to overcome constraints.
Writing Systems in Modern West Germanic
Authors: Evertz-Rittich Martin
Published: April 2024

The writing systems of the modern West Germanic languages have many features in common: They are all written using the Modern Roman Alphabet and exhibit a certain depth, that is, in addition to the pure grapheme–phoneme correspondences, prosodic, morphological, and syntactic information that is systematically encoded in their writing systems. A notable exception is the writing system of Yiddish, which is not only written with an alphabet evolved from the Hebrew script but is also almost completely transparent.

Except for Yiddish, all writing systems of modern West Germanic languages use graphematic syllable and foot structures to encode suprasegmental properties such as vowel quantity. Paradigmatic relations are represented by morphological spellings (especially stem and affix constancy). Syntagmatic relations are expressed, for example, in compound spelling, which adheres to the same principles in all writing systems under discussion.

The writing systems of modern West Germanic languages have been studied by grapholinguists in varying depth. While German is probably the best researched writing system in the world, some writing systems, such as Luxembourgish, await thorough grapholinguistic investigation.
Shannon, Mary Coleen
Authors: Jordan Catheleen , Cobb Norman H. , Cory David L.
Published: April 2024

Mary Coleen Shannon (1940–2001) was a pioneer in biofeedback and autogenic training and in advocating for gender equity among faculty and practitioners. She was instrumental in integrating biofeedback into social work practice and made further contributions to social work, particularly in the area of gender equity. Her influence was felt during her years as an associate professor of social work at the University of Texas at Arlington from 1970 until her death in 2001 and posthumous professor emerita recognition.
Exemplary Damages Practice in Late Eighteenth and Early Nineteenth-Century England
Authors: Sinanis Nicholas
Published: April 2024

A longer perspective on the modern Anglo-American law of exemplary (or punitive) damages views it as having first begun to emerge after the cases of Huckle v Money and Wilkes v Wood were decided in 1763. This article seeks to further deepen and clarify this perspective. It does so by systematically tracing the evolution of the adjudicative practice according to which English civil juries awarded ‘exemplary damages’ from the period circa 1764 to the early nineteenth century. It shows that this practice scarcely ‘hardened into law’ in the aftermath of the Huckle and Wilkes decisions. In fact, as had been the case long before 1763, for a long time after it, jury determinations as to exemplary damages in common law tort actions remained entirely outside the control of any formal legal doctrine which either of these decisions were taken to have authoritatively recognized.
MGCNSS: miRNA–disease association prediction with multi-layer graph convolution and distance-based negative sample selection strategy
Authors: Tian Zhen , Han Chenguang , Xu Lewen , Teng Zhixia , Song Wei
Published: April 2024

Identifying disease-associated microRNAs (miRNAs) could help understand the deep mechanism of diseases, which promotes the development of new medicine. Recently, network-based approaches have been widely proposed for inferring the potential associations between miRNAs and diseases. However, these approaches ignore the importance of different relations in meta-paths when learning the embeddings of miRNAs and diseases. Besides, they pay little attention to screening out reliable negative samples which is crucial for improving the prediction accuracy. In this study, we propose a novel approach named MGCNSS with the multi-layer graph convolution and high-quality negative sample selection strategy. Specifically, MGCNSS first constructs a comprehensive heterogeneous network by integrating miRNA and disease similarity networks coupled with their known association relationships. Then, we employ the multi-layer graph convolution to automatically capture the meta-path relations with different lengths in the heterogeneous network and learn the discriminative representations of miRNAs and diseases. After that, MGCNSS establishes a highly reliable negative sample set from the unlabeled sample set with the negative distance-based sample selection strategy. Finally, we train MGCNSS under an unsupervised learning manner and predict the potential associations between miRNAs and diseases. The experimental results fully demonstrate that MGCNSS outperforms all baseline methods on both balanced and imbalanced datasets. More importantly, we conduct case studies on colon neoplasms and esophageal neoplasms, further confirming the ability of MGCNSS to detect potential candidate miRNAs. The source code is publicly available on GitHub https://github.com/15136943622/MGCNSS/tree/master
Community cohesion looseness in gene networks reveals individualized drug targets and resistance
Authors: Wang Seunghyun , Lee Doheon
Published: April 2024

Community cohesion plays a critical role in the determination of an individual’s health in social science. Intriguingly, a community structure of gene networks indicates that the concept of community cohesion could be applied between the genes as well to overcome the limitations of single gene-based biomarkers for precision oncology. Here, we develop community cohesion scores which precisely quantify the community ability to retain the interactions between the genes and their cellular functions in each individualized gene network. Using breast cancer as a proof-of-concept study, we measure the community cohesion score profiles of 950 case samples and predict the individualized therapeutic targets in 2-fold. First, we prioritize them by finding druggable genes present in the community with the most and relatively decreased scores in each individual. Then, we pinpoint more individualized therapeutic targets by discovering the genes which greatly contribute to the community cohesion looseness in each individualized gene network. Compared with the previous approaches, the community cohesion scores show at least four times higher performance in predicting effective individualized chemotherapy targets based on drug sensitivity data. Furthermore, the community cohesion scores successfully discover the known breast cancer subtypes and we suggest new targeted therapy targets for triple negative breast cancer (e.g. KIT and GABRP). Lastly, we demonstrate that the community cohesion scores can predict tamoxifen responses in ER+ breast cancer and suggest potential combination therapies (e.g. NAMPT and RXRA inhibitors) to reduce endocrine therapy resistance based on individualized characteristics. Our method opens new perspectives for the biomarker development in precision oncology.
Clinical phenotype of the PIK3R1-related vascular overgrowth syndrome
Authors: Kuentz Paul , Engel Camille , Laeng Mathieu , Chevarin Martin , Duffourd Yannis , Martel Jéhanne , Piard Juliette , Morice-Picard Fanny , Aubert Helene , Bessis Didier , Guerrot Anne-Marie , Maruani Annabel , Boccara Olivia , Mazereeuw-Hautier Juliette , Ott Hagen , Phan Alice , Puzenat Eve , Quelin Chloe , Thauvin-Robinet Christel , Faivre Laurence , Vabres Pierre
Published: April 2024

Here we report 19 additional patients with PIK3R1 mosaic variants with clinical phenotyping, showing that the PIK3R1 phenotype is indistinguishable from the PIK3CA-related phenotypes, although the megalencephaly-capillary malformation phenotype is consistently absent in patients with PIK3R1 variants. We also report novel PIK3R1 variants. We consider that the meaning of PROS should shift from ‘PIK3CA-related overgrowth spectrum’ to ‘PI3-kinase-related overgrowth spectrum’.
Dysregulated lipid metabolism networks modulate T-cell function in people with relapsing-remitting multiple sclerosis
Authors: Martin-Gutierrez Lucia , Waddington Kirsty E , Maggio Annalisa , Coelewij Leda , Oppong Alexandra E , Yang Nina , Adriani Marsilio , Nytrova Petra , Farrell Rachel , Pineda-Torra Inés , Jury Elizabeth C
Published: April 2024

Altered cholesterol, oxysterol, sphingolipid, and fatty acid concentrations are reported in blood, cerebrospinal fluid, and brain tissue of people with relapsing-remitting multiple sclerosis (RRMS) and are linked to disease progression and treatment responses. CD4 + T cells are pathogenic in RRMS, and defective T-cell function could be mediated in part by liver X receptors (LXRs)—nuclear receptors that regulate lipid homeostasis and immunity. RNA-sequencing and pathway analysis identified that genes within the ‘lipid metabolism’ and ‘signalling of nuclear receptors’ pathways were dysregulated in CD4 + T cells isolated from RRMS patients compared with healthy donors. While LXRB and genes associated with cholesterol metabolism were upregulated, other T-cell LXR-target genes, including genes involved in cellular lipid uptake (inducible degrader of the LDL receptor, IDOL), and the rate-limiting enzyme for glycosphingolipid biosynthesis (UDP-glucosylceramide synthase, UGCG) were downregulated in T cells from patients with RRMS compared to healthy donors. Correspondingly, plasma membrane glycosphingolipids were reduced, and cholesterol levels increased in RRMS CD4 + T cells, an effect partially recapitulated in healthy T cells by in vitro culture with T-cell receptor stimulation in the presence of serum from RRMS patients. Notably, stimulation with LXR-agonist GW3965 normalized membrane cholesterol levels, and reduced proliferation and IL17 cytokine production in RRMS CD4 + T-cells. Thus, LXR-mediated lipid metabolism pathways were dysregulated in T cells from patients with RRMS and could contribute to RRMS pathogenesis. Therapies that modify lipid metabolism could help restore immune cell function.
Synthesis of N-oxide Poly(1-vinylimidazole) for pDNA delivery systems in vivo
Authors: Misaizu Ren , Negishi Yoichi , Asayama Shoichiro
Published: April 2024

N-oxide poly(1-vinylimidazole) (PVIm+–O−) has been synthesized as a unique biocompatible polyampholyte. Measurements of solution turbidity prove that PVIm+–O− had no significant effect on rapid aggregate formation with serum proteins. Agarose gel retardation assay, particle size/ζ-potential measurement, and cytotoxicity evaluation prove that the PVIm+–O− coated binary complexes between branched poly(ethyleneimine) (bPEI) and plasmid DNA (pDNA). The resulting PVIm+–O−/bPEI/pDNA ternary complex mediated higher gene expression than the bPEI/pDNA binary complex in vivo mouse skeletal muscle. These results suggest that PVIm+–O− is a polyampholyte for biocompatibility.
Hardly water-soluble pseudo-polyrotaxane nanosheets comprising polyethylene-oxide-modified polydimethylsiloxane and gamma-cyclodextrin
Authors: Sugiyama Kazuhiro , Hayashi Kaori , Sakaihara Yuji , Uenuma Shuntaro , Ito Kohzo
Published: April 2024

We have successfully prepared hardy water-soluble pseudo-polyrotaxane nanosheets composed of carboxy group-terminated polyethylene oxide (PEO)-modified polydimethylsiloxane and γ-cyclodextrin (CD). These pseudo-polyrotaxane nanosheets are more water-insoluble than previously reported pseudo-polyrotaxane nanosheets composed of pluronic—a triblock polymer comprising PEO, polypropylene oxide (PPO), and PEO—and β-CD, and have potential applications as surface treatment agents.
Ten tips on how to assess bone health in patients with chronic kidney disease
Authors: Jørgensen Hanne Skou , Lloret Maria Jesús , Lalayiannis Alexander D , Shroff Rukshana , Evenepoel Pieter ,   European Renal Osteodystrophy (EUROD) initiative of the CKD-MBD working group of the European Renal Association (ERA), and the CKD-MBD and Dialysis working groups of the European Society of Pediatric Nephrology, Bacchetta Justine , Bravenboer Nathalie , Ferreira Anibal , Fusaro Maria , Haarhaus Mathias , Lafage-Proust Marie-Helene
Published: April 2024

Patients with chronic kidney disease (CKD) experience a several-fold increased risk of fracture. Despite the high incidence and the associated excess morbidity and premature mortality, bone fragility in CKD, or CKD-associated osteoporosis, remains a blind spot in nephrology with an immense treatment gap. Defining the bone phenotype is a prerequisite for the appropriate therapy of CKD-associated osteoporosis at the patient level. In the present review, we suggest 10 practical ‘tips and tricks’ for the assessment of bone health in patients with CKD. We describe the clinical, biochemical, and radiological evaluation of bone health, alongside the benefits and limitations of the available diagnostics. A bone biopsy, the gold standard for diagnosing renal bone disease, is invasive and not widely available; although useful in complex cases, we do not consider it an essential component of bone assessment in patients with CKD-associated osteoporosis. Furthermore, we advocate for the deployment of multidisciplinary expert teams at local, national, and potentially international level. Finally, we address the knowledge gaps in the diagnosis, particularly early detection, appropriate “real-time” monitoring of bone health in this highly vulnerable population, and emerging diagnostic tools, currently primarily used in research, that may be on the horizon of clinical practice.
Online calls for protest and offline mobilization in autocracies: evidence from the 2017 Dey Protests in Iran
Authors: Kadivar Mohammad Ali , Ketchley Neil , Sotoudeh-Sherbaf Abolfazl , Barrie Christopher
Published: April 2024

A body of research suggests that social media has afforded new opportunities for orchestrating mobilization in autocracies. However, the mechanisms linking online coordination with offline mobilization are rarely demonstrated. We address this lacuna by exploring the impact of Farsi-language social media posts that called for protest on precise days and locations in Iran during the 2017 ‘Dey Protests’. To conduct our analysis, we match a dataset of posts with an original protest event catalogue. Our results show that if a district was the subject of a protest call, it was much more likely to witness higher levels of mobilization on the target date. This relationship was especially pronounced for calls that received more online engagement. The findings suggest that the digital commons can play a role akin to an analogue protest flyer: social media posts can inform broad audiences of the where and when of upcoming mobilization.
Unstable employment careers and (quasi-)completed fertility: evidence from the labour market deregulation in Italy
Authors: Alderotti Giammarco , Guetto Raffaele , Barbieri Paolo , Scherer Stefani , Vignoli Daniele
Published: April 2024

Most research on the fertility consequences of labour market instability has focussed on the transition to parenthood, ignoring potential ‘catching up’ effects and, thus, the more encompassing view on cohort fertility. This work extends on this point by analysing the consequences of employment instability on (quasi-)completed fertility for men and women in Italy. From a cohort perspective, we look at fertility outcomes at age 41 among those who experienced labour market deregulation (cohorts born between 1966 and 1975) in comparison with the previous cohorts (those born between 1951 and 1965) and relate the fertility outcome to the instability of their employment histories. Based on data from a large-scale, nationally representative retrospective survey, we find that fragmented employment careers and atypical employment periods come with a lower likelihood of ever becoming a parent and a higher probability of having fewer children compared to those with continuous, stable careers. Our study suggests that the consequences of rising labour market instability not only lead to a postponement of childbearing but also lead to overall lower numbers of children, especially for men and younger cohorts. This study adds to previous research by suggesting that recuperation in employment instability-induced childbearing postponement does not take place to a sufficient extent, at least in Italy.
Body mass index, waist circumference, and mortality in subjects older than 80 years: a Mendelian randomization study
Authors: Lv Yuebin , Zhang Yue , Li Xinwei , Gao Xiang , Ren Yongyong , Deng Luojia , Xu Lanjing , Zhou Jinhui , Wu Bing , Wei Yuan , Cui Xingyao , Xu Zinan , Guo Yanbo , Qiu Yidan , Ye Lihong , Chen Chen , Wang Jun , Li Chenfeng , Luo Yufei , Yin Zhaoxue , Mao Chen , Yu Qiong , Lu Hui , Kraus Virginia Byers , Zeng Yi , Tong Shilu , Shi Xiaoming
Published: April 2024

Background and Aims

Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China.

Methods

A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality.

Results

During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955–0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950–0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928–0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036–1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064–1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016–1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC.

Conclusions

Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.
Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry
Authors: Ahn Hyun Jin , Oh Il-Young , Choi JungMin , Lee Kyung-Yeon , Ahn Hyo-Jeong , Kwon Soonil , Choi Eue-Keun , Oh Seil , Kim Ju Youn , Cha Myung-Jin , Kwon Chang Hee , Lee Sung Ho , Park Junbeom , Kim Ki-Hun , Yang Pil-Sung , Kim Jun-Hyung , Shim Jaemin , Lim Hong Euy , Lee So-Ryoung
Published: April 2024

Aims

Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians.

Methods and results

Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5–23, normal, NW; 23–25, overweight, OW; 25–30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18–5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94–8.99, P = 0.07), mainly due to transient phrenic nerve palsy.

Conclusion

Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.
Comparative population genomics reveals convergent and divergent selection in the apricot–peach–plum–mei complex
Authors: Yang Xuanwen , Su Ying , Huang Siyang , Hou Qiandong , Wei Pengcheng , Hao Yani , Huang Jiaqi , Xiao Hua , Ma Zhiyao , Xu Xiaodong , Wang Xu , Cao Shuo , Cao Xuejing , Zhang Mengyan , Wen Xiaopeng , Ma Yuhua , Peng Yanling , Zhou Yongfeng , Cao Ke , Qiao Guang
Published: April 2024

The economically significant genus Prunus includes fruit and nut crops that have been domesticated for shared and specific agronomic traits; however, the genomic signals of convergent and divergent selection have not been elucidated. In this study, we aimed to detect genomic signatures of convergent and divergent selection by conducting comparative population genomic analyses of the apricot–peach–plum–mei (APPM) complex, utilizing a haplotype-resolved telomere-to-telomere (T2T) genome assembly and population resequencing data. The haplotype-resolved T2T reference genome for the plum cultivar was assembled through HiFi and Hi-C reads, resulting in two haplotypes 251.25 and 251.29 Mb in size, respectively. Comparative genomics reveals a chromosomal translocation of ~1.17 Mb in the apricot genomes compared with peach, plum, and mei. Notably, the translocation involves the D locus, significantly impacting titratable acidity (TA), pH, and sugar content. Population genetic analysis detected substantial gene flow between plum and apricot, with introgression regions enriched in post-embryonic development and pollen germination processes. Comparative population genetic analyses revealed convergent selection for stress tolerance, flower development, and fruit ripening, along with divergent selection shaping specific crop, such as somatic embryogenesis in plum, pollen germination in mei, and hormone regulation in peach. Notably, selective sweeps on chromosome 7 coincide with a chromosomal collinearity from the comparative genomics, impacting key fruit-softening genes such as PG, regulated by ERF and RMA1H1. Overall, this study provides insights into the genetic diversity, evolutionary history, and domestication of the APPM complex, offering valuable implications for genetic studies and breeding programs of Prunus crops.