bluuebunny/crossref_metadata_2025_split huggingface dataset:
G-quadruplexes control hepatitis B virus replication by promoting cccDNA transcription and phase separation in hepatocytes
Authors: Giraud Guillaume , Rodà Mélanie , Huchon Pélagie , Michelet Maud , Maadadi Sarah , Jutzi Daniel , Montserret Roland , Ruepp Marc-David , Parent Romain , Combet Christophe , Zoulim Fabien , Testoni Barbara 
Published: December 2023

Abstract
Phase separation regulates fundamental processes in gene expression and is mediated by the local concentration of proteins and nucleic acids, as well as nucleic acid secondary structures such as G-quadruplexes (G4s). These structures play fundamental roles in both host gene expression and in viral replication due to their peculiar localisation in regulatory sequences. Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is an episomal minichromosome whose persistence is at the basis of chronic infection. Identifying the mechanisms controlling its transcriptional activity is indispensable to develop new therapeutic strategies against chronic hepatitis B. The aim of this study was to determine whether G4s are formed in cccDNA and regulate viral replication. Combining biochemistry and functional studies, we demonstrate that cccDNA indeed contains ten G4s structures. Furthermore, mutations disrupting two G4s located in the enhancer I HBV regulatory region altered cccDNA transcription and viral replication. Finally, we showed for the first time that cccDNA undergoes phase separation in a G4-dependent manner to promote its transcription in infected hepatocytes. Altogether, our data give new insight in the transcriptional regulation of the HBV minichromosome that might pave the way for the identification of novel targets to destabilize or silence cccDNA.
An impaired ubiquitin-proteasome system increases APOBEC3A abundance
Authors: Coxon Margo , Dennis Madeline A , Dananberg Alexandra , Collins Christopher D , Wilson Hannah E , Meekma Jordyn , Savenkova Marina I , Ng Daniel , Osbron Chelsea A , Mertz Tony M , Goodman Alan G , Duttke Sascha H , Maciejowski John , Roberts Steven A 
Published: December 2023

Abstract
Apolipoprotein B messenger RNA (mRNA) editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases cause genetic instability during cancer development. Elevated APOBEC3A (A3A) levels result in APOBEC signature mutations; however, mechanisms regulating A3A abundance in breast cancer are unknown. Here, we show that dysregulating the ubiquitin-proteasome system with proteasome inhibitors, including Food and Drug Administration-approved anticancer drugs, increased A3A abundance in breast cancer and multiple myeloma cell lines. Unexpectedly, elevated A3A occurs via an ∼100-fold increase in A3A mRNA levels, indicating that proteasome inhibition triggers a transcriptional response as opposed to or in addition to blocking A3A degradation. This transcriptional regulation is mediated in part through FBXO22, a protein that functions in SKP1–cullin–F-box ubiquitin ligase complexes and becomes dysregulated during carcinogenesis. Proteasome inhibitors increased cellular cytidine deaminase activity, decreased cellular proliferation and increased genomic DNA damage in an A3A-dependent manner. Our findings suggest that proteasome dysfunction, either acquired during cancer development or induced therapeutically, could increase A3A-induced genetic heterogeneity and thereby influence therapeutic responses in patients.
Genome-wide association studies reconstructing chronic kidney disease
Authors: Fountoglou Anastasios , Deltas Constantinos , Siomou Ekaterini , Dounousi Evangelia 
Published: December 2023

ABSTRACT
Chronic kidney disease (CKD) is a major health problem with an increasing epidemiological burden, and is the 16th leading cause of years of life lost worldwide. It is estimated that more than 10% of the population have a variable stage of CKD, while about 850 million people worldwide are affected. Nevertheless, public awareness remains low, clinical access is inappropriate in many circumstances and medication is still ineffective due to the lack of clear therapeutic targets. One of the main issues that drives these problems is the fact that CKD remains a clinical entity with significant causal ambiguity. Beyond diabetes mellitus and hypertension, which are the two major causes of kidney disease, there are still many gray areas in the diagnostic context of CKD. Genetics nowadays emerges as a promising field in nephrology. The role of genetic factors in CKD’s causes and predisposition is well documented and thousands of genetic variants are well established to contribute to the high burden of disease. Next-generation sequencing is increasingly revealing old and new rare variants that cause Mendelian forms of chronic nephropathy while genome-wide association studies (GWAS) uncover common variants associated with CKD-defining traits in the general population. In this article we review how GWAS has revolutionized—and continues to revolutionize—the old concept of CKD. Furthermore, we present how the investigation of common genetic variants with previously unknown kidney significance has begun to expand our knowledge on disease understanding, providing valuable insights into disease mechanisms and perhaps paving the way for novel therapeutic targets.
Ibogaine and Noribogaine
Authors: Mash Deborah C. , Karukin Michael 
Published: December 2023

Abstract
Ibogaine is an indole alkaloid derived from the root bark of Tabernanthe iboga. The anti-addictive actions of ibogaine were first reported in the 1960s by persons using heroin. They offered personal testimonials that single oral doses of ibogaine abruptly blocked opioid withdrawal, and they remained drug-free after ibogaine exposure. Today, online forums describe ibogaine use for opioid withdrawal management by for-profit clinics and unskilled lay people, despite a lack of regulatory testing of ibogaine in human clinical trials. Discontinuation of opioid agonist therapy results in severely painful opioid withdrawal symptoms (OWS) that are followed by a persistent negative affect. For many patients seeking to discontinue opioids, the post-acute emotional disruption is a major obstacle for completion of full withdrawal. This chapter summarizes ibogaine’s clinical experience and open-label observational evidence that the drug is useful for treating the OWS and facilitating a transition to drug-free abstinence. The drug’s polypharmacy mode of action is considered in light of neuroadaptations in mu-opioid processes observed during acute withdrawal, which are mechanistically related to the protracted negative mood state that follows during opioid abstinence. Finally, the dark side of the unregulated use of ibogaine and concerns for patient safety are considered. The value proposition for development of ibogaine as a psychedelic drug product for addiction treatment will ultimately depend on the drug’s single dose regimen, benefits, risks, and safety measures demonstrated in controlled clinical trials.
Hate Speech Detection and Bias in Supervised Text Classification
Authors: Davidson Thomas R. 
Published: December 2023

Abstract
This chapter introduces hate speech detection, describing the process of developing annotated datasets, training machine learning models, and outlining the cutting-edge techniques used to improve these methods. The case of hate speech detection provides valuable insight into the promises and pitfalls of supervised text classification for sociological analyses. A key theme running through the chapter is that ostensibly minor methodological decisions—particularly those related to the development of training datasets—can have profound downstream impacts. In particular, the chapter examines racial bias in these systems, explaining why models intended to detect hate speech can discriminate against the groups they are designed to protect and discussing efforts to mitigate these problems. It argues that hate speech detection and other forms of content moderation should be an important topic of sociological inquiry as platforms increasingly use these tools to govern speech on a global scale.
Race and Intersecting Inequalities in Machine Learning
Authors: Alegria Sharla 
Published: December 2023

Abstract
The central problem of race and gender inequality in machine learning (ML) reflects how inequalities of the past can be captured and reproduced in the content, solutions, and applications that use large amounts of data to make decisions. This chapter provides examples to explain four key areas of concern about race and gender inequalities in ML technology: (a) in the data itself, (b) in the ways data are used in algorithms, (c) in the ways algorithms are optimized, and (d) in the ways ML applications are used in the social world. The chapter further extends the discussion to examine issues of privacy and data collection and the inequalities that emerge around the human work needed to create and sustain highly data-intensive ML tools. Finally, the chapter explores strategies for improving fairness and equity.
The Influence of International Law on Constitutional Law
Authors: Ejima Akiko 
Published: December 2023

Abstract
This chapter explores the dynamic relationship between international law and constitutional law in Asia. The chapter begins by examining how constitution building in Asian countries has been influenced by international law. Afterwards, it considers how constitutional systems in Asia address the applicability of international law in the domestic realm. It addresses questions such as whether international law is superior or subordinate to constitutional law. Finally, the chapter looks specifically at the implementation of international human rights treaties within constitutional systems in Asia. This chapter considers these issues in the context of East and Southeast Asia. The chapter also examines Japan, China, and South Korea as case studies.
The Baltic States
Authors: Mälksoo Lauri 
Published: December 2023

Abstract
This chapter focuses on how the three Baltic States—the Republics of Estonia, Latvia, and Lithuania—have encountered international law. Created in 1918, these nations have had a tumultuous history, being illegally occupied and annexed by the Soviet Union from 1940 to 1991 (with the interlude of German occupation in 1941–1944). Nevertheless, the role of international legal arguments goes further back in time, including during the periods of the Livonian War (1558–1583) and the Great Nordic War (1700–1721). The chapter demonstrates how the Baltic States are archetypical small States and how their experience of international law has oscillated between triumphalism and desperation.
Information-sharing and cooperation in networked collective action groups
Authors: Harrell Ashley , Wolff Tom 
Published: December 2023

Abstract
When people provide for large-scale public goods, they often do not know what each individual group member is contributing. Instead, they commonly have access to the behaviors of their ties, in a broader network of others whose decisions are unknown. But network ties also serve as channels of communication, allowing behaviors to reach a larger audience. Here, we ask how public good production is affected in networks when people can share information about their ties’ behaviors with their other connections—and what behaviors they tend to share. We predict that networked collective action groups demonstrate higher levels of cooperation when their members can share information about their ties’ decisions with their other connections, compared with when they cannot. Informed by prior work, we consider two pathways by which information-sharing opportunities might shape cooperation in networked collective action groups: (i) as a means of coordinating one's own decisions with those of the larger group, including those to whom one is not directly tied, and (ii) as a reminder of possible reputational consequences for selfishness. Across two exploratory experiments (combined n = 7,014 contribution decisions, 49 groups), we demonstrate that opportunities to share information about others’ decisions promote public good production. The benefits occur even though people tend to share information about relatively selfish behaviors that, at first blush, might seem detrimental to cooperation. Our results build on prior work by showing that information-sharing prevents selfishness from becoming contagious by raising reputational concerns.
To be or not to be hallucinating: Implications of hypnagogic/hypnopompic experiences and lucid dreaming for brain disorders
Authors: Foffani Guglielmo 
Published: December 2023

Abstract
The boundaries between waking and sleeping—when falling asleep (hypnagogic) or waking up (hypnopompic)—can be challenging for our ability to monitor and interpret reality. Without proper understanding, bizarre but relatively normal hypnagogic/hypnopompic experiences can be misinterpreted as psychotic hallucinations (occurring, by definition, in the fully awake state), potentially leading to stigma and misdiagnosis in clinical contexts and to misconception and bias in research contexts. This Perspective proposes that conceptual and practical understanding for differentiating hallucinations from hypnagogic/hypnopompic experiences may be offered by lucid dreaming, the state in which one is aware of dreaming while sleeping. I first introduce a possible systematization of the phenomenological range of hypnagogic/hypnopompic experiences that can occur in the transition from awake to REM dreaming (including hypnagogic perceptions, transition symptoms, sleep paralysis, false awakenings, and out-of-body experiences). I then outline how metacognitive strategies used by lucid dreamers to gain/confirm oneiric lucidity could be tested for better differentiating hypnagogic/hypnopompic experiences from hallucinations. The relevance of hypnagogic/hypnopompic experiences and lucid dreaming is analyzed for schizophrenia and narcolepsy, and discussed for neurodegenerative diseases, particularly Lewy-body disorders (i.e. Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies), offering testable hypotheses for empirical investigation. Finally, emotionally positive lucid dreams triggered or enhanced by training/induction strategies or by a pathological process may have intrinsic therapeutic value if properly recognized and guided. The overall intention is to raise awareness and foster further research about the possible diagnostic, prognostic, and therapeutic implications of hypnagogic/hypnopompic experiences and lucid dreaming for brain disorders.
Of the Perfect and the Ordinary: Indistinguishability and Hallucination
Authors: Patel Shivam 
Published: December 2023

Abstract
The claim that perfect hallucination is introspectively indistinguishable from perception has been a centrepiece of philosophical theorizing about sense experience. The most common interpretation of the indistinguishability claim is modal: that it is impossible to distinguish perfect hallucination from perception through introspection alone. I run through various models of introspection and show that none of them can accommodate the modal interpretation. Rejecting the modal interpretation opens up two alternative interpretations of the indistinguishability claim. According to the generic interpretation, hallucination is indistinguishable from perception despite the existence of possible exceptions, while according to the actuality interpretation, the indistinguishability of hallucination from perception consists in the actual failure to distinguish hallucination from perception. These alternative understandings of the indistinguishability claim have a number of significant implications for the problem of perception, including the rejection of perfect hallucination and illusion in favour of our ordinary, non-philosophical concepts of these states.
A deep neural network based reverse radio spectrogram search algorithm
Authors: Ma Peter Xiangyuan , Croft Steve , Lintott Chris , Siemion Andrew P V 
Published: December 2023

Abstract
Modern radio astronomy instruments generate vast amounts of data, and the increasingly challenging radio frequency interference (RFI) environment necessitates ever-more sophisticated RFI rejection algorithms. The ‘needle in a haystack’ nature of searches for transients and technosignatures requires us to develop methods that can determine whether a signal of interest has unique properties, or is a part of some larger set of pernicious RFI. In the past, this vetting has required onerous manual inspection of very large numbers of signals. In this paper, we present a fast and modular deep learning algorithm to search for lookalike signals of interest in radio spectrogram data. First, we trained a β-variational autoencoder on signals returned by an energy detection algorithm. We then adapted a positional embedding layer from classical transformer architecture to a embed additional metadata, which we demonstrate using a frequency-based embedding. Next we used the encoder component of the β-variational autoencoder to extract features from small (∼715 Hz, with a resolution of 2.79 Hz per frequency bin) windows in the radio spectrogram. We used our algorithm to conduct a search for a given query (encoded signal of interest) on a set of signals (encoded features of searched items) to produce the top candidates with similar features. We successfully demonstrate that the algorithm retrieves signals with similar appearance, given only the original radio spectrogram data. This algorithm can be used to improve the efficiency of vetting signals of interest in technosignature searches, but could also be applied to a wider variety of searches for ‘lookalike’ signals in large astronomical data sets.
Preparing Compassionate Nurses
Authors: Thiel Linda M. , Wodwaski Nadine , Webber Elaine D. 
Published: December 2023

ABSTRACT:
In preparation for a curriculum revision, a cross-sectional, descriptive mixed-method research study sought to describe senior-level students' perspectives of Mercy and Jesuit faith-based tradition values integration in a pre-licensure BSN program. Integration of values was examined in both clinical settings and didactic classes. Students strongly articulated the importance of the school's values and mission to their future role as professional nurses. However, although value integration is occurring, greater attention to mission and values is needed in the clinical area.
The association of menopause with cardiometabolic disease risk factors in low- and middle-income countries: a systematic review and meta-analyses
Authors: Chikwati Raylton P. , Chikowore Tinashe , Mahyoodeen Nasrin Goolam , Jaff Nicole G. , George Jaya A. , Crowther Nigel J. 
Published: December 2023

Abstract

Importance
Menopause is an integral part of women's health, and studies in high-income countries have shown an increase in cardiometabolic disease (CMD) risk factors in postmenopausal compared with premenopausal women. However, to date, no study has combined and assessed such studies across low- and middle-income countries. This would better inform early monitoring and intervention strategies for reducing CMD risk factor levels in midlife women in these regions.

Objective
This study aimed to evaluate evidence from the literature on differences in CMD risk factors between premenopausal and postmenopausal midlife women living in low- and middle-income countries.

Evidence Review
A systematic review with meta-analysis of original articles of all study designs from the databases PubMed, PubMed Central, Scopus, and ISI Web of Science was conducted from conception until April 24, 2023. Studies that met the inclusion criteria were included in the analysis. Quality assessment of the articles was done using the Newcastle-Ottawa Scale, adapted for each study design. The study protocol was registered with the International Prospective Register of Systematic Reviews and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. For the meta-analysis, fixed-effects models were used to pool the odds ratios (OR), as measures of association.

Findings
Our search identified 4,849 relevant articles: 44 for the systematic review and 16 for the meta-analysis, in accordance with our inclusion criteria. Compared with premenopausal women, the postmenopausal stage was associated with metabolic syndrome (OR, 1.18 [95% CI, 1.11-1.27]), high waist-to-hip ratio (OR, 1.22 [95% CI, 1.12-1.32]), hypertension (OR, 1.10 [95% CI, 1.04-1.16]), elevated triglycerides (OR, 1.16 [95% CI, 1.11-1.21]), and elevated plasma glucose (OR, 1.21 [95% CI, 1.15-1.28]).

Conclusions and Relevance
This study confirmed that CMD risk factors are present at higher levels in postmenopausal than premenopausal women. This demonstrates an urgent need for public health policies that focus on early monitoring and interventions targeted at reducing CMD risk and related adverse outcomes in midlife women in these nations.
Assessing spontaneous sensory neuron activity using in vivo calcium imaging
Authors: Ingram Sonia , Chisholm Kim I. , Wang Feng , De Koninck Yves , Denk Franziska , Goodwin George L. 
Published: December 2023

Abstract
Heightened spontaneous activity in sensory neurons is often reported in individuals living with chronic pain. It is possible to study this activity in rodents using electrophysiology, but these experiments require great skill and can be prone to bias. Here, we have examined whether in vivo calcium imaging with GCaMP6s can be used as an alternative approach. We show that spontaneously active calcium transients can be visualised in the fourth lumbar dorsal root ganglion (L4 DRG) through in vivo imaging in a mouse model of inflammatory pain. Application of lidocaine to the nerve, between the inflamed site and the DRG, silenced spontaneous firing and revealed the true baseline level of calcium for spontaneously active neurons. We used these data to train a machine learning algorithm to predict when a neuron is spontaneously active. We show that our algorithm is accurate in 2 different models of pain: intraplantar complete Freund adjuvant and antigen-induced arthritis, with accuracies of 90.0% ±1.2 and 85.9% ±2.1, respectively, assessed against visual inspection by an experienced observer. The algorithm can also detect neuronal activity in imaging experiments generated in a different laboratory using a different microscope configuration (accuracy = 94.0% ±2.2). We conclude that in vivo calcium imaging can be used to assess spontaneous activity in sensory neurons and provide a Google Colaboratory Notebook to allow anyone easy access to our novel analysis tool, for the assessment of spontaneous neuronal activity in their own imaging setups.