A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes

Background: Medical students report high levels of stress related to their medical training as well as to other personal and financial factors. The aim of this study is to investigate whether there are differences in course-related stressors reported by medical students on undergraduate problem-based learning (PBL) and non-PBL programmes in the UK. Method: A cross-sectional study of second-year medical students in two UK medical schools (one PBL and one non-PBL programme) was conducted. A 16-question self-report questionnaire, derived from the Perceived Medical Student Stress Scale and the Higher Education Stress Inventory, was used to measure course-related stressors. Following univariate analysis of each stressor between groups, multivariate logistic regression was used to determine which stressors were the best predictors of each course type, while controlling for socio-demographic differences between the groups. Results: A total of 280 students responded. Compared to the non-PBL students (N = 197), the PBL students (N = 83) were significantly more likely to agree that: they did not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03); there were too many small group sessions facilitated only by students resulting in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They were significantly more likely to disagree that: there was a lack of encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course fostered a sense of anonymity and feelings of isolation amongst students (OR = 3.42, p = 0.008). Conclusion: There are significant differences in the perceived course-related stressors affecting medical students on PBL and non-PBL programmes. Course designers and student support services should therefore tailor their work to minimise, or help students cope with, the specific stressors on each course type to ensure optimum learning and wellbeing among our future doctors

OpenAssistant Conversations -- Democratizing Large Language Model Alignment

Aligning large language models (LLMs) with human preferences has proven to drastically improve usability and has driven rapid adoption as demonstrated by ChatGPT. Alignment techniques such as supervised fine-tuning (SFT) and reinforcement learning from human feedback (RLHF) greatly reduce the required skill and domain knowledge to effectively harness the capabilities of LLMs, increasing their accessibility and utility across various domains. However, state-of-the-art alignment techniques like RLHF rely on high-quality human feedback data, which is expensive to create and often remains proprietary. In an effort to democratize research on large-scale alignment, we release OpenAssistant Conversations, a human-generated, human-annotated assistant-style conversation corpus consisting of 161,443 messages in 35 different languages, annotated with 461,292 quality ratings, resulting in over 10,000 complete and fully annotated conversation trees. The corpus is a product of a worldwide crowd-sourcing effort involving over 13,500 volunteers. Models trained on OpenAssistant Conversations show consistent improvements on standard benchmarks over respective base models. We release our code and data under a fully permissive licence.Comment: Published in NeurIPS 2023 Datasets and Benchmark

‘Genome design’ model and multicellular complexity: golden middle

Human tissue-specific genes were reported to be longer than housekeeping genes (both in coding and intronic parts). The competing neutralist and adaptationist models were proposed to explain this observation. Here I show that in human genome the longest are genes with the intermediate expression pattern. From the standpoint of information theory, the regulation of such genes should be most complex. In the genomewide context, they are found here to have the higher informational load on all available levels: from participation in protein interaction networks, pathways and modules reflected in Gene Ontology categories through transcription factor regulatory sets and protein functional domains to amino acid tuples (words) in encoded proteins and nucleotide tuples in introns and promoter regions. Thus, the intermediately expressed genes have the higher functional and regulatory complexity that is reflected in their greater length (which is consistent with the ‘genome design’ model). The dichotomy of housekeeping versus tissue-specific entities is more pronounced on the modular level than on the molecular level. There are much lesser intermediate-specific modules (modules overrepresented in the intermediately expressed genes) than housekeeping or tissue-specific modules (normalized to gene number). The dichotomy of housekeeping versus tissue-specific genes and modules in multicellular organisms is probably caused by the burden of regulatory complexity acted on the intermediately expressed genes

Could consumption of insects, cultured meat or imitation meat reduce global agricultural land use?

Animal products, i.e. meat, milk and eggs, provide an important component in global diets, but livestock dominate agricultural land use by area and are a major source of greenhouse gases. Cultural and personal associations with animal product consumption create barriers to moderating consumption, and hence reduced environmental impacts. Here we review alternatives to conventional animal products, including cultured meat, imitation meat and insects (i.e. entomophagy), and explore the potential change in global agricultural land requirements associated with each alternative. Stylised transformative consumption scenarios where half of current conventional animal products are substituted to provide at least equal protein and calories are considered. The analysis also considers and compares the agricultural land area given shifts between conventional animal product consumption. The results suggest that imitation meat and insects have the highest land use efficiency, but the land use requirements are only slightly greater for eggs and poultry meat. The efficiency of insects and their ability to convert agricultural by-products and food waste into food, suggests further research into insect production is warranted. Cultured meat does not appear to offer substantial benefits over poultry meat or eggs, with similar conversion efficiency, but higher direct energy requirements. Comparison with the land use savings from reduced consumer waste, including over-consumption, suggests greater benefits could be achieved from alternative dietary transformations considered. We conclude that although a diet with lower rates of animal product consumption is likely to create the greatest reduction in agricultural land, a mix of smaller changes in consumer behaviour, such as replacing beef with chicken, reducing food waste and potentially introducing insects more commonly into diets, would also achieve land savings and a more sustainable food system

Attitudes toward Methadone among Out-of-Treatment Minority Injection Drug Users: Implications for Health Disparities

Injection drug use (IDU) continues to be a significant public health issue in the U.S. and internationally, and there is evidence to suggest that the burden of injection drug use and associated morbidity and mortality falls disproportionately on minority communities. IDU is responsible for a significant portion of new and existing HIV/AIDS cases in many parts of the world. In the U.S., the prevalence of HIV and hepatitis C virus is higher among populations of African-American and Latino injection drug users (IDUs) than among white IDUs. Methadone maintenance therapy (MMT) has been demonstrated to effectively reduce opiate use, HIV risk behaviors and transmission, general mortality and criminal behavior, but opiate-dependent minorities are less likely to access MMT than whites. A better understanding of the obstacles minority IDUs face accessing treatment is needed to engage racial and ethnic disparities in IDU as well as drug-related morbidity and mortality. In this study, we explore knowledge, attitudes and beliefs about methadone among 53 out-of-treatment Latino and African-American IDUs in Providence, RI. Our findings suggest that negative perceptions of methadone persist among racial and ethnic minority IDUs in Providence, including beliefs that methadone is detrimental to health and that people should attempt to discontinue methadone treatment. Additional potential obstacles to entering methadone therapy include cost and the difficulty of regularly attending a methadone clinic as well as the belief that an individual on MMT is not abstinent from drugs. Substance use researchers and treatment professionals should engage minority communities, particularly Latino communities, in order to better understand the treatment needs of a diverse population, develop culturally appropriate MMT programs, and raise awareness of the benefits of MMT

RNPomics: Defining the ncRNA transcriptome by cDNA library generation from ribonucleo-protein particles

Up to 450 000 non-coding RNAs (ncRNAs) have been predicted to be transcribed from the human genome. However, it still has to be elucidated which of these transcripts represent functional ncRNAs. Since all functional ncRNAs in Eukarya form ribonucleo-protein particles (RNPs), we generated specialized cDNA libraries from size-fractionated RNPs and validated the presence of selected ncRNAs within RNPs by glycerol gradient centrifugation. As a proof of concept, we applied the RNP method to human Hela cells or total mouse brain, and subjected cDNA libraries, generated from the two model systems, to deep-sequencing. Bioinformatical analysis of cDNA sequences revealed several hundred ncRNP candidates. Thereby, ncRNAs candidates were mainly located in intergenic as well as intronic regions of the genome, with a significant overrepresentation of intron-derived ncRNA sequences. Additionally, a number of ncRNAs mapped to repetitive sequences. Thus, our RNP approach provides an efficient way to identify new functional small ncRNA candidates, involved in RNP formation

Identification of small non-coding RNAs from mitochondria and chloroplasts

Small non-protein-coding RNAs (ncRNAs) have been identified in a wide spectrum of organisms ranging from bacteria to humans. In eukarya, systematic searches for ncRNAs have so far been restricted to the nuclear or cytosolic compartments of cells. Whether or not small stable non-coding RNA species also exist in cell organelles, in addition to tRNAs or ribosomal RNAs, is unknown. We have thus generated cDNA libraries from size-selected mammalian mitochondrial RNA and plant chloroplast RNA and searched for small ncRNA species in these two types of DNA-containing cell organelles. In total, we have identified 18 novel candidates for organellar ncRNAs in these two cellular compartments and confirmed expression of six of them by northern blot analysis or RNase A protection assays. Most candidate ncRNA genes map to intergenic regions of the organellar genomes. As found previously in bacteria, the presumptive ancestors of present-day chloroplasts and mitochondria, we also observed examples of antisense ncRNAs that potentially could target organelle-encoded mRNAs. The structural features of the identified ncRNAs as well as their possible cellular functions are discussed. The absence from our libraries of abundant small RNA species that are not encoded by the organellar genomes suggests that the import of RNAs into cell organelles is of very limited significance or does not occur at all

lincRNAs act in the circuitry controlling pluripotency and differentiation

Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state.Broad InstituteHarvard UniversityNational Human Genome Research Institute (U.S.)Merkin Family Foundation for Stem Cell Researc

Expression and Processing of a Small Nucleolar RNA from the Epstein-Barr Virus Genome

Small nucleolar RNAs (snoRNAs) are localized within the nucleolus, a sub-nuclear compartment, in which they guide ribosomal or spliceosomal RNA modifications, respectively. Up until now, snoRNAs have only been identified in eukaryal and archaeal genomes, but are notably absent in bacteria. By screening B lymphocytes for expression of non-coding RNAs (ncRNAs) induced by the Epstein-Barr virus (EBV), we here report, for the first time, the identification of a snoRNA gene within a viral genome, designated as v-snoRNA1. This genetic element displays all hallmark sequence motifs of a canonical C/D box snoRNA, namely C/C′- as well as D/D′-boxes. The nucleolar localization of v-snoRNA1 was verified by in situ hybridisation of EBV-infected cells. We also confirmed binding of the three canonical snoRNA proteins, fibrillarin, Nop56 and Nop58, to v-snoRNA1. The C-box motif of v-snoRNA1 was shown to be crucial for the stability of the viral snoRNA; its selective deletion in the viral genome led to a complete down-regulation of v-snoRNA1 expression levels within EBV-infected B cells. We further provide evidence that v-snoRNA1 might serve as a miRNA-like precursor, which is processed into 24 nt sized RNA species, designated as v-snoRNA124pp. A potential target site of v-snoRNA124pp was identified within the 3′-UTR of BALF5 mRNA which encodes the viral DNA polymerase. V-snoRNA1 was found to be expressed in all investigated EBV-positive cell lines, including lymphoblastoid cell lines (LCL). Interestingly, induction of the lytic cycle markedly up-regulated expression levels of v-snoRNA1 up to 30-fold. By a computational approach, we identified a v-snoRNA1 homolog in the rhesus lymphocryptovirus genome. This evolutionary conservation suggests an important role of v-snoRNA1 during γ-herpesvirus infection