bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordance among apoB, non–high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention
Authors: Sniderman Allan D , Dufresne Line , Pencina Karol M , Bilgic Selin , Thanassoulis George , Pencina Michael J 
Published: May 2024

Abstract

Background and Aims
Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care.

Methods
A sample of 293 876 UK Biobank adults (age: 40–73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C.

Results
ApoB was highly correlated with LDL-C and non-HDL-C (Pearson’s r = .96, P &lt; .001 for both) but less so with log triglycerides (r = .42, P &lt; .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8–108.8 md/dL when LDL-C 130 mg/dL, 88.3–112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8–147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean − 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P &lt; .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0–1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03–1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12–1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model.

Conclusions
High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.
Robust and heritable knockdown of gene expression using a self-cleaving ribozyme in Drosophila
Authors: Nyberg Kevin G , Navales Fritz Gerald , Keles Eren , Nguyen Joseph Q , Hertz Laura M , Carthew Richard W 
Published: May 2024

Abstract
The current toolkit for genetic manipulation in the model animal Drosophila melanogaster is extensive and versatile but not without its limitations. Here, we report a powerful and heritable method to knockdown gene expression in D. melanogaster using the self-cleaving N79 hammerhead ribozyme, a modification of a naturally occurring ribozyme found in the parasite Schistosoma mansoni. A 111-bp ribozyme cassette, consisting of the N79 ribozyme surrounded by insulating spacer sequences, was inserted into 4 independent long noncoding RNA genes as well as the male-specific splice variant of doublesex using scarless CRISPR/Cas9-mediated genome editing. Ribozyme-induced RNA cleavage resulted in robust destruction of 3′ fragments typically exceeding 90%. Single molecule RNA fluorescence in situ hybridization results suggest that cleavage and destruction can even occur for nascent transcribing RNAs. Knockdown was highly specific to the targeted RNA, with no adverse effects observed in neighboring genes or the other splice variants. To control for potential effects produced by the simple insertion of 111 nucleotides into genes, we tested multiple catalytically inactive ribozyme variants and found that a variant with scrambled N79 sequence best recapitulated natural RNA levels. Thus, self-cleaving ribozymes offer a novel approach for powerful gene knockdown in Drosophila, with potential applications for the study of noncoding RNAs, nuclear-localized RNAs, and specific splice variants of protein-coding genes.
High parasite diversity maintained after an alga–virus coevolutionary arms race
Authors: Lievens Eva J P , Kühn Samuel , Horas Elena L , Le Pennec Guénolé , Peter Sarah , Petrosky Azade D , Künzel Sven , Feulner Philine G D , Becks Lutz 
Published: May 2024

Abstract
Arms race dynamics are a common outcome of host–parasite coevolution. While they can theoretically be maintained indefinitely, realistic arms races are expected to be finite. Once an arms race has ended, for example due to the evolution of a generalist-resistant host, the system may transition into coevolutionary dynamics that favour long-term diversity. In microbial experiments, host–parasite arms races often transition into a stable coexistence of generalist-resistant hosts, (semi-)susceptible hosts, and parasites. While long-term host diversity is implicit in these cases, parasite diversity is usually overlooked. In this study, we examined parasite diversity after the end of an experimental arms race between a unicellular alga (Chlorella variabilis) and its lytic virus (PBCV-1). First, we isolated virus genotypes from multiple time points from two replicate microcosms. A time-shift experiment confirmed that the virus isolates had escalating host ranges, i.e., that arms races had occurred. We then examined the phenotypic and genetic diversity of virus isolates from the post-arms race phase. Post-arms race virus isolates had diverse host ranges, survival probabilities, and growth rates; they also clustered into distinct genetic groups. Importantly, host range diversity was maintained throughout the post-arms race phase, and the frequency of host range phenotypes fluctuated over time. We hypothesize that this dynamic polymorphism was maintained by a combination of fluctuating selection and demographic stochasticity. Together with previous work in prokaryotic systems, our results link experimental observations of arms races to natural observations of long-term host and parasite diversity.
Performance and preference of larval parasitoid, Microplitis pallidipes (Hymenoptera: Braconidae), on 2 Spodoptera pest species
Authors: Xu Wei , Lyu Baoqian , Yan Sanqiang , Song Yaoyao , Tang Jihong , Zhou Xiaojuan , Wang Chongtian 
Published: May 2024

Abstract
Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) and Spodoptera litura (Fabricius) are the main pests on corn (Poaceae: Gramineae). The performance of the larval wasp, Microplitis pallidipes Szépligeti (Hymenoptera: Braconidae), was reported on S. frugiperda and S. litura. In this study, we evaluated host selectivity, constructed an age–stage, 2-sex life table, and assessed the pest control potential of M. pallidipes against these 2 pests under laboratory conditions. In a 2-choice host preference experiment, M. pallidipes exhibited a stronger preference for S. frugiperda over S. litura and a distinct preference for second instars. We also investigated the parasitism of females that were either unfed or fed with 10% honey–water solution under different host densities and found that the highest parasitism rate was observed when M. pallidipes were fed with honey–water solution on the first day after mating and a presented female wasp:host ratio of 1:90. In a nonselective assay, M. pallidipes successfully completed a full generation on both hosts. However, the parasitoids exhibited higher fitness and population growth potential when reared on S. frugiperda, with a net reproductive rate (R0) of 24.24, an intrinsic rate of increase (r) of 0.20 per day, a finite rate of increase (λ) of 1.23 per day, and a mean generation time (T) of 15.69 days. This study elucidates the performance of M. pallidipes on 2 Spodoptera host species and offers insights into its biological control potential on lepidopteran pests.
Pandemic Forms
Authors: Krishnan Lakshmi 
Published: May 2024

Abstract
Narrative structures, though invisible to the naked eye, guide our understanding of pandemics. Like curves and graphs, we can plot them, identify their patterns and organizing principles. These structures act upon our understanding of social and biological events just as much as the rhythms of viral replication and mutation. They order not only themselves but also social and health outcomes. This essay uses narrative precision to expand beyond Charles Rosenberg’s influential dramaturgic model and develops new pandemic forms, scaled from the level of an individual line break to the multi-part series: Arc, a form of sequence. Cycle, a form of repetition. Sequel, a form of elongation. Caesura, a form of break. It investigates the potentialities and limitations of these forms, how they intersect, collide, and contradict, and how analysis of these interactions contributes to a deeper understanding of pandemics, their effects, and the diverse perspectives defining their structures. In doing so, it prototypes how literary methods offer conceptual frameworks for pandemic historiography and how a transdisciplinary, medical humanities analysis produces novel understandings at the intersection of health, culture, and society.
Ganglioglioma with anaplastic/high-grade transformation: Histopathologic, molecular, and epigenetic characterization of 3 cases
Authors: Vizcaino M Adelita , Giannini Caterina , Lalich Daniel , Nael Ali , Jenkins Robert B , Tran Quynh , Orr Brent A , Abdullaev Zied , Aldape Kenneth , Vaubel Rachael A 
Published: May 2024

Abstract
Ganglioglioma (GG) with anaplasia (anaplastic ganglioglioma) is a rare and controversial diagnosis. When present, anaplasia involves the glial component of the tumor, either at presentation or at recurrence. To date, most published cases lack molecular characterization. We describe the histologic and molecular features of 3 patients presenting with BRAF p. V600E-mutant GG (CNS WHO grade 1) with high-grade glial transformation at recurrence. The tumors occurred in pediatric patients (age 9–16 years) with time to recurrence from 20 months to 7 years. At presentation, each tumor was low-grade, with a BRAFV600E-positive ganglion cell component and a glial component resembling pleomorphic xanthoastrocytoma (PXA) or fibrillary astrocytoma. At recurrence, tumors resembled anaplastic PXA or high-grade astrocytomas without neuronal differentiation. CDKN2A homozygous deletion (HD) was absent in all primary tumors. At recurrence, 2 cases acquired CDKN2A HD; the third case showed loss of p16 and MTAP immunoexpression, but no CDKN2A/B HD or mutation was identified. By DNA methylation profiling, all primary and recurrent tumors either grouped or definitely matched to different methylation classes. Our findings indicate that malignant progression of the glial component can occur in GG and suggest that CDKN2A/B inactivation plays a significant role in this process.
Evaluating Bacterial Spore Preparation Methods for Scanning Electron Microscopy
Authors: Malyshev Dmitry , Lee Cheng Choo , Andersson Magnus 
Published: May 2024

Abstract
Scanning electron microscopy (SEM) can reveal the ultrastructure of bacterial spores, including morphology, surface features, texture, spore damage, germination, and appendages. Understanding these features can provide a basis for adherence, how physical and environmental stressors affect spore viability, integrity, and functionality, as well as the distribution and function of surface appendages. However, the spore sample preparation method can significantly impact the SEM images’ appearance, resolution, and overall quality. In this study, we compare different spore preparation methods to identify optimal approaches for preparation time, spore appearance and resolved features, including the exosporium and spore pili, for SEM imaging. We use Bacillus paranthracis as model species and evaluate the efficacy of preparation protocols using different fixation and drying methods, as well as imaging under room- and cryogenic temperatures. We compare and assess method complexity to the visibility of the spore exosporium and spore appendages across different methods. Additionally, we use Haralick texture features to quantify the differences in spore surface appearance and determine the most suitable method for preserving spore structures and surface features during SEM evaluation. The findings from this study will help establish protocols for preparing bacterial spores for SEM and facilitating accurate and reliable analysis of spores’ characteristics.
What drives the variability in AGN? Explaining the UV-Xray disconnect through propagating fluctuations
Authors: Hagen Scott , Done Chris , Edelson Rick 
Published: May 2024

ABSTRACT
Intensive broad-band reverberation mapping campaigns have shown that AGN variability is significantly more complex than expected from disc reverberation of the variable X-ray illumination. The UV/optical variability is highly correlated and lagged, with longer lags at longer wavelengths as predicted, but the observed time-scales are longer than expected. Worse, the UV/optical light curves are not well correlated with the X-rays, which should drive them. Instead, we consider an intrinsically variable accretion disc, where slow mass accretion rate fluctuations are generated in the optical-UV disc, propagating down to modulate intrinsically faster X-ray variability from the central regions. We match our model to Fairall 9, a well-studied AGN with L ∼ 0.1LEdd, where the spectrum is dominated by the UV/EUV. Our model produces light curves where the X-rays and UV have very different fast variability, yet are well correlated on longer time-scales, as observed. It predicts that the intrinsic variability has optical/UV leading the X-rays, but including reverberation of the variable EUV from an inner wind produces a lagged bound-free continuum that matches the observed UV-optical lags. We conclude that optical/UV AGN variability is likely driven by intrinsic fluctuations within the disc, not X-ray reprocessing: the observed longer than expected lags are produced by reverberation of the EUV illuminating a wind, not by X-ray illumination of the disc: the increasing lag with increasing wavelength is produced by the increased contribution of the (constant lag) bound-free continuum to the spectrum, rather than indicating intrinsically larger reverberation distances for longer wavelengths.
Highly mass-loaded hot galactic winds are unstable to cool filament formation
Authors: Nguyen Dustin D , Thompson Todd A , Schneider Evan E , Tarrant Ashley P 
Published: May 2024

ABSTRACT
As cool clouds are entrained by a hot supersonic galactic wind, they may be shredded by hydrodynamical instabilities and incorporated into the hot flow. One-dimensional steady-state calculations show how cool cloud entrainment affects the bulk thermodynamics and kinematics of the hot gas: mass-loading decelerates the hot flow and changes its entropy. Here, we investigate the stability of mass-loaded hot winds using both perturbation analysis and 3D time-dependent radiative hydrodynamical simulations. We show that mass-loading is stable over a broad range of parameters and that the 1D time-steady analytic solutions exactly reproduce the 3D time-dependent calculations, provided that the flow does not decelerate sufficiently to become subsonic. For higher values of the mass-loading, the flow develops a second sonic point, with the first being at the edge of the wind-driving region. Strong deceleration increases the wind density and the flow becomes radiative, undergoing a thermal instability to form elongated dense cometary filaments. We explore the mass-loading parameters required to trigger this behaviour. For certain approximations, we can derive analytic criteria. In general, a mass-loading rate similar to the initial hot-mass outflow rate is required. In this sense, the destruction of small cool clouds by a hot flow may ultimately spontaneously generate fast cool filaments, as observed in starburst winds. Lastly, we find that the kinematics of filaments is sensitive to the slope of the mass-loading function. Filaments move faster than the surrounding wind if mass-loading is over long distances whereas filaments move slower than their surroundings if mass-loading is abrupt.
CRISPR/Cas9-generated mutations in a sugar transporter gene reduce cassava susceptibility to bacterial blight
Authors: Elliott Kiona , Veley Kira M , Jensen Greg , Gilbert Kerrigan B , Norton Joanna , Kambic Lukas , Yoder Marisa , Weil Alex , Motomura-Wages Sharon , Bart Rebecca S 
Published: May 2024

Abstract
Bacteria from the genus Xanthomonas are prolific phytopathogens that elicit disease in over 400 plant species. Xanthomonads carry a repertoire of specialized proteins called transcription activator-like (TAL) effectors that promote disease and pathogen virulence by inducing the expression of host susceptibility (S) genes. Xanthomonas phaseoli pv. manihotis (Xpm) causes bacterial blight on the staple food crop cassava (Manihot esculenta Crantz). The Xpm effector TAL20 induces ectopic expression of the S gene Manihot esculenta Sugars Will Eventually be Exported Transporter 10a (MeSWEET10a), which encodes a sugar transporter that contributes to cassava bacterial blight (CBB) susceptibility. We used CRISPR/Cas9 to generate multiple cassava lines with edits to the MeSWEET10a TAL20 effector binding site and/or coding sequence. In several of the regenerated lines, MeSWEET10a expression was no longer induced by Xpm, and in these cases, we observed reduced CBB disease symptoms post Xpm infection. Because MeSWEET10a is expressed in cassava flowers, we further characterized the reproductive capability of the MeSWEET10a promoter and coding sequence mutants. Lines were crossed to themselves and to wild-type plants. The results indicated that expression of MeSWEET10a in female, but not male, flowers is critical to produce viable F1 seed. In the case of promoter mutations that left the coding sequence intact, viable F1 progeny were recovered. Taken together, these results demonstrate that blocking MeSWEET10a induction is a viable strategy for decreasing cassava susceptibility to CBB and that ideal lines will contain promoter mutations that block TAL effector binding while leaving endogenous expression of MeSWEET10a unaltered.
Belief Updating, Childhood Maltreatment, and Paranoia in Schizophrenia-Spectrum Disorders
Authors: Sloan Ali F , Kittleson Andrew R , Torregrossa Lénie J , Feola Brandee , Rossi-Goldthorpe Rosa , Corlett Philip R , Sheffield Julia M 
Published: May 2024

Abstract

Background and Hypothesis
Exposure to childhood maltreatment—a risk factor for psychosis that is associated with paranoia—may impact one’s beliefs about the world and how beliefs are updated. We hypothesized that increased exposure to childhood maltreatment is related to volatility-related belief updating, specifically higher expectations of volatility, and that these relationships are strongest for threat-related maltreatment. Additionally, we tested whether belief updating mediates the relationship between maltreatment and paranoia.

Study Design
Belief updating was measured in 75 patients with schizophrenia-spectrum disorders and 76 nonpsychiatric controls using a 3-option probabilistic reversal learning (3PRL) task. A Hierarchical Gaussian Filter (HGF) was used to estimate computational parameters of belief updating, including prior expectations of volatility (μ03). The Childhood Trauma Questionnaire (CTQ) was used to assess cumulative maltreatment, threat, and deprivation exposure. Paranoia was measured using the Positive and Negative Syndrome Scale (PANSS) and the revised Green et al. Paranoid Thoughts Scale (R-GPTS).

Results
Greater exposure to childhood maltreatment is associated with higher prior expectations of volatility in the whole sample and in individuals with schizophrenia-spectrum disorders. This was specific to threat-related maltreatment, rather than deprivation, in schizophrenia-spectrum disorders. Paranoia was associated with both exposure to childhood maltreatment and volatility priors, but we did not observe a significant indirect effect of volatility priors on the relationship between maltreatment and paranoia.

Conclusions
Our study suggests that individuals with schizophrenia-spectrum disorders who were exposed to threatening experiences during childhood expect their environment to be more volatile, potentially facilitating aberrant belief updating and conferring risk for paranoia.
Androgen synthesis cell‐specific CREBZF deficiency alters adrenal cortex steroid secretion and develops behavioral abnormalities in adult male mice
Authors: Niu Hongyu , Li Chao , Zhang Hexin , Liu Haokun , Shang Chunmei , Jia Yanni , Wuenjiya  , Li Zuhui , Wang Aihua , Jin Yaping , Lin Pengfei 
Published: May 2024

AbstractThe global challenge of male infertility is escalating, notably due to the decreased testosterone (T) synthesis in testicular Leydig cells under stress, underscoring the critical need for a more profound understanding of its regulatory mechanisms. CREBZF, a novel basic region‐leucine zipper transcription factor, regulates testosterone synthesis in mouse Leydig cells in vitro; however, further validation through in vivo experiments is essential. Our study utilized Cyp17a1‐Cre to knock out CREBZF in androgen‐synthesis cells and explored the physiological roles of CREBZF in fertility, steroid hormone synthesis, and behaviors in adult male mice. Conditional knockout (cKO) CREBZF did not affect fertility and serum testosterone level in male mice. Primary Leydig cells isolated from CREBZF‐cKO mice showed impaired testosterone secretion and decreased mRNA levels of Star, Cyp17a1, and Hsd3b1. Loss of CREBZF resulted in thickening of the adrenal cortex, especially X‐zone, with elevated serum corticosterone and dehydroepiandrosterone levels and decreased serum dehydroepiandrosterone sulfate levels. Immunohistochemical staining revealed increased expression of StAR, Cyp11a1, and 17β‐Hsd3 in the adrenal cortex of CREBZF‐cKO mice, while the expression of AR was significantly reduced. Along with the histological changes and abnormal steroid levels in the adrenal gland, CREBZF‐cKO mice showed higher anxiety‐like behavior and impaired memory in the elevated plus maze and Barnes maze, respectively. In summary, CREBZF is dispensable for fertility, and CREBZF deficiency in Leydig cells promotes adrenal function in adult male mice. These results shed light on the requirement of CREBZF for fertility, adrenal steroid synthesis, and stress response in adult male mice, and contribute to understanding the crosstalk between testes and adrenal glands.