Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors.

G protein-coupled receptors (GPCRs) mediate diverse signaling in part through interaction with arrestins, whose binding promotes receptor internalization and signaling through G protein-independent pathways. High-affinity arrestin binding requires receptor phosphorylation, often at the receptor's C-terminal tail. Here, we report an X-ray free electron laser (XFEL) crystal structure of the rhodopsin-arrestin complex, in which the phosphorylated C terminus of rhodopsin forms an extended intermolecular ß sheet with the N-terminal ß strands of arrestin. Phosphorylation was detected at rhodopsin C-terminal tail residues T336 and S338. These two phospho-residues, together with E341, form an extensive network of electrostatic interactions with three positively charged pockets in arrestin in a mode that resembles binding of the phosphorylated vasopressin-2 receptor tail to ß-arrestin-1. Based on these observations, we derived and validated a set of phosphorylation codes that serve as a common mechanism for phosphorylation-dependent recruitment of arrestins by GPCRs.

Using the ACMG/AMP framework to capture evidence related to predicted and observed impact on splicing: Recommendations from the ClinGen SVI Splicing Subgroup.

The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) framework for classifying variants uses six evidence categories related to the splicing potential of variants: PVS1, PS3, PP3, BS3, BP4, and BP7. However, the lack of guidance on how to apply such codes has contributed to variation in the specifications developed by different Clinical Genome Resource (ClinGen) Variant Curation Expert Panels. The ClinGen Sequence Variant Interpretation Splicing Subgroup was established to refine recommendations for applying ACMG/AMP codes relating to splicing data and computational predictions. We utilized empirically derived splicing evidence to (1) determine the evidence weighting of splicing-related data and appropriate criteria code selection for general use, (2) outline a process for integrating splicing-related considerations when developing a gene-specific PVS1 decision tree, and (3) exemplify methodology to calibrate splice prediction tools. We propose repurposing the PVS1_Strength code to capture splicing assay data that provide experimental evidence for variants resulting in RNA transcript(s) with loss of function. Conversely, BP7 may be used to capture RNA results demonstrating no splicing impact for intronic and synonymous variants. We propose that the PS3/BS3 codes are applied only for well-established assays that measure functional impact not directly captured by RNA-splicing assays. We recommend the application of PS1 based on similarity of predicted RNA-splicing effects for a variant under assessment in comparison with a known pathogenic variant. The recommendations and approaches for consideration and evaluation of RNA-assay evidence described aim to help standardize variant pathogenicity classification processes when interpreting splicing-based evidence.

Disentangling Temporal and Rate Codes in the Primate Somatosensory Cortex.

Millisecond-scale temporal spiking patterns encode sensory information in the periphery, but their role in the neocortex remains controversial. The sense of touch provides a window into temporal coding because tactile neurons often exhibit precise, repeatable, and informative temporal spiking patterns. In the somatosensory cortex (S1), responses to skin vibrations exhibit phase locking that faithfully carries information about vibratory frequency. However, the respective roles of spike timing and rate in frequency coding are confounded because vibratory frequency shapes both the timing and rates of responses. To disentangle the contributions of these two neural features, we measured S1 responses as rhesus macaques performed frequency discrimination tasks in which differences in frequency were accompanied by orthogonal variations in amplitude. We assessed the degree to which the strength and timing of responses could account for animal performance. First, we showed that animals can discriminate frequency, but their performance is biased by amplitude variations. Second, rate-based representations of frequency are susceptible to changes in amplitude but in ways that are inconsistent with the animals' behavioral biases, calling into question a rate-based neural code for frequency. In contrast, timing-based representations are highly informative about frequency but impervious to changes in amplitude, which is also inconsistent with the animals' behavior. We account for the animals' behavior with a model wherein frequency coding relies on a temporal code, but frequency judgments are biased by perceived magnitude. We conclude that information about vibratory frequency is not encoded in S1 firing rates but primarily in temporal patterning on millisecond timescales.

Multiple errors correction for position-limited DNA sequences with GC balance and no homopolymer for DNA-based data storage.

Deoxyribonucleic acid (DNA) is an attractive medium for long-term digital data storage due to its extremely high storage density, low maintenance cost and longevity. However, during the process of synthesis, amplification and sequencing of DNA sequences with homopolymers of large run-length, three different types of errors, namely, insertion, deletion and substitution errors frequently occur. Meanwhile, DNA sequences with large imbalances between GC and AT content exhibit high dropout rates and are prone to errors. These limitations severely hinder the widespread use of DNA-based data storage. In order to reduce and correct these errors in DNA storage, this paper proposes a novel coding schema called DNA-LC, which converts binary sequences into DNA base sequences that satisfy both the GC balance and run-length constraints. Furthermore, our coding mode is able to detect and correct multiple errors with a higher error correction capability than the other methods targeting single error correction within a single strand. The decoding algorithm has been implemented in practice. Simulation results indicate that our proposed coding scheme can offer outstanding error protection to DNA sequences. The source code is freely accessible at https://github.com/XiayangLi2301/DNA.

Representational Geometries Reveal Differential Effects of Response Correlations on Population Codes in Neurophysiology and Functional Magnetic Resonance Imaging.

Two sensory neurons usually display trial-by-trial spike-count correlations given the repeated representations of a stimulus. The effects of such response correlations on population-level sensory coding have been the focal contention in computational neuroscience over the past few years. In the meantime, multivariate pattern analysis (MVPA) has become the leading analysis approach in functional magnetic resonance imaging (fMRI), but the effects of response correlations among voxel populations remain underexplored. Here, instead of conventional MVPA analysis, we calculate linear Fisher information of population responses in human visual cortex (five males, one female) and hypothetically remove response correlations between voxels. We found that voxelwise response correlations generally enhance stimulus information, a result standing in stark contrast to the detrimental effects of response correlations reported in empirical neurophysiological studies. By voxel-encoding modeling, we further show that these two seemingly opposite effects actually can coexist within the primate visual system. Furthermore, we use principal component analysis to decompose stimulus information in population responses onto different principal dimensions in a high-dimensional representational space. Interestingly, response correlations simultaneously reduce and enhance information on higher- and lower-variance principal dimensions, respectively. The relative strength of the two antagonistic effects within the same computational framework produces the apparent discrepancy in the effects of response correlations in neuronal and voxel populations. Our results suggest that multivariate fMRI data contain rich statistical structures that are directly related to sensory information representation, and the general computational framework to analyze neuronal and voxel population responses can be applied in many types of neural measurements.SIGNIFICANCE STATEMENT Despite the vast research interest in the effect of spike-count noise correlations on population codes in neurophysiology, it remains unclear how the response correlations between voxels influence MVPA in human imaging. We used an information-theoretic approach and showed that unlike the detrimental effects of response correlations reported in neurophysiology, voxelwise response correlations generally improve sensory coding. We conducted a series of in-depth analyses and demonstrated that neuronal and voxel response correlations can coexist within the visual system and share some common computational mechanisms. These results shed new light on how the population codes of sensory information can be evaluated via different neural measurements.

Development and multicentre validation of the FLEX score: personalised preoperative surgical risk prediction using attention-based ICD-10 and Current Procedural Terminology set embeddings.

BACKGROUND: Preoperative knowledge of surgical risks can improve perioperative care and patient outcomes. However, assessments requiring clinician examination of patients or manual chart review can be too burdensome for routine use. METHODS: We conducted a multicentre retrospective study of 243 479 adult noncardiac surgical patients at four hospitals within the Mass General Brigham (MGB) system in the USA. We developed a machine learning method using routinely collected coding and patient characteristics data from the electronic health record which predicts 30-day mortality, 30-day readmission, discharge to long-term care, and hospital length of stay. RESULTS: Our method, the Flexible Surgical Set Embedding (FLEX) score, achieved state-of-the-art performance to identify comorbidities that significantly contribute to the risk of each adverse outcome. The contributions of comorbidities are weighted based on patient-specific context, yielding personalised risk predictions. Understanding the significant drivers of risk of adverse outcomes for each patient can inform clinicians of potential targets for intervention. CONCLUSIONS: FLEX utilises information from a wider range of medical diagnostic and procedural codes than previously possible and can adapt to different coding practices to accurately predict adverse postoperative outcomes.

Standardization of coding definitions for sickle cell disease complications: A systematic literature review.

PURPOSE: Sickle cell disease (SCD) affects all organ systems and is characterized by numerous acute and chronic complications and comorbidities. Standardized codes are needed for complications/comorbidities used in real-world evidence (RWE) studies that rely on administrative and medical coding. This systematic literature review was conducted to produce a comprehensive list of complications/comorbidities associated with SCD, along with their diagnosis codes used in RWE studies. METHODS: A search in MEDLINE and Embase identified studies published from 2016 to 2023. Studies were included if they were conducted in US SCD populations and reported complications/comorbidities and respective International Classification of Diseases, Clinical Modification (ICD-CM) codes. All identified complications/comorbidities and codes were reviewed by a certified medical coding expert and hematologist. RESULTS: Of 1851 identified studies, 39 studies were included. The most reported complications/comorbidities were stroke, acute chest syndrome, pulmonary embolism, venous thromboembolism, and vaso-occlusive crisis. Most of the studies used ICD-9-CM codes (n = 21), while some studies used ICD-10-CM codes (n = 3) or both (n = 15), depending on the study period. Most codes reported in literature were heterogeneous across complications/comorbidities. The medical coding expert and hematologist recommended modifications for several conditions. CONCLUSION: While many studies we identified did not report their codes and were excluded from this review, the studies with codes exhibited diverse coding definitions. By providing a standardized set of diagnosis codes that were reported by studies and reviewed by a coding expert and hematologist, our review can serve as a foundation for accurately identifying complications/comorbidities in future research, and may reduce heterogeneity, enhance transparency, and improve reproducibility. Future efforts focused on validating these code lists are needed.

Information, Coding, and Biological Function: The Dynamics of Life.

In the mid-20th century, two new scientific disciplines emerged forcefully: molecular biology and information-communication theory. At the beginning, cross-fertilization was so deep that the term genetic code was universally accepted for describing the meaning of triplets of mRNA (codons) as amino acids. However, today, such synergy has not taken advantage of the vertiginous advances in the two disciplines and presents more challenges than answers. These challenges not only are of great theoretical relevance but also represent unavoidable milestones for next-generation biology: from personalized genetic therapy and diagnosis to Artificial Life to the production of biologically active proteins. Moreover, the matter is intimately connected to a paradigm shift needed in theoretical biology, pioneered a long time ago, that requires combined contributions from disciplines well beyond the biological realm. The use of information as a conceptual metaphor needs to be turned into quantitative and predictive models that can be tested empirically and integrated in a unified view. Successfully achieving these tasks requires a wide multidisciplinary approach, including Artificial Life researchers, to address such an endeavour.

Establishing a valid cohort of patients with acromegaly by combining the National Patient Register with the Swedish Pituitary Register.

PURPOSE: The aim of this study was to establish a valid national cohort of patients diagnosed with acromegaly by combining data from the general National Patient Register (NPR) and the disease-specific Swedish Pituitary Register (SPR). METHODS: Patients ≥ 18 years of age at diagnosis of acromegaly reported from 1991 to 2018 who were registered in the NPR and/or SPR were included. The diagnosis of acromegaly was considered correct for patients identified in both registers or confirmed through chart review. Medical records were reviewed in two of Sweden´s six health care regions if the patient was reported only in the NPR. An algorithm for the NPR, with criteria requiring multiple diagnosis registrations and tumour and/or surgery codes, was constructed to reduce the number of patients to review in the remaining four regions. RESULTS: A total of 1866 patients were identified. Among these, 938 were reported in both registers. After application of the algorithm and chart review, the diagnosis was confirmed for 83 of the 906 patients found only in the NPR. Among 22 patients only registered in the SPR, a review of medical records confirmed acromegaly in 13. This resulted in a total of 1034 cases with acromegaly during the study period. The incidence rate of acromegaly in Sweden 1991-2018 was calculated to 4.0/million/year in the entire population and 5.1/million/year among subjects ≥ 18 years of age. CONCLUSION: The combination of the SPR and NPR established a valid cohort of patients diagnosed with acromegaly and increased the estimated incidence in Sweden.

Validation of human immunodeficiency virus diagnosis codes among women enrollees of a U.S. health plan.

BACKGROUND: Efficiently identifying patients with human immunodeficiency virus (HIV) using administrative health care data (e.g., claims) can facilitate research on their quality of care and health outcomes. No prior study has validated the use of only ICD-10-CM HIV diagnosis codes to identify patients with HIV. METHODS: We validated HIV diagnosis codes among women enrolled in a large U.S. integrated health care system during 2010-2020. We examined HIV diagnosis code-based algorithms that varied by type, frequency, and timing of the codes in patients' claims data. We calculated the positive predictive values (PPVs) and 95% confidence intervals (CIs) of the algorithms using a medical record-confirmed diagnosis of HIV as the gold standard. RESULTS: A total of 272 women with ≥ 1 HIV diagnosis code in the administrative claims data were identified and medical records were reviewed for all 272 women. The PPV of an algorithm classifying women as having HIV as of the first HIV diagnosis code during the observation period was 80.5% (95% CI: 75.4-84.8%), and it was 93.9% (95% CI: 90.0-96.3%) as of the second. Little additional increase in PPV was observed when a third code was required. The PPV of an algorithm based on ICD-10-CM-era codes was similar to one based on ICD-9-CM-era codes. CONCLUSION: If the accuracy measure of greatest interest is PPV, our findings suggest that use of ≥ 2 HIV diagnosis codes to identify patients with HIV may perform well. However, health care coding practices may vary across settings, which may impact generalizability of our results.

Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases.

Nonribosomal peptides (NRPs) are biosynthesized by nonribosomal peptide synthetases (NRPSs) and are widely distributed in both terrestrial and marine organisms. Many NRPs and their analogs are biologically active and serve as therapeutic agents. The adenylation (A) domain is a key catalytic domain that primarily controls the sequence of a product during the assembling of NRPs and thus plays a predominant role in the structural diversity of NRPs. Engineering of the A domain to alter substrate specificity is a potential strategy for obtaining novel NRPs for pharmaceutical studies. On the basis of introducing the catalytic mechanism and multiple functions of the A domains, this article systematically describes several representative NRPS engineering strategies targeting the A domain, including mutagenesis of substrate-specificity codes, substitution of condensation-adenylation bidomains, the entire A domain or its subdomains, domain insertion, and whole-module rearrangements.

Recurrent dynamics in the cerebral cortex: Integration of sensory evidence with stored knowledge.

Current concepts of sensory processing in the cerebral cortex emphasize serial extraction and recombination of features in hierarchically structured feed-forward networks in order to capture the relations among the components of perceptual objects. These concepts are implemented in convolutional deep learning networks and have been validated by the astounding similarities between the functional properties of artificial systems and their natural counterparts. However, cortical architectures also display an abundance of recurrent coupling within and between the layers of the processing hierarchy. This massive recurrence gives rise to highly complex dynamics whose putative function is poorly understood. Here a concept is proposed that assigns specific functions to the dynamics of cortical networks and combines, in a unifying approach, the respective advantages of recurrent and feed-forward processing. It is proposed that the priors about regularities of the world are stored in the weight distributions of feed-forward and recurrent connections and that the high-dimensional, dynamic space provided by recurrent interactions is exploited for computations. These comprise the ultrafast matching of sensory evidence with the priors covertly represented in the correlation structure of spontaneous activity and the context-dependent grouping of feature constellations characterizing natural objects. The concept posits that information is encoded not only in the discharge frequency of neurons but also in the precise timing relations among the discharges. Results of experiments designed to test the predictions derived from this concept support the hypothesis that cerebral cortex exploits the high-dimensional recurrent dynamics for computations serving predictive coding.

Validation of Vascular Location Subcodes for Acute Ischemic Stroke by the International Classification of Diseases-10.

BACKGROUND: Vascular region of infarct is part of the International Classification of Diseases-10 (ICD-10) coding scheme for ischemic stroke. These data could potentially be used for studies about vascular location, such as comparisons of anterior versus posterior circulation stroke. The objective of this study was to evaluate the validity of these subcodes. METHODS: We selected a random sample of 100 hospitalizations specifying 50 with anterior circulation ICD-10 ischemic stroke (carotid, anterior cerebral artery [CA], middle CA) and 50 with posterior circulation stroke (vertebral, basilar, cerebellar, posterior CA). The gold standard primary vascular distribution was scored using imaging studies and reports, blinded to the subcode. We compared gold-standard distribution to coded distribution and calculated the operating characteristics of ICD-10 posterior circulation versus anterior circulation codes with the gold standard. We also calculated the kappa statistic for agreement across all 7 vascular regions. RESULTS: In our population of 100 strokes, mean NIHSS was 8 (SD, 8). Head CT was performed in 95 % (95/100) and MRI in 77 % (77/100). The gold standard classified 55 primary posterior circulation strokes (26 PCA, 16 cerebellar, 8 basilar, 5 vertebral), 44 primary anterior circulation strokes (35 MCA, 6 carotid, 3 ACA), and 1 stroke with no infarct on imaging. The accuracy of the ICD-10 classification for primary posterior circulation stroke versus anterior circulation/no infarct was: sensitivity 89 % (49/55); specificity 98 % (44/45); positive predictive value 98 % (49/50); negative predictive value 88 % (44/50). The reliability of the 7-region classification was excellent (kappa 0.85). CONCLUSIONS: We found that ICD-10 classification of vascular location in routine practice correlates strongly with gold-standard localization for hospitalized ischemic stroke and supports validity in differentiating posterior versus anterior circulation. At a more granular vascular level, the location reliability was excellent, although limited data were available for some subcodes.

An analytical overview of the composition and characteristics of China's food safety standards.

This paper discusses the framework of China's food safety standards and provides a brief overview of the problems and developmental characteristics of food safety in China. The composition and characteristics of China's food safety standards are revealed by an analysis of the changes in China's general food standards, an overview of the characteristics of the hygiene requirements in the production and operation process, and an introduction to food product and test method standards. In conclusion, Chinese food safety standards are still being improved, but they must also be effectively implemented and followed up in real time in order to continuously improve the quality of food and reduce food safety incidents. © 2024 Society of Chemical Industry.

Inhibitors and facilitators of compliance with professional ethics standards: nurses' perspective.

INTRODUCTION: The clinical practices of nurses should be in accordance with the principles of professional ethics. Respecting professional ethics principles depends on several factors. The present study was conducted to investigate the effective inhibitors and facilitators in compliance with professional ethics and their importance from the nurses' perspective. METHODS: During this cross-sectional descriptive study, 452 nurses were included by the census sampling method. The data were collected via the "inhibitors of compliance with professional ethics standards by the nurses' perspective" and "facilitators of compliance with professional ethics standards by the nurses' perspective" questionnaires. Additionally, by designing the "open-ended question" section, other inhibiting and facilitating factors of professional ethics standards from the nurses' perspective were investigated. The data were analyzed using descriptive and inferential statistics (Wilcoxon signed ranks test). RESULTS: The individual care-related dimension as a facilitator had the highest mean score compared to the other dimensions (76.62 ± 4.92). Furthermore, seven items in the inhibitor section, 19 items in the facilitator section had higher scores. Among them, there were seven items in common. Strong or weak belief in compliance with ethical issues had the highest mean scores in the role of facilitator and inhibitor (90.54 ± 12.13 and 89.54 ± 14.88, respectively). CONCLUSION: Strong or weak belief in compliance with ethical issues was the most important inhibitor and facilitator from the nurses' perspective, which makes it necessary to examine individual beliefs about ethical issues among applicants to enter the nursing profession.

Between mandatory and aspirational ethics in nursing codes: a case study of the Italian nursing code of conduct.

BACKGROUND: Over the years, national and international nurses' organisations have drawn up Codes of Conduct and Codes of Ethics. A new differentiation has emerged over time between mandatory and aspirational approaches underlying how nurses can be supported by documents with rules to be respected (mandatory ethics) or by incentives (aspirational ethics). However, to date, no research has applied these approaches to analyse available Codes and to identify which approach are predominantly used. METHODS: In this case study, the Italian Nursing Code of Conduct (NCC), published in 2019, composed of 53 articles distributed in eight chapters, was first translated, and then analysed using a developed matrix to identify the articles that refer to mandatory or aspirational ethics. A nominal group technique was used to minimise subjectivity in the evaluation process. RESULTS: A total of 49 articles addressing the actions of the individual nurse were considered out of 53 composing the NNC. Articles were broken down into 97 units (from one to four for each article): 89 units (91.8%) were attributed to a unique category, while eight (8.2%) to two categories according to their meaning. A total of 38 units (39.2%) were categorised under the mandatory ethics and 58 (59.8%) under the aspirational ethics; however, one (1.0%) reflected both mandatory and aspirational ethics. CONCLUSIONS: According to the findings, the Italian Professional Body (FNOPI) has issued a modern code for nursing professionals in which an aspirational perspective is dominant offering a good example for other nursing organisations in the process of updating their codes when aimed at embodying an aspirational ethics.

Exploring a guide for codes of ethics for the development of ethical competence in Iranian nursing students: a systematic review and meta-synthesis.

BACKGROUND: Improving the ethical competencies of nursing students, as an important dimension of professional competence, is a primary objective of nursing education. Thus, this study aimed to explore a guide for codes of ethics for the development of ethical competence among nursing students in the healthcare system of Iran. METHODS: This is a systematic review and meta-synthesis of qualitative studies conducted in the healthcare system of Iran. The review included studies published between January 1, 2000 and March 2024. We conducted a comprehensive search in various international and national databases, including Web of Science, PubMed, Embase, PsycINFO, Cochrane Library, CINAHL, Scopus, Barakatns, MagIran and SID. Initially, 86 qualitative studies were identified, and after a meticulous screening process, 39 studies were carefully reviewed. Finally, 10 qualitative studies were selected for analysis. The meta-synthesis employed an interpretive approach by thematic synthesis. RESULTS: Based on our results, four main themes and 10 categories, along with summarized codes, were extracted as crucial elements of the codes of ethics for the professional competence of Iranian nursing students. The main themes identified were knowledge, standards, experiences, and attitudes (KSEA). CONCLUSIONS: The concept of codes of ethics for developing professional competencies in Iranian nursing students was detected as a multidimensional concept with four major areas. By emphasizing the rights of clients and the standardization of nursing practice, this set of ethical codes can contribute to preventing clinical errors and legal issues at hospitals and educational settings. Furthermore, it fosters a positive environment that encourages professional behaviors among nursing students. Nursing students, as future nurses, should apply codes of ethics when facing emerging ethical challenges. Nurse educators have a crucial role in providing students with the necessary preparation and guidance during their professional socialization process in nursing schools.

Political action in nursing and medical codes of ethics.

Political action has a long history in the health workforce. There are multiple historical examples, from civil disobedience to marches and even sabotage that can be attributed to health workers. Such actions remain a feature of the healthcare community to this day; their status with professional and regulatory bodies is far less clear, however. This has created uncertainty for those undertaking such action, particularly those who are engaged in what could be termed 'contentious' forms of action. This study explored how advocacy and activism were presented in nursing and medical codes of ethics, comparing disciplinary and temporo-spatial differences to understand how such action may be promoted or constrained by codes. The data for this study comes from 217 codes of ethics. Because of the size of the corpus and to facilitate analysis, natural language processing was utilised, which allowed for an automated exploration of the data and for comparisons to be drawn between groups. This was complemented by a manual search and contextualisation of the data. While there were noticeable differences between medical and nursing codes, overall, advocacy, activism and even politics were rarely discussed explicitly in most codes. When such action was spoken about, this was often vague and imprecise with codes speaking of 'political action' and 'advocacy' in general terms. While some codes were far more forthright in what they meant about advocacy or broader political action (i.e., Nursing codes in Denmark, Norway, Canada) more forceful language that spoke in specific terms or in terms of oppositional or specific actions (e.g., civil disobedience or marches) was almost completely avoided. These results are discussed in relation to the broader literature on codes and the normative questions they raise, namely whether such action should be included in codes of ethics at all.

Nursing vaccine mandates: Ethically justified, an infringement on autonomy, or both?

After almost a year and a half of the COVID-19 pandemic, many healthcare institutions in the United States announced that they would mandate COVID-19 vaccination, with medical and religious exceptions, as a term of employment. The mandates resulted in widely publicized protests from hospital staff, including some nurses, who argued that these medical institutions violated the ethical principle of autonomy. As the world enters the "post-pandemic period," decisions such as these, made during times of crisis, must be reviewed to provide clarity for when the next pandemic occurs. In this paper, we support the argument that such mandates are ethically justifiable. We explore the framework of objections that were brought forward by dissenters of this vaccine mandate. Next, we provide an analysis of conflicting ethical principles present when such mandates were deployed. Utilizing the American Nurses Association's Code of Ethics for Nurses, notably provisions 2, 3, and 6 we argue that it is an ethical duty of the nurse to be vaccinated. Specifically, we turn to provision two, which most explicitly underscores the necessity of vaccination as a function of the nurse's primary commitment to the patient. Next, we highlight the International Council of Nurses Code of Ethics which provides similar guidance internationally. Finally, we examine the applicability of the principles of public health, care ethics, and the nursing role as frameworks to underpin such mandates both for the current and for potential future pandemics, arguing that the nurse's ethical duty to be vaccinated spans these contexts.

Use and impact of the ANA Code: a scoping review.

Adherence to professional ethics in nursing is fundamental for high-quality ethical care. However, analysis of the use and impact of nurses' codes of ethics as a part of professional ethics is limited. To fill this gap in knowledge, the aim of our review was to describe the use and impact of the Code of Ethics for Nurses with Interpretive Statements published by the American Nurses Association as an example of one of the earliest and most extensive codes of ethics for nurses with their interpretative statements and constituting a strong basis for the International Council of Nurses' Code of Ethics for Nurses. We based our review on previous literature using a scoping review method. We included both non-scientific and scientific publications to provide an analysis of codes of ethics which can be utilized in development and revision of other nurses' codes of ethics. In the searches, we used CINAHL and PubMed databases limiting publications to texts with a connection to the Code of Ethics for Nurses published from January 2001 to November 2022 and written in English. Searches yielded 1739 references, from which 785 non-scientific and 71 scientific publications were included for analysis of the data. Although non-scientific and scientific publications addressed different number of categories, the results indicated that in the both groups the use and impact focused on professional ethics, nursing practice, and work environment and less on education, research, or social health issues. Nurses' ethical standards were not addressed in non-scientific publications, and clinical issues and leadership were not in focus in scientific publications. To increase evidence-based knowledge of the impact of codes of ethics additional research is needed. Good scientific conduct was followed.