Subject Of Controversy Research Articles

The transcriptional landscape of cancer stem-like cell functionality in breast cancer

BackgroundCancer stem-like cells (CSCs) have been extensively researched as the primary drivers of therapy resistance and tumor relapse in patients with breast cancer. However, due to lack of specific molecular markers, increased phenotypic plasticity and no clear clinicopathological features, the assessment of CSCs presence and functionality in solid tumors is challenging. While several potential markers, such as CD24/CD44, have been proposed, the extent to which they truly represent the stem cell potential of tumors or merely provide static snapshots is still a subject of controversy. Recent studies have highlighted the crucial role of the tumor microenvironment (TME) in influencing the CSC phenotype in breast cancer. The interplay between the tumor and TME induces significant changes in the cancer cell phenotype, leading to the acquisition of CSC characteristics, therapeutic resistance, and metastatic spread. Simultaneously, CSCs actively shape their microenvironment by evading immune surveillance and attracting stromal cells that support tumor progression.MethodsIn this study, we associated in vitro mammosphere formation assays with bulk tumor microarray profiling and deconvolution algorithms to map CSC functionality and the microenvironmental landscape in a large cohort of 125 breast tumors.ResultsWe found that the TME score was a significant factor associated with CSC functionality. CSC-rich tumors were characterized by an immune-suppressed TME, while tumors devoid of CSC potential exhibited high immune infiltration and activation of pathways involved in the immune response. Gene expression analysis revealed IFNG, CXCR5, CD40LG, TBX21 and IL2RG to be associated with the CSC phenotype and also displayed prognostic value for patients with breast cancer.ConclusionThese results suggest that the characterization of CSCs content and functionality in tumors can be used as an attractive strategy to fine-tune treatments and guide clinical decisions to improve patients therapy response.

Allergic Rhinitis and Keratoconus: A Systematic Review and Meta-Analysis

BackgroundThe relationship between keratoconus and various allergic diseases has been a subject of controversy. ObjectiveIn the present study, a systematic review and meta-analysis was conducted to investigate the association between allergic rhinitis (AR) and keratoconus. MethodsRelevant and eligible studies from PubMed, Web of Science, and Cochrane Library were systematically reviewed to evaluate the association between AR and keratoconus. Observational studies containing the number of patients with and without keratoconus and the number of patients with keratoconus diagnosed with or without AR were included. Two reviewers independently screened for eligible studies and extracted data from the included studies. A bivariate meta-analysis was conducted to compare the odds of keratoconus occurrence in patients with and without AR. The main outcome was the odds ratio of keratoconus occurrence in patients with AR. A sensitivity test was performed using the adjusted odds ratio reported in the included studies to validate the findings. ResultsSeven studies involving 775,574 participants were included in this meta-analysis. Among them, 29,082 patients had keratoconus. The pooled odds ratio of keratoconus occurrence in patients with AR was 1.71 (95% confidence interval [CI]: 1.36–2.15; P < 0.001; I2 = 96%), and the pooled adjusted odds ratio was 1.72 (95% CI: 1.23–2.40; P = 0.001; I2 = 97%). ConclusionPatients with AR showed significantly higher odds of keratoconus occurrence than those without AR. Future studies are warranted to investigate the causal relationship and evaluate the cost-effectiveness of early screening using methods such as corneal topography and referral for keratoconus in patients with AR.

American Privacy Rights Act: A first glance at the US Congress's newest comprehensive privacy bill

The recently introduced the American Privacy Rights Act (APRA) represents the latest attempt to pass a comprehensive federal privacy law in the US that would vern privacy generally across the country. The draft bill proposes novel compromises on controversial topics such as federal pre-emption and rights of private action, which need refinement and are likely to be changed in the legislative process. The attempt to cover not-for-profit entities without accounting for their different purposes seems ill conceived and raises constitutional concerns. This paper examines the APRA in its constitutional, historical and policy contexts.

Practice Pearls for Stimulant Treatment of Attention-Deficit/Hyperactivity Disorder in Youth.

Over half of youth with attention-deficit/hyperactivity disorder (ADHD) have co-occurring psychiatric or medical conditions that present treatment challenges. Stimulants are the most effective pharmacologic treatment of ADHD for preschoolers to adults but questions about safety with co-occurring conditions frequently arise. In addition, stigma surrounding diagnosis and treatment can negatively impact care. This manuscript presents evidence-based practice pearls to guide treatment decisions for youth with ADHD and common coexisting psychiatric and medical conditions. Recommendations address specific stimulant adverse effects (i.e., anxiety, cardiac, growth, mania, psychosis) along with management strategies. Pearls were developed for the most common clinical questions, controversial topics, or therapeutic issues that may not be widely known. The goals of this manuscript are to: 1) provide a detailed resource for interprofessional teams regarding stimulant use in youth with ADHD, 2) improve therapeutic outcomes for youth with ADHD and co-occurring psychiatric and/or medical conditions through evidence-based recommendations, and 3) decrease stigma associated with stimulant use through education.

The necessity of implementing the consent of the victim as a cause which removes the criminal character of the act

Consent of the victim is a controversial subject in the criminal law theory. Moreover, in our national doctrine it is an unexplored one. In the content of this article, we aimed to elucidate if it is necessary or it is not relevant to implent the consent of victim as a cause which removes the criminal character of the act. In order to accomplish this goal, we have used the method of comparative law and studied other countries’ judicial and legal practice related to the consent of victim. Consequently, we have identified which are the main conditions for valability of victim’s consent and how should be formulated the proposal for a law which will implement the consent of victim as a cause which removes the criminal character of the act in the Republic of Moldova’s Criminal Code.

The Surge in Anti-Critical Race Theory Measures: Will It Affect How Teachers React to the Israel-Hamas Conflict?

The Israel-Hamas crisis that started in October of 2023 has led to an increase in hate acts targeted at Jewish and Arab students. In response, the U.S. Department of Education sent a letter reminding educational leaders of their responsibilities to address this behavior. This paper offers examples of the kind of conduct educational leaders are expected to address and reasons for including discussions about this crisis with students. Although students benefit from having discussions about this crisis and its outcomes, some teachers fear they will be disciplined for discussing controversial subjects with students because of the surge in anti-critical race theory measures. This paper includes a discussion on how the increase in these measures has impacted teachers. It also offers resources designed to promote a sense of safety and provide students with accurate information about the conflict.

That time I was reincarnated as a problematic trope: Viewer preferences and cultural trends in reincarnation isekai anime

The genre of reincarnation isekai anime, wherein a protagonist dies in their original world only to be reborn in a fantastical one, has grown significantly in global appeal. Yet, this genre’s expansion also normalizes controversial themes such as mental health issues, sexual and violent content, and the sexualisation of virtual minors. This article employs a data-driven approach, analysing user-generated coding of themes and properties from English-speaking fan sites, to critically examine three emergent and interconnected dimensions: the success of series deemed ‘trashy’, the complexities surrounding sexual themes, and the rising appeal of the ‘zero-to-hero’ motif in a post-pandemic world. The findings reveal a paradoxical allure of ‘trashy’ but popular content, complex ethical dilemmas surrounding sexual themes, and an increased resonance of empowerment motifs resulting from the pandemic. These discoveries provoke renewed discussions on anime’s role in shaping and reflecting societal values and raise questions about regulatory challenges in a globalized media setting. The study confirms the need for more nuanced understandings of the genre’s growing global influence, particularly outside of Japan, and calls for continued research to delve deeper into its complexities.

Predicting evolution acceptance among religious students using the predictive factors of evolution acceptance and reconciliation (pFEAR) instrument

Evolution is one of the controversial topics in biology primarily because of the perceived conflict between religion and evolution. Religiosity is one of the biggest predictors of evolution acceptance, i.e., the more religious an individual, the less accepting they are of evolution. Most students in the United States are religious, so how evolution is taught in the classroom is essential for a more inclusive experience. However, educators do not have a way to measure what factors influence students' evolution acceptance. We developed a survey instrument with validity evidence called the "predictive Factors of Evolution Acceptance and Reconciliation" (pFEAR). Using this measure, with data from eight religiously affiliated institutions in the United States, educators can understand how their religious and scientific worldview factors influence their students' views on evolution acceptance. Our study showed that religious influence was the most statistically significant predictor of evolution acceptance among religious students by a factor of 2, when compared to students scientific worldviews and the perceived conflict between science and religion. It also showed that perceived conflict between science and religion and being influenced by science were significant positive predictors of evolution acceptance. Further, this study identifies ways educators can use the pFEAR in the classroom to better understand their student's views and better modify how they approach teaching evolution in their classroom.

Effect of serum uric acid on the risk of aortic aneurysm and dissection: A mendelian randomization analysis

Aortic aneurysm and dissection (AAD) are severe vascular diseases with high mortality rates. However, the causal relationship between serum uric acid levels and the occurrence of AAD remains a subject of controversy. To address this issue, we conducted a two-sample Mendelian randomization (MR) analysis to investigate whether there is a causal association between these factors. We obtained single-nucleotide polymorphisms (SNPs) data related to serum uric acid levels from the FinnGen study and data on AAD from the UK Biobank. Various two-sample MR methods, including inverse variance weighted (IVW) analysis, MR-Egger regression analysis, weighted median analysis, and contamination mixture method, were employed to assess the causal relationship between serum uric acid and the risk of AAD. Sensitivity analysis was conducted to evaluate the stability and reliability of the results. The findings revealed a positive association between serum uric acid levels and the risk of aortic aneurysm (AA) (odds ratio [OR] = 1.200, 95 % confidence interval [CI]: 1.020–1.400, P = 0.0239). However, no significant correlation was observed between serum uric acid levels and the occurrence of aortic dissection (AD) (OR = 0.893, 95 % CI = 0.602–1.326, P = 0.576). Our study, which employed MR analysis, identified a positive association between serum uric acid levels and the risk of AA. However, we did not observe a significant correlation with AD.

OVERVIEW OF CONTROVERSIAL ISSUES IN CHARACTER AND VALUES EDUCATION PROVIDED THROUGH DISTANCE EDUCATION

The primary objective of education is to enhance individuals' thinking skills and their thought processes including the cultivation of character and the internalization of values. Engaging students in discussions on controversial topics encourage critical thinking. This research aims to investigate how students enrolled in the Non-Thesis Master's Degree Program on Character and Values Education through Distance Learning perceive controversial issues such as discrimination, violence, and gender. Furthermore, the study aims to examine the influence of the Global Education in Character and Values Education course on students' perceptions of these controversial issues. The course incorporates various activities, assignments, and discussions to connect these topics with character and values education. The study also seeks to provide insights into students' perspectives on controversial issues in character and values education and explore how a specific course shape their perception and understanding of these matters.

Association between serum vitamin D levels and prostate tumor: a systematic review and meta-analysis

Introduction: Prostate cancer is among the most frequent neoplasms of the male reproductive system, and its relationship with serum vitamin D level is a controversial subject. The present study intended to investigate the relationship between serum vitamin D levels and the risk of prostate carcinoma. Materials and Methods: This study is a systematic review and meta-analysis based on the PRISMA tool. The search was conducted in databases Web of Science, Cochrane, ProQuest, PubMed, and Google Scholar Search Engine until December 1, 2023. Data was analyzed using STATA 14 software. Results: There was no significant relationship between serum vitamin D levels lower than 50 nmol/L (vitamin D level &lt;50 nmol/L) and prostate cancer. In Finland, the risk of prostate carcinoma in male individuals with serum vitamin D levels lower than 50 nmol/L was 34% higher (OR: 1.34, 95% CI: 1.14, 1.54). In South Korea, on the other hand, serum vitamin D levels lower than 50 nmol/L prevented prostate cancer (OR: 0.94, 95% CI: 0.90, 0.99). There was no significant relationship between the serum vitamin D levels lower than 50 nmol/L and prostate neoplasm in men aged 60 to 69 years old (OR: 0.95, 95% CI: 0.83, 1.07), in men 50 to 59 years old. On the other hand, serum vitamin D levels lower than 50 nmol/L increased the risk of prostate tumor by 32% (OR: 1.32, 95% CI: 1.13, 1.55). Furthermore, no significant relationship was observed between serum vitamin D levels higher than 50 nmol/L (vitamin D level ≥ 50 nmol/L) and the risk of prostate cancer (OR: 1.06, 95% CI: 0.99, 1.14). Conclusion: Generally, there was no significant relationship between serum vitamin D levels and the risk of prostate carcinoma; however, the relationship in some subgroups was statistically significant. We therefore recommend conducting additional studies on this subject. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO (ID: CRD42023491012) and Research Registry (UIN: reviewregistry1773) website.

Mathematical explanations for knee osteotomies: "Dear engineer, how would you explain it in a simple way?"

Knee osteotomies are effective procedures to treat different deformities and to redistribute the load at the joint level, reducing the risk of wear and, consequently, the need for invasive procedures. Particularly, knee osteotomies are effective in treating early arthritis related to knee deformities in young and active patients with high functional demands, with excellent long-term results. Precise mathematical calculations are imperative during the preoperative phase to achieve tailored and accurate corrections for each patient and avoid complications, but sometimes those formulas are challenging to comprehend and apply. Four specific questions regarding controversial topics (planning methods, patellar height, tibial slope, and limb length variation) were formulated. An electronic search was performed on PubMed and Cochrane Library to find articles containing detailed mathematical or trigonometrical explanations. A team of orthopedic surgeons and an engineer summarized the available Literature and mathematical rules, with a final clear mathematical explanation given by the engineer. Wherever the explanation was not available in Literature, it was postulated by the same engineer. After the exclusion process, five studies were analyzed. For three questions, no studies were found that provided mathematical analyses or explanations. Through independent calculations, it was demonstrated why Dugdale's method underestimates the correction angle compared to Miniaci's method, and it was shown that the variation in patellar height after osteotomy can be predicted using simple formulas. The five included studies examine postoperative variations in limb length and tibial slope, providing formulas applicable in preoperative planning. New formulas were independently computed, using the planned correction angle and preoperatively obtained measurements to predict the studied variations. There is a strict connection among surgery, planning, and mathematics formulas in knee osteotomies. The aim of this study was to analyze the current literature and provide mathematical and trigonometric explanations to important controversial topics in knee osteotomies. Simple and easy applicable formulas are provided to enhance the accuracy and outcomes of this surgical procedure.

How Does Time Synchronization Affect Innovation Quality?

How location choice influences innovation in MNCs has been the subject of controversy, and the examination of geographic concentration or dispersion is particularly insufficient. The question is, how will the decentralization or centralization of MNCs affect the communication and management of information among employees. To address this deficiency, this study introduces the concept of time synchronization and attempts to examine the relationship between MNCs location choice and corporate innovation quality from a new perspective. By gathering data from the Chinese internationalized firms, we found that time synchronization between parents and subsidiaries is positively associated with the innovation quality of parent firms, and the degree of digitization strengthens this positive relationship. This study underscores the crucial role of overlapping work time for employee interactions between parents and subsidiaries to acquire information in comprehending and absorbing overseas knowledge to improve the innovation quality of parent firms.

Dissimulation as an Editorial Strategy in the Life of William Wilberforce

In 1838, Robert and Samuel Wilberforce published, in five volumes, The Life of William Wilberforce. Although the subject of some contemporary controversy, this work, containing extensive quotations from his diaries, rapidly established itself as the principal source for subsequent biographical writings about Wilberforce and strongly influenced later interpretations. The production of a complete initial transcription of the diaries by the Wilberforce Diaries Project for the first time enables a systematic comparison between the Life and its principal source. This reveals a systematic attempt by his sons to minimize references to Wilberforce's participation in some aspects of Hanoverian sociability, his use of medication to deal with his worsening health, his close associations with and respect for Nonconformists and his own evangelical commitment and spirituality. As a consequence, the Wilberforce we know from the biography is as much a product of early Victorian myth-making as the Wilberforce of 1759–1833.

Самопрезентация пользователя в социальных сетях и проблема коллапса контекста

This article discusses the social problems of communication in social networks that provide a platform and tools for the formation of a virtual network identity. The features of the behavior of users of social networks and the tactics of their self-presentation when constructing a personal network profile are described. It is argued that in the process of social communication, people present different versions of themselves depending on their audience and adapting their own self-presentation to the perceived values and preferences of the interlocutors. The difficulties of online communication are described, where, unlike real interaction, the user does not have the opportunity to correlate his/ her behavior with the situational context and carry out differentiated self-presentation. The problems of blurring the boundaries of public and private in social networks and the loss of information privacy, which is a necessary condition for personal freedom and autonomy, are raised. It is argued that the disclosure of private information is an important component of maintaining social relations. It is noted that currently there is a transformation of cultural norms regulating the degree of openness-closeness and publicity-privacy. The concept of "context collapse" is introduced – a situation caused by the mixing of heterogeneous audiences with different social values, norms and expectations into one homogeneous group. The strategies are proposed to overcome the negative consequences of this situation: dividing the audience into several segments, self-censorship, forcing to avoid discussing controversial topics and adapting the user's language style, suggesting a reduction in language variability. The work was based on the methods of symbolic interactionism and I. Hoffman's theory of roles, which he used to build the dramatic theory of social interaction and self-presentation in social interaction.

Acquisition of epithelial plasticity in human chronic liver disease

For many adult human organs, tissue regeneration during chronic disease remains a controversial subject. Regenerative processes are easily observed in animal models, and their underlying mechanisms are becoming well characterized1–4, but technical challenges and ethical aspects are limiting the validation of these results in humans. We decided to address this difficulty with respect to the liver. This organ displays the remarkable ability to regenerate after acute injury, although liver regeneration in the context of recurring injury remains to be fully demonstrated. Here we performed single-nucleus RNA sequencing (snRNA-seq) on 47 liver biopsies from patients with different stages of metabolic dysfunction-associated steatotic liver disease to establish a cellular map of the liver during disease progression. We then combined these single-cell-level data with advanced 3D imaging to reveal profound changes in the liver architecture. Hepatocytes lose their zonation and considerable reorganization of the biliary tree takes place. More importantly, our study uncovers transdifferentiation events that occur between hepatocytes and cholangiocytes without the presence of adult stem cells or developmental progenitor activation. Detailed analyses and functional validations using cholangiocyte organoids confirm the importance of the PI3K–AKT–mTOR pathway in this process, thereby connecting this acquisition of plasticity to insulin signalling. Together, our data indicate that chronic injury creates an environment that induces cellular plasticity in human organs, and understanding the underlying mechanisms of this process could open new therapeutic avenues in the management of chronic diseases.

Utilizing ChatGPT as a scientific reasoning engine to differentiate conflicting evidence and summarize challenges in controversial clinical questions.

Synthesizing and evaluating inconsistent medical evidence is essential in evidence-based medicine. This study aimed to employ ChatGPTas a sophisticated scientific reasoning engine to identify conflicting clinical evidence and summarize unresolved questions to inform further research. We evaluated ChatGPT's effectiveness in identifying conflicting evidence and investigated its principles of logical reasoning. An automated framework was developed to generate a PubMed dataset focused on controversial clinical topics. ChatGPT analyzed this dataset to identify consensus and controversy, and to formulate unsolved research questions. Expert evaluations were conducted 1) on the consensus and controversy for factual consistency, comprehensiveness, and potential harm and, 2) on the research questions for relevance, innovation, clarity, and specificity. The gpt-4-1106-preview model achieved a 90% recall rate in detecting inconsistent claim pairs within a ternary assertions setup. Notably, without explicit reasoning prompts, ChatGPT provided sound reasoning for the assertions between claims and hypotheses, based on an analysis grounded in relevance, specificity, and certainty. ChatGPT's conclusions of consensus and controversies in clinical literature were comprehensive and factually consistent. The research questions proposed by ChatGPT received high expert ratings. Our experiment implies that, in evaluating the relationship between evidence and claims, ChatGPT considered more detailed information beyond a straightforward assessment of sentimental orientation. This ability to process intricate information and conduct scientific reasoning regarding sentiment is noteworthy, particularly as this pattern emerged without explicit guidance or directives in prompts, highlighting ChatGPT's inherent logical reasoning capabilities. This study demonstrated ChatGPT's capacity to evaluate and interpret scientific claims. Such proficiency can be generalized to broader clinical research literature. ChatGPT effectively aids in facilitating clinical studies by proposing unresolved challenges based on analysis of existing studies. However, caution is advised as ChatGPT's outputs are inferences drawn from the input literature and could be harmful to clinical practice.

Arguing across spaces in an online epistemic community

Abstract Wikipedia is the most consulted source of information on the web, on a global level. The collective writing of articles, open to the participation of all, can give rise to major conflicts between contributors, in texts and debates, given the high stakes involved in achieving agreement on a public presentation of controversial topics. We present analyses of how disagreements are managed across socio-technical and dialogical spaces in French Wikipedia, with respect to two case studies, on Freud and the Turin Shroud. We adopt a mixed methods approach, combining results of analyses of interviews with moderators in these articles and argumentative discussions underlying them, within a broadly pragma-dialectical framework. We show, on one hand, that moderators’ attempts to resolve disagreements by requiring participants to cite sources simply displace conflicts to the nature of those sources, their validity, their authors and the good faith of their proponents. Debates concerning sources themselves draw on social actors’ perspectives in dialogical spaces, beyond the discussion itself. Disagreements are managed rather than resolved dialectically by displacing them to alternative socio-technical spaces, such as different sections of the text itself, or participants’ personal pages.

Metaphors across cultures

Abstract The way and degree to which people in different cultures consider a metaphor to be appropriate, acceptable, or apt has been the subject of controversy in recent decades. According to structure-mapping models, metaphors are understood by mapping relations from the base domain to relations in the target domain. However, previous research lacks literature on cross-cultural contexts and differences in the degree of acceptability of metaphors in different cultures. To address this gap, in this study we examined cross-cultural differences in metaphor aptness among participants from three different cultures. We developed two questionnaires, an acceptability judgment-task and a parallel-relation test using the COCA (English), PLDB (Persian), and KorAP (German) corpus databases. The results suggest striking differences in the acceptance of a metaphor in different cultures where the vehicle of a metaphor is not present. It is suggested that metaphors are considered apt through the process of categorizing the salient features that are considered structurally similar. This idea is partially consistent with studies that support class-inclusion models which suggest that hearers place the topic of a metaphor in a category in which the vehicle fits. The absence of a domain (whether topic or vehicle) may lead to unacceptability of a metaphor. Lack of cultural background in the use of these words hinders the process of finding a salient feature between them and the counter domain in a metaphor to form an appropriate alignment.

Stomatal evolution and plant adaptation to future climate.

Global climate change is affecting plant photosynthesis and transpiration processes, as well as increasing weather extremes impacting socio-political and environmental events and decisions for decades to come. One major research challenge in plant biology and ecology is the interaction of photosynthesis with the environment. Stomata control plant gas exchange and their evolution was a crucial innovation that facilitated the earliest land plants to colonize terrestrial environments. Stomata couple homoiohydry, together with cuticles, intercellular gas space, with the endohydric water-conducting system, enabling plants to adapt and diversify across the planet. Plants control stomatal movement in response to environmental change through regulating guard cell turgor mediated by membrane transporters and signaling transduction. However, the origin, evolution, and active control of stomata remain controversial topics. We first review stomatal evolution and diversity, providing fossil and phylogenetic evidence of their origins. We summarize functional evolution of guard cell membrane transporters in the context of climate changes and environmental stresses. Our analyses show that the core signaling elements of stomatal movement are more ancient than stomata, while genes involved in stomatal development co-evolved de novo with the earliest stomata. These results suggest that novel stomatal development-specific genes were acquired during plant evolution, whereas genes regulating stomatal movement, especially cell signaling pathways, were inherited ancestrally and co-opted by dynamic functional differentiation. These two processes reflect the different adaptation strategies during land plant evolution.