bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and construction of the near-earth space plasma simulation system of the Space Plasma Environment Research Facility
Authors: Ling W. , Jing C. , Wan J. , Mao A. , Xiao Q. , Guan J. , Cheng J. , Liu C. , E P.
Published: January 2024

Our earth is immersed in the near-earth space plasma environment, which plays a vital role in protecting our planet against the solar-wind impact and influencing space activities. It is significant to investigate the physical processes dominating the environment, for deepening our scientific understanding of it and improving the ability to forecast the space weather. As a crucial part of the National Major Scientific and Technological Infrastructure–Space Environment Simulation Research Infrastructure (SESRI) in Harbin, the Space Plasma Environment Research Facility (SPERF) builds a system to replicate the near-earth space plasma environment in the laboratory. The system aims to simulate the three-dimensional (3-D) structure and processes of the terrestrial magnetosphere for the first time in the world, providing a unique platform to reveal the physics of the 3-D asymmetric magnetic reconnection relevant to the earth's magnetopause, wave–particle interaction in the earth's radiation belt, particles’ dynamics during the geomagnetic storm, etc. The paper will present the engineering design and construction of the near-earth space plasma simulation system of the SPERF, with a focus on the critical technologies that have been resolved to achieve the scientific goals. Meanwhile, the possible physical issues that can be studied based on the apparatus are sketched briefly. The earth-based system is of great value in understanding the space plasma environment and supporting space exploration.
Special issue: avian malaria
Authors: Ranford-Cartwright Lisa C.
Published: January 2024

Avian malaria parasites or haemosporidia are found in bird species worldwide. This special issue focuses on 3 most commonly studied genera: Haemoproteus, Plasmodium and Leucocytozoon. Seven research articles and reviews are provided to illustrate the breadth of knowledge of the diversity of avian malaria parasites in different regional habitats and across bird species, and the use of avian haemosporidian systems to examine host–parasite eco-evolutionary questions.
The causal association between maternal depression, anxiety, and infection in pregnancy and neurodevelopmental disorders among 410 461 children: a population study using quasi-negative control cohorts and sibling analysis
Authors: Hope Holly , Pierce Matthias , Gabr Hend , Radojčić Maja R. , Swift Eleanor , Taxiarchi Vicky P. , Abel Kathryn M.
Published: January 2024

Background

To address if the long-standing association between maternal infection, depression/anxiety in pregnancy, and offspring neurodevelopmental disorder (NDD) is causal, we conducted two negative-control studies.

Methods

Four primary care cohorts of UK children (pregnancy, 1 and 2 years prior to pregnancy, and siblings) born between 1 January 1990 and 31 December 2017 were constructed. NDD included autism/autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disability, cerebral palsy, and epilepsy. Maternal exposures included depression/anxiety and/or infection. Maternal (age, smoking status, comorbidities, body mass index, NDD); child (gender, ethnicity, birth year); and area-level (region and level of deprivation) confounders were captured. The NDD incidence rate among (1) children exposed during or outside of pregnancy and (2) siblings discordant for exposure in pregnancy was compared using Cox-regression models, unadjusted and adjusted for confounders.

Results

The analysis included 410 461 children of 297 426 mothers and 2 793 018 person-years of follow-up with 8900 NDD cases (incidence rate = 3.2/1000 person years). After adjustments, depression and anxiety consistently associated with NDD (pregnancy-adjusted HR = 1.58, 95% CI 1.46–1.72; 1-year adj. HR = 1.49, 95% CI 1.39–1.60; 2-year adj. HR = 1.62, 95% CI 1.50–1.74); and to a lesser extent, of infection (pregnancy adj. HR = 1.16, 95% CI 1.10–1.22; 1-year adj. HR = 1.20, 95% CI 1.14–1.27; 2-year adj. HR = 1.19, 95% CI 1.12–1.25). NDD risk did not differ among siblings discordant for pregnancy exposure to mental illness HR = 0.97, 95% CI 0.77–1.21 or infection HR = 0.99, 95% CI 0.90–1.08.

Conclusions

Maternal risk appears to be unspecific to pregnancy: our study provided no evidence of a specific, and therefore causal, link between in-utero exposure to infection, common mental illness, and later development of NDD.
“Our roots run deep”: Historical myths as culturally evolved technologies for coalitional recruitment
Authors: Sijilmassi Amine , Safra Lou , Baumard Nicolas
Published: January 2024

One of the most remarkable manifestations of social cohesion in large-scale entities is the belief in a shared, distinct, and ancestral past. Human communities around the world take pride in their ancestral roots, commemorate their long history of shared experiences, and celebrate the distinctiveness of their historical trajectory. Why do humans put so much effort into celebrating a long-gone past? Integrating insights from evolutionary psychology, social psychology, evolutionary anthropology, political science, cultural history, and political economy, we show that the cultural success of historical myths is driven by a specific adaptive challenge for humans: The need to recruit coalitional support to engage in large-scale collective action and prevail in conflicts. By showcasing a long history of cooperation and shared experiences, these myths serve as super-stimuli, activating specific features of social cognition and drawing attention to cues of fitness interdependence. In this account, historical myths can spread within a population without requiring group-level selection, as long as individuals have a vested interest in their propagation and strong psychological motivations to create them. Finally, this framework explains not only the design features of historical myths, but also important patterns in their cross-cultural prevalence, interindividual distribution, and particular content.
Measuring Democratic Backsliding
Authors: Little Andrew T. , Meng Anne
Published: January 2024

Despite the general narrative that the world is in a period of democratic decline, there have been surprisingly few empirical studies that assess whether this is systematically true. Most existing studies of global backsliding are based largely if not entirely on subjective indicators that rely on expert coder judgment. Our study surveys objective indicators of democracy (e.g., incumbent performance in elections) and finds little evidence of global democratic decline during the past decade. To explain the discrepancy in trends between expert-coded and objective indicators, we consider the role of coder bias and leaders strategically using more subtle undemocratic action. Although we cannot rule out the possibility that the world is becoming less democratic exclusively in ways that require subjective judgment to detect, this claim is not justified by existing evidence.
Conceptual and Measurement Issues in Assessing Democratic Backsliding
Authors: Knutsen Carl Henrik , Marquardt Kyle L. , Seim Brigitte , Coppedge Michael , Edgell Amanda B. , Medzihorsky Juraj , Pemstein Daniel , Teorell Jan , Gerring John , Lindberg Staffan I.
Published: January 2024

During the past decade, analyses drawing on several democracy measures have shown a global trend of democratic retrenchment. While these democracy measures use radically different methodologies, most partially or fully rely on subjective judgments to produce estimates of the level of democracy within states. Such projects continuously grapple with balancing conceptual coverage with the potential for bias (Munck and Verkuilen 2002; Przeworski et al. 2000). Little and Meng (L&M) (2023) reintroduce this debate, arguing that “objective” measures of democracy show little evidence of recent global democratic backsliding.1 By extension, they posit that time-varying expert bias drives the appearance of democratic retrenchment in measures that incorporate expert judgments. In this article, we engage with (1) broader debates on democracy measurement and democratic backsliding, and (2) L&M’s specific data and conclusions.
The Resilience of Democracy’s Third Wave
Authors: Levitsky Steven , Way Lucan
Published: January 2024

The literature on democratization has experienced radical mood swings in recent decades, from extreme optimism in the 1990s to extreme pessimism today. These mood swings have resulted in not only misguided claims about the state of democracy in the world but also a muddied understanding of what drives both democratization and democratic erosion.
Difficult to Count, Important to Measure: Assessing Democratic Backsliding
Authors: Gorokhovskaia Yana
Published: January 2024

Assessing the state of democracy and freedom is an important but difficult task. The stakes are high, not only for researchers interested in uncovering the drivers of democratic consolidation or decline but also for policy makers, civil society organizations, journalists, activists, and citizens who work daily to promote and protect human rights at home and abroad. In light of the significance of the task, it is not surprising that the issue of how to measure democracy most accurately continues to be hotly debated.
An Events-Based Approach to Understanding Democratic Erosion
Authors: Baron Hannah , Blair Robert A. , Gottlieb Jessica , Paler Laura
Published: January 2024

This article introduces and demonstrates the utility of a new event dataset on democratic erosion around the world. Through case studies of Turkey and Brazil, we show that our Democratic Erosion Event Dataset (DEED) can help to resolve debates about the extent to which democracy is backsliding based on prominent cross-national indicators, focusing in particular on the Varieties of Democracy (V-Dem) and Little and Meng (L&M) indices. V-Dem suggests that democracies are deteriorating worldwide; L&M argue that this may be an artifact of subjectivity and coder bias and that more “objective” indicators reveal little to no global democratic backsliding in recent years. Using DEED, we show that—at least in these cases—objective indices may underestimate the extent of democratic erosion whereas subjective indices may overestimate it. Our analyses illustrate the ways in which DEED can complement existing indices by illuminating the nature and dynamics of democratic erosion as it occurs on the ground.
What We Do and Do Not Know about Democratic Backsliding
Authors: Little Andrew T. , Meng Anne
Published: January 2024

We are humbled by the quantity and quality of the commentaries on our article in this special issue. Our goal was not to answer definitively how global democracy has changed in recent years but rather to provoke a debate about how we collectively can improve the scholarship on this question. The range of viewpoints raised in this special issue have made important advances on this goal.
How Little and Meng’s Objective Approach Fails in Democracies
Authors: Miller Michael K.
Published: January 2024

Little and Meng (L&M) (2023) question the prevailing narrative of widespread democratic backsliding by showing that various objective indicators of democracy are flat over time. However, because recent democratic decline is concentrated in democracies, the objective indicators can accurately test for backsliding only if they can track democratic quality within democracies. This response article shows that they cannot, for conceptual and empirical reasons. The indicators generally can distinguish democracies from autocracies but are blind to variation in quality within democracies. L&M, therefore, are showing that one form of variation in democracy is stagnant but are systematically missing the very type of variation that has most informed current warnings about backsliding.
What the Schwartzes Told Me about Allomorph Priority
Authors: Faust Noam
Published: January 2024

In Standard Yiddish, -s and -ən are used as default allomorphs for plural word formation. It is argued here that the choice is left to the phonology, with -s acting as a default within a default. This status is used to explain the exclusive use of -s in the pluralization of proper names, which are claimed to be formed with no sensitivity to the phonological form of the base.
Characterizing Ice Nucleating Particles Over the Southern Ocean Using Simultaneous Aircraft and Ship Observations
Authors: Moore Kathryn A. , Hill Thomas C. J. , McCluskey Christina S. , Twohy Cynthia H. , Rainwater Bryan , Toohey Darin W. , Sanchez Kevin J. , Kreidenweis Sonia M. , DeMott Paul J.
Published: January 2024

Supercooled liquid clouds are ubiquitous over the Southern Ocean (SO), even to temperatures below −20°C, and comprise a large fraction of the marine boundary layer (MBL) clouds. Earth system models and reanalysis products have struggled to reproduce the observed cloud phase distribution and occurrence of cloud ice in the region. Recent simulations found the microphysical representation of ice nucleation and growth has a large impact on these properties, however, measurements of SO ice nucleating particles (INPs) to validate simulations are sparse. This study presents measurements of INPs from simultaneous aircraft and ship campaigns conducted over the SO in austral summer 2018, which include the first in situ observations in and above cloud in the region. Our results confirm recent observations that INP concentrations are uniformly lower than measurements made in the late 1960s. While INP concentrations below and above cloud are similar, higher ice nucleation efficiency above cloud supports model simulations that the dominant INP composition varies with height. Model parameterizations based solely on aerosol properties capture the mean relationship between INP concentration and temperature but not the observed variability, which is likely related to the only modest correlations observed between INPs and environmental or aerosol metrics. Including wind speed in addition to activation temperature in a marine INP parameterization reduces bias but does not explain the large range of observed INP concentrations. Direct and indirect inference of marine INP size suggests MBL INPs, at least during Austral summer, are dominated by particles with diameters smaller than 500 nm.
Prognostic utility of rhythmic components in 24-h ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity
Authors: El Jamal Nadim , Brooks Thomas G. , Cohen Jordana , Townsend Raymond R. , Sosa Giselle Rodriguez de , Shah Vallabh ,   Chronic Renal Insufficiency Cohort Study (CRIC) Consortium, Nelson Robert G. , Drawz Paul E. , Rao Panduranga , Bhat Zeenat , Chang Alexander , Yang Wei , FitzGerald Garret A. , Skarke Carsten
Published: January 2024

Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-h profiles of ambulatory blood pressure monitoring (ABPM) in the Chronic Renal Insufficiency Cohort (CRIC) and the African American Study for Kidney Disease and Hypertension (AASK) cohort using Cox proportional hazards models. We find that rhythmic profiling of BP through JTK_CYCLE analysis identifies subgroups of CRIC participants that were more likely to die due to cardiovascular causes. While our fully adjusted model shows a trend towards a significant association between absent cyclic components and cardiovascular death in the full CRIC cohort (HR: 1.71,95% CI: 0.99–2.97, p = 0.056), CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.37, 95% CI: 1.45–7.87, p = 0.005). This increased risk was not explained by the dipping or non-dipping pattern in ABPM. Due to the large differences in patient characteristics, the results do not replicate in the AASK cohort. This study suggests rhythmic blood pressure components as a potential novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.
Efficacy and safety of mineralocorticoid receptor antagonists for the treatment of low-renin hypertension: a systematic review and meta-analysis
Authors: Shah Sonali S. , Zhang Jinghong , Gwini Stella May , Young Morag J. , Fuller Peter J. , Yang Jun
Published: January 2024

Hypertension is the leading risk factor for premature death. The optimal treatment of low-renin hypertension (LRH), present in 30% of hypertensive individuals, is not known. LRH likely reflects a state of excess salt, expanded volume and/or mineralocorticoid receptor (MR) activation. Therefore, targeted treatment with MR antagonists (MRA) may be beneficial. The objective of this systematic review was to assess the efficacy of MRA therapy in LRH. MEDLINE, Embase and Cochrane databases were searched for randomised controlled trials of adults with LRH that compared the efficacy of MRA to placebo or other antihypertensive treatments. Risk of bias was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using a random-effects model to estimate the difference in blood pressure and the certainty of evidence was assessed using the GRADE approach. The protocol is registered on PROSPERO (CRD42022318763). From the 1612 records identified, 17 studies met the inclusion criteria with a total sample size of 1043 participants. Seven studies (n = 345) were assessed as having a high risk of bias. Meta-analysis indicated that MRA reduced systolic blood pressure by −6.8 mmHg (95% confidence interval −9.6 to −4.1) and −4.8 mmHg (95% confidence interval −11.9 to 2.4) compared to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) and diuretics. The certainty of the evidence was assessed as moderate and very low, respectively. The findings of this systematic review suggest that MRA is effective in lowering blood pressure in LRH and may be better than ACEi/ARB. Translation to clinical practice is limited by the uncertainty of evidence.
Amplitude-determined seizure-threshold, electric field modeling, and electroconvulsive therapy antidepressant and cognitive outcomes
Authors: Abbott Christopher C. , Miller Jeremy , Farrar Danielle , Argyelan Miklos , Lloyd Megan , Squillaci Taylor , Kimbrell Brian , Ryman Sephira , Jones Thomas R. , Upston Joel , Quinn Davin K. , Peterchev Angel V. , Erhardt Erik , Datta Abhishek , McClintock Shawn M. , Deng Zhi-De
Published: January 2024

Electroconvulsive therapy (ECT) pulse amplitude, which dictates the induced electric field (E-field) magnitude in the brain, is presently fixed at 800 or 900 milliamperes (mA) without clinical or scientific rationale. We have previously demonstrated that increased E-field strength improves ECT’s antidepressant effect but worsens cognitive outcomes. Amplitude-determined seizure titration may reduce the E-field variability relative to fixed amplitude ECT. In this investigation, we assessed the relationships among amplitude-determined seizure-threshold (STa), E-field magnitude, and clinical outcomes in older adults (age range 50 to 80 years) with depression. Subjects received brain imaging, depression assessment, and neuropsychological assessment pre-, mid-, and post-ECT. STa was determined during the first treatment with a Soterix Medical 4×1 High Definition ECT Multi-channel Stimulation Interface (Investigation Device Exemption: G200123). Subsequent treatments were completed with right unilateral electrode placement (RUL) and 800 mA. We calculated Ebrain defined as the 90th percentile of E-field magnitude in the whole brain for RUL electrode placement. Twenty-nine subjects were included in the final analyses. Ebrain per unit electrode current, Ebrain/I, was associated with STa. STa was associated with antidepressant outcomes at the mid-ECT assessment and bitemporal electrode placement switch. Ebrain/I was associated with changes in category fluency with a large effect size. The relationship between STa and Ebrain/I extends work from preclinical models and provides a validation step for ECT E-field modeling. ECT with individualized amplitude based on E-field modeling or STa has the potential to enhance neuroscience-based ECT parameter selection and improve clinical outcomes.
Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HT2A receptor the unique player?
Authors: Sekssaoui Mehdi , Bockaert Joël , Marin Philippe , Bécamel Carine
Published: January 2024

Major depressive disorder (MDD) is one of the most disabling psychiatric disorders in the world. First-line treatments such as selective serotonin reuptake inhibitors (SSRIs) still have many limitations, including a resistance to treatment in 30% of patients and a delayed clinical benefit that is observed only after several weeks of treatment. Increasing clinical evidence indicates that the acute administration of psychedelic agonists of the serotonin 5-HT2A receptor (5-HT2AR), such as psilocybin, to patients with MDD induce fast antidepressant effects, which persist up to five weeks after the treatment. However, the involvement of the 5-HT2AR in these antidepressant effects remains controversial. Furthermore, whether the hallucinogenic properties of 5-HT2AR agonists are mandatory to their antidepressant activity is still an open question. Here, we addressed these issues by investigating the effect of two psychedelics of different chemical families, DOI and psilocybin, and a non-hallucinogenic 5-HT2AR agonist, lisuride, in a chronic despair mouse model exhibiting a robust depressive-like phenotype. We show that a single injection of each drug to wild type mice induces anxiolytic- and antidepressant-like effects in the novelty-suppressed feeding, sucrose preference and forced swim tests, which last up to 15 days. DOI and lisuride administration did not produce antidepressant-like effects in 5-HT2A−/− mice, whereas psilocybin was still effective. Moreover, neither 5-HT1AR blockade nor dopamine D1 or D2 receptor blockade affected the antidepressant-like effects of psilocybin in 5-HT2A−/− mice. Collectively, these findings indicate that 5-HT2AR agonists can produce antidepressant-like effects independently of hallucinogenic properties through mechanisms involving or not involving the receptor.
Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy
Authors: Nie Tian , Venkatesh Varun S. , Golub Suzanne , Stok Kathryn S. , Hemmatian Haniyeh , Desai Reena , Handelsman David J. , Zajac Jeffrey D. , Grossmann Mathis , Davey Rachel A.
Published: January 2024

The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown. To address this knowledge gap, we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment. Puberty was suppressed by orchidectomy in male mice at 5 weeks of age. At 3 weeks post-surgery, male-to-female mice were treated with a high dose of estradiol (~0.85 mg) by intraperitoneal silastic implantation for 12 weeks. Controls included intact and orchidectomized males at 3 weeks post-surgery, vehicle-treated intact males, intact females and orchidectomized males at 12 weeks post-treatment. Compared to male controls, orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture. Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis, while the periosteal circumference increased to a level that was intermediate between intact male and female controls, resulting in increased maximal force and stiffness. In trabecular bone, estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate, consistent with the anabolic action of estradiol on osteoblast proliferation. These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT. Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.
The heterogeneity of signaling pathways and drug responses in intrahepatic cholangiocarcinoma with distinct genetic mutations
Authors: Feng Yangyang , Zhao Ming , Wang Lijian , Li Ling , Lei Josh Haipeng , Zhou Jingbo , Chen Jinghong , Wu Yumeng , Miao Kai , Deng Chu-Xia
Published: January 2024

Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy among primary liver cancers, with an increasing overall incidence and poor prognosis. The intertumoral and intratumoral heterogeneity of ICC makes it difficult to find efficient drug therapies. Therefore, it is essential to identify tumor suppressor genes and oncogenes that induce ICC formation and progression. Here, we performed CRISPR/Cas9-mediated genome-wide screening in a liver-specific Smad4/Pten knockout mouse model (Smad4co/co;Ptenco/co;Alb-Cre, abbreviated as SPC), which normally generates ICC after 6 months, and detected that mutations in Trp53, Fbxw7, Inppl1, Tgfbr2, or Cul3 markedly accelerated ICC formation. To illustrate the potential mechanisms, we conducted transcriptome sequencing and found that multiple receptor tyrosine kinases were activated, which mainly upregulated the PI3K pathway to induce cell proliferation. Remarkably, the Cul3 mutation stimulated cancer progression mainly by altering the immune microenvironment, whereas other mutations promoted the cell cycle. Moreover, Fbxw7, Inppl1, Tgfbr2, and Trp53 also affect inflammatory responses, apelin signaling, mitotic spindles, ribosome biogenesis, and nucleocytoplasmic transport pathways, respectively. We further examined FDA-approved drugs for the treatment of liver cancer and performed high-throughput drug screening of the gene-mutant organoids. Different drug responses and promising drug therapies, including chemotherapy and targeted drugs, have been discovered for ICC.
FBXO5-mediated RNF183 degradation prevents endoplasmic reticulum stress-induced apoptosis and promotes colon cancer progression
Authors: Ji Jing , Jing Aixin , Ding Yuanyuan , Ma Xinhui , Qian Qilan , Geng Ting , Cheng Wenhao , Zhang Meiqi , Sun Qian , Ma Shaojie , Wang Xiujun , Yuan Qing , Xu Menghan , Qin Jingting , Ma Lin , Yang Jiayan , He Jingliang , Du Qianming , Xia Mengbei , Xu Yuting , Chen Ziyun , Zhu Lan , Liu Wei , Liu Shunfang , Liu Bin
Published: January 2024

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment.
Field control of quasiparticle decay in a quantum antiferromagnet
Authors: Hasegawa Shunsuke , Kikuchi Hodaka , Asai Shinichiro , Wei Zijun , Winn Barry , Sala Gabriele , Itoh Shinichi , Masuda Takatsugu
Published: January 2024

Dynamics in a quantum material is described by quantized collective motion: a quasiparticle. The single-quasiparticle description is useful for a basic understanding of the system, whereas a phenomenon beyond the simple description such as quasiparticle decay which affects the current carried by the quasiparticle is an intriguing topic. The instability of the quasiparticle is phenomenologically determined by the magnitude of the repulsive interaction between a single quasiparticle and the two-quasiparticle continuum. Although the phenomenon has been studied in several materials, thermodynamic tuning of the quasiparticle decay in a single material has not yet been investigated. Here we show, by using neutron scattering, magnetic field control of the magnon decay in a quantum antiferromagnet RbFeCl3, where the interaction between the magnon and continuum is tuned by the field. At low fields where the interaction is small, the single magnon decay process is observed. In contrast, at high fields where the interaction exceeds a critical magnitude, the magnon is pushed downwards in energy and its lifetime increases. Our study demonstrates that field control of quasiparticle decay is possible in the system where the two-quasiparticle continuum covers wide momentum-energy space, and the phenomenon of the magnon avoiding decay is ubiquitous.
Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system
Authors: Zhen Xiangkai , Xu Xiaolong , Ye Le , Xie Song , Huang Zhijie , Yang Sheng , Wang Yanhui , Li Jinyu , Long Feng , Ouyang Songying
Published: January 2024

Argonaute (Ago) proteins are ubiquitous across all kingdoms of life. Eukaryotic Agos (eAgos) use small RNAs to recognize transcripts for RNA silencing in eukaryotes. In contrast, the functions of prokaryotic counterparts (pAgo) are less well known. Recently, short pAgos in conjunction with the associated TIR or Sir2 (SPARTA or SPARSA) were found to serve as antiviral systems to combat phage infections. Herein, we present the cryo-EM structures of nicotinamide adenine dinucleotide (NAD+)-bound SPARSA with and without nucleic acids at resolutions of 3.1 Å and 3.6 Å, respectively. Our results reveal that the APAZ (Analogue of PAZ) domain and the short pAgo form a featured architecture similar to the long pAgo to accommodate nucleic acids. We further identified the key residues for NAD+ binding and elucidated the structural basis for guide RNA and target DNA recognition. Using structural comparisons, molecular dynamics simulations, and biochemical experiments, we proposed a putative mechanism for NAD+ hydrolysis in which an H186 loop mediates nucleophilic attack by catalytic water molecules. Overall, our study provides mechanistic insight into the antiphage role of the SPARSA system.
Diabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila
Authors: Lee Daewon , Yoon Eunju , Ham Su Jin , Lee Kunwoo , Jang Hansaem , Woo Daihn , Lee Da Hyun , Kim Sehyeon , Choi Sekyu , Chung Jongkyeong
Published: January 2024

Diabetic sensory neuropathy (DSN) is one of the most common complications of type 2 diabetes (T2D), however the molecular mechanistic association between T2D and DSN remains elusive. Here we identify ubiquitin C-terminal hydrolase L1 (UCHL1), a deubiquitinase highly expressed in neurons, as a key molecule underlying T2D and DSN. Genetic ablation of UCHL1 leads to neuronal insulin resistance and T2D-related symptoms in Drosophila. Furthermore, loss of UCHL1 induces DSN-like phenotypes, including numbness to external noxious stimuli and axonal degeneration of sensory neurons in flies’ legs. Conversely, UCHL1 overexpression improves DSN-like defects of T2D model flies. UCHL1 governs insulin signaling by deubiquitinating insulin receptor substrate 1 (IRS1) and antagonizes an E3 ligase of IRS1, Cullin 1 (CUL1). Consistent with these results, genetic and pharmacological suppression of CUL1 activity rescues T2D- and DSN-associated phenotypes. Therefore, our findings suggest a complete set of genetic factors explaining T2D and DSN, together with potential remedies for the diseases.
Non-collinear magnetic atomic cluster expansion for iron
Authors: Rinaldi Matteo , Mrovec Matous , Bochkarev Anton , Lysogorskiy Yury , Drautz Ralf
Published: January 2024

The Atomic Cluster Expansion (ACE) provides a formally complete basis for the local atomic environment. ACE is not limited to representing energies as a function of atomic positions and chemical species, but can be generalized to vectorial or tensorial properties and to incorporate further degrees of freedom (DOF). This is crucial for magnetic materials with potential energy surfaces that depend on atomic positions and atomic magnetic moments simultaneously. In this work, we employ the ACE formalism to develop a non-collinear magnetic ACE parametrization for the prototypical magnetic element Fe. The model is trained on a broad range of collinear and non-collinear magnetic structures calculated using spin density functional theory. We demonstrate that the non-collinear magnetic ACE is able to reproduce not only ground state properties of various magnetic phases of Fe but also the magnetic and lattice excitations that are essential for a correct description of finite temperature behavior and properties of crystal defects.
Kagami Ogata syndrome: a small deletion refines critical region for imprinting
Authors: Kilich Gonench , Hassey Kelly , Behrens Edward M. , Falk Marni , Vanderver Adeline , Rader Daniel J. , Cahill Patrick J. , Raper Anna , Zhang Zhe , Westerfer Dawn , Jadhav Tanaya , Conlin Laura , Izumi Kosuke , Rajagopalan Ramakrishnan , Sullivan Kathleen E. ,   UDN Consortium
Published: January 2024

Kagami–Ogata syndrome is a rare imprinting disorder and its phenotypic overlap with multiple different etiologies hampers diagnosis. Genetic etiologies include paternal uniparental isodisomy (upd(14)pat), maternal allele deletions of differentially methylated regions (DMR) in 14q32.2 or pure primary epimutations. We report a patient with Kagami–Ogata syndrome and an atypical diagnostic odyssey with several negative standard-of-care genetic tests followed by epigenetic testing using methylation microarray and a targeted analysis of whole-genome sequencing to reveal a 203 bp deletion involving theMEG3transcript andMEG3:TSS-DMR. Long-read sequencing enabled the simultaneous detection of the deletion, phasing, and biallelic hypermethylation of theMEG3:TSS-DMR region in a single assay. This case highlights the challenges in the sequential genetic testing paradigm, the utility of long-read sequencing as a single comprehensive diagnostic assay, and the smallest reported deletion causing Kagami–Ogata syndrome allowing important insights into the mechanism of imprinting effects at this locus.
Extending loophole-free nonlocal correlations to arbitrarily large distances
Authors: Chaturvedi Anubhav , Viola Giuseppe , Pawłowski Marcin
Published: January 2024

Quantum theory allows spatially separated observers to share nonlocal correlations, which enable them to accomplish classically inconceivable information processing and cryptographic feats. However, the distances over which nonlocal correlations can be realized remain severely limited due to their high fragility to noise and high threshold detection efficiencies. To enable loophole-free nonlocality across large distances, we introduce Bell experiments wherein the spatially separated parties randomly choose the location of their measurement devices. We demonstrate that when devices close to the source are perfect and witness extremal nonlocal correlations, such correlations can be extended to devices placed arbitrarily far from the source. To accommodate imperfections close to the source, we demonstrate an analytic trade-off: the higher the loophole-free nonlocality close to the source, the lower the threshold requirements away from the source. We utilize this trade-off and formulate numerical methods to estimate the critical requirements of individual measurement devices in such experiments.
In vivo human T cell engineering with enveloped delivery vehicles
Authors: Hamilton Jennifer R. , Chen Evelyn , Perez Barbara S. , Sandoval Espinoza Cindy R. , Kang Min Hyung , Trinidad Marena , Ngo Wayne , Doudna Jennifer A.
Published: January 2024

Viruses and virally derived particles have the intrinsic capacity to deliver molecules to cells, but the difficulty of readily altering cell-type selectivity has hindered their use for therapeutic delivery. Here, we show that cell surface marker recognition by antibody fragments displayed on membrane-derived particles encapsulating CRISPR–Cas9 protein and guide RNA can deliver genome editing tools to specific cells. Compared to conventional vectors like adeno-associated virus that rely on evolved capsid tropisms to deliver virally encoded cargo, these Cas9-packaging enveloped delivery vehicles (Cas9-EDVs) leverage predictable antibody–antigen interactions to transiently deliver genome editing machinery selectively to cells of interest. Antibody-targeted Cas9-EDVs preferentially confer genome editing in cognate target cells over bystander cells in mixed populations, both ex vivo and in vivo. By using multiplexed targeting molecules to direct delivery to human T cells, Cas9-EDVs enable the generation of genome-edited chimeric antigen receptor T cells in humanized mice, establishing a programmable delivery modality with the potential for widespread therapeutic utility.
A new genomic framework to categorize pediatric acute myeloid leukemia
Authors: Umeda Masayuki , Ma Jing , Westover Tamara , Ni Yonghui , Song Guangchun , Maciaszek Jamie L. , Rusch Michael , Rahbarinia Delaram , Foy Scott , Huang Benjamin J. , Walsh Michael P. , Kumar Priyadarshini , Liu Yanling , Yang Wenjian , Fan Yiping , Wu Gang , Baker Sharyn D. , Ma Xiaotu , Wang Lu , Alonzo Todd A. , Rubnitz Jeffrey E. , Pounds Stanley , Klco Jeffery M.
Published: January 2024

Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To comprehensively define the genomic landscape of pAML, we systematically categorized 887 pAML into 23 mutually distinct molecular categories, including new major entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3 or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a new prognostic framework for pAML based on these updated molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.
Synthesis of novel azo pyrazole disperse dyes for dyeing and antibacterial finishing of PET fabric under supercritical carbon dioxide
Authors: Sofan Mamdouh , El-Taweel Fathy , Abdel-Rahman Adel , Salman Hagar , Negm Elham
Published: January 2024

Supercritical carbon dioxide (scCO2) has been suggested as a good substitution to environmentally harmful water-based tincturing. The present study describes the successful synthesis of some biologically active dispersion tinctures for supercritical carbon dioxide tincturing of polyester fabric. The coupling of 1-cyanoacetylpiperidine (1) with the diazonium salt of aryl amine derivatives (2a–d) produced 1-((aryldiazenyl) cyanoacetyl piperidines (3a–d). To create the derivatives of 4-(phenyldiazenyl)-5-(piperidin-1-yl)-1H-pyrazol-3-amine (5a), the propane nitriles (3a–d) were condensed with hydrazine hydrate. However, the unexpected 3-aminopyrazol-5-ol yellow–red dispersion dyes (4a–d) were identified as the reaction results. The MS, IR, and NMR spectra were used to describe the novel dyes, and the results exactly matched the suggested structures. The antibacterial test, which was conducted using the AATCC method, revealed that some of the compounds (3a–d) and (4a–d) had impressive antibacterial capabilities against the researched +ve and gram −ve bacteria. For eight dyestuffs, the dyeability, color strength, and color fastness of the tincturing process were evaluated. The evaluation focused on determining color uptake using a gauge for color strength (K/S). All dyes displayed excellent rubbing, washing, and light fastness (color change and staining grade of 4–5).
Hybrid parameters for fluid identification using an enhanced quantum neural network in a tight reservoir
Authors: Luo Dejiang , Liang Yuan , Yang Yuanjun , Wang Xingyue
Published: January 2024

This paper proposes a fluid classifier for a tight reservoir using a quantum neural network (QNN). It is difficult to identify the fluid in tight reservoirs, and the manual interpretation of logging data, which is an important means to identify the fluid properties, has the disadvantages of a low recognition rate and non-intelligence, and an intelligent algorithm can better identify the fluid. For tight reservoirs, the logging response characteristics of different fluid properties and the sensitivity and relevance of well log parameter and rock physics parameters to fluid identification are analyzed, and different sets of input parameters for fluid identification are constructed. On the basis of quantum neural networks, a new method for combining sample quantum state descriptions, sensitivity analysis of input parameters, and wavelet activation functions for optimization is proposed. The results of identifying the dry layer, gas layer, and gas–water co-layer in the tight reservoir in the Sichuan Basin of China show that different input parameters and activation functions affect recognition performance. The proposed quantum neural network based on hybrid parameters and a wavelet activation function has higher fluid identification accuracy than the original quantum neural network model, indicating that this method is effective and warrants promotion and application.
Risk of cardiocerebrovascular diseases is increased in Korean women with polycystic ovary syndrome: a nationwide cohort study
Authors: Ryu Ki-Jin , Park Hyuntae , Kim Min Sun , Jeong Hye Gyeong , Kim Tak
Published: January 2024

To investigate the relationship between polycystic ovary syndrome (PCOS) and risk of cardiocerebrovascular disease in Korean women. This longitudinal cohort study using data from the Korean National Health Insurance Service included the women aged 15–44 years diagnosed with PCOS between 2002 and 2019, and the controls were matched 1:3 by age group, income, and region of residence. The endpoint outcomes of this study were the occurrence of ischemic heart disease, cerebrovascular diseases, and combined cardiocerebrovascular diseases in the PCOS and control groups. A stratified Cox proportional hazards regression analysis for matched data was performed to evaluate the relative hazard of events in the PCOS group compared to that in the control group. Among a total of 549,400 participants in the cohort, 137,416 women had a diagnosis of PCOS and 412,118 women did not have it. During a median follow-up of 54 months (interquartile range, 30–78 months), the incidence rates of all cardiovascular, ischemic heart, and cerebrovascular diseases were 6.6, 4.0, and 2.9, respectively, per 1000 person-years for women with PCOS, and 4.8, 2.8, and 2.3, respectively, per 1000 person-years for healthy control women. Women with PCOS had a higher hazard ratio of 1.224 (95% confidence interval, 1.18–1.27) of the composite cardiocerebrovascular diseases than those in the controls after propensity score matching for confounding variables, including body mass index, diabetes mellitus, hypertension, dyslipidemia, physical exercise level, alcohol consumption, current smoking, systolic and diastolic blood pressures, total cholesterol, and triglyceride levels. Hazard ratio for ischemic heart and cerebrovascular diseases was higher in women with PCOS than in the control group (hazard ratio, 1.254; 95% confidence interval, 1.20–1.31 and hazard ratio, 1.201; 95% confidence interval, 1.14–1.27, respectively). PCOS is associated with an increased risk of cardiocerebrovascular diseases in Korean women irrespective of their obesity. Counselling on the management of long-term risk of cardiovascular diseases should be offered to women with PCOS in East Asian countries where PCOS is characterized by a relatively low BMI.
Diagnosis of disease affecting gait with a body acceleration-based model using reflected marker data for training and a wearable accelerometer for implementation
Authors: Takallou Mohammad Ali , Fallahtafti Farahnaz , Hassan Mahdi , Al-Ramini Ali , Qolomany Basheer , Pipinos Iraklis , Myers Sara , Alsaleem Fadi
Published: January 2024

This paper demonstrates the value of a framework for processing data on body acceleration as a uniquely valuable tool for diagnosing diseases that affect gait early. As a case study, we used this model to identify individuals with peripheral artery disease (PAD) and distinguish them from those without PAD. The framework uses acceleration data extracted from anatomical reflective markers placed in different body locations to train the diagnostic models and a wearable accelerometer carried at the waist for validation. Reflective marker data have been used for decades in studies evaluating and monitoring human gait. They are widely available for many body parts but are obtained in specialized laboratories. On the other hand, wearable accelerometers enable diagnostics outside lab conditions. Models trained by raw marker data at the sacrum achieve an accuracy of 92% in distinguishing PAD patients from non-PAD controls. This accuracy drops to 28% when data from a wearable accelerometer at the waist validate the model. This model was enhanced by using features extracted from the acceleration rather than the raw acceleration, with the marker model accuracy only dropping from 86 to 60% when validated by the wearable accelerometer data.