Miracle-dz/UniFAR-FTUs huggingface dataset:
A Survey of Nursing Staff’s Perspective Regarding Reasons for Medication Errors

Background: Health care services are associated with risks for their recipients. Medication errors can lead to many negative consequences for the health care system, including prolonged hospital stay and increased cost per patient. The aim of this study was to investigate the nursing staff’s perspective regarding reasons for medication errors in Ayatollah Kashani hospital, Shahrekord, Iran. Methods: 207 nurses working in the ICUs of the hospital were selected by convenience sampling and their comments about effective factors in the incidence of medication errors were investigated by a researcher-made questionnaire. To examine the reliability and validity of the questionnaire, we offered it to 5 nursing experts and necessary corrections were made based on the comments. The reliability of the questionnaire was also investigated by Cronbach’s alpha coefficient that gave the value of 85%. The first section of the questionnaire consisted of questions about demographic characteristics and the second section investigated the reasons for medication errors in nursing-related area, workplace-related area, director of nursing-related area, and drug-related area. For each item, there were four choices, i.e. none, little, moderate, and much and therefore, the level of importance scored between 0 and 3. The data were analyzed by SPSS 17. Results: In this study, the most important reasons for medication errors were related to workload-induced fatigue (mean: 2.37) in the nurses-related area, high labor-intensity in department (mean: 2.32) in the workplace-related area, insufficient nursing staff proportional to the number of patients in department (mean: 2.41) in the director of nursing-related area, and drug name confusion in the drug-related area (mean: 2.04). Conclusions: The officials of health care systems should focus on the effective processes in reducing medication errors including appropriate training of the staff and holding in-service training sessions about drug information as well as appropriate planning for employment of adequate workforce.
Systematic genome-wide querying of coding and non-coding functional elements in E. coli using CRISPRi

Genome-wide repression screens using CRISPR interference (CRISPRi) have enabled the high-throughput identification of essential genes in bacteria. However, there is a lack of functional studies leveraging CRISPRi to systematically explore targeting of both the coding and non-coding genome in bacteria. Here we perform CRISPRi screens in Escherichia coli MG1655 K-12 targeting ~13,000 genomic features, including nearly all protein-coding genes, non-coding RNAs, promoters, and transcription factor binding sites (TFBSs) using a ~33,000-member sgRNA library, which represents the most compact and comprehensive genome-wide CRISPRi library in E. coli to date. Our data reveal insights into the conditional essentiality of the genome with key refinements to screen design and profiling. First, we demonstrate that strong fitness defects associated with essential cellular processes can be resolved using inducible time-series measurements. We show that knockdowns of different classes of genes exhibit distinct, transient responses that are correlated to gene function with genes involved in translation exhibiting the strongest responses. We also query feature essentiality across several biochemical conditions and show that several genes, sRNAs, and operons exhibit conditional phenotypes not reported by previous high-throughput efforts. Second, we evaluate systematically targeting non-genic features (promoters and TFBSs) in the E. coli genome. We show that promoter-targeting guides can be used to add phenotypic confidence to promoter annotations and verify computationally predicted promoters. In contrast to prior studies, we find that promoter knockdowns exhibit a strong targeting orientation dependency where targeting the non-template strand of the promoter closest to the target gene is more effective in knocking down gene expression than other promoter targeting orientations. Unlike eukaryotic genomes, we note that interpreting the effects of TFBS targeting is particularly challenging due to the small size of such features and their proximity to and overlap with other genomic features. Together, this work reveals novel conditionally essential gene phenotypes, provides a characterized set of sgRNAs for future E. coli CRISPRi screens, and highlights considerations for CRISPRi library design and screening for microbial genome characterization.
Recollection-related hippocampal fMRI effects predict longitudinal memory change in healthy older adults

Prior fMRI studies have reported relationships between memory-related activity in the hippocampus and in-scanner memory performance, but whether such activity is predictive of longitudinal memory change remains unclear. Here, we administered a neuropsychological test battery to a sample of cognitively healthy older adults on three occasions, the second and third sessions occurring one month and three years after the first session. Structural and functional MRI data were acquired between the first two sessions. The fMRI data were derived from an associative recognition procedure and allowed estimation of hippocampal effects associated with both successful associative encoding and successful associative recognition (recollection). Baseline memory performance and memory change were evaluated using memory component scores derived from a principal components analysis of the neuropsychological test scores. Across participants, right hippocampal encoding effects correlated significantly with baseline memory performance after controlling for chronological age. Additionally, both left and right hippocampal associative recognition effects correlated significantly with longitudinal memory change after controlling for age, and the relationship with the left hippocampal effect remained after also controlling for left hippocampal volume. Thus, in cognitively healthy older adults, the magnitude of hippocampal recollection effects appears to be a robust predictor of future memory change.
A generalized robust allele‐based genetic association test

The allele-based association test, comparing allele frequency difference between case and control groups, is locally most powerful. However, application of the classical allelic test is limited in practice, because the method is sensitive to the Hardy–Weinberg equilibrium (HWE) assumption, not applicable to continuous traits, and not easy to account for covariate effect or sample correlation. To develop a generalized robust allelic test, we propose a new allele-based regression model with individual allele as the response variable. We show that the score test statistic derived from this robust and unifying regression framework contains a correction factor that explicitly adjusts for potential departure from HWE, and encompasses the classical allelic test as a special case. When the trait of interest is continuous, the corresponding allelic test evaluates a weighted difference between individual-level allele frequency estimate and sample estimate where the weight is proportional to an individual’s trait value, and the test remains valid under Y - dependent sampling. Finally, the proposed allele-based method can analyze multiple (continuous or binary) phenotypes simultaneously and multi-allelic genetic markers, while accounting for covariate effect, sample correlation and population heterogeneity. To support our analytical findings, we provide empirical evidence from both simulation and application studies.
Self-antigen driven affinity maturation is required for pathogenic monovalent IgG4 autoantibody development

Pathogenic IgG4 autoantibodies in autoimmune myasthenia gravis (MG) are functionally monovalent as a result of Fab-arm exchange. The origin and development of these unique autoantibodies are not well understood. We examined MG patient-derived monoclonal autoantibodies (mAbs), their corresponding germline-encoded unmutated common ancestors (UCA) and monovalent antigen-binding fragments (Fabs) to investigate how antigen-driven affinity maturation contributes to both binding and immunopathology. Mature mAbs, their UCA counterparts and mature monovalent Fabs bound to the autoantigen and retained their pathogenic capacity. However, monovalent UCA Fabs still bound the autoantigen but lost their pathogenic capacity. The mature Fabs were characterized by very high affinity (sub-nanomolar) driven by a rapid on-rate and slow off-rate. However, the UCA affinity was approximately 100-fold less than that of the mature Fabs, which was driven by a rapid off-rate. Crystal structures of two Fabs shed light on how mutations acquired during affinity maturation may contribute to increased MuSK binding affinity. These collective findings indicate that the autoantigen initiates the autoimmune response in MuSK MG and drives autoimmunity through the accumulation of somatic hypermutation such that monovalent IgG4 Fab-arm exchanged MG autoantibodies reach a high affinity threshold required for pathogenic capacity. Summary IgG4 autoantibodies in autoimmune myasthenia gravis are functionally monovalent, requiring a high affinity threshold featuring fast on/slow off rates, to reach pathogenic capacity. This capacity is dependent on self-antigen initiated and driven maturation, which includes the accumulation of indispensable somatic hypermutations that may alter electrostatic interactions with the antigen.
Injury risk factors and preventive strategies in schoolboy Rugby Union

The injury risk associated with schoolboy Rugby has been raised as a matter of public concern, leading to calls to formulate appropriate preventive strategies. Consequently, this programme of research was undertaken to investigate characteristics that might influence injury risk in schoolboy rugby players, as well as interventions to reduce injury risk. The first study of this thesis (Chapter Three) presents a two-season prospective cohort study, which identifies several anthropometric characteristics and physical fitness components associated with injury risk in schoolboy Rugby players. Chapter Four outlines a staged approach to formulating a preventive exercise programme for use in schoolboy Rugby based on scientific evidence, expert knowledge, and end user opinion. In Chapter Five, the efficacy of a preventive exercise programme to reduce injury risk in schoolboy Rugby players is evaluated, demonstrating clinically meaningful reductions in concussion risk when compared with a standardised control exercise programme. In addition, greater programme compliance and dose are found to accentuate reductions across many match-derived injury outcomes measures. Finally, Chapter Six highlights meaningful associations between coach-related psychosocial factors and coaches’ compliance with using a preventive exercise programme, which may be useful in future with formulating strategies to enhance compliance with programme use. To summarise, this thesis addresses the identification of potentially modifiable risk factors and applies a novel approach to reduce injury risk in schoolboy Rugby players, emphasises the importance of compliance and dose in moderating the influence of preventive exercise programme efficacy, and outlines the associations between coach-related psychosocial factors and coaches’ compliance with using a preventive exercise programme in a schoolboy Rugby population.
A semi-automated approach to dense segmentation of 3D white matter electron microscopy

Purpose Neuroscience methods working on widely different scales can complement and inform each other. At the macroscopic scale, magnetic resonance imaging methods that estimate microstructural measures have much to gain from ground truth validation and models based on accurate measurement of that microstructure. We present an approach to generate rich and accurate geometric models of white matter microstructure through dense segmentation of 3D electron microscopy (EM). Methods Volumetric data of the white matter of the genu of the corpus callosum of the adult mouse brain were acquired using serial blockface scanning electron microscopy (SBF-SEM). A segmentation pipeline was developed to separate the 3D EM data into compartments and individual cellular and subcellular constituents, making use of established tools as well as newly developed algorithms to achieve accurate segmentation of various compartments. Results The volume was segmented into six compartments comprising myelinated axons (axon, myelin sheath, nodes of Ranvier), oligodendrocytes, blood vessels, mitochondria, and unmyelinated axons. The myelinated axons had an average inner diameter of 0.56 μm and an average outer diameter of 0.87 μm. The diameter of unmyelinated axons was 0.43 μm. A mean g-ratio of 0.61 was found for myelinated axons, but the g-ratio was highly variable between as well as within axons. Conclusion The approach for segmentation of 3D EM data yielded a dense annotation of a range of white matter compartments that can be interrogated for their properties and used for in silico experiments of brain structure. We provide the resulting dense annotation as a resource to the neuroscience community.
Trial-by-trial predictions of subjective time from human brain activity

Human experience of time exhibits systematic, context-dependent deviations from clock time; for example, time is experienced differently at work than on holiday. Here we test the proposal that differences from clock time in subjective experience of time arise because time estimates are constructed by accumulating the same quantity that guides perception: salient events. Healthy human participants watched naturalistic, silent videos of up to 24 seconds in duration and estimated their duration while fMRI was acquired. We were able to reconstruct trial-by-trial biases in participants’ duration reports, which reflect subjective experience of duration, purely from salient events in their visual cortex BOLD activity. By contrast, salient events in neither of two control regions–auditory and somatosensory cortex–were predictive of duration biases. These results held despite being able to (trivially) predict clock time from all three brain areas. Our results reveal that the information arising during perceptual processing of a dynamic environment provides a sufficient basis for reconstructing human subjective time duration.
Tead1 reciprocally regulates adult β-cell proliferation and function to maintain glucose homeostasis

Proliferative quiescence in β-cells is required to maintain functional competence. While this presents a significant hurdle in regenerative therapy for diabetes, the molecular underpinnings of this reciprocal relationship remain unclear. Here, we demonstrate that TEAD1, the transcription effector of the mammalian-Hippo pathway, drives developmental stage-specific β-cell proliferative capacity in conjunction with its functional maturation. TEAD1 promotes adult β-cell mature identity by direct transcriptional control of a network of critical β-cell transcription factors, including, Pdx1, Nkx6.1, and MafA, while its regulation of Cdkn2a maintains proliferative quiescence. Consequently, mice with either constitutive or inducible genetic deletion of TEAD1 in β-cells developed overt diabetes due to a severe loss of secretory function despite induction of proliferation. Furthermore, we show that TEAD1 has a similar regulatory role in human β-cells. Consistent with this function in β-cells, variants in TEAD1 have been associated with c-HOMA-B in American Indians. We propose that TEAD1 is an essential intrinsic molecular switch coordinating adult β-cell proliferative quiescence with mature identity and its differential modulation may be necessary to overcome the challenge of inducing proliferation with functional competence in human beta cells.
Translational adaptation to heat stress is mediated by 5-methylcytosine RNA modification in Caenorhabditis elegans

Methylation of carbon-5 of cytosines (m5C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m5C-methyltransferases have been studied, the impact of the global cytosine-5 methylome on development, homeostasis and stress remains unknown. Here, using Caenorhabditis elegans, we generated the first organism devoid of m5C in RNA, demonstrating that this modification is non-essential. We determined the localisation and enzymatic specificity of m5C sites in RNA in vivo and showed that animals devoid of m5C are sensitive to temperature stress. At the molecular level, we showed that loss of m5C specifically impacts decoding of leucine and proline thus reducing the translation efficiency of transcripts enriched in these amino acids. Finally, we found translation of leucine UUG codons to be the most strongly affected upon heat shock, suggesting a role of m5C tRNA wobble methylation in the adaptation to heat stress.
TRAF6 controls spinogenesis instructing synapse density and neuronal activity through binding neuroplastin

Synaptogenic mechanisms and their relevance to achieve a correct synapse density and activity in mature neurons are poorly understood. Here, we show that the tumor necrosis factor receptor-associated factor 6 (TRAF6) controls early spinogenesis by binding the cell adhesion molecule neuroplastin which is has been related to synapse formation in vivo. TRAF6-neuroplastin co-precipitations from brain samples and co-transfected HEK cells is explained by direct interaction of the proteins based on three-dimensional modelling and biochemical identification of intracellular amino acids of neuroplastin binding the TRAF-C domain of TRAF6 with micromolar affinity. TRAF6 was not only required for normal spinogenesis but also was strictly necessary to restore failed spinogenesis in neuroplastin-deficient neurons. Independently from neuroplastin’s extracellular adhesive properties or interaction with another known partner i.e. the plasma membrane Ca2+ ATPases, TRAF6 mediated formation of new postsynapses by neuroplastin overexpression in rat hippocampal neurons. Furthermore, TRAF6-controlled spinogenesis was required for the establishment of a correct synapse density as well as proper synaptic activity and intrinsic neuronal activity as demonstrated with intracellular and extracellular electrophysiological recordings. These findings provide a novel mechanism for early synapse formation that shapes connectivity and functioning of hippocampal neurons.
Comparative transcriptomic and epigenomic analysis identifies key regulators of injury response and neurogenic competence in retinal glia

Injury induces retinal Müller glia of lower vertebrates, but not mammalian, to generate neurons. To identify gene regulatory networks that control neurogenic competence in retinal glia, we comprehensively profiled injury-dependent changes in gene expression and chromatin conformation in Müller glia from zebrafish, chick and mice using bulk RNA and ATAC-Seq, as well as single-cell RNA-Seq. Integration of these data, together with functional analysis of candidate genes, identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, gliosis, and neurogenic competence. In zebrafish and chick, transition from quiescence to gliosis is a critical stage in acquisition of neurogenic competence, while in mice a dedicated network suppresses this transition and rapidly restores quiescence. Selective disruption of NFI family transcription factors in mice, which maintain and restore quiescence, confers injury-dependent proliferative and neurogenic competence on Müller glia. These findings may help guide the design of cell-based therapies aimed at restoring retinal neurons lost in disease.
Use of dietary supplements among Brazilian athletes

Objective: To investigate the prevalence and establish the profile of the consumption of dietary supplements among Brazilian athletes. Methods: A total of 182 athletes of both genders from 20 different sports participated in this study. The athletes answered a questionnaire containing sociodemographic and sports-related questions and were interviewed about the consumption of dietary supplements. Results: Forty seven percent of athletes reported having consumed at least one type of dietary supplement and 38% said they use more than three different types of supplements concurrently. Whey protein was the most commonly consumed supplement, and the most frequently mentioned reason for its consumption was performance improvement. The main source of information was coaches, and individual sport athletes were the greatest consumers and the most likely to seek dietary supplement. Conclusion: Approximately half of the participants used dietary supplements, which on most occasions were recommended by coaches. The consumption profile also revealed multiple supplementation practice and showed that nutrition education is essential for this specific population.
Potassium nutrition recover impacts on stomatal, mesophyll and biochemical limitations to photosynthesis in Carya cathayensis and Hickory illinoensis

Potassium (K) influences the photosynthesis process in a number of ways; However, the mechanism of photosynthetic response to the long-term supply of potassium is not yet clear. Concurrent measurements of gas exchange and chlorophyll fluorescence were made to investigate the effect of potassium nutrition on photosynthetic efficiency and stomatal conductance (gs), mesophyll conductance (gm) in Pecan (Carya illinoensis K.Kock) and Hickory (Carya cathayensis Sarg.) seedlings in a greenhouse. The results show that the photosynthetic capacity of Pecan and Hickory plants was not limited when the leaves had potassium concentrations >1.4% and 1.42% of dry weight. Most of limitation under potassium deficiency were dominated by MCL for Pecan and Hickory. Both cultivars showed remarkable improvement in SL, MCL, J and Vc,max with additional K supplies. However, effect from potassium deficiency on photosynthesis in plant leaves was irreversible. All of SL, MCL, and BL nearly half down with recovery K supply in both species. These results emphasize the important role of potassium on regulation of photosynthesis by three limitations.
“The Heidelberg Five” Personality Dimensions: Genome-wide Associations, Polygenic Risk for Neuroticism, and Psychopathology 20 Years after Assessment

The HeiDE study (‘‘Heidelberger Langzeitstudie zu Risikofaktoren und Diagnose chronischer Erkrankungen’’) is a longitudinal population-based study that started in the 1990s and, at baseline, assessed an array of health-related personality questionnaires in 5 133 individuals. Five latent personality dimensions (The Heidelberg Five) were identified and interpreted as Emotional Lability (ELAB), Lack of Behavioral Control (LBCN), Type A Behavior (TYAB), Locus of Control over Disease (LOCC), and Psychoticism (PSYC). A subset of participants (n=3 268; after quality control) were genotyped on whole-genome arrays at follow-up. To further characterize The Heidelberg Five, we analyzed genomic underpinnings, their relations to the genetic basis of the Big Five trait Neuroticism, and longitudinal associations with lifetime psychiatric symptoms. SNP-based heritability was significant for ELAB (34%) and LBCN (29%). Five separate genome-wide association studies (GWAS) using factor scores on personality dimensions as phenotypes were conducted, only the phenotype PSYC yielded a genome-wide significant finding (p<5×10−8, top SNP rs138223660). Gene-based analyses identified significant findings for ELAB (Integrin Subunit Beta 5), TYAB (Coiled-coil Domain Containing 83), and PSYC (Nuclear Receptor Subfamily 1 Group H Member 4). Polygenic risk scores for Neuroticism, phenotypically related to ELAB, were associated with ELAB, but not with the remaining Heidelberg Five. Longitudinally, all personality dimensions were related to depressive symptoms at follow-up, with ELAB, LBCN, and PSYC also associated with lifetime anxiety symptoms. These results highlight the clinical importance of health-related personality traits, and identify LBCN as a heritable “executive function” personality trait.