Scanning Electron Microscopy.

Scanning electron microscopy (SEM) remains distinct in its ability to allow topographical visualization of structures. Key elements to consider for successful examination of biological specimens include appropriate preparative and imaging techniques. Chemical processing induces structural artifacts during specimen preparation, and several factors need to be considered when selecting fixation protocols to reduce these effects while retaining structures of interest. Particular care for proper dehydration of specimens is essential to minimize shrinkage and is necessary for placement under the high-vacuum environment required for routine operation of standard SEMs. Choice of substrate for mounting and coating specimens can reduce artifacts known as charging, and a basic understanding of microscope settings can optimize parameters to achieve desired results. This article describes fundamental techniques and tips for routine specimen preparation for a variety of biological specimens, preservation of labile or fragile structures, immune-labeling strategies, and microscope imaging parameters for optimal examination by SEM. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Chemical preparative techniques for preservation of biological specimens for examination by SEM Alternate Protocol 1: Practical considerations for the preparation of soft tissues Alternate Protocol 2: Removal of debris from the exoskeleton of invertebrates Alternate Protocol 3: Fixation of colonies grown on agar plates Alternate Protocol 4: Stabilization of polysaccharide structures with alcian blue and lysine Alternate Protocol 5: Preparation of non-adherent particulates in solution for SEM Support Protocol 1: Application of thin layer of adhesive on substrate to improve adherence Support Protocol 2: Poly-L-lysine coating specimen substrates for improved adherence Support Protocol 3: Microwave processing of biological specimens for examination by SEM Basic Protocol 2: Critical point drying of specimens Alternate Protocol 6: Chemical alternative to critical point drying Basic Protocol 3: Sputter coating Alternate Protocol 7: Improved bulk conductivity through "OTOTO" Basic Protocol 4: Immune-labeling strategies Alternate Protocol 8: Immune-labeling internal antigens with small gold probes Alternate protocol 9: Quantum dot or fluoronanogold preparations for correlative techniques Basic Protocol 5: Exposure of internal structures by mechanical fracturing Basic Protocol 6: Exposure of internal structures of tissues by fracturing with liquid nitrogen Basic Protocol 7: Anaglyph production from stereo pairs to produce 3D images.

Evaluation of Ergot Resistance in Hard Red Spring Wheat in North Dakota.

Higher levels of ergot (Claviceps purpurea (Fr.)) Tul. were reported in North Dakota hard red spring wheat (HRSW) in 2018, leading to questions pertaining to management and cultivar resistance. To better understand pathogen and HRSW cultivar responses, greenhouse experiments were conducted from 2020 to 2021 to evaluate aggressiveness of nine C. purpurea isolates and ergot resistance in 21 HRSW cultivars. Results from the aggressiveness assay indicated significant cultivar by isolate interactions for total weight of sclerotia produced and ergot incidence. Mean data across all cultivar by isolate combinations suggested isolates CC-3 and IA-Tim were the most aggressive and subsequently used in ergot resistance experiments. Results from ergot resistance screening indicated none of the HRSW cultivars were immune to C. purpurea as all cultivars produced sclerotia. However, differences in ergot incidence, kernel incidence, aborted kernel incidence, total sclerotia weight, sclerotia length, and sclerotia width occurred among cultivars. Both 'ND-Frohberg' and 'TCG-Spitfire' had the lowest ergot incidence values and were among the lowest in total sclerotia weight. 'Waldron' and 'LCS-Trigger' had the highest ergot incidence and the highest total sclerotia weight. Given that most concerns with ergot occur post-harvest, we suggest two categories to describe ergot resistance: host resistance (fate of inoculation for a stigma) and logistical resistance (size characteristics of a sclerotium that influence its ability to remain with a seed lot after harvest and cleaning). This research provides a strong foundation on our understanding of HRSW resistance to ergot that will influence variety decisions in ergot-prone areas in North Dakota.

Effect of fungicide and timing of application on management of Phoma black stem of cultivated sunflowers in the United States.

Phoma black stem (PBS), caused by Phoma macdonaldii Boerema (teleomorph Leptosphaeria lindquistii Frezzi), is the most common stem disease of sunflower (Helianthus annuus L.) in the Northern Great Plains (NGP) region of the United States (US). However, the impact of PBS on sunflower yield in the US is unclear, and a near complete absence of information on the impact of fungicides on disease management exists. The objectives of this study were to determine the impact of PBS on sunflower yield, the efficacy of available fungicides, the optimal fungicide application timing, and the economic viability of fungicides as a management tool. Fungicide timing efficacy was evaluated by applying single and/or sequential applications of pyraclostrobin fungicide at three sunflower growth stages in ten field experiments between 2017 and 2019. Efficacy of ten fungicides from FRAC groups 3, 7, and 11 were evaluated in four field experiments between 2018 and 2019. The impact of treatments on PBS were evaluated by determination of incidence, severity, maximum lesion height (MLH), disease severity index (DSI) and harvested yield. Nine of the ten fungicides evaluated, and all fungicide timings that included an early bud application, resulted in disease reductions when compared to the non-treated controls. The DSI was negatively correlated to sunflower yield in high-yield environments (p=0.0004; R2 = 0.3425), but not in low- or moderate- yield environments. Although FRAC 7 fungicides were generally most efficacious, the sufficient efficacy and lower cost of FRAC 11 fungicides make them more economically viable in high-yielding environments at current market conditions.

The Impact of Measurement-Based Care in Psychiatry: An Integrative Review.

BACKGROUND: The quality of mental health treatment has not progressed to the same extent as physical health treatment. Suboptimal mental health outcomes may be attributed to the lack of a systematic approach to tracking and measuring patient progress. In psychiatry, Measurement-Based Care (MBC) offers an objective, systematic approach to monitor clinical progress, evaluate treatment efficacy, and inform clinical decisions, yet remains seldom used in daily practice. AIMS: To identify the clinical impact of using MBC in psychiatry. METHODS: Using the Johns Hopkins Nursing Evidence-Based Practice Model as a guideline, this integrative review focused on the research query, "What is the clinical impact of Measurement-Based Care when treating patients with mental illness?" RESULTS: A total of nine articles met the inclusion criteria for this integrative review. The articles ranged from 2008 to 2021. The following themes were identified from the analysis of these articles: (1) the clinical impact of MBC, (2) provider attitudes about MBC, and (3) barriers to MBC implementation. CONCLUSIONS: MBC, augmenting usual standard care, provides an objective, systematic approach using quantifiable data to monitor symptom severity and treatment effectiveness. This review highlights the clinical benefits of MBC, including increased remission rates, lower risk of relapse, improved medication adherence, and strengthening the therapeutic alliance. Although this review provides an overview of the benefits of MBC in psychiatry, there remains a substantial practice gap warranting further investigation. Strategies must be developed to address barriers at the individual and organizational levels which impede the successful adoption of MBC.

Increase of Bacterial Leaf Streak in Hard Red Spring Wheat in North Dakota and Yield Loss Considerations.

Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa, has increased in both prevalence and severity in the major hard red spring wheat (HRSW)-producing state North Dakota. The disease is readily observed after flag leaf emergence and can quickly lead to defoliation and severe yield loss. The objectives of this research were to document the prevalence and incidence of BLS in North Dakota and provide estimations of yield and economic losses. Trained field scouts determined the incidence and prevalence of BLS in ND on HRSW plants between Feekes growth stage (FGS) 8 and FGS 11.2 from 2015 to 2021, and data were used to determine BLS-affected hectares. Yield data in combination with BLS ratings were obtained from HRSW performance trials to estimate the impact of BLS on yield. The combination of variety identity, hectarage data, BLS-affected hectarage estimates, and yield loss estimates was used to estimate economic losses from BLS in 2019 and 2020. Our data suggest that BLS-affected hectares ranged from 747 to 141,680 between 2015 and 2021. Yield loss was observed at multiple HRSW performance trial locations, with estimated yield losses as high as 60% on susceptible varieties. The amount of BLS-affected hectares was the highest in 2019 and 2020, and direct economic losses for North Dakota HRSW producers were estimated to be as high as $4.7 and $8.0 million, respectively. These data highlight the importance of BLS in HRSW and the need to procure resources for breeding efforts and grower education on management of BLS.

Considerations of Intersectionality for Older Adults with Palliative Care Needs in the Emergency Department: An Integrative Review.

Purpose of Review: We sought to identify current interventions, research, or non-research evidence that has direct or indirect consideration of intersectionality in the care of older adults in the emergency department (ED). An integrative review informed by Crenshaw's Theory of Intersectionality was conducted in accordance with Whittemore and Knafl's five-stage methodology. A rigorous review process determined appropriateness for inclusion, and articles were analyzed for areas related to direct or indirect relationship to intersectionality. Recent Findings: Older adults aged 60 and above in the United States (US) account for more than 20% of ED visits annually, and half of older adults will visit the ED in their last year of life. There has been a growing focus on adapting the ED to meet the palliative care needs of older adults, but relatively little consideration has been given to older adults' intersectional identities. Summary: Six articles were identified that provided indirect insights into the status of intersectionality in ED-based palliative care for older adults. Two areas of interest were identified: (1) intersectional elements or reference to such elements embedded within the studies; and (2) the challenges of adapting quantitative methodologies to incorporate variables and approaches that would allow for intersectional analysis. This review highlights areas for future research along with recommendations for adopting an intersectional framing into commonly used methodologies.

Cryo-EM structure of anchorless RML prion reveals variations in shared motifs between distinct strains.

Little is known about the structural basis of prion strains. Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register ß-sheet-based core. Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three ß-arches. However, detailed comparisons reveal variations in these shared structural topologies and other features. Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. This work demonstrates both common and divergent structural features of prion strains at the near-atomic level.

Learning by Exposure in the Visual System.

It is increasingly being understood that perceptual learning involves different types of plasticity. Thus, whereas the practice-based improvement in the ability to perform specific tasks is believed to rely on top-down plasticity, the capacity of sensory systems to passively adapt to the stimuli they are exposed to is believed to rely on bottom-up plasticity. However, top-down and bottom-up plasticity have never been investigated concurrently, and hence their relationship is not well understood. To examine whether passive exposure influences perceptual performance, we asked subjects to test their orientation discrimination performance around and orthogonal to the exposed orientation axes, at an exposed and an unexposed location while oriented sine-wave gratings were presented in a fixed position. Here we report that repetitive passive exposure to oriented sequences that are not linked to a specific task induces a persistent, bottom-up form of learning that is stronger than top-down practice learning and generalizes across complex stimulus dimensions. Importantly, orientation-specific exposure learning led to a robust improvement in the discrimination of complex stimuli (shapes and natural scenes). Our results indicate that long-term sensory adaptation by passive exposure should be viewed as a form of perceptual learning that is complementary to practice learning in that it reduces constraints on speed and generalization.

Capturing the value and core concepts of the Clinical Research Nurse.

Background: As nurses, we identify our profession as a caring one, but how does this identity translate from a conceptual definition, to real-world practice for the Clinical Research Nurse? Aim: To offer a novel, four-point conceptual model that encapsulates the Clinical Research Nurse's intrinsic value, active leadership, and direct contribution to high quality, person-centered, safe care, addressing current misperceptions of research nursing. Methods: This paper describes the provision of 'care', safely delivered by the Clinical Research Nurse through a four-point conceptual model and case-driven example. Discussion: Clinical research nursing is conceptualized within the domains of Care and Trust, Role, Impact, and Integration. The case example demonstrates real-world application of these domains and the expertise required to balance the complexities of clinical needs and research demands in a healthcare environment. Conclusions: This paper offers a mechanism for understanding the importance of the Clinical Research Nurse and their role in maintaining safety and a high-level view of the care arena. These reflections are considered with an international application for the role.

Facial and Vocal Markers of Schizophrenia Measured Using Remote Smartphone Assessments: Observational Study.

BACKGROUND: Machine learning-based facial and vocal measurements have demonstrated relationships with schizophrenia diagnosis and severity. Demonstrating utility and validity of remote and automated assessments conducted outside of controlled experimental or clinical settings can facilitate scaling such measurement tools to aid in risk assessment and tracking of treatment response in populations that are difficult to engage. OBJECTIVE: This study aimed to determine the accuracy of machine learning-based facial and vocal measurements acquired through automated assessments conducted remotely through smartphones. METHODS: Measurements of facial and vocal characteristics including facial expressivity, vocal acoustics, and speech prevalence were assessed in 20 patients with schizophrenia over the course of 2 weeks in response to two classes of prompts previously utilized in experimental laboratory assessments: evoked prompts, where subjects are guided to produce specific facial expressions and speech; and spontaneous prompts, where subjects are presented stimuli in the form of emotionally evocative imagery and asked to freely respond. Facial and vocal measurements were assessed in relation to schizophrenia symptom severity using the Positive and Negative Syndrome Scale. RESULTS: Vocal markers including speech prevalence, vocal jitter, fundamental frequency, and vocal intensity demonstrated specificity as markers of negative symptom severity, while measurement of facial expressivity demonstrated itself as a robust marker of overall schizophrenia symptom severity. CONCLUSIONS: Established facial and vocal measurements, collected remotely in schizophrenia patients via smartphones in response to automated task prompts, demonstrated accuracy as markers of schizophrenia symptom severity. Clinical implications are discussed.

Oncology Nursing Telephone Triage Workshop: Impact on Nurses' Knowledge, Confidence, and Skill.

BACKGROUND: Outpatient oncology nurses are responsible for symptom assessment/management and care coordination during telephone triage. Nursing telephone triage interventions can improve patient outcomes and clinical efficiency. Therefore, the lack of education and training in telephone triage can greatly impact patient care. OBJECTIVE: Using a prospective pretest/posttest design, we sought to determine if a telephone triage educational workshop would improve oncology nurses' knowledge, confidence, and skill over 12 weeks. INTERVENTION/METHODS: The educational intervention incorporated an online didactic lecture, group case scenario, and feedback on a virtual triage simulation. Evaluation was conducted before and after the intervention through an online, 13-item survey (knowledge and confidence) and simulation utilizing a 56-item checklist (skills). RESULTS: Thirteen oncology nurses were enrolled; 54% did not have telephone triage experience before this job. A total of 12 participants completed the workshop. From pretest to posttest, there was a median 1.0 out of 5.0 (interquartile range, 2.8) improvement in confidence (P = .008) and a 26.3% (interquartile range, 15.2) improvement in skills (P = .002). There was no difference in knowledge scores from pretest to posttest (P = .11). CONCLUSIONS: This workshop was associated with an improvement in oncology nurse confidence and skill, using telephone triage models. It benefits an existing process within the outpatient center and it highlights a new educational strategy that may optimize nursing practice and improve patient care and experience. IMPLICATIONS FOR PRACTICE: This workshop contributes to existing evidence of telephone triage models and nursing education. The findings can guide future research, nursing orientation, and educational activities within the field of nursing and telehealth.

HPV immunization among young adults (HIYA!) in family practice: A quality improvement project.

AIMS: Thousands of anogenital and oropharyngeal cancers every year might be prevented through increased receipt of vaccination against the human papillomavirus (HPV). This project aimed to (1) increase the rate of HPV vaccination status assessment, and (2) improve HPV vaccine initiation and completion rates among 18 to 26-year-old patients in the family practice setting. DESIGN: Quality improvement project, pre/post intervention design. METHODS: This project implemented the HIYA! (HPV Immunization among Young Adults) Intervention in a private sports and family practice in central New Jersey. HIYA! implemented 10 pre-, during, and post-visit outcome measures during every family medicine visit with an 18 to 26-year-old patient for HPV. Data collection involved retrospective chart review of every eligible patient during the 12-week implementation period from 17 August to 06 November 2020 and during the same 12-week control period in 2019. RESULTS/FINDINGS: One hundred sixteen charts from 2019 and 129 charts from 2020 were reviewed for assessment of HPV vaccination status and HPV vaccine initiation and/or completion. Multivariable logistic regression analysis demonstrated that participants in the control group were 84% less likely to be assessed for HPV vaccination status and were 91% less likely to initiate and complete HPV vaccination compared with the intervention group. CONCLUSION: This QI project found HIYA! to be an effective and feasible strategy to improve HPV vaccination rates among 18 to 26-year-old patients in a family practice setting. IMPACT: The human papillomavirus (HPV) is the most common sexually transmitted disease in the United States, and causes thousands of cancers annually. Although vaccination against HPV can prevent these cancers, vaccination rates remain low, particularly among young adults ages 18 to 26 years. The positive impact of HIYA! was evident based on its success despite the unique challenges presented during the implementation period due to the COVID-19 pandemic.

Changes in Nursing Students' Attitudes and Perceptions After Receipt of Enhanced Substance Use-Related Curricular Content.

BACKGROUND: Negative attitudes toward persons who use alcohol and other drugs contribute to suboptimal care. Nurses are in key roles to address the needs of this population, yet they lack the education needed to identify persons who may be at risk because of substance use and intervene accordingly. The purpose of this study was to evaluate the impact of a substance-use-related curriculum on nursing students' attitudes and therapeutic commitment for working with patients with alcohol- and drug-use-related problems. METHODS: Data were collected for four cohorts of 169 nursing students enrolled in a Master's Entry into Nursing program. Questionnaires included the Person-Centered Alcohol and Alcohol Problems Perception Questionnaire and the Drug and Drug Problems Perception Questionnaire, completed before and after completing the curriculum. Paired samples t test were used to examine pre/post differences for each measure's subscale. RESULTS: Four of the seven Person-Centered Alcohol and Alcohol Problems Perception Questionnaire subscales showing significant increases were role adequacy, role support, role legitimacy, and general perceptions. Four of the five Drug and Drug Problems Perception Questionnaire subscales showing significant increases were role adequacy, role support, job satisfaction, and role legitimacy; there was a significant change in role-related self-esteem, however, in a negative direction. CONCLUSIONS: This study adds to the growing evidence of the positive impact of providing evidence-based information and skill development, which enhance alcohol- and drug-related knowledge and competence for nurses entering professional practice.

Corrigendum to Older adult and family caregiver preferences for emergency department based-palliative care: An experience-based co-design study.

[This corrects the article DOI: 10.1016/j.ijnsa.2020.100016.].

Does the Length of Time to Complete an Online Program Matter?

Health care providers are challenged to meet the simultaneous demands of delivering clinical care and acquiring new information, especially in the context of the coronavirus disease 2019 pandemic, the opioid epidemic, and concurrent escalation in alcohol and other drug use. To address the gap in knowledge related to substance use, screening, brief intervention, and referral to treatment (SBIRT), a self-paced online educational program, was developed and delivered to 169 learners. Posttest knowledge scores increased for all learners and did not differ based on their pace of completion. Results indicated that this module provides a means for busy clinicians to increase their ability to manage substance use, even if their learning occurs in multiple sessions interrupted by other pressing demands. Future iterations of this course could further enhance clinical competency by addition of an online clinical simulation component. [J Contin Educ Nurs. 2021;52(11):505-510.].

Compelling Voices of Diversity, Equity, and Inclusion in Prelicensure Nursing Students: Application of the Cultural Humility Framework.

BACKGROUND: Diversity, equity, and inclusion are increasingly recognized as core values for guiding nursing education, practice, and research. The conceptual framework of cultural humility has been adapted in a variety of health care settings, fostering a culture of diversity, equity, and inclusion through openness, supportive interaction, self-awareness, self-reflection, and critique. PROBLEM: Nurse educators have the opportunity, but may find it challenging, to teach students about the changing landscape of health care and the populations we serve. APPROACH: This article describes the integration of the cultural humility framework into nursing curricula to teach principles of diversity, equity, and inclusivity. We provide a practical example of a diversity panel, with student and panelist reflections, exploring the intersectionality of experiences in health care and integration of personal accounts and perspectives. CONCLUSION: Dialogue about diversity, equity, and inclusion is essential for preparing future nurses to deliver culturally competent care and promote health equity.

High-resolution structure and strain comparison of infectious mammalian prions.

Within the extensive range of self-propagating pathologic protein aggregates of mammals, prions are the most clearly infectious (e.g., ∼109 lethal doses per milligram). The structures of such lethal assemblies of PrP molecules have been poorly understood. Here we report a near-atomic core structure of a brain-derived, fully infectious prion (263K strain). Cryo-electron microscopy showed amyloid fibrils assembled with parallel in-register intermolecular ß sheets. Each monomer provides one rung of the ordered fibril core, with N-linked glycans and glycolipid anchors projecting outward. Thus, single monomers form the templating surface for incoming monomers at fibril ends, where prion growth occurs. Comparison to another prion strain (aRML) revealed major differences in fibril morphology but, like 263K, an asymmetric fibril cross-section without paired protofilaments. These findings provide structural insights into prion propagation, strains, species barriers, and membrane pathogenesis. This structure also helps frame considerations of factors influencing the relative transmissibility of other pathologic amyloids.

Place of Death for Persons With and Without Cognitive Impairment in the United States.

BACKGROUND/OBJECTIVES: There is increasing recognition that place of death is an important component of quality of end-of-life care (EOLC) and quality of death. This study examined where older persons with and without cognitive impairment die in the United States, what factors contribute to place of death, and whether place of death influences satisfaction with EOLC. DESIGN: Cross-sectional secondary data analysis. SETTING: In-person interviews with community-dwelling proxy respondents. PARTICIPANTS: Data were collected from 1,500 proxies for deceased participants in the National Health and Aging Trends Study (NHATS), a nationally-representative sample of community-dwelling Medicare beneficiaries aged 65 and older. MEASUREMENTS: Study variables were obtained from the NHATS "last month of life" interview data. Survey weights were applied to all analyses. RESULTS: Persons with cognitive impairment (CI) most often died at home, while cognitively healthy persons (CHP) were equally likely to die at home or in a hospital. Persons with CI who utilized the Medicare Hospice Benefit were 14.5 times more likely to die at home than in a hospital, and 3.4 times more likely to die at home than a nursing home. CHP who use this benefit were over six times more likely to die at home than in a hospital, and more than twice as likely to die at home than a nursing home. Place of death for CHP was also associated with age and race. Proxies of persons with CI who died at home rated EOLC as more favorable, while proxies of CHP rated in-home and hospital care equally. CONCLUSION: Findings add to the scant literature identifying factors associated with place of death for older adults with and without CI and results suggest that place of death is a quality of care indicator for these populations. These findings may inform EOLC planning and policy-making and facilitate greater well-being at end-of-life.

Interprofessional education and collaboration among healthcare students and professionals: a systematic review and call for action.

Interprofessional education (IPE) is a prerequisite to building a collaborative practice environment and optimizing patient care. The purpose of this systematic review was to assess the impact of IPE on outcomes related to health-care pre-licensure learners and professionals, including: changes in attitudes/perceptions; acquisition of knowledge regarding other disciplines' roles and development of collaborative skills; and change in collaborative behavior. We searched PubMed, CINAHL, Embase, and ERIC for studies published from 2007 to 2017 in English; 19 studies were eligible. The Joanna Briggs Institute appraisal tool was used to assess the quality of the studies. Thirteen studies used a quasi-experimental design. The studies varied in terms of setting, teaching methods, assessment measures, and quality. Seventeen of the 19 studies (89%) that assessed change in attitudes toward other disciplines and value placed on a team-based approach for improving patient care, found statistically significant improvements. All seven of the studies that assessed change in collaborative behavior found statistically significant improvements. Among the 12 studies that assessed the development of collaborative skills, there were mixed results. Future directions include: conducting more studies among health-care professionals, assessing the long-term impact of IPE, objectively assessing change in collaborative behavior, and assessing the impact of IPE on patient-centered outcomes.

Digitally Enabled, Patient-Centric Clinical Trials: Shifting the Drug Development Paradigm.

The rapidly advancing field of digital health technologies provides a great opportunity to radically transform the way clinical trials are conducted and to shift the clinical trial paradigm from a site-centric to a patient-centric model. Merck's (Kenilworth, NJ) digitally enabled clinical trial initiative is focused on introduction of digital technologies into the clinical trial paradigm to reduce patient burden, improve drug adherence, provide a means of more closely engaging with the patient, and enable higher quality, faster, and more frequent data collection. This paper will describe the following four key areas of focus from Merck's digitally enabled clinical trials initiative, along with corresponding enabling technologies: (i) use of technologies that can monitor and improve drug adherence (smart dosing), (ii) collection of pharmacokinetic (PK), pharmacodynamic (PD), and biomarker samples in an outpatient setting (patient-centric sampling), (iii) use of digital devices to collect and measure physiological and behavioral data (digital biomarkers), and (iv) use of data platforms that integrate digital data streams, visualize data in real-time, and provide a means of greater patient engagement during the trial (digital platform). Furthermore, this paper will discuss the synergistic power in implementation of these approaches jointly within a trial to enable better understanding of adherence, safety, efficacy, PK, PD, and corresponding exposure-response relationships of investigational therapies as well as reduced patient burden for clinical trial participation. Obstacle and challenges to adoption and full realization of the vision of patient-centric, digitally enabled trials will also be discussed.