How Should Health Care Respond to Threats Antimicrobial Resistance Poses to Workers?

Antimicrobial resistance (AMR) is a looming pandemic whose poor health outcomes are unlikely to be equitably distributed. This article focuses on intersections between AMR and inequities in health care workplaces in the United States and identifies the following as key problems: lack of published data on task-specific occupational health risks related to colonization and infection with antimicrobial-resistant pathogens, limited scientific literature reporting on race and ethnicity, and poor access to infection control educational opportunities for minoritized health care workers. This article argues that an equitable approach to remediating these problems requires improving surveillance and expanding research on how AMR is likely to influence health outcomes among members of the US-based health care workforce.

Using ACGME General Surgery Milestones to Define the Competent Foundational Surgical Resident.

OBJECTIVE: In transitioning to competency-based surgical training, the need to clearly define competency is paramount. The purpose of this study is to define the well-prepared foundational resident using the ACGME General Surgery Milestones as our conceptual framework. DESIGN: Participants reflected on their expectations of a well-prepared resident at the end of PGY1, then assigned milestone levels reflecting this level of competence for General Surgery Milestones 1.0 and 2.0. Subcompetency scores were averaged among residents and faculty. The level of the well-prepared foundational resident was determined based on the highest level within one standard deviation of faculty, resident, and total group averages. SETTING: This took place during a dedicated education retreat at a single, large academic general surgery residency program. PARTICIPANTS: Key faculty stakeholders and a representative sample of residents (PGY 1-5) within our institution participated. RESULTS: Eight faculty and five residents completed Milestones 1.0 and 2.0 scoring. Mean scores between faculty and residents were compared. For 1.0, mean scores for Practice-Based Learning and Improvement 3 (PBLI 3) and Interpersonal Communication Skills 3 (ICS 3) were discernably lower for residents than for faculty (PBLI 3 1.3 (0.3) v 0.9 (0.2), p = 0.01; ICS3 1.6 (0.6) v 1.1 (1), p = 0.01). Scores of 2.0 were comparable across all subcompetency domains. With this broad agreement, Milestone-based competency standards were determined. Descriptive narratives of the KSAs were created for each subcompetency, combining the determined Milestones 1.0 and 2.0 levels. CONCLUSIONS: We were able to clearly define the competent foundational resident using the ACGME Milestones as a conceptual framework. These Milestone levels reflect the culture and expectations in our department, providing a foundation upon which to build a program of assessment. This methodology can be readily replicated in other programs to reflect specific expectations of the program within the larger ACGME frameworks of competency.

Examining the relation between bilingualism and age of symptom onset in frontotemporal dementia.

Bilingualism is thought to confer advantages in executive functioning, thereby contributing to cognitive reserve and a later age of dementia symptom onset. While the relation between bilingualism and age of onset has been explored in Alzheimer's dementia, there are few studies examining bilingualism as a contributor to cognitive reserve in frontotemporal dementia (FTD). In line with previous findings, we hypothesized that bilinguals with behavioral variant FTD would be older at symptom onset compared to monolinguals, but that no such effect would be found in patients with nonfluent/agrammatic variant primary progressive aphasia (PPA) or semantic variant PPA. Contrary to our hypothesis, we found no significant difference in age at symptom onset between monolingual and bilingual speakers within any of the FTD variants, and there were no notable differences on neuropsychological measures. Overall, our results do not support a protective effect of bilingualism in patients with FTD-spectrum disease in a U.S. based cohort.

Race and ethnicity as risk factors for colonization and infection with key bacterial pathogens: a scoping review.

Background: Racial and ethnic disparities in infectious disease burden have been reported in the USA and globally, most recently for COVID-19. It remains unclear whether such disparities also exist for priority bacterial pathogens that are increasingly antibiotic-resistant. We conducted a scoping review to summarize published studies that report on colonization or community-acquired infection with pathogens among different races and ethnicities. Methods: We conducted an electronic literature search of MEDLINE®, Daily, Global Health, Embase, Cochrane Central, and Web of Science from inception to January 2022 for eligible observational studies. Abstracts and full-text publications were screened in duplicate for studies that reported data for race or ethnicity for at least one of the pathogens of interest. Results: Fifty-four observational studies in 59 publications met our inclusion criteria. Studies reported results for Enterobacterales, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus, and were conducted in Australia, Brazil, Israel, New Zealand, and USA. USA studies most often examined Black and Hispanic minority groups with studies regularly reporting a higher risk of these pathogens in Black persons and mixed results for Hispanic persons. Ethnic minority groups (e.g. Bedouins in Israel, Aboriginals in Australia) were often reported to be at a higher risk in other countries. Conclusion: Sufficient evidence was identified in this scoping review justifying future systematic reviews and meta-analyses evaluating the relationship between community-acquired pathogens and race and ethnicity. However, we noted that only a fraction of studies reported data stratified by race and ethnicity, highlighting a substantial gap in the literature.

Socioeconomic status and the risk for colonization or infection with priority bacterial pathogens: a global evidence map.

Low socioeconomic status (SES) is thought to exacerbate risks for bacterial infections, but global evidence for this relationship has not been synthesized. We systematically reviewed the literature for studies describing participants' SES and their risk of colonization or community-acquired infection with priority bacterial pathogens. Fifty studies from 14 countries reported outcomes by participants' education, healthcare access, income, residential crowding, SES deprivation score, urbanicity, or sanitation access. Low educational attainment, lower than average income levels, lack of healthcare access, residential crowding, and high deprivation were generally associated with higher risks of colonization or infection. There is limited research on these outcomes in low- and middle-income countries (LMICs) and conflicting findings regarding the effects of urbanicity. Only a fraction of studies investigating pathogen colonization and infection reported data stratified by participants' SES. Future studies should report stratified data to improve understanding of the complex interplay between SES and health, especially in LMICs.

COS-PPA: protocol to develop a core outcome set for primary progressive aphasia.

INTRODUCTION: The term primary progressive aphasia (PPA) describes a group of language-led dementias. Disease-modifying treatments that delay, slow or reverse progression of PPA are currently lacking, though a number of interventions to manage the symptoms of PPA have been developed in recent years. Unfortunately, studies exploring the effectiveness of these interventions have used a variety of different outcome measures, limiting comparability. There are more constructs, apart from word retrieval, that are important for people with PPA that have not received much attention in the research literature. Existing core outcome sets (COS) for dementia and non-progressive aphasia do not meet the needs of people with PPA, highlighting a need to develop a specific COS for PPA. METHODS AND ANALYSIS: This protocol describes a three-stage study to identify a COS for PPA interventions in research and clinical practice. The stage 1 systematic review will identify existing speech, language and communication measures used to examine the effectiveness of interventions for PPA in the research literature. Employing a nominal group technique, stage 2 will identify the most important outcomes for people with PPA and their families. The data collected in stages 1 and 2 will be jointly analysed with the project PPI group and will inform the stage 2 modified Delphi consensus study to identify a core outcome measurement set for PPA among a range of research disciplines undertaking intervention studies for people with PPA. ETHICS AND DISSEMINATION: Ethical approval for stage 2 of the study has been sought individually in each country at collaborating institutions and is stated in detail in the manuscript. Stage 3 has been granted ethical approval by the Chairs of UCL Language and Cognition Department Ethics, Project ID LCD-2023-06. Work undertaken at stages 1, 2 and 3 will be published in open-access peer-reviewed journal articles and presented at international scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42022367565.

A quality of care assessment for women of childbearing potential with epilepsy in Bhutan: An observational study.

BACKGROUND & OBJECTIVE: In lower-middle income countries such as Bhutan, the treatment gap for epilepsy is over 50% as compared to a treatment gap of less than 10% in high-income countries. We aim to analyze the quality of epilepsy care for women of childbearing potential in Bhutan using the Quality Indicators in Epilepsy Treatment (QUIET) tool, and to assess the usefulness of the tool's section for women with active epilepsy (WWE) in the Bhutanese setting. METHODS: A prospective convenience cohort was enrolled in Thimphu, Paro, Punakha, and Wangdue, Kingdom of Bhutan, in 2022. Bhutanese women of childbearing potential at the time of enrollment (18-44 years old) were evaluated for the diagnosis of active epilepsy and underwent a structured survey-based interview with Bhutanese staff. Participants were surveyed on their epilepsy, pregnancy, and antiseizure medicine (ASM) histories. The clinical history and quality of epilepsy care of adult WWE were assessed using a section of the QUIET tool for women, an instrument originally developed by the U.S. Department of Veterans Affairs to analyze the quality of epilepsy care for American adults. RESULTS: There were 82 Bhutanese WWE of childbearing potential, with mean age of 30.6 years at enrollment (range 18-44, standard deviation (SD) 6.6) and mean age of 20.3 years at epilepsy diagnosis (range 3-40, SD 8.0)). 39 % (n = 32) had a high school or above level of education, and 42 % (n = 34) were employed. 35 % (n = 29) reported a seizure within the prior week, and 88 % (n = 72) reported a seizure within the prior year. 49 % (n = 40) of participants experienced > 100 lifetime seizures. All but one participant took antiseizure medications (ASMs). At enrollment, participants presently took no (n = 1), one (n = 3), two (n = 37), three (n = 25), four (n = 11), or over five (n = 5) ASMs. The most common ASMs taken were levetiracetam (n = 40), phenytoin (n = 27), carbamazepine (n = 23), phenobarbital (n = 22), and sodium valproate (n = 20). 61 % of all WWE took folic acid. Of the 40 previously pregnant WWE, eight (20 %) took folic acid during any time of their pregnancy. 35 % (n = 29) used betel nut (doma, quid) and 53 % (n = 21) of pregnant WWE used betel nut during pregnancy. CONCLUSIONS: Based on data about WWE participants' ASM, supplement, and substance use, our study identified the high use of first generation ASMs (including valproate), frequently in polytherapy, and betel nut use as treatment gaps in women of childbearing potential age with active epilepsy in Bhutan. To address these gaps for locations such as Bhutan, we propose modifications to the QUIET tool's "Chronic Epilepsy Care for Women" section.

The freeze-avoiding mountain pine beetle (Dendroctonus ponderosae) survives prolonged exposure to stressful cold by mitigating ionoregulatory collapse.

Insect performance is linked to environmental temperature, and surviving through winter represents a key challenge for temperate, alpine and polar species. To overwinter, insects have adapted a range of strategies to become truly cold hardy. However, although the mechanisms underlying the ability to avoid or tolerate freezing have been well studied, little attention has been given to the challenge of maintaining ion homeostasis at frigid temperatures in these species, despite this limiting cold tolerance for insects susceptible to mild chilling. Here, we investigated how prolonged exposure to temperatures just above the supercooling point affects ion balance in freeze-avoidant mountain pine beetle (Dendroctonus ponderosae) larvae in autumn, mid-winter and spring, and related it to organismal recovery times and survival. Hemolymph ion balance was gradually disrupted during the first day of exposure, characterized by hyperkalemia and hyponatremia, after which a plateau was reached and maintained for the rest of the 7-day experiment. The degree of ionoregulatory collapse correlated strongly with recovery times, which followed a similar asymptotical progression. Mortality increased slightly during extensive cold exposures, where hemolymph K+ concentration was highest, and a sigmoidal relationship was found between survival and hyperkalemia. Thus, the cold tolerance of the freeze-avoiding larvae of D. ponderosae appears limited by the ability to prevent ionoregulatory collapse in a manner similar to that of chill-susceptible insects, albeit at much lower temperatures. Based on these results, we propose that a prerequisite for the evolution of insect freeze avoidance may be a convergent or ancestral ability to maintain ion homeostasis during extreme cold stress.

Coding-complete genome sequences of two bovine viral diarrhea virus 1a isolates from Uruguay.

Bovine viral diarrhea virus (BVDV) is an economically relevant pathogen affecting cattle production and reproduction worldwide. We report the coding-complete sequences of two BVDV-1a subtype isolates, circulating in Uruguay.

Multifocal Hepatocellular Carcinoma in a Malayan Wreathed Hornbill (Rhyticeros undulatus).

A 30-year-old female intact Malayan wreathed hornbill (Rhyticeros undulatus) was presented for presumed nesting behavior, progressive anorexia, dropping food, and coelomic distension. A complete blood count and plasma biochemistry analysis revealed marked inflammation, severe electrolyte abnormalities, elevated liver enzyme activities and bile acids, and normal plasma iron concentrations. Radiographic images of the patient were consistent with hepatomegaly and loss of serosal detail in the coelomic cavity. A computed tomography study revealed multiple poorly contrast-enhancing hepatic nodules, hepatoperitoneal and intestinal peritoneal fluid and gas, and a contrast-enhancing mass in the ventral coelom. Cytologic samples of the liver were consistent with necrosis, and the coelomic effusion was characterized as an aseptic suppurative exudate. An exploratory coeliotomy was performed and biopsy samples of the liver and a mesenteric mass were histologically interpreted as a tubular carcinoma with metastasis to the liver and secondary portal hepatitis. Euthanasia was elected and multiple liver masses and a peripancreatic mass were identified on necropsy. Histopathological samples collected during the postmortem gross examination showed multiple well-demarcated hepatic masses consisting of neoplastic hepatocytes encapsulated by fibrous tissue and proliferation of dysplastic biliary ductules, as well as a peripancreatic heterophilic granuloma with adjacent pancreatic atrophy and ductular proliferation. Ultimately, the patient was diagnosed with multifocal hepatocellular carcinoma and chronic granulomatous and heterophilic pancreatitis, steatitis, and coelomitis with intralesional bacteria. Malignant hepatobiliary neoplasia has been poorly documented in hornbills despite high anecdotal incidence in this and other avian species predisposed to iron storage disease. This report illustrates clinical and pathological information, including advanced imaging, which could aid in the diagnosis of this condition in hornbills and other avian species.

Discriminating nonfluent/agrammatic and logopenic PPA variants with automatically extracted morphosyntactic measures from connected speech.

Morphosyntactic assessments are important for characterizing individuals with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard tests are subject to examiner bias and often fail to differentiate between nfvPPA and logopenic variant PPA (lvPPA). Moreover, relevant neural signatures remain underexplored. Here, we leverage natural language processing tools to automatically capture morphosyntactic disturbances and their neuroanatomical correlates in 35 individuals with nfvPPA relative to 10 healthy controls (HC) and 26 individuals with lvPPA. Participants described a picture, and ensuing transcripts were analyzed via part-of-speech tagging to extract sentence-related features (e.g., subordinating and coordinating conjunctions), verbal-related features (e.g., tense markers), and nominal-related features (e.g., subjective and possessive pronouns). Gradient boosting machines were used to classify between groups using all features. We identified the most discriminant morphosyntactic marker via a feature importance algorithm and examined its neural correlates via voxel-based morphometry. Individuals with nfvPPA produced fewer morphosyntactic elements than the other two groups. Such features robustly discriminated them from both individuals with lvPPA and HCs with an AUC of .95 and .82, respectively. The most discriminatory feature corresponded to subordinating conjunctions was correlated with cortical atrophy within the left posterior inferior frontal gyrus across groups (pFWE < .05). Automated morphosyntactic analysis can efficiently differentiate nfvPPA from lvPPA. Also, the most sensitive morphosyntactic markers correlate with a core atrophy region of nfvPPA. Our approach, thus, can contribute to a key challenge in PPA diagnosis.

Effects of breastfeeding on children's gut colonization with multidrug-resistant Enterobacterales in peri-urban Lima, Peru.

Children living in low-resource settings are frequently gut-colonized with multidrug-resistant bacteria. We explored whether breastfeeding may protect against children's incident gut colonization with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and Klebsiella, Enterobacter, or Citrobacter spp. (ESBL-KEC). We screened 937 monthly stool samples collected from 112 children aged 1-16 months during a 2016-19 prospective cohort study of enteric infections in peri-urban Lima. We used 52,816 daily surveys to examine how exposures to breastfeeding in the 30 days prior to a stool sample were associated with children's risks of incident gut-colonization, controlling for antibiotic use and other covariates. We sequenced 78 ESBL-Ec from 47 children to explore their diversity. Gut-colonization with ESBL-Ec was increasingly prevalent as children aged, approaching 75% by 16 months, while ESBL-KEC prevalence fluctuated between 18% and 36%. Through 6 months of age, exclusively providing human milk in the 30 days prior to a stool sample did not reduce children's risk of incident gut-colonization with ESBL-Ec or ESBL-KEC. From 6 to 16 months of age, every 3 additional days of breastfeeding in the prior 30 days was associated with 6% lower risk of incident ESBL-Ec gut-colonization (95% CI: 0.90, 0.98, p = .003). No effects were observed on incident ESBL-KEC colonization. We detected highly diverse ESBL-Ec among children and few differences between children who were predominantly breastfed (mean age: 4.1 months) versus older children (10.8 months). Continued breastfeeding after 6 months conferred protection against children's incident gut colonization with ESBL-Ec in this setting. Policies supporting continued breastfeeding should be considered in efforts to combat antibiotic resistance.

Presence and Relevance of Myocardial Bridge in LAD-PCI of CTO and Non-CTO Lesions.

BACKGROUND: Intravascular ultrasound (IVUS) studies show that one-quarter of left anterior descending (LAD) arteries have a myocardial bridge. An MB may be associated with stent failure when the stent extends into the MB. OBJECTIVES: The aim of this study was to investigate: 1) the association between an MB and chronic total occlusion (CTO) in any LAD lesions; and 2) the association between an MB and subsequent clinical outcomes after percutaneous coronary intervention in LAD CTOs. METHODS: A total of 3,342 LAD lesions with IVUS-guided percutaneous coronary intervention (280 CTO and 3,062 non-CTO lesions) were included. The primary outcome was target lesion failure (cardiac death, target vessel myocardial infarction, definite stent thrombosis, and ischemic-driven target lesion revascularization). RESULTS: An MB by IVUS was significantly more prevalent in LAD CTOs than LAD non-CTOs (40.4% [113/280] vs 25.8% [789/3,062]; P < 0.0001). The discrepancy in CTO length between angiography and IVUS was greater in 113 LAD CTOs with an MB than 167 LAD CTOs without an MB (6.0 [Q1, Q3: 0.1, 12.2] mm vs 0.2 [Q1, Q3: -1.4, 8.4] mm; P < 0.0001). Overall, 48.7% (55/113) of LAD CTOs had a stent that extended into an MB after which target lesion failure was significantly higher compared to a stent that did not extend into an MB (26.3% vs 0%; P = 0.0004) or compared to an LAD CTO without an MB (26.3% vs 9.6%; P = 0.02). CONCLUSIONS: An MB was more common in LAD CTO than non-CTO LAD lesions. If present, approximately one-half of LAD CTOs had a stent extending into an MB that, in turn, was associated with worse outcomes.

Computer-Based Naming Treatment for Semantic Variant Primary Progressive Aphasia With History of Traumatic Brain Injury: A Single-Case Experimental Design.

PURPOSE: The purpose of this study was to investigate the effectiveness of a self-administered naming treatment for one individual, B.N., presenting with semantic variant primary progressive aphasia (svPPA) and a history of traumatic brain injury (TBI). METHOD: Naming treatment included components of Lexical Retrieval Cascade Treatment and was self-administered using an adaptive spaced retrieval software, Anki. Using a multiple-baseline, single-case experimental design, naming accuracy probes were taken during pretreatment, treatment, posttreatment, and follow-up (through 12 months) for 60 trained words and 10 untrained words. Item-level Bayesian generalized mixed-effects models were used to estimate (a) the treatment effect for trained words, (b) change in untrained words, and (c) maintenance of treatment effects from posttreatment to each subsequent follow-up. RESULTS: Statistical analyses revealed that a gain of 35 out of 60 trained words (35.3; 90% CI [30.6, 39.5]) was directly attributable to treatment. Following treatment, evidence of generalization to untrained words was not observed. During the follow-up period, there was gradual decline in naming accuracy of trained items. CONCLUSIONS: The positive treatment results reported here support the use of self-administered naming treatments for those with svPPA and a history of TBI. Although the utility of this treatment approach is constrained by patient factors including motivation, self-administered naming treatments represent a unique opportunity to expand access to speech-language intervention for people with svPPA, including those with concomitant diagnoses. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25119080.

Adaptive sequential surveillance with network and temporal dependence.

Strategic test allocation is important for control of both emerging and existing pandemics (eg, COVID-19, HIV). It supports effective epidemic control by (1) reducing transmission via identifying cases and (2) tracking outbreak dynamics to inform targeted interventions. However, infectious disease surveillance presents unique statistical challenges. For instance, the true outcome of interest (positive infection status) is often a latent variable. In addition, presence of both network and temporal dependence reduces data to a single observation. In this work, we study an adaptive sequential design, which allows for unspecified dependence among individuals and across time. Our causal parameter is the mean latent outcome we would have obtained, if, starting at time t given the observed past, we had carried out a stochastic intervention that maximizes the outcome under a resource constraint. The key strength of the method is that we do not have to model network and time dependence: a short-term performance Online Super Learner is used to select among dependence models and randomization schemes. The proposed strategy learns the optimal choice of testing over time while adapting to the current state of the outbreak and learning across samples, through time, or both. We demonstrate the superior performance of the proposed strategy in an agent-based simulation modeling a residential university environment during the COVID-19 pandemic.

Cognitive stimulation as a mechanism linking socioeconomic status and neural function supporting working memory: a longitudinal fMRI study.

Childhood experiences of low socioeconomic status are associated with alterations in neural function in the frontoparietal network and ventral visual stream, which may drive differences in working memory. However, the specific features of low socioeconomic status environments that contribute to these disparities remain poorly understood. Here, we examined experiences of cognitive deprivation (i.e. decreased variety and complexity of experience), as opposed to experiences of threat (i.e. violence exposure), as a potential mechanism through which family income contributes to alterations in neural activation during working memory. As part of a longitudinal study, 148 youth between aged 10 and 13 years completed a visuospatial working memory fMRI task. Early childhood low income, chronicity of low income in early childhood, and current income-to-needs were associated with task-related activation in the ventral visual stream and frontoparietal network. The association of family income with decreased activation in the lateral occipital cortex and intraparietal sulcus during working memory was mediated by experiences of cognitive deprivation. Surprisingly, however, family income and deprivation were not significantly related to working memory performance, and only deprivation was associated with academic achievement in this sample. Taken together, these findings suggest that early life low income and associated cognitive deprivation are important factors in neural function supporting working memory.

Evidence that Ophiostomatoid Fungal Symbionts of Mountain Pine Beetle Do Not Play a Role in Overcoming Lodgepole Pine Defenses During Mass Attack.

Mountain pine beetle (MPB; Dendroctonus ponderosae Hopkins) is a devastating forest insect pest that has killed millions of hectares of pines in western North America over the past two decades. Like other bark beetles, MPB vectors ophiostomatoid fungal species, some of which are pathogenic to host pine species. The phytopathogenicity of these fungal symbionts has sparked considerable debate regarding their role in facilitating MPB attack success. We tested the hypothesis that MPB ophiostomatoid fungal associates like Grosmannia clavigera (Robinson-Jeffrey and Davidson) Zipfel, de Beer and Wingfield contribute to overwhelming host defenses during MPB mass attack. We compared responses of mature lodgepole pine (Pinus contorta Dougl. ex Loud. var. latifolia Engelm.) trees growing in natural stands that were mass attacked by MPB with those inoculated with G. clavigera by examining host defense hormones, secondary metabolites, and gene expression profiles. The jasmonate and ethylene signatures of necrotrophic pathogen-triggered response were identified in G. clavigera-inoculated trees, but only the jasmonate signature of a herbivore-triggered response was measured in MPB-attacked trees. Several G. clavigera-induced changes in pine phenolic metabolite profiles and phenolic biosynthesis gene expression patterns were absent in MPB-attacked pines. These findings indicate that ophiostomatoid fungi like G. clavigera are not a major factor in overwhelming host defenses during MPB mass attack. Instead, fungal pathogenicity likely is more important in aiding MPB colonization and development within the host tree. Phenolics appear to play a larger role in the host response to G. clavigera than to MPB, although phenolics may also influence MPB feeding and behavior. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion.

RNA-binding proteins (RBPs) modulate alternative splicing outcomes to determine isoform expression and cellular survival. To identify RBPs that directly drive alternative exon inclusion, we developed tethered function luciferase-based splicing reporters that provide rapid, scalable and robust readouts of exon inclusion changes and used these to evaluate 718 human RBPs. We performed enhanced cross-linking immunoprecipitation, RNA sequencing and affinity purification-mass spectrometry to investigate a subset of candidates with no prior association with splicing. Integrative analysis of these assays indicates surprising roles for TRNAU1AP, SCAF8 and RTCA in the modulation of hundreds of endogenous splicing events. We also leveraged our tethering assays and top candidates to identify potent and compact exon inclusion activation domains for splicing modulation applications. Using these identified domains, we engineered programmable fusion proteins that outperform current artificial splicing factors at manipulating inclusion of reporter and endogenous exons. This tethering approach characterizes the ability of RBPs to induce exon inclusion and yields new molecular parts for programmable splicing control.