Discovery of Potent, Selective, and Orally Available IRE1α Inhibitors Demonstrating Comparable PD Modulation to IRE1 Knockdown in a Multiple Myeloma Model.

The lack of selective and safe in vivo IRE1α tool molecules has limited the evaluation of IRE1α as a viable target to treat multiple myeloma. Focus on improving the physicochemical properties of a literature compound by decreasing lipophilicity, molecular weight, and basicity allowed the discovery of a novel series with a favorable in vitro safety profile and good oral exposure. These efforts culminated in the identification of a potent and selective in vivo tool compound, G-5758, that was well tolerated following multiday oral administration of doses up to 500 mg/kg. G-5758 demonstrated comparable pharmacodynamic effects to induced IRE1 knockdown as measured by XBP1s levels in a multiple myeloma model (KMS-11).

Trauma-Informed Care in Medical Imaging and Radiation Therapy to Reduce Retraumatization.

PURPOSE: To provide an overview of trauma-informed care, including the neurobiology of trauma, interventions to reduce retraumatizing patients who have experienced trauma, and implications of trauma-informed care in medical imaging and radiation therapy. METHODS: A comprehensive search of electronic databases related to the purpose of this project resulted in the collection of 12 peer-reviewed journal articles. Two conference papers, 1 behavioral science textbook, 1 trauma neurobiology textbook, 1 professional conference presentation, and 1 governmental report also were reviewed to complement the journal articles. A thematic analysis was performed to identify commonalities among the selected sources. RESULTS: Four themes identified in the literature included definitions of trauma-informed care, neurobiology of trauma, pillars of trauma-informed care for intervention, and implications in medical imaging and radiation therapy. DISCUSSION: A trauma-informed health care professional realizes the prevalence of trauma, recognizes the signs and symptoms of trauma, responds by integrating knowledge about trauma into practice, and actively resists retraumatizing the patient (ie, avoids creating an environment that inadvertently reminds patients of their traumatic experiences and causes them to experience emotional and biological stress). The pillars of trauma-informed care include safety, trustworthiness or transparency, peer support, collaboration, empowerment, and responsiveness or cultural considerations. Delivery of health care often involves assessment and interventions in locations on the patient's body where trauma has previously occurred, increasing the probability of retraumatization and manifestation of signs and symptoms of trauma. Radiologic technologists and radiation therapists should be trauma-informed when they are interacting with and caring for patients to reduce retraumatization. A hypothetical case study also is presented to show how radiologic technologists can use the pillars of trauma-informed care in the clinic. CONCLUSION: Because many aspects of care, including routine care in medical imaging and radiation therapy, can be an unintentional reminder of a traumatic experience, health care professionals should be trauma-informed when they are interacting with and caring for patients.

Analysis of Peer-Reviewed Articles in ASRT Scholarly Journals.

PURPOSE: To analyze peer-reviewed articles in the American Society of Radiologic Technologists (ASRT) scholarly journals, Radiologic Technology and Radiation Therapist, and identify types of research and collaborative efforts among top producers. METHODS: A retrospective analysis was conducted by searching the Radiologic Technology and Radiation Therapist archives on the ASRT website to evaluate peer-reviewed articles from 2011 to 2021. A Microsoft Excel spreadsheet was created to document the types of research being published in the ASRT journals, as well as the number of authors for each peer-reviewed article, education levels of authors, collaborative efforts of top producers of scholarship, and mean authorship index of top producers. RESULTS: During this 11-year period, 217 peer-reviewed articles were published in the ASRT journals with most being original research studies (152, 70.0%). Most of the articles were written by 2 authors (68, 31.3%) or 4 or more authors (65, 30.0%). Of the 635 total authors, most held a doctoral degree (247, 38.9%) or a master's degree (212, 33.4%). Five top producers of research were identified as having published 5 or more peer-reviewed articles, and their mean authorship index was 95.5. Four top producers routinely collaborated on research articles. DISCUSSION: Initiatives, such as mentorships, to promote continued publication of original research studies and increase standalone literature reviews and case studies specific to the ASRT journals might be warranted. Medical imaging and radiation therapy educators can capitalize on collaboration by mentoring undergraduate and graduate students in various research opportunities to prepare future scholars in the profession. Further, medical imaging and radiation therapy authors should consider rotating author responsibilities on a collaborative team. Because the ASRT is the premier professional association for the medical imaging and radiation therapy community, authors should consider publishing in their 2 journals to advance and add to the profession's body of knowledge. CONCLUSION: Research articles in the ASRT journals demonstrate high collaborative authorship efforts. This study provides a foundation for future research to improve advancement of knowledge in the medical imaging and radiation therapy profession.

Leading past COVID-19: An analysis of remote work now and beyond.

In response to the coronavirus disease 2019 (COVID-19) pandemic, many cancer centers and clinics deployed remote work options for their employees. Due to the rapid response needed during this crisis, little to no feedback was obtained from dosimetrists. This study aimed to assess the productivity level and job satisfaction of medical dosimetrists in response to changes in working conditions due to the COVID-19 pandemic. With the assistance from the medical dosimetrists certification board (MDCB), critical data was gathered via an original instrument conducted and distributed by The University of Texas MD Anderson Cancer Center-School of Health Professions to all current practicing certified medical dosimetrists registered with the MDCB. Data were collected using Qualtrics and analyzed with IBM's SPSS. Most (326, 77.7%) participants indicated they transitioned to a version of remote work due to COVID-19. Almost half of the participants (208, 49.5%) reported increased job satisfaction due to the option to work remotely. The participants reported being extremely satisfied with the individual (247, 58.8%) and department (201, 47.9%) productivity levels even after implementing remote work options. Most participants (225, 53.6%), independent of age and years of experience, would prefer to stay in a hybrid role even after COVID-19 abates. These findings suggest that most dosimetrists prefer to perform their job remotely or asynchronously. A one size fits all job model design may make it difficult for organizations to attract, retain, and grow top dosimetrists. Industry leaders and employers may benefit by embracing this change as dosimetrists may value work-set-up flexibility over other employer-based benefits. Further research is needed to assess the unintended consequences of remote work environments in this profession.

COVID-19 Contingency Planning Among Radiologic Science Programs.

PURPOSE: To examine radiologic science programs' contingency planning related to the COVID-19 pandemic. METHODS: Using a mixed-methods approach, educators in magnetic resonance, medical dosimetry, radiation therapy, and radiography programs were surveyed to identify curricular changes, policy implementation, and financial implications related to pandemic recovery efforts. Quantitative data were summarized using descriptive statistics and percentages. Thematic analyses were performed on the qualitative responses. RESULTS: Continued curricular changes involved using technology to teach in the online environment and ensuring the safety and protection of students during clinical rotations. Institutional policies implemented because of the pandemic included social distancing guidelines, mask requirements, and availability of vaccine. The greatest financial implication witnessed among the sample of educators at their respective institutions was the halting of employer-related travel. Faced with the spontaneous shift to online learning while not being equipped with the appropriate training, most of the educator participants experienced COVID-19 fatigue and burnout related to teaching online. DISCUSSION: Social distancing guidelines make it difficult for large classes to meet in person, so virtual lectures using video conferencing platforms were an essential part of teaching during the pandemic. Most educators in this study selected recording technology for lectures as the most useful educational technology tool integrated into the didactic portion of their program. For many educators, having administration realize the adoption of technology is integral to and viable for radiologic science programs was a positive outcome of COVID-19. The pandemic caused educators in the study to experience fatigue and burnout related to online learning; however, the educators also expressed a high degree of comfort with using technology in the online learning environment. This implies that the source of fatigue and burnout was likely not associated with the technology, but with the focused and swift transition to predominately online learning. CONCLUSION: Although educators in this sample felt moderately prepared to handle future viral outbreaks and extremely comfortable using technology in the virtual classroom, additional research is needed to develop viable contingency plans and explore pedagogical approaches to content delivery beyond the traditional, in-person structure.

Shift Work and Mental Health Among Radiologic Technologists.

PURPOSE: To determine the relationships between mental health (depression and anxiety) and engaging in shift work, working weekend shifts, and taking call for radiologic technologists, and to identify coping strategies used to manage depression and anxiety. METHODS: Validated instruments were used to measure depression and anxiety levels among a sample of radiologic technologists who were members of Advanced Health Education Center. The participants also identified their primary work shift and their frequency of working weekends and taking call. RESULTS: There were 173 completed survey responses for this study. Most radiologic technologists in this study experienced mild symptoms of depression (62, 35.8%) and anxiety (57, 32.9%). Nearly half of the participants indicated that their depression and anxiety made it difficult for them to perform their jobs effectively, and about one-third of the participants believed those symptoms were intensified by shift work. A strong, positive relationship was identified between participants' total depression and anxiety scores (P < .001). There were no significant differences between shift work and total depression score (P = .06) or total anxiety score (P = .28). A significant association was found between the frequency of working weekend shifts and depression levels (P < .001) with a moderate effect size. Most of the participants identified support from family or friends, prayer and spiritual activities, and prescribed medication as common coping strategies. DISCUSSION: Findings revealed that the radiologic technologists in this study did not rely heavily on employer-based resources, such as employee assistance programs, to cope with their depression and anxiety symptoms. One speculation for underuse of these employer-based resources might be fear of being stigmatized by management or personal perceived stigma against asking for help. There is an opportunity for increased awareness of available mental health resources and acceptance of mental health management to erase the common, negative stigma associated with seeking out professional resources. CONCLUSION: Radiologic technologists in this study experienced depression and anxiety symptoms that affected their work performance and correlated with working weekend shifts; however, there was no significant relationship between shift work and depression or anxiety in this sample of radiologic technologists.

Reducing Pediatric Patients' Dose by Manipulating Radiographic Projections.

PURPOSE: To determine whether radiologic technologists are manipulating projections to lower patient dose in routine pediatric radiography examinations. METHODS: Using a descriptive survey approach, members from the American Society of Radiologic Technologists with a primary registration in radiography were randomly selected and invited to share their experiences using alternative projections during routine pediatric radiography examinations. RESULTS: For this study, 404 completed responses were analyzed. More than half of the participants (67.6%) strongly agreed or somewhat agreed that the use of alternative projections can reduce pediatric dose during routine radiography examinations, and more than half (61.3%) strongly agreed, agreed, or somewhat agreed that the use of alternative projections is beneficial for dose reduction. Incidentally, the most common response from participants regarding their use of alternative projections during routine pediatric radiography examinations was occasionally or sometimes. Nearly three-fourths of the participants strongly agreed that radiation protection guidelines are important to follow during routine pediatric radiography examinations. Although many radiologic technologists in this sample felt proficient using alternative projections during pediatric procedures, they also believed additional training in such methods would be beneficial. DISCUSSION: Most institutions have imaging protocols in place; however, the use of alternative methods of projection during routine pediatric radiography examinations might heighten current radiation protection guidelines, leading to protocol changes to reduce dose and improve the overall wellbeing of pediatric patients. Furthermore, recent recommendations in the field of medical imaging regarding patient shielding practices might deem positioning to be a more important method for dose reduction. Consultations from radiologists might be necessary to ensure that image quality is sufficient and diagnostic detail is not compromised. Additional training specific to using alternative projections during routine pediatric radiography examinations also might be warranted. CONCLUSION: Current practices do not suggest alternative methods of projection are applied regularly during routine pediatric radiography examinations. Considerations should be made to allow technologists to manipulate projections when permitted.

Assessment of C-arm Confidence Among ASRT Graduate Bridge Program Members.

PURPOSE: To identify the amount of C-arm preparation or instruction that recent graduates received in their radiography programs before starting clinical rotations and to determine whether completing more rotations increased their confidence in operating C-arm equipment. METHODS: Members of the American Society of Radiologic Technologists' Graduate Bridge program who indicated a primary pathway in radiography received an invitation to complete the C-arm confidence survey and self-report their C-arm experiences during clinical education. RESULTS: A third of the participants indicated they received preparation or instruction on C-arm equipment before beginning clinical rotations, with the majority of those indicating they had completed a C-arm laboratory. Almost half of the participants indicated that they were assigned to a minimum of 4 surgical rotations during their radiography program; nearly two-thirds indicated that they were not assigned additional clinical experience with C-arm equipment beyond those rotations. DISCUSSION: Participants who completed 4 or more surgical rotations during their radiography clinical education reported significantly higher confidence levels regarding operating C-arm equipment compared with those participants who completed 3 surgical rotations (P = .005), 2 surgical rotations (P< .001), or 1 surgical rotation (P< .001). Those participants who completed more C-arm rotations reported significantly higher confidence in operating C-arm equipment than did those who completed only surgical rotations (P< .01). A Pearson correlation coefficient also revealed a significant positive relationship between participants' confidence levels after completing surgical and other C-arm rotations (P< .01). Participants' confidence levels increased after completing surgical rotations and other C-arm rotations such as in pain management and interventional radiography. CONCLUSION: Program directors, clinical coordinators, and radiography educators should consider implementing specific instruction on C-arm use and assigning students to more clinical rotations to increase students' confidence in their C-arm skills.

Gadolinium Deposition: A Study Review.

PURPOSE: To analyze literature specific to gadolinium deposition and inform medical imaging professionals about potential risks of contrast retention related to magnetic resonance (MR) imaging examinations as well as alternative imaging techniques that reduce or eliminate the need for gadolinium-based contrast agents (GBCAs). METHODS: Peer-reviewed journal articles were collected using PubMed, Academic Search Complete, and Science Direct electronic databases. Information from an MR textbook and reports from various organizations complemented the scholarly sources. RESULTS: The literature focused on classifications of GBCAs, associated risks, deposition rates, current recommendations, and alternative imaging techniques. DISCUSSION: Less stable nonionic linear agents accumulate in tissues at a higher rate than do ionic macrocyclic agents. Deposition still occurs with more stable macrocyclic agents but at lower levels. MR technologists are responsible for checking their patients' renal function and choosing the most appropriate GBCA while adhering to current recommendations regarding contrast administration. The clinical significance of retained gadolinium in the brain is unknown. Long-term studies are necessary to determine whether gadolinium deposition in the brain causes neurological deficits. Until those clinical implications are understood fully, discussions will continue about the use of alternative imaging techniques that reduce or eliminate the need for GBCAs. CONCLUSION: Decisions regarding patients at risk for gadolinium retention should be made on a case-by-case basis, with the risks and benefits weighed. Every effort should be made to minimize residual gadolinium, especially in patients who have renal insufficiency and in patients who require repeated contrast examinations. When contrast is necessary, MR technologists should use the most stable type in the lowest possible dose.

Activation of the IRE1 RNase through remodeling of the kinase front pocket by ATP-competitive ligands.

Inositol-Requiring Enzyme 1 (IRE1) is an essential component of the Unfolded Protein Response. IRE1 spans the endoplasmic reticulum membrane, comprising a sensory lumenal domain, and tandem kinase and endoribonuclease (RNase) cytoplasmic domains. Excess unfolded proteins in the ER lumen induce dimerization and oligomerization of IRE1, triggering kinase trans-autophosphorylation and RNase activation. Known ATP-competitive small-molecule IRE1 kinase inhibitors either allosterically disrupt or stabilize the active dimeric unit, accordingly inhibiting or stimulating RNase activity. Previous allosteric RNase activators display poor selectivity and/or weak cellular activity. In this study, we describe a class of ATP-competitive RNase activators possessing high selectivity and strong cellular activity. This class of activators binds IRE1 in the kinase front pocket, leading to a distinct conformation of the activation loop. Our findings reveal exquisitely precise interdomain regulation within IRE1, advancing the mechanistic understanding of this important enzyme and its investigation as a potential small-molecule therapeutic target.

Identification of BRaf-Sparing Amino-Thienopyrimidines with Potent IRE1α Inhibitory Activity.

Amino-quinazoline BRaf kinase inhibitor 2 was identified from a library screen as a modest inhibitor of the unfolded protein response (UPR) regulating potential anticancer target IRE1α. A combination of crystallographic and conformational considerations were used to guide structure-based attenuation of BRaf activity and optimization of IRE1α potency. Quinazoline 6-position modifications were found to provide up to 100-fold improvement in IRE1α cellular potency but were ineffective at reducing BRaf activity. A salt bridge contact with Glu651 in IRE1α was then targeted to build in selectivity over BRaf which instead possesses a histidine in this position (His539). Torsional angle analysis revealed that the quinazoline hinge binder core was ill-suited to accommodate the required conformation to effectively reach Glu651, prompting a change to the thienopyrimidine hinge binder. Resulting analogues such as 25 demonstrated good IRE1α cellular potency and imparted more than 1000-fold decrease in BRaf activity.

COVID-19 Planning Among Radiologic Science Programs: Response Mitigation Activities.

PURPOSE: To examine radiologic science programs' mitigation activities and educators' experiences related to coronavirus disease 2019 (COVID-19) response planning. METHODS: Using a mixed-methods approach, educators in magnetic resonance, medical dosimetry, radiation therapy, and radiography programs were surveyed to capture their experiences and mitigation strategies related to COVID-19 response planning. Quantitative data were summarized using descriptive statistics and percentages. Thematic analyses were performed on the qualitative responses. RESULTS: A total of 274 educators responded. Educators reported being somewhat comfortable with modifying clinical experiences (79, 28.8%), moderately comfortable with adjusting assessment procedures (112, 40.9%), and extremely comfortable with changing delivery of didactic content (115, 42%). Incidentally, 220 (80.3%) educators thought adjusting to a new course delivery approach (eg, face-to-face to online format) was the greatest challenge for faculty during the pandemic. Notably, half of the educators in this study questioned the quality of online (remote) learning. Specific to program policies, educators indicated that access restrictions to campus buildings (263, 96%) and removal of students from clinical sites (254, 92.7%) were implemented during the pandemic. DISCUSSION: Educators self-reported a moderate to strong comfort level with curricular modification. The area of modification that yielded the most uncertainty arose from alterations of clinical experiences. Thematic analyses revealed concerns related to personal protective equipment procurement and clinical sites prohibiting students from completing rotations. However, educators created innovative alternatives to enhance clinical education by providing simulations, case study analyses, and virtual tours of facilities during the pandemic. Securing educational technology resources, such as lockdown browser software, and working with institutional instructional designers might provide some resolution to educators' concerns regarding the quality of online (remote) learning. CONCLUSION: Archiving radiologic science programs' COVID-19 response efforts is important. The compilation of mitigation strategies will inform and guide programs on contingency planning for future pandemic and emergent conditions.

Scholarly Productivity Among Educators in Radiologic Sciences and Other Health Care Professions: A Comparative Approach.

PURPOSE: To compare scholarly productivity among dental hygiene, medical imaging and radiation therapy, medical laboratory science, nursing, and respiratory care educators. METHODS: Using a mixed-methods approach, educators were surveyed to compare their engagement in scholarly activities and identify motivators, employer support measures, and barriers associated with scholarship engagement. Quantitative data were analyzed using percentages, descriptive statistics, Kruskal-Wallis H tests, and Welch F tests. Thematic analyses were performed on the qualitative responses. RESULTS: Of the 360 completed surveys, 295 (81.9%) participants indicated that they engaged in scholarly activities. Medical laboratory science educators wrote significantly more peer-reviewed journal articles than did medical imaging and radiation therapy educators (P = .004). Medical laboratory science educators ranked career advancement as a significantly higher motivator than did nursing educators (P = .045); nursing educators ranked personal satisfaction as a significantly higher motivator than did educators from respiratory care (P = .002) and medical laboratory science (P = .009); and medical laboratory science educators ranked pressure from institution hierarchy as a significantly higher motivator than did dental hygiene educators (P = .005) and medical imaging and radiation therapy educators (P = .043). Thematic analyses revealed that participants consider collaboration to be a motivating factor to engage in scholarship; employer support measures should include guidance with grant writing and funding; and barriers that limit productivity include a lack of time, program faculty, and understanding where to begin. DISCUSSION: Initiatives such as mentoring programs should be implemented to promote collaborative efforts among medical imaging and radiation therapy educators to increase productivity in scholarship, particularly in peer-reviewed publications, and minimize potential barriers. In addition, the ASRT Foundation created new grant tiers for radiologic technologists and radiation therapists who have an interest in conducting research and publishing their results. This opportunity can advance scholarly productivity in the profession. CONCLUSION: Communicating the value of scholarship engagement to medical imaging and radiation therapy educators is important so that the profession can advance to its full potential as a distinct allied health profession.