bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hallucination-Proneness is Associated With a Decrease in Robust Averaging of Perceptual Evidence
Authors: Larsen Emmett M , Jin Jingwen , Zhang Xian , Donaldson Kayla R , Liew Megan , Horga Guillermo , Luhmann Christian , Mohanty Aprajita 
Published: August 2023

AbstractBackground and HypothesisHallucinations are characterized by disturbances in perceptual decision-making about environmental stimuli. When integrating across multiple stimuli to form a perceptual decision, typical observers engage in “robust averaging” by down-weighting extreme perceptual evidence, akin to a statistician excluding outlying data. Furthermore, observers adapt to contexts with more unreliable evidence by increasing this down-weighting strategy. Here, we test the hypothesis that hallucination-prone individuals (n = 38 high vs n = 91 low) would show a decrease in this robust averaging and diminished sensitivity to changes in evidence variance.Study DesignWe used a multielement perceptual averaging task to elicit dichotomous judgments about the “average color” (red/blue) of an array of stimuli in trials with varied strength (mean) and reliability (variance) of decision-relevant perceptual evidence. We fitted computational models to task behavior, with a focus on a log-posterior-ratio (LPR) model which integrates evidence as a function of the log odds of each perceptual option and produces a robust averaging effect.Study ResultsHallucination-prone individuals demonstrated less robust averaging, seeming to weigh inlying and outlying extreme or untrustworthy evidence more equally. Furthermore, the model that integrated evidence as a function of the LPR of the two perceptual options and produced robust averaging showed poorer fit for the group prone to hallucinations. Finally, the weighting strategy in hallucination-prone individuals remained insensitive to evidence variance.ConclusionsOur findings provide empirical support for theoretical proposals regarding evidence integration aberrations in psychosis and alterations in the perceptual systems that track statistical regularities in environmental stimuli.
City of Gauze: Medicine and the Governance of Urban Poverty
Authors: Seim Josh , DiMario Anthony 
Published: August 2023

Abstract
How is urban poverty governed? Scholarship emphasizes the significance of social assistance programs and criminal legal systems, but considerably less attention has been given to medical institutions. Drawing on contemporary and historical evidence across journalistic, bureaucratic, and academic texts, we conceptualize and compare three arenas for medically governing the poor in Los Angeles, California: clinical medicine, welfare medicine, and penal medicine. In addition to detailing the differences between these formations of medicine, we illustrate how each is embedded in similar political and productive relations. Ending with a call to reframe medicine as a primary institution for governing the poor, this article helps advance a relational vision of governance.
Biomarkers in aortic dissection: Diagnostic and prognostic value from clinical research
Authors: Zhao Yufei , Fu Weiguo , Wang Lixin 
Published: August 2023

Abstract
Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations, while reliable biomarkers to detect or monitor are still under investigation. Recent advances in technologies provide an unprecedented opportunity to yield the identification of clinically valuable biomarkers, including proteins, ribonucleic acids (RNAs), and deoxyribonucleic acids (DNAs), for early detection of pathological changes in susceptible patients, rapid diagnosis at the bedside after onset, and a superior therapeutic regimen primarily within the concept of personalized and tailored endovascular therapy for aortic dissection.
Direct and INdirect effects analysis of Genetic lOci (DINGO): A software package to increase the power of locus discovery in GWAS meta-analyses of perinatal phenotypes and traits influenced by indirect genetic effects
Authors: Hwang Liang-Dar , Cuellar-Partida Gabriel , Yengo Loic , Zeng Jian , Beaumont Robin N. , Freathy Rachel M. , Moen Gunn-Helen , Warrington Nicole M. , Evans David M. 
Published: August 2023

AbstractPerinatal traits are influenced by genetic variants from both fetal and maternal genomes. Genome-wide association studies (GWAS) of these phenotypes have typically involved separate fetal and maternal scans, however, this approach may be inefficient as it does not utilize the information shared across the individual GWAS. In this manuscript we investigate the performance of three strategies to detect loci in maternal and fetal GWAS of the same trait: (i) the traditional strategy of analysing maternal and fetal GWAS separately; (ii) a novel two degree of freedom test which combines information from maternal and fetal GWAS; and (iii) a novel one degree of freedom test where signals from maternal and fetal GWAS are meta-analysed together conditional on the estimated sample overlap. We demonstrate through a combination of analytical formulae and data simulation that the optimal strategy depends on the extent of sample overlap/relatedness between the maternal and fetal GWAS, the correlation between own and offspring phenotypes, whether loci jointly exhibit fetal and maternal effects, and if so, whether these effects are directionally concordant. We apply our methods to summary results statistics from a recent GWAS meta-analysis of birth weight from deCODE, the UK Biobank and the Early Growth Genetics (EGG) consortium. Both the two degree of freedom (213 loci) and meta-analytic approach (226 loci) dramatically increase the number of robustly associated genetic loci for birth weight relative to separately analysing the scans (183 loci). Our best strategy identifies an additional 62 novel loci compared to the most recent published meta-analysis of birth weight and implicates both known and new biological pathways in the aetiology of the trait. We implement our methods in the online DINGO (Direct andINdirect effects analysis ofGenetic lOci) software package, which allows users to perform one and/or two degree of freedom tests easily and computationally efficiently across the genome. We conclude that whilst the novel two degree of freedom test may be particularly useful for the analysis of certain perinatal phenotypes where many loci exhibit discordant maternal and fetal genetic effects, for most phenotypes, a simple meta-analytic strategy is likely to perform best, particularly in situations where maternal and fetal GWAS only partially overlap.
Identifying Factors Associated with Lower Quarter Performance-Based Balance and Strength Tests: the Project Baseline Health Study
Authors: Taylor Kenneth A. , Carroll Megan K. , Short Sarah A. , Celestin Bettia E. , Gilbertson Adam , Olivier Christoph B. , Haddad Francois , Cauwenberghs Nicholas 
Published: August 2023

ABSTRACTBackgroundPhysical performance tests are predictive of mortality and have been proposed for screening for certain health conditions (e.g., sarcopenia); however, the diagnostic screening and prognostic value of physical performance tests has primarily been studied in age-limited or disease-specific cohorts. In this study, we sought to identify the most salient characteristics associated with three lower quarter balance and strength tests in a deeply phenotyped cohort of community-dwelling adults.MethodsWe applied a stacked elastic net approach on detailed data on sociodemographic, health and health-related behaviors, and biomarker data from the first visit of the Project Baseline Health Study (N=2502) to determine which variables were most associated with three physical performance measures: single-legged balance test (SLBT), sitting-rising test (SRT), and 30-second chair-stand test (30CST). Analyses were stratified by age (<65 and ≥65).ResultsFemale sex, Black or African American race, lower educational attainment, and health conditions such as non-alcoholic fatty liver disease and cardiovascular conditions (e.g., hypertension) were consistently associated with worse performance across all three tests. Several other health conditions were associated with either better or worse test performance, depending on age group and test. C-reactive protein was the only laboratory value associated with performance across age and test groups with some consistency.ConclusionsOur results highlighted previously identified and several novel salient factors associated with performance on the SLBT, SRT, and 30CST. Future research should discern and validate the value of these tests as affordable, noninvasive biomarkers of prevalent and/or future disease in the community.
Effect of prior somatosensory electrical stimulation on the wrist in biasing human hand choice
Authors: Hirayama Kento , Takahashi Toru , Koga Takayuki , Osu Rieko 
Published: August 2023

AbstractHand choice is an unconscious decision frequently made in daily life. A correlation has been found between the state of brain activity before target presentation and hand choice for the target, around which the hand choice probability is in equilibrium. However, whether the neural state before target presentation affects hand choice remains unknown. Therefore, this study aimed to examine whether instantaneous somatosensory electrical stimulation administered to the unilateral wrist at 0, 300, or 600 ms before the target presentation facilitates or inhibits stimulated hand choice for targets around the hand selection equilibrium point. A single electrical stimulation comprised five trains of 1 ms electrical pulses, with a 20 ms inter-pulse interval. The stimulus intensity was set at 80% of the motor threshold. Fourteen right- handed healthy adults (five females, nine males; mean age, 25.1 ± 4.64 years) participated. Unilateral wrist stimulation significantly increased the probability of choosing the stimulated hand and led to a faster reaction time than bilateral wrist stimulation and no-stimulation conditions. The results suggest that prior somatosensory stimulation significantly affects the hand-choice process, effectively promoting selection of the stimulated hand. These findings highlight the potential application of this stimulation method in stroke rehabilitation to facilitate use of the paretic hand.Impact StatementPrior neural stimulation significantly affected the hand-selection process by promoting the selection of the stimulated hand, thus potentially beneficial in rehabilitating the paretic hand of patients with stroke.
The ubiquitin ligase STUB1 suppresses tumorigenesis of renal cell carcinomas through regulating YTHDF1 stability
Authors: Ma Siquan , Sun Yi , Gao Guoyao , Zeng Jin , Chen Ke , Zhao Zhenyu 
Published: August 2023

AbstractSTIP1 homology and U-box protein 1 (STUB1), a key RING family E3 ubiquitin ligase, plays both oncogenic and tumor-suppressive roles in a variety of human cancers. However, the role and mechanism of STUB1 in clear cell renal cell carcinoma (ccRCC) remains poorly defined. Here, we identified YTHDF1 as a novel STUB1 interactor by affinity purification mass spectrometry (AP-MS). STUB1 polyubiquitylates YTHDF1 and promotes YTHDF1 degradation. STUB1 depletion stabilizes YTHDF1 in renal cancer cells. STUB1-knockdown renal cancer cells exhibit increased migration and invasion in YTHDF1 dependent manner. Further study demonstrates that STUB1 knockdown promoted the tumorigenicity of ccRCC in a xenograft model. Clinically, STUB1 expression is down-regulated in ccRCC tissues, and the low expression level of STUB1 was associated with higher tumor stage and poor overall survival in patients with ccRCC. These findings reveal that STUB1 acts as an E3 ubiquitin ligase and promotes degradation of YTHDF1, and STUB1 inhibits the tumorigenicity of ccRCC through ubiquitinating YTHDF1.Novelty & Impact StatementsSTUB1 plays both oncogenic and tumor-suppressive roles in a variety of human cancers. Here, the authors demonstrated that STUB1 acts as a tumor suppressor in ccRCC, and the low expression level of STUB1 was associated with higher tumor stage and poor overall survival in patients with ccRCC. In addition, STUB1-knockdown renal cancer cells exhibit increased migration and invasion in YTHDF1 dependent manner. Mechanistically, STUB1 polyubiquitylates YTHDF1 and promotes YTHDF1 degradation.
Proportionality-based association metrics in count compositional data
Authors: McGregor Kevin , Okaeme Nneka , Khorasaniha Reihane , Veniamin Simona , Jovel Juan , Miller Richard , Mahmood Ramsha , Graham Morag , Bonner Christine , Bernstein Charles N. , Arnold Douglas L. , Bar-Or Amit , Hart Janace , Marrie Ruth Ann , O’Mahony Julia , Yeh E. Ann , Zhao Yinshan , Banwell Brenda , Waubant Emmanuelle , Knox Natalie , Van Domselaar Gary , Zhu Feng , Mirza Ali I. , Tremlett Helen , Armstrong Heather 
Published: August 2023

AbstractMotivationCompositional data comprise vectors that describe the constituent parts of a whole. Data arising from various -omics platforms such as 16S and RNA-sequencing are compositional in nature. However, correlations between features on raw counts have no meaningful interpretation. Metrics of proportionality were formulated to address this problem. However, there is an inherent bias that arises when calculating these metrics empirically on count-based measures due to variability in read depths.ResultsWe quantify the bias introduced by empirically calculating proportionality-based association metrics in count data. Additionally, we propose a means of estimating these metrics within a logit-normal multinomial model in pursuit of more accurate estimates. The model-based estimates are shown to outperform empirical estimates in simulated data, and are additionally applied to a mouse embryonic stem-cell single-cell sequencing dataset as well as a pediatric-onset multiple sclerosis metagenomic dataset.Availability and ImplementationAn R package is available athttps://CRAN.R-project.org/package=countprop.Supplementary informationSupplementary data are available at Bioinformatics online.
Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling
Authors: Mühlenbeck Henning , Tsutsui Yuko , Lemmon Mark A. , Bender Kyle W. , Zipfel Cyril 
Published: August 2023

AbstractTransmembrane signaling by plant receptor kinases (RKs) has long been thought to involve reciprocal trans-phosphorylation of their intracellular kinase domains. The fact that many of these are pseudokinase domains, however, suggests that additional mechanisms must govern RK signaling activation. Non-catalytic signaling mechanisms of protein kinase domainshave been described in metazoans, but information is scarce for plants. Recently, a non-catalytic function was reported for the leucine-rich repeat (LRR)-RK subfamily XIIa member EFR (ELONGATION FACTOR TU RECEPTOR) and phosphorylation-dependent conformational changes were proposed to regulate signaling of RKs with non-RD kinase domains. Here, using EFR as a model, we describe a non-catalytic activation mechanism for LRR-RKs with non-RD kinase domains. EFR is an active kinase, but a kinase-dead variant retains the ability to enhance catalytic activity of its co-receptor kinase BAK1/SERK3 (BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1/SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3). Applying hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis and designing homology-based intragenic suppressor mutations, we provide evidence that the EFR kinase domain must adopt its active conformation in order to activate BAK1 allosterically, likely by supporting αC-helix positioning in BAK1. Our results suggest a conformational toggle model for signaling, in which BAK1 first phosphorylates EFR in the activation loop to stabilize its active conformation, allowing EFR in turn to allosterically activate BAK1.
Genetic and Structural Basis of Colistin Resistance inKlebsiella pneumoniae: Unraveling the Molecular Mechanisms
Authors: Alousi Sahar , Saad Jamal , Panossian Balig , Makhlouf Rita , Al Khoury Charbel , Rahy Kelven , Thoumi Sergio , Araj George F. , Khnayzer Rony , Tokajian Sima 
Published: August 2023

AbstractAntimicrobial Antimicrobial resistance (AMR), together with extensively drug resistant (XDR), mainly among Gram-negative bacteria, has been on the rise. Colistin (polymyxin E) remains one of the primary available last resorts to treat infections by XDR bacteria with the rapid emergence of global resistance. Since the exact mechanism of bacterial resistance to colistin remains unfolded, this study warranted elucidating the underlying mechanism of colistin resistance and heteroresistance among carbapenem-resistant (CR)Klebsiella pneumoniaeisolates.Molecular analysis was carried out on the resistant isolates using a genome-wide characterization approach, and MALDI-TOF MS for lipid A. Among the 32 CRK. pneumoniaeisolates, three and seven isolates showed resistance and intermediate resistance, respectively, to colistin. The seven isolates with intermediate resistance exhibited the “skip-well” phenomenon, attributed to the presence of resistant subpopulations. The three isolates with full resistance to colistin showed ions using MALDI-TOF MS at m/z 1840 and 1824 representing bisphosphorylated and hexaacylated lipid A with or without hydroxylation, at position C’-2 of the fatty acyl chain, respectively. Studying the genetic environment ofmgrBlocus revealed the presence of insertion sequences that disrupted themgrBlocus in the three colistin resistant isolates: IS1R and IS903B. Our findings showed that colistin resistance/heteroresistance was inducible with mutations in chromosomal regulatory networks controlling lipid A moiety and IS sequences disrupting themgrBgene leading to elevated MIC values and treatment failure. IS monitoring inK. pneumoniaecould help prevent the spread of colistin resistance and decrease colistin treatment failure.
M4-mediated cholinergic transmission is reduced in parkinsonian mice and its restoration alleviates motor deficits and levodopa-induced dyskinesia
Authors: Nielsen Beatriz E. , Ford Christopher P. 
Published: August 2023

ABSTRACTThe dynamic equilibrium between dopamine (DA) and acetylcholine (ACh) in the dorsal striatum is thought to be essential for motor function, as imbalances in their levels are associated with Parkinson’s disease (PD) and levodopa-induced dyskinesia (LID). While loss of DA leads to enhanced striatal ACh, whether this translates to specific alterations in transmission remains unclear. To address this, we examined how the strength of ACh release and signaling onto direct-pathway medium spiny neurons is altered in parkinsonian mice. Rather than the predicted cholinergic enhancement, we found that the strength of muscarinic M4-receptor mediated transmission was reduced following DA loss, resulting from downregulated receptors and downstream signaling. Despite M4-receptors being thought to mediate anti-kinetic effects, restoring M4-receptor function partially rescued parkinsonian balance and coordination deficits and limited the development of levodopa-induced dyskinetic behaviors, indicating that decreased M4-function contributed to circuit and motor dysfunctions in response to DA loss.
The histidine kinase NahK regulates pyocyanin production through the PQS system
Authors: Mendoza Alicia G. , Guercio Danielle , Smiley Marina K. , Sharma Gaurav K. , Withorn Jason M. , Hudson-Smith Natalie V. , Ndukwe Chika , Dietrich Lars E. P. , Boon Elizabeth M. 
Published: August 2023

AbstractMany bacterial histidine kinases work in two-component systems that combine into larger multi-kinase networks. NahK is one of the kinases in the GacS Multi-Kinase Network (MKN), which is the MKN that controls biofilm regulation in the opportunistic pathogenPseudomonas aeruginosa (P. aeruginosa). This network has also been associated with regulating many virulence factorsP. aeruginosasecretes to cause disease. However, the individual role of each kinase is unknown. In this study, we identify NahK as a novel regulator of the phenazine pyocyanin (PYO). Deletion ofnahKled to a four-fold increase in PYO production, almost exclusively through upregulation of phenazine operon two (phz2). We determined that this upregulation is due to mis-regulation of allP. aeruginosaquorum sensing systems, with a large upregulation of thePseudomonasquinolone signal (PQS) system and a decrease in production of the acyl-homoserine lactone-producing system,las.In addition, we see differences in expression of quorum sensing inhibitor proteins that align with these changes. Together, this data contributes to understanding how the GacS MKN modulates QS and virulence.ImportancePseudomonas aeruginosais a Gram-negative bacterium that establishes biofilms as part of its pathogenicity.P. aeruginosainfections are associated with nosocomial infections. As the prevalence of multi-drug resistantP. aeruginosaincreases, it is essential to understand underlying virulence molecular mechanisms. Histidine kinase NahK is one of several kinases inP. aeruginosaimplicated in biofilm formation and dispersal. Previous work has shown that the nitric oxide sensor, NosP, triggers biofilm dispersal by inhibiting NahK. The data presented here demonstrates that NahK plays additional important roles in theP. aeruginosalifestyle, including regulating bacterial communication mechanisms such as quorum sensing. These effects have larger implications in infection as they affect toxin production and virulence.
The floral development of the allotetraploidCoffea arabicaL. correlates with a small RNA dynamic reprogramming
Authors: Ribeiro Thales Henrique Cherubino , Baldrich Patricia , de Oliveira Raphael Ricon , Fernandes-Brum Christiane Noronha , Mathioni Sandra Marisa , Cardoso Thaís Cunha de Sousa , Gomes Matheus de Souza , Amaral Laurence Rodrigues do , de Oliveira Kellen Kauanne Pimenta , dos Reis Gabriel Lasmar , Meyers Blake C. , Chalfun-Junior Antonio 
Published: August 2023

SummaryNon-coding and coding RNAs are key regulators of plant growth, development, and stress responses. To investigate the types of transcripts accumulated during the vegetative to reproductive transition and floral development in theCoffea arabicaL., we sequenced small RNA libraries from eight developmental stages, up to anthesis.We combined this data with messenger RNA and PARE sequencing of two important development stages that marks the transition of an apparent latent to a rapid growth stage. In addition, we took advantage of multiplein silicotools to characterize genomic loci producing small RNAs such as phasiRNAs, miRNAs and tRFs.Our differential and co-expression analysis showed that some types of small RNAs such as tRNAs, snoRNAs, snRNAs and phasiRNAs preferentially accumulate in a stage- specific manner.Members of the miR482/miR2118 superfamily and their 21-nucleotide phasiRNAs originating from resistance genes show a robust co-expression pattern that is maintained across all the evaluated developmental stages. Finally, the majority of miRNAs accumulate in a family-stage specific manner, related to modulated hormonal responses and transcription factors expression.Societal Impact StatementThis research holds potential to benefit millions of coffee-producing families in over 60 countries. We uncovered molecular regulatory mechanisms governing flower development, one of the causes for theCoffea arabica’s uneven ripening. The absence of uniformity in coffee production, spanning from floral induction to branch senescence, has a detrimental impact on the final product’s quality. These insights will inform strategies for controlled coffee maturation, leading to improved, uniform harvests.