bluuebunny/crossref_metadata_2025 huggingface dataset:
Smooth muscle α-actin missense variant promotes atherosclerosis through modulation of intracellular cholesterol in smooth muscle cells
Authors: Kaw Kaveeta , Chattopadhyay Abhijnan , Guan Pujun , Chen Jiyuan , Majumder Suravi , Duan Xue-yan , Ma Shuangtao , Zhang Chen , Kwartler Callie S , Milewicz Dianna M
Published: June 2023

Aims

The variant p.Arg149Cys in ACTA2, which encodes smooth muscle cell (SMC)-specific α-actin, predisposes to thoracic aortic disease and early onset coronary artery disease in individuals without cardiovascular risk factors. This study investigated how this variant drives increased atherosclerosis.

Methods and results

Apoe−/− mice with and without the variant were fed a high-fat diet for 12 weeks, followed by evaluation of atherosclerotic plaque formation and single-cell transcriptomics analysis. SMCs explanted from Acta2R149C/+ and wildtype (WT) ascending aortas were used to investigate atherosclerosis-associated SMC phenotypic modulation. Hyperlipidemic Acta2R149C/+Apoe−/− mice have a 2.5-fold increase in atherosclerotic plaque burden compared to Apoe−/− mice with no differences in serum lipid levels. At the cellular level, misfolding of the R149C α-actin activates heat shock factor 1, which increases endogenous cholesterol biosynthesis and intracellular cholesterol levels through increased HMG-CoA reductase (HMG-CoAR) expression and activity. The increased cellular cholesterol in Acta2R149C/+ SMCs induces endoplasmic reticulum stress and activates PERK-ATF4-KLF4 signaling to drive atherosclerosis-associated phenotypic modulation in the absence of exogenous cholesterol, while WT cells require higher levels of exogenous cholesterol to drive phenotypic modulation. Treatment with the HMG-CoAR inhibitor pravastatin successfully reverses the increased atherosclerotic plaque burden in Acta2R149C/+Apoe−/− mice.

Conclusion

These data establish a novel mechanism by which a pathogenic missense variant in a smooth muscle-specific contractile protein predisposes to atherosclerosis in individuals without hypercholesterolemia or other risk factors. The results emphasize the role of increased intracellular cholesterol levels in driving SMC phenotypic modulation and atherosclerotic plaque burden.
Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice
Authors: Zhang Yang , Wang Xiaoman , Li Xun-Kai , Lv Shuang-Jie , Wang He-Ping , Liu Yang , Zhou Jingyue , Gong Hui , Chen Xiao-Feng , Ren Si-Chong , Zhang Huina , Dai Yuxiang , Cai Hua , Yan Bo , Chen Hou-Zao , Tang Xiaoqiang
Published: June 2023

Aims

The mechanisms underlying ageing-induced vascular remodelling remain unclear. This study investigates the role and underlying mechanisms of the cytoplasmic deacetylase sirtuin 2 (SIRT2) in ageing-induced vascular remodelling.

Methods and results

Transcriptome and quantitative real-time PCR data were used to analyse sirtuin expression. Young and old wild-type and Sirt2 knockout mice were used to explore vascular function and pathological remodelling. RNA-seq, histochemical staining, and biochemical assays were used to evaluate the effects of Sirt2 knockout on the vascular transcriptome and pathological remodelling and explore the underlying biochemical mechanisms. Among the sirtuins, SIRT2 had the highest levels in human and mouse aortas. Sirtuin 2 activity was reduced in aged aortas, and loss of SIRT2 accelerated vascular ageing. In old mice, SIRT2 deficiency aggravated ageing-induced arterial stiffness and constriction–relaxation dysfunction, accompanied by aortic remodelling (thickened vascular medial layers, breakage of elastin fibres, collagen deposition, and inflammation). Transcriptome and biochemical analyses revealed that the ageing-controlling protein p66Shc and metabolism of mitochondrial reactive oxygen species (mROS) contributed to SIRT2 function in vascular ageing. Sirtuin 2 repressed p66Shc activation and mROS production by deacetylating p66Shc at lysine 81. Elimination of reactive oxygen species by MnTBAP repressed the SIRT2 deficiency–mediated aggravation of vascular remodelling and dysfunction in angiotensin II–challenged and aged mice. The SIRT2 coexpression module in aortas was reduced with ageing across species and was a significant predictor of age-related aortic diseases in humans.

Conclusion

The deacetylase SIRT2 is a response to ageing that delays vascular ageing, and the cytoplasm–mitochondria axis (SIRT2–p66Shc–mROS) is important for vascular ageing. Therefore, SIRT2 may serve as a potential therapeutic target for vascular rejuvenation.
Robust deep learning-based fault detection of planetary gearbox using enhanced health data map under domain shift problem
Authors: Hwang Taewan , Ha Jong Moon , Youn Byeng D
Published: June 2023

The conventional deep learning-based fault diagnosis approach faces challenges under the domain shift problem, where the model encounters different working conditions from the ones it was trained on. This challenge is particularly pronounced in the diagnosis of planetary gearboxes due to the complicated vibrations they generate, which can vary significantly based on the system characteristics of the gearbox. To solve this challenge, this paper proposes a robust deep learning-based fault-detection approach for planetary gearboxes by utilizing an enhanced health data map (HDMap). Although there is an HDMap method that visually expresses the vibration signal of the planetary gearbox according to the gear meshing position, it is greatly influenced by machine operating conditions. In this study, domain-specific features from the HDMap are further removed, while the fault-related features are enhanced. Autoencoder-based residual analysis and digital image-processing techniques are employed to address the domain-shift problem. The performance of the proposed method was validated under significant domain-shift problem conditions, as demonstrated by studying two gearbox test rigs with different configurations operated under stationary and non-stationary operating conditions. Validation accuracy was measured in all 12 possible domain-shift scenarios. The proposed method achieved robust fault detection accuracy, outperforming prior methods in most cases.
Documenting Twenty Years of the Contracted Labor-Intensive Forestry Workforce on National Forest System Lands in the United States
Authors: Deak Alison , Huber-Stearns Heidi , Crandall Mindy , Poudel Kamana , Davis Emily Jane , Coughlan Michael R , Wilmsen Carl
Published: June 2023

This paper presents the first nationwide analysis detailing the scope and scale of labor-intensive forestry contracts performed on National Forest System lands and examines the businesses contracted, location and types of work performed, and distance traveled by businesses between 2001 and 2020. During the study period, 61,698 contracts were awarded to 7,896 businesses, totaling $12.9 billion, to perform labor-intensive forestry work, with most work being contracted for wildfire-related activities. Businesses were typically located in western states and non-minority owned businesses received the majority of contracts. Of minority-owned businesses, Hispanic American–owned businesses received the most contracts. The median distance that businesses traveled to accomplish work increased significantly through time but differed by business type. Understanding the scope and work of businesses awarded contracts provides insight into the workforce and its relationship to marginalized populations. Strategic investment in this workforce may have widespread impacts on federal, state, and local economies and the livelihoods of forest workers.

Study Implications: Between 2001–2020, the USDA Forest Service spent billions of dollars on contracts with thousands of businesses to conduct labor-intensive forestry projects; however, project locations and awarded businesses were not evenly distributed through space and time. Emerging and minority businesses represented a small proportion of contracts awarded. Advancing understanding of the businesses conducting labor-intensive forestry work lays the foundation for inquiry into the working conditions forest workers experience as well as disparities in contract capture. Some regions may have benefitted more from contract capture than others. Understanding factors enabling places and businesses to capture these contract dollars may help identify others that may benefit from investment.
Genome shock in a synthetic allotetraploid wheat invokes subgenome-partitioned gene regulation, meiotic instability, and karyotype variation
Authors: Sha Yan , Li Yang , Zhang Deshi , Lv Ruili , Wang Han , Wang Ruisi , Ji Heyu , Li Shuhang , Gong Lei , Li Ning , Liu Bao
Published: June 2023

It is becoming increasingly evident that interspecific hybridization at the homoploid level or coupled with whole-genome duplication (i.e. allopolyploidization) has played a major role in biological evolution. However, the direct impacts of hybridization and allopolyploidization on genome structure and function, phenotype, and fitness remains to be fully understood. Synthetic hybrids and allopolyploids are trackable experimental systems that can be used to address this issue. In this study, we resynthesized a pair of reciprocal F1 hybrids and corresponding reciprocal allotetraploids using the two diploid progenitor species of bread wheat (Triticum aestivum, BBAADD), namely T. urartu (AA) and Aegilops tauschii (DD). By comparing phenotypes related to growth, development, and fitness, and by analysing genome expression in both hybrids and allotetraploids in relation to the parents, we found that the types and trends of karyotype variation in the immediately formed allotetraploids were correlated with both instability of meiosis and chromosome- and subgenome-biased expression. We determined clear advantages of allotetraploids over diploid F1 hybrids in several morphological traits including fitness that mirrored the tissue- and developmental stage-dependent subgenome-partitioning of the allotetraploids. The allotetraploids were meiotically unstable primarily due to homoeologous pairing that varied dramatically among the chromosomes. Nonetheless, the manifestation of organismal karyotype variation and the occurrence of meiotic irregularity were not concordant, suggesting a role of functional constraints probably imposed by subgenome- and chromosome-biased gene expression. Our results provide new insights into the direct impacts and consequences of hybridization and allopolyploidization that are relevant to evolution and likely to be informative for future crop improvement approaches using synthetic polyploids.
Very massive stars and pair-instability supernovae: mass-loss framework for low metallicity
Authors: Sabhahit Gautham N , Vink Jorick S , Sander Andreas A C , Higgins Erin R
Published: June 2023

Very massive stars (VMS) up to 200–300 M⊙ have been found in the Local Universe. If they would lose little mass, they produce intermediate-mass black holes or pair-instability supernovae (PISNe). Until now, VMS modellers have extrapolated mass-loss versus metallicity (Z) exponents from optically thin winds, resulting in a range of PISN thresholds that might be unrealistically high in Z, as VMS develop optically thick winds. We utilize the transition mass-loss rate of Vink and Gräfener (2012) that accurately predicts mass-loss rates of Of/WNh (‘slash’) stars that characterize the morphological transition from absorption-dominated O-type spectra to emission-dominated WNh spectra. We develop a wind efficiency framework, where optically thin winds transition to enhanced winds, enabling us to study VMS evolution at high redshift where individual stars cannot be resolved. We present a MESA grid covering Z⊙/2 to Z⊙/100. VMS above the transition evolve towards lower luminosity, skipping the cool supergiant phase but directly forming pure He stars at the end of hydrogen burning. Below the transition, VMS evolve as cooler luminous blue variables (LBVs) or yellow hypergiants (YHGs), naturally approaching the Eddington limit. Strong winds in this YHG/LBV regime – combined with a degeneracy in luminosity – result in a mass-loss runaway, where a decrease in mass increases wind mass loss. Our models indicate an order-of-magnitude lower metallicity threshold for PISN than usually assumed, at Z⊙/20 due to our mass-loss runaway. While future work on LBV mass loss could affect the PISN threshold, our framework will be critical for establishing definitive answers on the PISN threshold and galactic chemical evolution modelling.
Catching a nova X-ray/UV flash in the visible? Early spectroscopy of the very slow Nova Velorum 2022 (Gaia22alz)
Authors: Aydi E , Chomiuk L , Mikołajewska J , Brink J , Metzger B D , Strader J , Buckley D A H , Harvey E J , Holoien T W -S , Izzo L , Kawash A , Linford J D , Molaro P , Molina I , Mróz P , Mukai K , Orio M , Panurach T , Senchyna P , Shappee B J , Shen K J , Sokoloski J L , Sokolovsky K V , Urquhart R , Williams R E
Published: June 2023

We present early spectral observations of the very slow Galactic nova Gaia22alz, over its gradual rise to peak brightness that lasted 180 d. During the first 50 d, when the nova was only 3–4 mag above its normal brightness, the spectra showed narrow (FWHM ≈ 400 km s−1) emission lines of H Balmer, He i, He ii, and C iv but no P Cygni absorption. A few weeks later, the high-excitation He ii and C iv lines disappeared, and P Cygni profiles of Balmer, He i, and eventually Fe ii lines emerged, yielding a spectrum typical of classical novae before peak. We propose that the early (first 50 d) spectra of Gaia22alz, particularly the emission lines with no P Cygni profiles, are produced in the white dwarf’s optically thin envelope or accretion disc, reprocessing ultraviolet and potentially X-ray emission from the white dwarf after a dramatic increase in the rate of thermonuclear reactions, during a phase known as the ‘early X-ray/UV flash’. If true, this would be one of the rare times that the optical signature of the early X-ray/UV flash has been detected. While this phase might last only a few hours in other novae and thus be easily missed, it was possible to detect in Gaia22alz due to its very slow and gradual rise and thanks to the efficiency of new all-sky surveys in detecting transients on their rise. We also consider alternative scenarios that could explain the early spectral features of Gaia22alz and its gradual rise.
The oblateness of the Milky Way dark matter halo from the stellar streams of NGC 3201, M68, and Palomar 5
Authors: Palau Carles G , Miralda-Escudé Jordi
Published: June 2023

We explore constraints on the Milky Way dark matter halo oblateness using three stellar streams from globular clusters NGC3201, M68, and Palomar 5. Previous constraints on the gravitational potential from dynamical equilibrium of stellar populations and distant Milky Way satellites are included. We model the dark halo as axisymmetric with axis ratio $q_\rho ^{\rm h}$ and four additional free parameters of a two power-law density profile. The halo axis ratio, while barely constrained by the NGC3201 stream alone, is required to be close to spherical by the streams of Palomar 5 ($q_\rho ^{\rm h}=1.01\pm 0.09$) and M68 ($q_\rho ^{\rm h}=1.14^{+0.21}_{-0.14}$), the latter allowing a more prolate shape. The three streams together are well fitted with a halo axis ratio $q_\rho ^{\rm h}=1.06 \pm 0.06$ and core radius ∼20 kpc. Our estimate of the halo shape agrees with previous studies using other observational data and is in tension with cosmological simulations, predicting that most spiral galaxies have oblate dark matter haloes with the short axis perpendicular to the disc. We discuss why the impact of the Magellanic Clouds tide is too small to change our conclusion on the halo axis ratio. We note that dynamical equilibrium of a spherical halo in the oblate disc potential implies an anisotropic dark matter velocity dispersion, larger along the vertical direction than the horizontal ones, which should relate to the assembly history of the Milky Way.
Connecting the young pulsars in Milky Way globular clusters with white dwarf mergers and the M81 fast radio burst
Authors: Kremer Kyle , Fuller Jim , Piro Anthony L , Ransom Scott M
Published: June 2023

The detections of four apparently young radio pulsars in the Milky Way globular clusters are difficult to reconcile with standard neutron star formation scenarios associated with massive star evolution. Here, we discuss formation of these young pulsars through white dwarf mergers in dynamically old clusters that have undergone core collapse. Based on observed properties of magnetic white dwarfs, we argue neutron stars formed via white dwarf merger are born with spin periods of roughly $10{\!-\!}100\,$ ms and magnetic fields of roughly $10^{11}{\!-\!}10^{13}\,$ G. As these neutron stars spin down via magnetic dipole radiation, they naturally reproduce the four observed young pulsars in the Milky Way clusters. Rates inferred from N-body cluster simulations as well as the binarity, host cluster properties, and cluster offsets observed for these young pulsars hint further at a white dwarf merger origin. These young pulsars may be descendants of neutron stars capable of powering fast radio bursts analogous to the bursts observed recently in a globular cluster in M81.
Direct m6A recognition by IMP1 underlays an alternative model of target selection for non-canonical methyl-readers
Authors: Nicastro Giuseppe , Abis Giancarlo , Klein Pierre , Esteban-Serna Sofia , Gallagher Christopher , Chaves-Arquero Belen , Cai Yuyang , Figueiredo Angelo Miguel , Martin Stephen R , Patani Rickie , Taylor Ian A , Ramos Andres
Published: June 2023

m6A methylation provides an essential layer of regulation in organismal development, and is aberrant in a range of cancers and neuro-pathologies. The information encoded by m6A methylation is integrated into existing RNA regulatory networks by RNA binding proteins that recognise methylated sites, the m6A readers. m6A readers include a well-characterised class of dedicated proteins, the YTH proteins, as well as a broader group of multi-functional regulators where recognition of m6A is only partially understood. Molecular insight in this recognition is essential to build a mechanistic understanding of global m6A regulation. In this study, we show that the reader IMP1 recognises the m6A using a dedicated hydrophobic platform that assembles on the methyl moiety, creating a stable high-affinity interaction. This recognition is conserved across evolution and independent from the underlying sequence context but is layered upon the strong sequence specificity of IMP1 for GGAC RNA. This leads us to propose a concept for m6A regulation where methylation plays a context-dependent role in the recognition of selected IMP1 targets that is dependent on the cellular concentration of available IMP1, differing from that observed for the YTH proteins.
A precise and efficient circular RNA synthesis system based on a ribozyme derived from Tetrahymena thermophila
Authors: Cui Jingyi , Zhang Lanxin , Zhang Zaifeng , Luo Xuanmei , Liu Ye , Li Chang , Huang Wei , Zou Lihui , Yu Xue , Xiao Fei
Published: June 2023

Classic strategies for circular RNA (circRNA) preparation always introduce large numbers of linear transcripts or extra nucleotides to the circularized product. In this study, we aimed to develop an efficient system for circRNA preparation based on a self-splicing ribozyme derived from an optimized Tetrahymena thermophila group Ⅰ intron. The target RNA sequence was inserted downstream of the ribozyme and a complementary antisense region was added upstream of the ribozyme to assist cyclization. Then, we compared the circularization efficiency of ribozyme or flanking intronic complementary sequence (ICS)-mediated methods through the DNMT1, CDR1as, FOXO3, and HIPK3 genes and found that the efficiency of our system was remarkably higher than that of flanking ICS-mediated method. Consequently, the circularized products mediated by ribozyme are not introduced with additional nucleotides. Meanwhile, the overexpressed circFOXO3 maintained its biological functions in regulating cell proliferation, migration, and apoptosis. Finally, a ribozyme-based circular mRNA expression system was demonstrated with a split green fluorescent protein (GFP) using an optimized Coxsackievirus B3 (CVB3) internal ribosome entry site (IRES) sequence, and this system achieved successful translation of circularized mRNA. Therefore, this novel, convenient, and rapid engineering RNA circularization system can be applied for the functional study and large-scale preparation of circular RNA in the future.
PKM2 dictates the poised chromatin state of PFKFB3 promoter to enhance breast cancer progression
Authors: Pandkar Madhura R , Raveendran Adarsh , Biswas Kajal , Mutnuru Srinivas Abhishek , Mishra Jharna , Samaiya Atul , Malys Tyler , Mitrophanov Alexander Y , Sharan Shyam K , Shukla Sanjeev
Published: June 2023

The hypoxic milieu is a critical modulator of aerobic glycolysis, yet the regulatory mechanisms between the key glycolytic enzymes in hypoxic cancer cells are largely unchartered. In particular, the M2 isoform of pyruvate kinase (PKM2), the rate-limiting enzyme of glycolysis, is known to confer adaptive advantages under hypoxia. Herein, we report that non-canonical PKM2 mediates HIF-1α and p300 enrichment at PFKFB3 hypoxia-responsive elements (HREs), causing its upregulation. Consequently, the absence of PKM2 activates an opportunistic occupancy of HIF-2α, along with acquisition of a poised state by PFKFB3 HREs-associated chromatin. This poised nature restricts HIF-2α from inducing PFKFB3 while permitting the maintenance of its basal-level expression by harboring multiple histone modifications. In addition, the clinical relevance of the study has been investigated by demonstrating that Shikonin blocks the nuclear translocation of PKM2 to suppress PFKFB3 expression. Furthermore, TNBC patient-derived organoids and MCF7 cells-derived xenograft tumors in mice exhibited substantial growth inhibition upon shikonin treatment, highlighting the vitality of targeting PKM2. Conclusively, this work provides novel insights into the contributions of PKM2 in modulating hypoxic transcriptome and a previously unreported poised epigenetic strategy exhibited by the hypoxic breast cancer cells for ensuring the maintenance of PFKFB3 expression.
Genome-wide association study of a semicontinuous trait: illustration of the impact of the modeling strategy through the study of Neutrophil Extracellular Traps levels
Authors: Munsch Gaëlle , Proust Carole , Labrouche-Colomer Sylvie , Aïssi Dylan , Boland Anne , Morange Pierre-Emmanuel , Roche Anne , de Chaisemartin Luc , Harroche Annie , Olaso Robert , Deleuze Jean-François , James Chloé , Emmerich Joseph , Smadja David M , Jacqmin-Gadda Hélène , Trégouët David-Alexandre
Published: June 2023

Over the last years, there has been a considerable expansion of genome-wide association studies (GWAS) for discovering biological pathways underlying pathological conditions or disease biomarkers. These GWAS are often limited to binary or quantitative traits analyzed through linear or logistic models, respectively. In some situations, the distribution of the outcome may require more complex modeling, such as when the outcome exhibits a semicontinuous distribution characterized by an excess of zero values followed by a non-negative and right-skewed distribution. We here investigate three different modeling for semicontinuous data: Tobit, Negative Binomial and Compound Poisson-Gamma. Using both simulated data and a real GWAS on Neutrophil Extracellular Traps (NETs), an emerging biomarker in immuno-thrombosis, we demonstrate that Compound Poisson-Gamma was the most robust model with respect to low allele frequencies and outliers. This model further identified the MIR155HG locus as significantly (P = 1.4 × 10−8) associated with NETs plasma levels in a sample of 657 participants, a locus recently highlighted to be involved in NETs formation in mice. This work highlights the importance of the modeling strategy for GWAS of a semicontinuous outcome and suggests Compound Poisson-Gamma as an elegant but neglected alternative to Negative Binomial for modeling semicontinuous outcome in the context of genomic investigations.
Intrauterine life to adulthood: a potential risk factor for chronic kidney disease
Authors: Kanbay Mehmet , Copur Sidar , Yildiz Abdullah B , Covic Andreea , Covic Adrian , Ciceri Paola , Magagnoli Lorenza , Cozzolino Mario
Published: June 2023

Multiple risk factors for chronic kidney disease (CKD), one of the major causes of morbidity and mortality in the adult population globally, have been identified, including older age, male gender, family history, smoking, diabetes mellitus, hypertension, ischaemic heart diseases and various medications. Preterm delivery, affecting >10% of the newborns in the USA, is a global concern with increasing incidence in recent decades. Preterm birth has been linked to multiple medical comorbidities such as diabetes mellitus, hypertension and cardiovascular diseases, while its association with CKD has recently been investigated. Prematurity and intrauterine growth restriction (IUGR) have been associated with an increased risk for CKD, specific histopathological examination findings and CKD-associated risk factors such as diabetes mellitus, hypertension and dyslipidaemia. In this narrative review, our aim is to evaluate and summarize the association between the risk for CKD and prematurity, low birthweight and IUGR along with potential underlying pathophysiological mechanisms.
Treatment and outcome of the Dutch Childhood Craniopharyngioma Cohort study: First results after centralization of care
Authors: Van Schaik Jiska , Schouten-van Meeteren Antoinette Y N , Vos-Kerkhof Evelien , Janssens Geert O , Porro Giorgio L , Fiocco Marta , Bakker Boudewijn , Tissing Wim J E , Hoving Eelco W , van Santen Hanneke M
Published: June 2023

Background

Childhood craniopharyngioma (cCP) has excellent survival, but quality of life may be severely hampered by hypothalamic dysfunction. We aimed to evaluate treatment and hypothalamic outcomes of a Dutch cCP cohort, and evaluate the effect of centralization of care.

Methods

A retrospective cohort study was performed, including cCP patients diagnosed between 2004 and 2021. Treatment characteristics and hypothalamic outcomes were evaluated and compared before and since centralization of care in May 2018.

Results

We included 87 cCP patients. Cyst drainage/fenestration was performed in 29.9%, limited resection in 27.6%, near-total resection in 16.1%, and gross total resection (GTR) in 25.4%. Radiotherapy was given in 46.0%. After a median follow-up of 6.5 years, hypothalamic obesity (HO) was present in 24.7% and panhypopituitarism with diabetes insipidus in 71.3%. Higher body mass index (BMI) SDS at diagnosis and Muller grade II at last magnetic resonance imaging of follow-up were associated with overweight/obesity. No association was found between extensiveness of resection and overweight/obesity at last follow-up. When comparing before and after centralization of care, rates of GTR remained similar, but BMI outcomes changed; mean ΔBMI SDS 1 year after diagnosis from 1.12 (SD 1.15) to 0.81 (SD 1.24), and HO after 1 year decreased from 33.3% to 12.0% (P = .067), and after 2 years from 28.6% to 6.7% (P = NS).

Conclusions

In our nationwide cohort, GTR was performed in a relatively low percentage of patients and extensiveness of resection was no longer associated with HO at follow-up. A trend toward improvement of BMI is observed since centralization of care, which needs further exploration.
Continuity and Change of Traditional Islamic Law in Modern Times: tarjīḥ as a Method of Adaptation and Development of Legal Doctrines
Authors: Gad Makhlouf Ahmed
Published: June 2023

In addition to ijtihād (independent legal reasoning), tarjīḥ (weighing up and preference) serves as a fundamental instrument of traditional Islamic law's operational work and was used on different levels. In modern times, tarjīḥ is still applied not only by individual scholars but also by collective fiqh institutions. However, the conception of tarjīḥ is undergoing a transformation in its current application. In the scope of this article, the first purpose is to provide a comprehensive overview of the conception and the diverse practical forms of the tarjīḥ in traditional Islamic law. The focus then lies on setting out how to apply tarjīḥ in modern Islamic jurisprudence. This article also aims to illustrate the conceptual and operational changes of tarjīḥ, paying special attention to the relation between tarjīḥ and ijtihād. Overall, this article intends, on the one hand, to contribute to the study of present Islamic law's developments; on the other hand, it examines the continuity and change of tarjīḥ from traditional Islamic law to contemporary fiqh institutions. It is argued that tarjīḥ in the modern age is not only used as a method of weighing and choosing a legal view that among the diverse views of pre-modern law most closely adapts to the current social circumstances, but that it is also integrated in the process of development of new legal doctrines.
Data processing pipeline for multiple-exposure photo-plate digital archives
Authors: Jia Peng , Yang Zhimin , Shang Zhengjun , Yu Yong , Zhao Jianhai
Published: June 2023

Photo-plates are an invaluable historical legacy that have been used for over a hundred years to capture images of celestial objects. By digitizing these photo-plates and processing the images with digital image processing methods, scientists can study celestial objects that exhibit temporal variations. Multiple-exposure photo-plates are a unique type of observation data that can capture images of the same sky at different observation times in a single photo-plate. Such photo-plates can be used to discover flares or moving targets with rapid variations, but they are difficult to process automatically due to their complex observation strategies. This paper proposes a pipeline based on classical data-processing algorithms and machine-learning algorithms to detect flares or moving targets in multiple-exposure photo-plate images automatically. The pipeline was used to process several digitized multiple-exposure photo-plate images from the China Astronomical Plates Data, and preliminary results indicate that the pipeline is effective. In the future, we plan to use our method to discover more celestial objects with temporal variations from photo-plate digital archives.
Is Ambiguity Good or Bad for Democratic Governance?
Authors: Fowler Luke
Published: June 2023

Ambiguity is often a double-edged sword that provides opportunity to further a democratic agenda in the face of institutional barriers, but with that comes a more complicated and unclear causal pathway that connects citizens to decisions that impact public goods and services. Does ambiguity enhance or hinder the ability of public servants to represent the wants and needs of citizens during the course of designing, developing, and implementing public service programs? The authors examine this at the institutional, organizational, and individual levels to understand its cascading impacts across the complex pathways that connect citizens to the sources of power and decision-making in democratic societies. Conclusions indicate that there are both normative and practical trade-offs created by ambiguity at each level, and the question of whether ambiguity enhances or hinders democratic governance comes down to how representation is balanced against coherence and consistency.
A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes
Authors: Yang Shanshan , Liu Chengyu , Jiang Mengmeng , Liu Xiaoqian , Geng Lingling , Zhang Yiyuan , Sun Shuhui , Wang Kang , Yin Jian , Ma Shuai , Wang Si , Belmonte Juan Carlos Izpisua , Zhang Weiqi , Qu Jing , Liu Guang-Hui
Published: June 2023

Aging increases the risk of liver diseases and systemic susceptibility to aging-related diseases. However, cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized. Here, we constructed the first single-nucleus transcriptomic landscape of primate liver aging, in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell–cell interactions between hepatocytes and niche cells. Upon in-depth dissection of this rich dataset, we identified impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging. In particular, hyperactivated sterol regulatory element-binding protein (SREBP) signaling was a hallmark of the aged liver, and consequently, forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes, manifesting as impaired detoxification and accelerated cellular senescence. This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.
Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia
Authors: Kolar David , Krajcovic Branislav , Kleteckova Lenka , Kuncicka Daniela , Vales Karel , Brozka Hana
Published: June 2023

Background and Hypothesis

Schizophrenia is associated with altered energy metabolism, but the cause and potential impact of these metabolic changes remain unknown. 22q11.2 deletion syndrome (22q11.2DS) represents a genetic risk factor for schizophrenia, which is associated with the loss of several genes involved in mitochondrial physiology. Here we examine how the haploinsufficiency of these genes could contribute to the emergence of schizophrenia in 22q11.2DS.

Study Design

We characterize changes in neuronal mitochondrial function caused by haploinsufficiency of mitochondria-associated genes within the 22q11.2 region (PRODH, MRPL40, TANGO2, ZDHHC8, SLC25A1, TXNRD2, UFD1, and DGCR8). For that purpose, we combine data from 22q11.2DS carriers and schizophrenia patients, in vivo (animal models) and in vitro (induced pluripotent stem cells, IPSCs) studies. We also review the current knowledge about seven non-coding microRNA molecules located in the 22q11.2 region that may be indirectly involved in energy metabolism by acting as regulatory factors.

Study Results

We found that the haploinsufficiency of genes of interest is mainly associated with increased oxidative stress, altered energy metabolism, and calcium homeostasis in animal models. Studies on IPSCs from 22q11.2DS carriers corroborate findings of deficits in the brain energy metabolism, implying a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS.

Conclusions

The haploinsufficiency of genes within the 22q11.2 region leads to multifaceted mitochondrial dysfunction with consequences to neuronal function, viability, and wiring. Overlap between in vitro and in vivo studies implies a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS.
Squaring the circle - the account of profits and the equitable allowance: Recovery Partners GP Ltd v Rukhadze [2023] EWCA Civ 305
Authors: Bond Eliza , Liu Zihang
Published: June 2023

How do we reconcile the all-embracing remedy of the account of profits with the willingness to grant an equitable allowance to an errant fiduciary? Once again, the Court of Appeal in Recovery Partners GP Ltd v Rukhadze was confronted with the challenge of squaring this circle, ostensibly confining the equitable allowance to exceptional circumstances. However, a close analysis of Recovery Partners suggests that the Court is simultaneously emphasising the deterrent effect of the account of profits, whilst developing principles which operate to substantively limit the amount which a principal/beneficiary can recover from a defaulting fiduciary/trustee.
Water-based medium-expansion foam depopulation of adult cattle
Authors: Capria Vittoria M , Arruda Andréia G , Cheng Ting-Yu , Campler Magnus R , Youngblood Brad L , Moeller Steven J , Bowman Andrew S , Kieffer Justin D
Published: June 2023

Current options for depopulation of adult cattle are limited, have logistic constraints, and may not be practical on a large scale. Aspirated water-based foam (WBF) has been shown to be successful in depopulating poultry and swine but has yet to be tested in cattle. WBF is advantageous because necessary equipment can be readily available, easy to use, and presents minimal personnel risk. With the use of a modified rendering trailer in a field setting, we evaluated the efficacy of aspirated WBF for depopulation of adult cattle. Water-based medium-expansion foam was added to the trailer holding cattle to a depth of approximately 50 cm greater than head height. The study was conducted as a gated design and the initial trial was conducted using six anesthetized and six conscious animals for verification of the process and followed by four replicates each containing 18 conscious cattle. A total of 84 cattle were used, with a subset (n = 52) implanted with subcutaneous bio-loggers that recorded activity and electrocardiograms. Cattle were loaded onto the trailer and three gasoline-powered water pumps delivered foam into the trailer followed by a 15-min foam dwell period. Average (± SD) time to completely fill the trailer with foam was 84.8 ± 11.0 s. No animal vocalizations were heard during foam application or the dwell period, and all cattle were confirmed dead upon removal from the trailer after 15 min of immersion. Necropsies of a subset of cattle revealed foam extending to at least the tracheal bifurcation in all cattle and distal to this level in 67% (8/12) animals. Time to cessation of movement, which served as a proxy for loss of consciousness, was 2.5 ± 1.3 min and time to cardiac death was 8.5 ± 2.5 min as determined by data from animals carrying subcutaneous bio-loggers. The results of this study indicate that WBF is a rapid and effective method for depopulation of adult cattle with potential advantages in speed and carcass handling and disposal over current methods.
Grazing management and stocking strategy decisions for pasture-based beef systems: experimental confirmation vs. testimonials and perceptions
Authors: Rouquette Francis Monte , Sollenberger Lynn E , Vendramini João M B
Published: June 2023

Grazing management and stocking strategy decisions involve the manipulation of grazing intensity, grazing frequency, and timing of grazing to meet specific objectives for pasture sustainability and economic livestock production. Although there are numerous stocking systems used by stakeholders, these methods may be broadly categorized as either continuous or some form of rotational stocking. In approximately 30 published experiments comparing continuous vs. rotational stocking, there was no difference in liveweight gain per animal between stocking methods in 66% of studies. There was no difference in gain per hectare between methods in 69% of studies, although for gain per hectare the choice of fixed or variable stocking rate methodology affected the proportion (92% for fixed; 50% for variable). Despite these experimental results showing limited instances of difference between rotational and continuous stocking, rotational strategies (e.g., “mob stocking” or “regenerative grazing”) have received what appears to be unmerited acclaim for use for livestock production. Many proposed “mob stocking” or “regenerative grazing” systems are based on philosophies similar to high intensity-low frequency stocking, including provision for >60 d of rest period from grazing. In addition, grazing management practitioners and stakeholders have voiced and proposed major positive benefits from rotational stocking, “mob stocking”, or “regenerative grazing” for soil health attributes, carbon sequestration, and ecosystem services, without experimental evidence. The perceptions and testimonials supporting undefined stocking systems and methods have potential to mislead practitioners and result in economic disservices. Thus, we suggest that scientists, extension-industry professionals, and producers seek replicated experimental data as the basis for predicting outcomes of grazing decisions.
Translating Policy to Practice: An Association Between Medicare Access and Children’s Health Insurance Program Reauthorization Act Implementation and Palliative Care Consultations and Perioperative Mortality in Critical Care*
Authors: Olanipekun Titilope , Sanghavi Devang , Moreno Franco Pablo , Robinson Maisha T. , Thomas Mathew , Kiley Sean , Paghdar Smit , Sareyyupoglu Basar , Diaz Milian Ricardo
Published: June 2023

OBJECTIVES:

To evaluate the 30-day postoperative mortality and palliative care consultations in patients that underwent surgical procedures in the United States before and after Medicare Access and Children’s Health Insurance Program Reauthorization Act (MACRA) implementation.

DESIGN:

Retrospective, Observational cohort study.

SETTING:

Secondary data were collected from the U.S. National Inpatient Sample, the largest hospital database in the country. The time span was from 2011 to 2019.

PATIENTS:

Adult patients that electively underwent 1 of 19 major procedures.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was cumulative postoperative mortality in two study cohorts. The secondary outcome was palliative care use. We identified 4,900,451 patients and categorized them into two study cohorts: PreM: 2011–2014 (n = 2,103,836) and PostM: 2016–2019 (n = 2,796,615). Regression discontinuity estimates and multivariate analysis were used. Across all procedures, 149,372 patients (7.1%) and 156,610 patients (5%) died within 30 days of their index procedures in the PreM and PostM cohorts, respectively. There was no statistically significant increase in mortality rates around postoperative day (POD) 30 (POD 26–30 vs 31–35) for both cohorts. More patients had inpatient palliative consultations during POD 31–60 compared with POD 1–30 in PreM (8,533 of 2,081,207 patients [0.4%] vs 1,118 of 22,629 patients [4.9%]) and PostM (18,915 of 2,791,712 patients [0.7%] vs 417 of 4,903 patients [8.5%]). Patients were more likely to receive palliative care consultations during POD 31–60 compared with POD 1–30 in both the PreM (odds ratio [OR] 5.31; 95% CI, 2.22–8.68; p < 0.001) and the PostM (OR 7.84; 95% CI, 4.83–9.10; p < 0.001) cohorts.

CONCLUSIONS:

We did not observe an increase in postoperative mortality after POD 30 before or after MACRA implementation. However, palliative care use markedly increased after POD 30. These findings should be considered hypothesis-generating because of several confounders.
Post-Transplant Lymphoproliferative Disorder, Monomorphic Type, in a Kidney Transplant Patient After Administration of Anti-Influenza Vaccine
Authors: Fernandez-Flores Angel , Nieto Rodriguez Daniel , Fernandez-Parrado Miriam , Alzoghby-Abi Chaker Jacques , Sendagorta Cudós Elena , Sobral Costas Tristan Gabriel , Escudero Tornero Rafael , Valladares-Narganes Luis Miguel
Published: June 2023

Post-transplant lymphoproliferative disorders (PTLD) are rare complications in solid organ transplant patients. Their pathogenesis is largely unknown and closely linked to low immunity, which allows uncontrolled lymphocyte proliferation. Although transplant patients receive annual influenza vaccination as a preventive protocol, we have not found any cases where the flu vaccine triggered a PTLD. We present the case of a 49-year-old female kidney transplant recipient who developed an Epstein–Barr virus-negative PTLD, CD30+anaplastic monomorphic type, ALK-, which presented the day after a single dose of anti-influenza vaccine. The initial clinical presentation was subcutaneous, but imaging studies revealed multiorgan involvement.
The effect of opioid-free anaesthesia on the quality of recovery after endoscopic sinus surgery
Authors: Zhou Fengzhi , Cui Yulong ,   Opioid-Free Anesthesia Working Group†, Cao Lijun
Published: June 2023

BACKGROUND

It remains to be determined whether opioid-free anaesthesia (OFA) is consistently effective for different types of surgery.

OBJECTIVES

The current study hypothesised that OFA could effectively inhibit intraoperative nociceptive responses, reduce side effects associated with opioid use, and improve the quality of recovery (QoR) in endoscopic sinus surgery (ESS).

DESIGN

A multicentre randomised controlled study.

SETTING

Seven hospitals participated in this multicentre trial from May 2021 to December 2021.

PATIENTS

Of the 978 screened patients who were scheduled for elective ESS, 800 patients underwent randomisation, and 773 patients were included in the analysis; 388 patients in the OFA group and 385 patients in the opioid anaesthesia group.

INTERVENTIONS

The OFA group received balanced anaesthesia with dexmedetomidine, lidocaine, propofol and sevoflurane; the opioid anaesthesia group received opioid-based balanced anaesthesia using sufentanil, remifentanil, propofol and sevoflurane.

OUTCOME MEASURES

The primary outcome was 24-h postoperative QoR as evaluated by the Quality of Recovery-40 questionnaire. The key secondary outcomes were episodes of postoperative pain and postoperative nausea and vomiting (PONV).

RESULTS

A significant difference (P = 0.0014) in the total score of 24-h postoperative Quality of Recovery-40 was found between the OFA group, median [interquartile range], 191 [185 to 196] and the opioid anaesthesia group (194 [187 to 197]). There were significant differences between the opioid anaesthesia group and the OFA group in the numerical rating scale score for pain after surgery at 30 min (P 
= 0.0017), 1 h (P 
= 0.0052), 2 h (P 
= 0.0079) and 24 h (P = 0.0303). The difference in the area under the curve of pain scale scores between the OFA group (24.2 [3.0 to 47.5]) and the opioid anaesthesia group (11.5 [1.0 to 39.0]) was significant (P = 0.0042). PONV occurred in 58 of 385 patients (15.1%) in the opioid anaesthesia group compared with 27 of 388 patients (7.0%) in the OFA group, suggesting the incidence of PONV in the OFA group was significantly lower than in the opioid anaesthesia group (P 
= 0.0021).

CONCLUSION

OFA can provide good intraoperative analgesia and postoperative recovery quality as effectively as conventional opioid anaesthesia in patients undergoing ESS. OFA can be an alternative option in the pain management of ESS.

TRIAL REGISTRATION

The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100046158; registry URL: http://www.chictr.org.cn/enIndex.aspx.).