Subject Of Controversy Research Articles

Inhibitory properties of a latent inhibitor after its compound preexposure with several novel stimuli: evidence from human conditioning

Latent inhibition refers to the retardation in learning an association between a target stimulus and an outcome when the target stimulus has been pre-exposed in the absence of consequences. The inhibitory properties of latent inhibitors have been the subject of controversy, as standard latent inhibition training—consisting of pre-exposure to the target stimulus alone—does not provide the latent inhibitor with the ability to pass a summation test, a key criterion for demonstrating genuine inhibition. However, previous research with animals has shown that a specific pre-exposure procedure, in which the target stimulus (A) is presented in compound with successive novel stimuli (An1, An2, An3…), can endow the target with sufficient inhibitory properties to pass both retardation and summation tests. To examine whether this phenomenon generalizes to humans, we conducted two experiments using a video game-based conditioning paradigm. Experiment 1 demonstrated that this compound pre-exposure schedule enhanced the retardation effect compared to standard pre-exposure or control conditions. Experiment 2 revealed that the target stimulus pre-exposed with novel stimuli significantly reduced responding when tested in compound with an excitatory conditioned stimulus, thus passing the summation test. These results suggest that compound pre-exposure facilitates the acquisition of inhibitory properties in humans, consistent with findings from animal studies. The findings are discussed within the framework of Hall-Rodríguez model, emphasizing the role of expectancy violation during pre-exposure in strengthening inhibitory associations. Implications for clinical applications, particularly in enhancing exposure therapy for anxiety disorders, are also considered.

The prognostic utility of the ratio of lymphocyte to monocyte in patients with metastatic colorectal cancer: a systematic review and meta-analysis

BackgroundAlthough advancements in treatment have resulted in improved overall outcomes for patients diagnosed with colorectal cancer, the prognosis remains unfavorable for individuals with metastatic colorectal cancer (mCRC). The association between lymphocyte/monocyte ratio (LMR) and clinical outcomes in mCRC patients is a subject of controversy. To systematically evaluate the correlation between LMR and prognostic factors in individuals with mCRC, we conducted this meta-analysis.MethodsThe databases PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for all relevant studies from their inception until October 26, 2024. Study selection was conducted based on predetermined inclusion and exclusion criteria. The primary outcomes of interest included prognosis measures such as overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and cancer-specific survival (CSS) in patients with metastatic colorectal cancer. Random-effects models or fixed-effects models were used to determine the pooled risk ratio (HR) and corresponding 95% confidence interval (CI) for each outcome indicator. Additionally, the pooled odds ratio (OR) and its corresponding 95% CI were calculated for LMR and clinicopathological characteristics.ResultsFourteen studies involving 3,089 patients were included in the analysis. The pooled analysis found that high LMR was correlated with better OS (HR: 0.55, 95% CI: 0.49-0.62, p<0.00001), PFS (HR: 0.68, 95% CI: 0.57-0.81, p<0.0001) and CSS(HR: 0.55, 95% CI: 0.32-0.95, p=0.03),The prognostic value of high LMR values for DFS(HR: 0.93, 95% CI: 0.78-1.12, p=0.46) in patients with metastatic rectal cancer was not found to be significant. We performed subgroup analyses based on study characteristics to confirm the robustness of our findings. Further clinicopathological analysis showed no significant difference between patients with elevated LMR and those without elevated LMR.ConclusionsIn conclusion, the results demonstrate a robust correlation between elevated LMR levels and a favorable prognosis in terms of overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) among patients diagnosed with metastatic colorectal cancer. However, further high-quality prospective studies are warranted to validate our findings since the majority of current investigations have relied on retrospective study designs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024496467, identifier CRD42024496467.

The Significance of Anthropomorphism in Children's StoriesA Study of Rudy Kipling's The Jungle Book.

Anthropomorphism is giving human qualities and characteristics to non-humans, whether they are animals or plants, as in children’s stories. Because animals play an essential role in literature, this study examines the social and political aspects of anthropomorphism in The Jungle Book. Using animals in their real environment to represent stories directed at specific groups of people, instead of using humans to represent them, inevitably has great reasons and importance. Anthropomorphism gave these animals in stories abilities and characteristics related only to humans, including the ability to speak and other human qualities such as empathy, hatred, and friendship, as in the novel The Jungle Book. Enabling non-humans to speak, for example, opens new horizons for children and adults alike to learn about the behaviors and lifestyles of animals in their real environments and their relationships with other animals and humans alike. It also enables adults to obtain a broader and more comprehensive understanding of the writer’s messages about human societies, their types, behaviors, and political orientations by representing them in the form of animal groups. The study uses an objective approach by adapting the views of Adam Weitz and other theorists to analyze these aspects. The study concluded that giving human characteristics to non-humans, especially in literature, enables the writer to instill moral and cultural values ​​and customs in the hearts of children by making the characters their beloved animals. On the other hand, anthropomorphism allows drawing a picture in children's minds of human behaviors and feelings such as love, hate, love of power, and establishing friendships by embodying them with talking animals. Last but not least, anthropomorphism gives the writer a real opportunity to avoid directly presenting controversial and critical topics and representing them with non-human characters.

Thinking, recounting: the first Australian Screen Studies Association Conference (1982)

ABSTRACT Across its history, a crucial component in the formation and maintenance of film studies in Australia has been the local and international exchange of ideas and critical formations facilitated by film studies conferences. Arguably one of the most important events to influence the direction of film studies in Australia was the First Australian Screen Studies Association (ASSA) Conference held at La Trobe University, Melbourne in December 1982. This was an international event which brought together leading film academics from around the country, prominent overseas keynote speakers, representatives from national film institutions, film critics and independent filmmakers and scholars. The ASSA Conference broke new ground, explored controversial topics, stimulated national debate and highlighted the future direction of Australasian film studies. Informed by archival documents, this essay describes the planning, preparations and hosting of the first ASSA conference to provide a record of the ecology of Australian film (and television) studies – its institutions, personnel, and critical positions – at a key historical moment in its development. This account contributes to an understanding of the institutional and intellectual foundations of film studies as a discipline and illuminates the contours of Australian and international traditions of film and media studies, past and present.

Open Versus Minimally Invasive Morgagni Hernia Repair in Pediatric Surgery: A Review.

Background: Morgagni hernia (MH), a rare type of congenital diaphragmatic hernia, does not have an established protocol for surgical repair. Materials and Methods: A MEDLINE search with terms related to various surgical approaches to repair MH in children was conducted. Articles comprising robotic-assisted surgery, laparoscopy, laparotomy, thoracoscopy, and thoracotomy over the last 20 years were assessed. Results: This narrative review provides an overview of MH in the pediatric population, covering the epidemiology, diagnosis, and management of this rare diaphragmatic hernia. We discuss various surgical techniques, including open and minimally invasive approaches, and compare their advantages and limitations in childhood MH repair. In addition, we address arguments for and against controversial topics such as hernia sac excision and patch reinforcement. Conclusions: Regarding MH in children, transabdominal repair is superior to transthoracic due to improved visualization of bilateral defects and easier reduction of the hernia contents. Laparoscopy has been reported as a popular approach. Single-site laparoscopy has gained attention due to better outcomes than standard three-port laparoscopy. Considering a limited number of children in the literature who underwent robotic MH repair, perioperative complications were reported to be minor.

No Association Found Between Uric Acid Levels and Peripheral Vertigo Disorders: Results From a Two-Sample Mendelian Randomization Study.

The association between serum uric acid levels and peripheral vertigo diseases, namely Benign Paroxysmal Positional Vertigo (BPPV), Meniere's Disease (MD), and Vestibular Neuritis (VN), remains a subject of controversy. This study utilises the Mendelian Randomization (MR) approach to investigate the potential link between uric acid levels and these peripheral vertigo diseases, with the goal of informing preventative measures and early intervention strategies. Datasets pertaining to uric acid levels (sample size = 343 836) and BPPV (ncase = 3834, ncontrol = 209 582), MD (ncase = 1511, ncontrol = 209 582), and VN (ncase = 1224, ncontrol = 209 582) were selected from Genome-Wide Association Studies (GWAS). Two-sample MR was employed to analyse the correlation between the exposure (uric acid levels) and outcomes (BPPV, MD, VN). The MR analysis methods encompassed Inverse Variance Weighting (IVW), MR-Egger, Simple Mode, Weighted Mode, and Weighted Median methods. The results derived from the IVW analysis were considered as the primary analytical outcomes. The findings indicated no significant correlation between uric acid levels and BPPV (IVW: OR = 1.152, 95% CI: 0.971-1.367, p = 0.103), MD (IVW: OR = 1.010, 95% CI: 0.757-1.348, p = 0.943), and VN (IVW: OR = 1.005, 95% CI: 0.744-1.358, p = 0.969). This study employed a two-sample Mendelian randomization approach to conduct an in-depth analysis of the relationship between serum uric acid levels and peripheral vestibular diseases (BPPV, MD, and VN). Our findings indicate that no significant association was found between serum uric acid levels and these diseases. The results of the study do not support the hypothesis that uric acid is an independent risk factor for these conditions.

Assessing the diagnostic potential of SATB2 and β-catenin as biomarkers and therapeutic targets in pancreatic ductal adenocarcinoma

IntroductionPancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. The roles of the transcription factor special AT-rich binding protein-2 (SATB2) and β-catenin in PDAC have been a subject of controversy. We aimed to assess the diagnostic and prognostic impact of SATB2 and β-catenin in PDAC.MethodsWe analyzed 44 paraffin-embedded tissue blocks along with corresponding blood and pancreatic tissues. We evaluated SATB2 expression using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). β-catenin was assessed using IHC and real-time polymerase chain reaction (qPCR).ResultsHigh SATB2 expression and low β-catenin expression were associated with a poor prognosis in PDAC, including advanced pathological tumor stage (pT-stage), pathological lymph node stage (pN-stage), and TNM stage. We found a positive correlation between SATB2 expression assessed by IHC and the concentration of SATB2 in both serum and tissue samples measured by ELISA. We observed a positive correlation between β-catenin expression assessed by IHC and β-catenin levels measured by qPCR.ConclusionsSATB2 and β-catenin could provide valuable insights into the development of pancreatic cancer, and targeting them may be beneficial for the prevention and treatment of PDAC. The levels of SATB2 in serum show promise for the diagnosis and tumor invasion of pancreatic cancer.

Machine learning for the diagnosis accuracy of bipolar disorder: a systematic review and meta-analysis

BackgroundDiagnosing bipolar disorder poses a challenge in clinical practice and demands a substantial time investment. With the growing utilization of artificial intelligence in mental health, researchers are endeavoring to create AI-based diagnostic models. In this context, some researchers have sought to develop machine learning models for bipolar disorder diagnosis. Nevertheless, the accuracy of these diagnoses remains a subject of controversy. Consequently, we conducted this systematic review to comprehensively assess the diagnostic value of machine learning in the context of bipolar disorder.MethodsWe searched PubMed, Embase, Cochrane, and Web of Science, with the search ending on April 1, 2023. QUADAS-2 was applied to assess the quality of the literature included. In addition, we employed a bivariate mixed-effects model for the meta-analysis.Results18 studies were included, covering 3152 participants, including 1858 cases of bipolar disorder. 28 machine learning models were encompassed. Sensitivity and specificity in discriminating between bipolar disorder and normal individuals were 0.88 (9.5% CI: 0.74~0.95) and 0.89 (95% CI: 0.73~0.96) respectively, and the SROC curve was 0.94(95% CI: 0.92~0.96). The sensitivity and specificity for distinguishing between bipolar disorder and depression were 0.84 (95%CI: 0.80~0.87) and 0.82 (95%CI: 0.75~0.88) respectively. The SROC curve was 0.89 (95%CI: 0.86~0.91).ConclusionsMachine learning methods can be employed for discriminating and diagnosing bipolar disorder. However, in current research, they are predominantly utilized for binary classification tasks, limiting their progress in clinical practice. Therefore, in future studies, we anticipate the development of more multi-class classification tasks to enhance the clinical applicability of these methods.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023427290, identifier CRD42023427290.

The impact of a mental health-focused ethics lecture on pharmacy students’ perceptions of patients with mental illness: An observational study

Background: Societal perspectives that involve negative ideation and stereotyping behaviours from health care providers, even those still in training, toward individuals diagnosed with serious mental illness can reduce the likelihood of successful outcomes. Objective: To examine the impact of didactic, lecture-based, educational interventions on reducing the stigma of mental illness among pharmacy students. Methods: A survey was distributed pre- and post-lecture to all third-year pharmacy students who attended an “Ethics of Mental Health” lecture in 2021 and 2022. Data were collected and analysed using T-tests. Statistical significance was determined with an alpha of 0.05. Results: Higher affirmative post-survey responses were observed in 2022 (average 15.46%) and 2021 (average 9.5%). Respondents approved all controversial ethical rights except voting which was the only survey question with less positive responses-1.23% was allowed the right to vote. Respondents supported the rights to refuse medications and COVID-19 vaccinations, to engage in sexual relationships, to be given erectile dysfunction medications while hospitalised, and for gun ownership post-hospitalisation. Conclusion: Simple didactic dialogue about controversial topics, like those leading to potential discrimination, can be a productive avenue to ensure the development of non-biased clinicians.

Ben Weinstein, MD (1913-1974) and his enduring impact on the history of medicine experience in medical school.

The history of medicine as a component of the medical school curriculum has been a long-standing subject of debate and controversy. Ultimately, local factors may determine this experience and be aligned with or outside of the curriculum. The opportunity at Tulane University School of Medicine is long-standing and successful. It came to fruition through the efforts of Benjamin Bernard Weinstein, MD. A native New Orleanian, he received his undergraduate (1933) and medical (1937) degrees from Tulane as well as his training in obstetrics and gynaecology. He then joined the faculty and remained there until 1953 when he entered private practice with an interest in reproductive medicine. Weinstein was internationally known in the field, travelling the globe as a prominent educator and intersecting with world leaders. But his passion was the Tulane History of Medicine Society, founded by Weinstein in 1933 as a medical student. He became its guiding force and benefactor and built the foundation that remains highly relevant and successful 91 years later with a lengthy list of distinguished Weinstein Lecturers annually. Following his death in 1974, his family has continued to engage and support the Society. Weinstein's legacy of an enriched life through the study and knowledge of the history of medicine continues through the Society.

Evidence for Endogenous Collagen in Edmontosaurus Fossil Bone.

Reports of proteins in fossilized bones have been a subject of controversy in the scientific literature because it is assumed that fossilization results in the destruction of all organic components. In this paper, a novel combination of analytical techniques is used to address this question for an exceptionally well-preserved Edmontosaurus sacrum excavated from the Upper Cretaceous strata of the South Dakota Hell Creek Formation. Cross-polarized light microscopy (XPol) shows birefringence consistent with collagen presence. Tandem LC-MS unambiguously identified, and for the first time quantified, hydroxyproline, a unique collagen-indicator amino acid, in acid-digested samples from the Edmontosaurus. LC-MS/MS bottom-up proteomics shows identical collagen peptide sequences previously identified and reported for another hadrosaur and a T. rex sample.

Facilitating Student argumentation around socioscientific issues through productive discourse and negotiation toward consensus

ABSTRACT Controversial topics that arise in science classrooms, especially those of social relevance (e.g. the climate crisis), provide opportunities to help students learn about and discuss contradictory ideas they may encounter in their everyday experiences. Such topics may also be challenging to teach, but scaffolding may facilitate effective instruction. We describe 1 type of instructional scaffolding, the Model-Evidence Link (MEL) activity, that supports students’ reasoning when evaluating connections between lines of evidence and competing explanations about phenomena. We have developed and tested these activities in middle and high school classrooms, and empirical studies have shown that they help shift students’ thinking toward a more scientific stance via group discourse and collaborative argumentation. We developed a Negotiation Framework for productive discourse to facilitate students’ conversations toward consensus. This Negotiation Framework may be particularly effective in supporting argumentation and learning about topics in which scientific explanations compete with popular, but nonscientific, alternatives.

The clinical value of short-term insemination: a retrospective analysis of 3496 patients

BackgroundThe safety and effectiveness of short-term insemination remain a subject of controversy. This study aims to investigate the impact of short-term insemination on both embryo quality and pregnancy outcomes and whether it is necessary to apply short-term insemination to all patients underwent in vitro fertilization (IVF).MethodsA retrospective analysis was conducted on 3,496 patients from two centers over the period January 2016 to December 2022. Of these, 1307 patients underwent IVF, 1656 patients were treated with short-term IVF, 166 patients received early rescue intracytoplasmic sperm injection (R-ICSI) and 367 patients were treated with ICSI. The clinical and neonatal outcomes were compared between the two groups.ResultsThe rate of high-quality embryos was significantly lower in the short-term IVF group compared to the routine IVF group (59.89% vs. 68.16%) (P = 0.000), the rate of blastocyst formation was significantly lower in the short-term IVF group compared to the routine IVF group (44.99% vs. 61.34%) (P = 0.000). There were no significant differences in clinical outcomes or neonatal outcomes between the two groups, irrespective of whether fresh or frozen embryos were used (both P > 0.05). The incidence of ≥ 3PN demonstrated no significant difference between the early R-ICSI and ICSI groups (1.04% vs. 0.66%) (P = 0.114), furthermore, the clinical outcomes were similar in both groups, for both fresh and frozen embryos (both P > 0.05).ConclusionsFor patients with primary fertility, short-term IVF combined with early R-ICSI can effectively prevent potential low fertilization or fertilization failure, reduce the risk of patients with no transferable embryo, avoid the waste of resources and had no adverse effects on neonatal outcomes. However, short-term IVF reduced the oocytes utilization rate in one single oocyte pick-up cycle, for patients with no risk factors for fertilization failure, the overnight fertilization is still one of the most important ways of insemination worthy of affirmation.Trial registrationNA.

Comparison of Static and Spect Images on Tc-99m-PYP Bone Scintigraphy in the Diagnosis of Cardiac Amyloidosis

Amyloidosis is a systemic disease characterized by the extracellular accumulation of amyloid fibrils caused by misfolding of proteins. Cardiac amyloidosis has the worst prognosis of the type of organ involvements. The most common forms of cardiac amyloidosis are immunoglobulin light chain amyloidosis (AL) and transtretin (TTR) amyloidosis. The developing diagnostic methods give the clinician early diagnosis of cardiac amyloidosis. Scintigraphic imaging with Technetium (Tc-99m) labelled biphosponates may faciliate early detection of cardiac involvement and distinguish various forms of cardiac amyloidosis. Bone scintigraphy for evaluation of cardiac amyloidosis especially for ATTR type amyloidosis is one of the most sensitive imaging prosedures in recent years. In our study, we compared the 1st and 3rd hour planar and SPECT imaging to investigate the importance of the 3rd hour and the necessity of SPECT in cardiac amyloidosis (CA) imaging, which is one of the controversial topics from the Nuclear Medicine perspective.

Spectroscopic Study on Identifying Synergistic Extraction Complexes of Nd(III) with Bis(2,4,4-Trimethylpentyl)Dithiophosphinic Acids and TBP

ABSTRACT Selective separation of trivalent actinide ions, An(III), from trivalent actinide ions, Ln(III), has been of great importance and considerable challenge in terms of the overall nuclear fuel cycle strategy. The construction of the hard-soft synergistic extraction system, commonly S containing-O containing ligands, aims to achieve the effective separation of the two metal ions. Nevertheless, the precise mechanism by which this system extracts metal ions remains the subject of controversy. Herein, the complexation of Nd(III) with bis(2,4,4-trimethylpentyl)dithiophosphinic acid (HL) and tributyl phosphate (TBP) has been investigated with spectroscopy and extraction experiments under different conditions to clarify the mechanisms in synergistic extraction. Five complex species, NdL3(HL)(TBP), NdL2(NO3)(TBP)3, NdL3(H2O)2(TBP), NdL3(H2O)(TBP)2, and NdL3(TBP)3, are identified in the synergistic extraction system, their molar absorption spectra are deconvoluted, and the corresponding extraction equilibrium constants are determined. In addition, a complex species of Nd(III) fully coordinated by TBP, NdL3(TBP)n (n ≥ 6), is found in titrations of organic solution containing NdL3(TBP)3 with more TBP, but it is not found in synergistic extraction. Furthermore, Density Functional Theory (DFT) is employed to confirm the stability of the complexes. Investigation of the mechanism of this system will facilitate the acquisition of further insights into the selection of O-containing ligands and the development of synergistic extraction process for the separation of An(III) and Ln(III).

Analysis of the Jurisprudential Foundations of Financial Penalty in the Context of Tazirat (Disciplinary Measures)

Financial fines or penalties are among the most prevalent deterrent measures against crimes and offenses in contemporary times. This issue has long been a subject of controversy among Islamic jurists. Two viewpoints, the permissibility and impermissibility of monetary fines, have been advocated by Islamic scholars. Both sides present their arguments supported by evidence. The question arises: which viewpoint, in the present time, is more effective, the permissibility or impermissibility? This article, considering this question, examines the reasons presented by both factions, the permissibility, and the prohibition, and discusses the factors causing differences in opinions. The conclusion drawn is that the permissibility of monetary fines is preferred based on relying on verses, narrations, the actions of the companions of the Prophet, analogical reasoning (Qiyas), prioritizing public interest, societal well-being, the necessity of preserving order, and it appears to be more effective as a deterrent measure compared to other forms of disciplinary measures in this era.

In Search of an Integrative Method to Study Unconscious Processing: An Application of Bayesian and General Recognition Theory Models to the Processing of Hierarchical Patterns in the Absence of Awareness.

The dissociation between conscious and unconscious perception is one of the most relevant issues in the study of human cognition. While there is evidence suggesting that some stimuli might be unconsciously processed up to its meaning (e.g., high-level stimulus processing), some authors claim that most results on the processing of subliminal stimuli can be explained by a mixture of methodological artefacts and questionable assumptions about what can be considered non-conscious. Particularly, one of the most controversial topics involves the method by which the awareness of the stimuli is assessed. To address this question, we introduced an integrative approach to assess the extent to which masked hierarchical stimuli (i.e., global shapes composed of local elements) can be processed in the absence of awareness. We combined a priming task where participants had to report global or local shapes, with the use of subjective and objective awareness measures collected either in a separate block (offline), or trial-by-trial during the main task (online). The unconscious processing of the masked primes was then evaluated through two different novel model-based methods: a Bayesian and a General Recognition Theory modeling approach. Despite the high correlation between awareness measures, our results show that the use of alternative approaches based on different theoretical assumptions leads to diverging conclusions about the extent of the unconscious processing of the masked primes.

Insights from social media into public perspectives on investigative genetic genealogy.

Social media sites like X (formerly Twitter) increasingly serve as spaces for the public to discuss controversial topics. Social media can spark extreme viewpoints and spread biased or inaccurate information while simultaneously allowing for debate around policy-relevant topics. The arrest of Joseph J. DeAngelo in April 2018 ignited a barrage of social media conversations on how DNA and genetic genealogy led to the suspect. These conversations continued over the following years as policies changed and as the use of the approach expanded. We examined social media coverage of investigative genetic genealogy (IGG) to characterize the volume and temporal patterns in the topics and sentiments of these public conversations. First, using a data analytics tool Brandwatch Consumer Research, we built flexible search strings to collect tweets from the social media platform Twitter/X for IGG-relevant content published from 2018 to 2022, resulting in 24,209 tweets. Second, we applied informatics tools to the dataset to generate topic clusters and analyze trends in cluster volume and distribution over time to define the top 25 peaks in tweet volume, representing the 25 events that generated the highest volume of conversation over the 5-year period. Third, drawing on the contextual framework of key IGG events, we selected three of the top ten events to code for sentiment along with a randomly sampled subset of tweets across the timeframe. Qualitative coding for position on IGG revealed a majority of tweets were supportive of the use of IGG, but key concerns were also voiced about the ethics of IGG. Over a third of conversations on Twitter/X were on either cases solved or suggestions for use of IGG. We archived the social media data for future research. These data highlight key areas of public support and concern within IGG processes and across application contexts.

Referendum democracy in Ukraine: problems and ways to improve

The article is devoted to the analysis of the constitutional and legal framework of the all-Ukrainian referendum in Ukraine, consideration of the practice of its holding, and also to the identification of problems in legal regulation and implementation mechanisms. The article notes that an all-Ukrainian referendum is an important instrument of direct democracy which provides citizens with the opportunity to influence decision-making of national importance. However, the current legal framework governing referendums in Ukraine has significant regulatory and procedural shortcomings which create obstacles to the effective implementation of this institution. Imperfect legislation makes it difficult to conduct referendums in accordance with democratic standards, and political factors can impede the transparency and impartiality of the process. Solving these problems is a prerequisite for the development of a stable system of direct democracy in Ukraine. The article notes that the political situation in Ukraine, including the rule of law, the war in the east and economic instability, poses risks to referendums. In particular, there is a possibility of manipulation by politicians or the use of referendums to undermine democratic institutions. Such referendums may cause additional social polarisation, especially if the questions relate to controversial topics such as EU or NATO membership or language status. Special attention is paid to possible ways to improve the legal provisions to ensure the effectiveness and transparency of the referendum process. In particular, attention is drawn to the regulatory limitations, procedural shortcomings and political challenges that affect the possibility of implementing referendums in accordance with democratic standards. The article also examines the compliance of Ukrainian legislation with international norms and principles of referendums and analyses foreign experience that may be useful for improving the legal framework of the all-Ukrainian referendum. Ukraine’s referendum legislation is generally in line with international standards, but requires further harmonisation to be in line with democratic principles and international norms. The key recommendations of international organisations such as the Venice Commission include transparency of the referendum process, ensuring freedom of expression and involvement of the parliament in overseeing the referendum.

LLMS AND THE GENERATION OF MODERATE SPEECH

For the past year, using large language models (LLMs) for content moderation appears to have solved some of the perennial issues of online speech governance. Developers have promised 'revolutionary' improvements (Weng, Goel and Vallone, 2023), with large language models considered capable of bypassing some of the semantic and ideological ambiguities of human language that hinder moderation at scale (Wang et al., 2023). For this purpose, LLMs are trained to generate “moderate speech” – that is, not to utter offensive language; to provide neutral, balanced and reliable prompt outputs; and to demonstrate an appreciation for complexity and relativity when asked about controversial topics. But the search for optimal content moderation obscures broader questions about what kind of speech is being generated. How does generative AI speak “moderately”? That is: under what norms, training data and larger institutions does it produce “moderate speech”? By examining the regulatory frameworks AI labs, comparing responses to moderation prompts across three LLMs and scrutinising their training datasets, this paper seeks to shed light on the norms, techniques and regulatory cultures around the generation of “moderate speech” in LLM chat completion models.