bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental risk score of multiple pollutants for kidney damage among residents in vulnerable areas by occupational chemical exposure in Korea
Authors: Jang Hyuna , Choi Kyung-Hwa , Cho Yong Min , Han Dahee , Hong Young Seoub 
Published: May 2024

AbstractThis study aimed to develop an environmental risk score (ERS) of multiple pollutants (MP) causing kidney damage (KD) in Korean residents near abandoned metal mines or smelters and evaluate the association between ERS and KD by a history of occupational chemical exposure (OCE). Exposure to MP, consisting of nine metals, four polycyclic aromatic hydrocarbons, and four volatile organic compounds, was measured as urinary metabolites. The study participants were recruited from the Forensic Research via Omics Markers (FROM) study (n = 256). Beta-2-microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) were used as biomarkers of KD. Bayesian kernel machine regression (BKMR) was selected as the optimal ERS model with the best performance and stability of the predicted effect size among the elastic net, adaptive elastic net, weighted quantile sum regression, BKMR, Bayesian additive regression tree, and super learner model. Variable importance was estimated to evaluate the effects of metabolites on KD. When stratified with the history of OCE after adjusting for several confounding factors, the risks for KD were higher in the OCE group than those in the non-OCE group; the odds ratio (OR; 95% CI) for ERS in non-OCE and OCE groups were 2.97 (2.19, 4.02) and 6.43 (2.85, 14.5) for β2-MG, 1.37 (1.01, 1.86) and 4.16 (1.85, 9.39) for NAG, and 4.57 (3.37, 6.19) and 6.44 (2.85, 14.5) for eGFR, respectively. We found that the ERS stratified history of OCE was the most suitable for evaluating the association between MP and KD, and the risks were higher in the OCE group than those in the non-OCE group.
A Narrative Review of the Pathophysiology and Treatment of Methamphetamine-Associated Psychosis
Authors: Stacy Peter , Frantz Jenna , Miller Genevieve , Merrill Brian , Gainer Danielle 
Published: May 2024

AbstractThe evaluation and management of methamphetamine-associated psychosis (MAP) is an area of study with a paucity of large-scale, longitudinal data. Methamphetamine use has soared in popularity worldwide in the past decade, leading to a surge in individuals experiencing its neurotoxic effects. Current evidence suggests that methamphetamine causes neurodegeneration and psychosis through VMAT2 inhibition which raises dopamine and GABA levels in the brain’s dopaminergic pathways, leading to oxidative stress and inflammation. Differentiating MAP from primary psychotic disorders is challenging; high rates of persistent psychosis leading to a diagnosis of primary psychotic disorder and an absence of an etiologic differentiation amongst the DSM-5 diagnostic criteria further complicate the diagnostic process. Once a diagnosis of methamphetamine-associated psychosis is made, benzodiazepines have been shown to provide temporary relief; in addition, depending on the severity and impact of psychotic symptoms, antipsychotics may be indicated both short and long terms for ongoing symptom management. Robust data for these treatments is limited and primarily draws on animal studies or case reports. Further research is needed to codify MAP treatment standards of care.
Can social adversity alter the epigenome, trigger oral disease, and affect future generations?
Authors: Khalid Sakr , Kearney Michaela , McReynolds David E. 
Published: May 2024

AbstractThe nature versus nurture debate has intrigued scientific circles for decades. Although extensive research has established a clear relationship between genetics and disease development, recent evidence has highlighted the insufficiency of attributing adverse health outcomes to genetic factors alone. In fact, it has been suggested that environmental influences, such as socioeconomic position (SEP), may play a much larger role in the development of disease than previously thought, with extensive research suggesting that low SEP is associated with adverse health conditions. In relation to oral health, a higher prevalence of caries (tooth decay) exists among those of low SEP. Although little is known about the biological mechanisms underlying this relationship, epigenetic modifications resulting from environmental influences have been suggested to play an important role. This review explores the intersection of health inequalities and epigenetics, the role of early-life social adversity and its long-term epigenetic impacts, and how those living within the lower hierarchies of the socioeconomic pyramid are indeed at higher risk of developing diseases, particularly in relation to oral health. A deeper understanding of these mechanisms could lead to the development of targeted interventions for individuals of low SEP to improve oral health or identify those who are at higher risk of developing oral disease.
Microphysiological Systems as Organ-Specific In Vitro Vascular Models for Disease Modeling
Authors: Nam Ungsig , Lee Seokhun , Ahmad Ashfaq , Yi Hee-gyeong , Jeon Jessie S. 
Published: May 2024

AbstractThe vascular system, essential for human physiology, is vital for transporting nutrients, oxygen, and waste. Since vascular structures are involved in various disease pathogeneses and exhibit different morphologies depending on the organ, researchers have endeavored to develop organ-specific vascular models. While animal models possess sophisticated vascular morphologies, they exhibit significant discrepancies from human tissues due to species differences, which limits their applicability. To overcome the limitations arising from these discrepancies and the oversimplification of 2D dish cultures, microphysiological systems (MPS) have emerged as a promising alternative. These systems more accurately mimic the human microenvironment by incorporating cell interactions, physical stimuli, and extracellular matrix components, thus facilitating enhanced tissue differentiation and functionality. Importantly, MPS often utilize human-derived cells, greatly reducing disparities between model and patient responses. This review focuses on recent advancements in MPS, particularly in modeling the human organ-specific vascular system, and discusses their potential in biological adaptation.
Analyzing the dynamics of monetary policy and economic growth in Ethiopia: an autoregressive distributed lag (ARDL) approach
Authors: Abdulkadr Ahmed Abduletif , Asnakew Yibeltal Walle , Sendkie Fentahun Baylie , Workineh Ermias Berihun , Asfaw Dagmawe Menelek 
Published: May 2024

AbstractNumerous studies conducted by various scholars have aimed to ascertain the impact of monetary policy on economic growth. However, these empirical investigations have not reached a unanimous consensus. Therefore, this study analyzes the effect of monetary policy. To address this objective, this study employed ARDL and error correction model (ECM) based on annual data from 1993 to 2022. Granger causality test was also employed to check the direction of causal effects of one variable on the other variable. All required pre and post estimation tests were performed and verified that the model was statistically viable. The study revealed that, in the short run, deposit interest rate, reserve required amount, and open market operation have positive and statistically significant effects on real GDP growth of Ethiopia; however, money supply has negative and statistically significant effects on real GDP growth of Ethiopia. In the long run, money supply has positive and statistically significant effects on real GDP growth of Ethiopia; however, deposit interest rate and reserve required have negative and statistically significant effects on real GDP growth of Ethiopia. To sum up, in the short run, contractionary monetary policy was promising, and in the long run, expansionary monetary policy was favorable for economic growth. The Granger causality test result shows that there is bidirectional causality between monetary policy and economic growth; except there was a unidirectional relationship between deposit interest rate and economic growth. Ultimately, this research suggests the following policy recommendation: for short-term economic enhancement, it is advisable for the government to opt for a contractionary monetary policy rather than an expansionary one. On the other hand, for long-term economic improvement, an expansionary monetary policy is more favorable than a contractionary one.
Complete Artworks without Authors
Authors: Trogdon Kelly 
Published: May 2024

Abstract
Genetically complete yet authorless artworks seem possible, yet it is hard to understand how they might really be possible. A natural way to try to resolve this puzzle is by constructing an account of artwork completion on the model of accounts of artwork meaning that are compatible with meaningful yet authorless artworks. However, I argue that such an account of artwork completion is implausible. Therefore, I leave the puzzle unresolved.
PREPARING FOR THE NEXT PANDEMIC
Authors: Buchanan Allen 
Published: May 2024

AbstractMy aim in this essay is to argue for a better moral-conceptual framework and for institutional innovation in preparation for the next pandemic. My main conclusions are as follows. (1) The primary moral principle that should guide responses to the next pandemic is the duty to prevent and mitigate serious harms. (2) A proper understanding of the moral foundations and scope of the duty to prevent and mitigate serious harms requires rejecting both Extreme Nationalism and Extreme Cosmopolitanism. (3) A better response to the next pandemic requires transforming the moral landscape through institutional innovation by developing an international institution that can perfect indeterminate duties (i) by identifying duty-bearers, (ii) by specifying their duties to provide medical resources and other forms of aid, (iii) by allocating the specified duties to various public and private entities in such a way as to ensure effective coordination and that the costs of providing aid are fairly distributed, and (iv) by providing effective mechanisms for compliance with the specified duties. (4) Institutional innovation is morally required, regardless of whether the harm prevention and mitigation duties of the better-off are duties of justice or of beneficence, because without institutionalization, some duties of justice, including those requiring the prevention and mitigation of serious harms, suffer some of the same indeterminacies that are present in duties of beneficence.
“WAVING THE BANNER OF DEMOCRACY”: DEMOCRATIC SANCTIONS AND THREE HYPOCRISY PUZZLES
Authors: Nili Shmuel 
Published: May 2024

AbstractThis essay aims to advance the general discussion of hypocrisy in moral and political philosophy as well as normative policy debates regarding democratic sanctions against autocracies that often trigger charges of hypocrisy. In the process of making sense of these charges, I articulate and tackle three general puzzles regarding hypocrisy complaints. The first—the inaction puzzle—asks why a charge of hypocrisy should have any effect on the moral assessment of an agent’s actions, as distinct from the agent’s character or attitudes. The second—the ambivalence puzzle—asks why we often react to hypocrisy charges with seemingly paradoxical ambivalence, recognizing such charges for the transparent deflections they often are, but also granting their normative force. The third—the preemption puzzle—asks why hypocrisy charges do not entirely lose their force when their targets openly concede that they too have suffered from the same flaws that they highlight in others. I argue that sustained reflection on each of these puzzles can enrich—and be enriched by—normative analysis of democratic sanctions.
Start-up activity in the LLM ecosystem
Authors: Dale Robert 
Published: May 2024

AbstractThe technical and mainstream media’s headline coverage of AI invariably centers around the often astounding abilities demonstrated by large language models. That’s hardly surprising, since to all intents and purposes that’s where the newsworthy magic of generative AI lies. But it takes a village to raise a child: behind the scenes, there’s an entire ecosystem that supports the development and deployment of these models and the applications that are built on top of them. Some parts of that ecosystem are dominated by the Big Tech incumbents, but there are also many niches where start-ups are aiming to gain a foothold. We take a look at some components of that ecosystem, with a particular focus on ideas that have led to investment in start-ups over the last year or so.
Revisiting a Global Burnout Score With the Burnout Assessment Tool	(BAT) Across Nine Country Samples
Authors: De Beer Leon T. , Schaufeli Wilmar B. , De Witte Hans , Hakanen Jari J. , Kaltiainen Janne , Glaser Jürgen , Seubert Christian , Shimazu Akihito , Bosak Janine , Procházka Jakub , Kajzar Aleš , Christensen Marit 
Published: May 2024

Abstract: Studies published on the validity of the Burnout Assessment Tool (BAT), a novel burnout instrument, have gained traction in the literature over recent years. The BAT has been successfully shown to be equivalent across representative samples when modeled as a second-order/higher-order model. However, this specification is not free of criticism and the bifactor approach has been presented as the alternative model specification. Therefore, a study investigating the construct-relevant multidimensionality of the BAT across many representative samples is warranted to reassess a global burnout factor ( n = 9,041). We implemented bifactor exploratory structural equation modeling to ascertain the relevance of a global burnout factor and specific component factors (bifactor-ESEM). According to the standardized loadings and McDonald’s ω coefficients, the results showed that the bifactor-ESEM model had a strong global burnout factor with relevant specific factors beyond the global factor. The model also showed measurement invariance across countries and genders. We also present a figure that compares the global burnout mean scores of the countries. All in all, the results of this study reaffirmed that BAT-assessed burnout can be modeled with an equivalent global burnout score across conditions.
Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome
Authors: Sefik Esra , Duan Kuaikuai , Li Yiheng , Sholar Brittney , Evans Lindsey , Pincus Jordan , Ammar Zeena , Murphy Melissa M. , Klaiman Cheryl , Saulnier Celine A. , Pulver Stormi L. , Goldman-Yassen Adam E. , Guo Ying , Walker Elaine F. , Li Longchuan , Mulle Jennifer G. , Shultz Sarah 
Published: May 2024

AbstractHigh-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.
HAP40 modulates mutant Huntingtin aggregation and toxicity in Huntington’s disease mice
Authors: Chen Laiqiang , Qin Yiyang , Guo Tingting , Zhu Wenzhen , Lin Jingpan , Xing Tingting , Duan Xuezhi , Zhang Yiran , Ruan Eshu , Li Xiang , Yin Peng , Li Shihua , Li Xiao-Jiang , Yang Su 
Published: May 2024

AbstractHuntington’s disease (HD) is a monogenic neurodegenerative disease, caused by the CAG trinucleotide repeat expansion in exon 1 of the Huntingtin (HTT) gene. The HTT gene encodes a large protein known to interact with many proteins. Huntingtin-associated protein 40 (HAP40) is one that shows high binding affinity with HTT and functions to maintain HTT conformation in vitro. However, the potential role of HAP40 in HD pathogenesis remains unknown. In this study, we found that the expression level of HAP40 is in parallel with HTT but inversely correlates with mutant HTT aggregates in mouse brains. Depletion of endogenous HAP40 in the striatum of HD140Q knock-in (KI) mice leads to enhanced mutant HTT aggregation and neuronal loss. Consistently, overexpression of HAP40 in the striatum of HD140Q KI mice reduced mutant HTT aggregation and ameliorated the behavioral deficits. Mechanistically, HAP40 preferentially binds to mutant HTT and promotes Lysine 48-linked ubiquitination of mutant HTT. Our results revealed that HAP40 is an important regulator of HTT protein homeostasis in vivo and hinted at HAP40 as a therapeutic target in HD treatment.
METTL8 links mt-tRNA m3C modification to the HIF1α/RTK/Akt axis to sustain GBM stemness and tumorigenicity
Authors: Lee Bernice Woon Li , Chuah You Heng , Yoon Jeehyun , Grinchuk Oleg V. , Liang Yajing , Hirpara Jayshree L. , Shen Yating , Wang Loo Chien , Lim Yan Ting , Zhao Tianyun , Sobota Radoslaw M. , Yeo Tseng Tsai , Wong Andrea Li Ann , Teo Kejia , Nga Vincent Diong Weng , Tan Bryce Wei Quan , Suda Toshio , Toh Tan Boon , Pervaiz Shazib , Lin Zhewang , Ong Derrick Sek Tong 
Published: May 2024

AbstractEpitranscriptomic RNA modifications are crucial for the maintenance of glioma stem cells (GSCs), the most malignant cells in glioblastoma (GBM). 3-methylcytosine (m3C) is a new epitranscriptomic mark on RNAs and METTL8 represents an m3C writer that is dysregulated in cancer. Although METTL8 has an established function in mitochondrial tRNA (mt-tRNA) m3C modification, alternative splicing of METTL8 can also generate isoforms that localize to the nucleolus where they may regulate R-loop formation. The molecular basis for METTL8 dysregulation in GBM, and which METTL8 isoform(s) may influence GBM cell fate and malignancy remain elusive. Here, we investigated the role of METTL8 in regulating GBM stemness and tumorigenicity. In GSC, METTL8 is exclusively localized to the mitochondrial matrix where it installs m3C on mt-tRNAThr/Ser(UCN) for mitochondrial translation and respiration. High expression of METTL8 in GBM is attributed to histone variant H2AZ-mediated chromatin accessibility of HIF1α and portends inferior glioma patient outcome. METTL8 depletion impairs the ability of GSC to self-renew and differentiate, thus retarding tumor growth in an intracranial GBM xenograft model. Interestingly, METTL8 depletion decreases protein levels of HIF1α, which serves as a transcription factor for several receptor tyrosine kinase (RTK) genes, in GSC. Accordingly, METTL8 loss inactivates the RTK/Akt axis leading to heightened sensitivity to Akt inhibitor treatment. These mechanistic findings, along with the intimate link between METTL8 levels and the HIF1α/RTK/Akt axis in glioma patients, guided us to propose a HIF1α/Akt inhibitor combination which potently compromises GSC proliferation/self-renewal in vitro. Thus, METTL8 represents a new GBM dependency that is therapeutically targetable.
dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe
Authors: Rodrigues Joana S. , Chenlo Miguel , Bravo Susana B. , Perez-Romero Sihara , Suarez-Fariña Maria , Sobrino Tomas , Sanz-Pamplona Rebeca , González-Prieto Román , Blanco Freire Manuel Narciso , Nogueiras Ruben , López Miguel , Fugazzola Laura , Cameselle-Teijeiro José Manuel , Alvarez Clara V. 
Published: May 2024

AbstractThe E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA–directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.