Construction of a diagnostic model based on random forest and artificial neural network for peri-implantitis.

OBJECTIVES: This study aimed to reveal critical genes regulating peri-implantitis during its development and construct a diagnostic model by using random forest (RF) and artificial neural network (ANN). METHODS: GSE-33774, GSE106090, and GSE57631 datasets were obtained from the GEO database. The GSE33774 and GSE106090 datasets were analyzed for differential expression and functional enrichment. The protein-protein interaction networks (PPI) and RF screened vital genes. A diagnostic model for peri-implantitis was established using ANN and validated on the GSE33774 and GSE57631 datasets. A transcription factor-gene interaction network and a transcription factor-micro-RNA (miRNA) regulatory network were also established. RESULTS: A total of 124 differentially expressed genes (DEGs) involved in the regulation of peri-implantitis were screened. Enrichment analysis showed that DEGs were mainly associated with immune receptor activity and cytokine receptor activity and were mainly involved in processes such as leukocyte and neutrophil migration. The PPI and RF screened six essential genes, namely, CD38, CYBB, FCGR2A, SELL, TLR4, and CXCL8. The receiver operating characteristic curve (ROC) indicated that the ANN model had an excellent diagnostic performance. FOXC1, GATA2, and NF-κB1 may be essential transcription factors in peri-implantitis, and hsa-miR-204 may be a key miRNA. CONCLUSIONS: The diagnostic model of peri-implantitis constructed by RF and ANN has high confidence, and CD38, CYBB, FCGR2A, SELL, TLR4, and CXCL8 are potential diagnostic markers. FOXC1, GATA2, and NF-κB1 may be essential transcription factors in peri-implantitis, and hsa-miR-204 plays a vital role as a critical miRNA.

The role of hsa_circ_0042260/miR-4782-3p/LAPTM4A axis in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a common metabolic condition during pregnancy, posing risks to both mother and fetus. CircRNAs have emerged as important players in various diseases, including GDM. We aimed to investigate the role of newly discovered circRNA, hsa_circ_0042260, in GDM pathogenesis. Using GSE194119 dataset, hsa_circ_0042260 was identified and its expression in plasma, placenta, and HG-stimulated HK-2 cells was examined. Silencing hsa_circ_0042260 in HK-2 cells assessed its impact on cell viability, apoptosis, and inflammation. Bioinformatics analysis revealed downstream targets of hsa_circ_0042260, namely miR-4782-3p and LAPTM4A. The interaction between hsa_circ_0042260, miR-4782-3p, and LAPTM4A was validated through various assays. hsa_circ_0042260 was upregulated in plasma from GDM patients and HG-stimulated HK-2 cells. Silencing hsa_circ_0042260 improved cell viability, suppressed apoptosis and inflammation. Hsa_circ_0042260 interacted with miR-4782-3p, which exhibited low expression in GDM patient plasma and HG-stimulated cells. MiR-4782-3p targeted LAPTM4A, confirmed by additional assays. LAPTM4A expression increased in GDM patient plasma and HG-induced HK-2 cells following hsa_circ_0042260 knockdown or miR-4782-3p overexpression. In rescue assays, inhibition of miR-4782-3p or overexpression of LAPTM4A counteracted the effects of hsa_circ_0042260 downregulation on cell viability, apoptosis, and inflammation. In conclusion, the hsa_circ_0042260/miR-4782-3p/LAPTM4A axis plays a role in regulating GDM progression in HG-stimulated HK-2 cells.

The application of two drainage angles in neurocritical care patients with complicated pneumonia: a randomized controlled trial.

Background: Although head elevation is an early first-line treatment for elevated intracranial pressure (ICP), the use of the head-down or prone position in managing neurocritical patients is controversial because a change in a position directly affects the intracranial and cerebral perfusion pressure, which may cause secondary brain injury and affect patient outcomes. This study compared the effects of two postural drainage positions (30° head-up tilt and 0° head flat) on the prognosis of neurocritical care patients with complicated pneumonia and a clinical pulmonary infection score (CPIS) ≥5 points to provide a reference for selecting appropriate postural drainage positions for patients with pneumonia in neurocritical care units. Methods: A prospective randomized controlled study was conducted with 62 neurocritical care patients with complicated pneumonia. The patients were categorized into control (=31) and experimental (=31) groups in a 1:1 ratio using a simple randomized non-homologous pairing method. Emphasis was placed on matching the baseline characteristics of the two groups, including patient age, sex, height, weight, Glasgow Coma Scale score, heart rate, mean arterial pressure, cough reflex, and mechanical ventilation usage to ensure comparability. Both groups received bundled care for artificial airway management. The control group maintained a standard postural drainage position of 0° head-flat, whereas the experimental group maintained a 30° head-up tilt. The efficacy of the nursing intervention was evaluated by comparing the CPIS and other therapeutic indicators between the two groups after postural drainage. Results: After the intervention, the within-group comparison showed a significant decrease in the CPIS (P < 0.001); procalcitonin levels showed a significant decreasing trend (P < 0.05); the arterial oxygen pressure significantly increased (P < 0.05); the oxygenation index significantly increased (P < 0.001); and the aspiration risk score showed a significant decreasing trend (P < 0.001). A between-group comparison showed no significant differences in any of the indicators before and after the intervention (P < 0.05). Conclusion: Postural drainage positions of 30° head-up tilt and 0° head-flat can improve the CPIS and oxygenation in patients without adverse effects. Therefore, we recommend that patients under neurological intensive care and having pneumonia be drained in a 30° head-up tilt position with good centralized care of the lung infection. Trial registration: The study, "Study of Angles of Postural Drainage in Neurocritical Patients with Pneumonia," was registered in the Protocol Registration Data Element Definitions for Interventional Study database (# ChiCTR2100042155); date of registration: 2021-01-14.

Exploring the potential link between MitoEVs and the immune microenvironment of periodontitis based on machine learning and bioinformatics methods.

BACKGROUND: Periodontitis is a chronic inflammatory condition triggered by immune system malfunction. Mitochondrial extracellular vesicles (MitoEVs) are a group of highly heterogeneous extracellular vesicles (EVs) enriched in mitochondrial fractions. The objective of this research was to examine the correlation between MitoEVs and the immune microenvironment of periodontitis. METHODS: Data from MitoCarta 3.0, GeneCards, and GEO databases were utilized to identify differentially expressed MitoEV-related genes (MERGs) and conduct functional enrichment and pathway analyses. The random forest and LASSO algorithms were employed to identify hub MERGs. Infiltration levels of immune cells in periodontitis and healthy groups were estimated using the CIBERSORT algorithm, and phenotypic subgroups of periodontitis based on hub MERG expression levels were explored using a consensus clustering method. RESULTS: A total of 44 differentially expressed MERGs were identified. The random forest and LASSO algorithms identified 9 hub MERGs (BCL2L11, GLDC, CYP24A1, COQ2, MTPAP, NIPSNAP3A, FAM162A, MYO19, and NDUFS1). ROC curve analysis showed that the hub gene and logistic regression model presented excellent diagnostic and discriminating abilities. Immune infiltration and consensus clustering analysis indicated that hub MERGs were highly correlated with various types of immune cells, and there were significant differences in immune cells and hub MERGs among different periodontitis subtypes. CONCLUSION: The periodontitis classification model based on MERGs shows excellent performance and can offer novel perspectives into the pathogenesis of periodontitis. The high correlation between MERGs and various immune cells and the significant differences between immune cells and MERGs in different periodontitis subtypes can clarify the regulatory roles of MitoEVs in the immune microenvironment of periodontitis. Future research should focus on elucidating the functional mechanisms of hub MERGs and exploring potential therapeutic interventions based on these findings.

Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons.

ABSTRACT: Traumatic peripheral nerve injuries are at high risk of neuropathic pain for which novel effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance. Traumatic nerve injuries seen in the clinic commonly result in axonotmesis (ie, crush), yet the neuropathic phenotype of "painful" nerve crush injuries remains poorly understood. We report the neuropathology and sensory symptoms of a focal nerve crush injury using custom-modified hemostats resulting in either complete ("full") or incomplete ("partial") axonotmesis in adult mice. Assays of thermal and mechanically evoked pain-like behavior were paralleled by transmission electron microscopy, immunohistochemistry, and anatomical tracing of the peripheral nerve. In both crush models, motor function was equally affected early after injury; by contrast, partial crush of the nerve resulted in the early return of pinprick sensitivity, followed by a transient thermal and chronic tactile hypersensitivity of the affected hind paw, which was not observed after a full crush injury. The partially crushed nerve was characterized by the sparing of small-diameter myelinated axons and intraepidermal nerve fibers, fewer dorsal root ganglia expressing the injury marker activating transcription factor 3, and lower serum levels of neurofilament light chain. By day 30, axons showed signs of reduced myelin thickness. In summary, the escape of small-diameter axons from Wallerian degeneration is likely a determinant of chronic pain pathophysiology distinct from the general response to complete nerve injury.

Non-invasive detection of haemoglobin, platelets, and total bilirubin using hyperspectral cameras.

Hyperspectral imaging has emerged as a promising high-resolution and real-time imaging technology with potential applications in medical diagnostics and surgical guidance. In this study, we developed a high-speed hyperspectral camera by integrating a Fabry-Perot cavity filter on each CMOS pixel. We used it to non-invasively detect three blood components (haemoglobin, platelet, and total bilirubin). Specifically, we acquired transmission images of the subject's fingers, extracted spectral signals at each wavelength, and used dynamic spectroscopy to obtain non-invasive blood absorption spectra. The prediction models were established using the PLSR method and were modelled and validated based on the standard clinical-biochemical test values. The experimental results demonstrated excellent performance. The best predictions were obtained for haemoglobin, with a high related coefficient (R) of 0.85 or more in both the calibration and prediction sets and a mean absolute percentage error (MAPE) of only 5.7%. The results for total bilirubin were also ideal, with R values exceeding 0.8 in both sets and a MAPE of 10.6%. Although the prediction results for platelets were slightly less satisfactory, the error was still less than 15%, indicating that the results were also acceptable. Overall, our study highlights the potential of hyperspectral imaging technology for the development of portable and affordable devices for blood analysis, which can be used in various settings.

Comparing thoracic and abdominal subspecialists' follow-up recommendations for abdominal findings identified on chest CT.

PURPOSE: To compare thoracic and abdominal radiologists' follow-up recommendations for abdominal findings identified on chest CT. METHODS: This Institutional Review Board-exempt, retrospective study was performed at a large academic medical center with subspecialty radiology divisions. We used a combination of natural language processing and manual reviews to identify chest CT reports with and without abdominal findings that were interpreted by thoracic radiologists in 2019. Three random samples of reports were reviewed by two subspecialty trained abdominal radiologists for their agreement with thoracic radiologists' reporting: abdominal findings with follow-up recommendation (Group 1), abdominal findings without follow-up recommendation (Group 2), and no abdominal findings reported (Group 3). Primary outcome was agreement between thoracic and abdominal radiologists for the need for follow-up of abdominal findings. Secondary outcomes were agreement between subspecialists for the presence of abdominal findings and referring clinician adherence to recommendations. Fischer's exact test was used to compare proportions. RESULTS: Abdominal radiologists agreed with need for follow-up in 48.5% (16/33) of Group 1 cases and agreed follow-up was not necessary for 100% (34/34) of Group 2 cases (p < 0.001). Abdominal radiologists identified abdominal findings in 31.4% (11/35) of Group 3 cases, none of which required follow-up. Referring clinician adherence to thoracic radiologist follow-up recommendations for abdominal findings was 13/33 (39.4%). CONCLUSION: Abdominal radiologists frequently disagreed with thoracic radiologist recommendations for follow-up of abdominal findings on chest CT. Chest radiologists may consider abdominal subspecialty consultation or clinical decision support to reduce unnecessary imaging.

Frequency and Clinical Utility of Alerts for Intra-Institutional Radiologist Discrepant Opinions.

OBJECTIVE: Determine the rate of documented notification, via an alert, for intra-institutional discrepant radiologist opinions and addended reports and resulting clinical management changes. METHODS: This institutional review board-exempt, retrospective study was performed at a large academic medical center. We defined an intra-institutional discrepant opinion as when a consultant radiologist provides a different interpretation from that formally rendered by a colleague at our institution. We implemented a discrepant opinion policy requiring closed-loop notification of the consulting radiologist's second opinion to the original radiologist, who must acknowledge this alert within 30 days. This study included all discrepant opinion alerts created December 1, 2019, to December 31, 2021, of which two radiologists and an internal medicine physician performed consensus review. Primary outcomes were degree of discrepancy and percent of discrepant opinions leading to change in clinical management. Secondary outcome was report addendum rate compared with an existing peer learning program using Fisher's exact test. RESULTS: Of 114 discrepant opinion alerts among 1,888,147 reports generated during the study period (0.006%), 58 alerts were categorized as major (50.9%), 41 as moderate (36.0%), and 15 as minor discrepancies (13.1%). Clinical management change occurred in 64 of 114 cases (56.1%). Report addendum rate for discrepant opinion alerts was 4-fold higher than for peer learning alerts at our institution (66 of 315 = 21% versus 432 of 8,273 =5.2%; P < .0001). DISCUSSION: Although discrepant intra-institutional radiologist second opinions were rare, they frequently led to changes in clinical management. Capturing these discrepancies by encouraging alert use may help optimize patient care and document what was communicated to the referring or consulting care team by consulting radiologists.

Cerebral endothelial cell derived small extracellular vesicles improve cognitive function in aged diabetic rats.

Small extracellular vesicles (sEVs) mediate cell-cell communication by transferring their cargo biological materials into recipient cells. Diabetes mellitus (DM) induces cerebral vascular dysfunction and neurogenesis impairment, which are associated with cognitive decline and an increased risk of developing dementia. Whether the sEVs are involved in DM-induced cerebral vascular disease, is unknown. Therefore, we studied sEVs derived from cerebral endothelial cells (CEC-sEVs) of aged DM rats (DM-CEC-sEVs) and found that DM-CEC-sEVs robustly inhibited neural stem cell (NSC) generation of new neuroblasts and damaged cerebral endothelial function. Treatment of aged DM-rats with CEC-sEVs derived from adult healthy normal rats (N-CEC-sEVs) ameliorated cognitive deficits and improved cerebral vascular function and enhanced neurogenesis. Intravenously administered N-CEC-sEVs crossed the blood brain barrier and were internalized by neural stem cells in the neurogenic region, which were associated with augmentation of miR-1 and -146a and reduction of myeloid differentiation primary response gene 88 and thrombospondin 1 proteins. In addition, uptake of N-CEC-sEVs by the recipient cells was mediated by clathrin and caveolin dependent endocytosis signaling pathways. The present study provides ex vivo and in vivo evidence that DM-CEC-sEVs induce cerebral vascular dysfunction and neurogenesis impairment and that N-CEC-sEVs have a therapeutic effect on improvement of cognitive function by ameliorating dysfunction of cerebral vessels and increasing neurogenesis in aged DM rats, respectively.

Assessment of a Large-Scale Peer Learning Program's Value by Manual Review of Case Submissions.

OBJECTIVE: Prior studies used submission numbers or report addendum rates to measure peer learning programs' (PLP) impact. We assessed the educational value of a PLP by manually reviewing cases submitted to identify factors correlating with meaningful learning opportunities (MLOs). METHODS: This institutional review board-exempted, retrospective study was performed in a large academic radiology department generating >800,000 reports annually. A PLP facilitating radiologist-to-radiologist feedback was implemented May 1, 2017, with subsequent pay-for-performance initiatives encouraging increasing submissions, >18,000 by 2019. Two radiologists blinded to submitter and receiver identity categorized 336 randomly selected submissions as a MLO, not meaningful, or equivocal, resolving disagreements in consensus review. Primary outcome was proportion of MLOs. Secondary outcomes included percent engagement by subspecialty clinical division and comparing MLO and report addendum rates via Fisher's exact tests. We assessed association between peer learning category, pay-for-performance interventions, and subspecialty division with MLOs using logistic regression. RESULTS: Of 336 PLP submissions, 65.2% (219 of 336) were categorized as meaningful, 27.4% (92 of 336) not meaningful, and 7.4% (25 of 336) equivocal, with substantial reviewer agreement (86.0% [289 of 336], κ = 0.71, 95% confidence interval 0.64-0.78). MLO rate (65.2% [219 of 336]) was five times higher than addendum rate (12.9% [43 of 333]) for the cohort. MLO proportion (adjusted odds ratios 0.05-1.09) and percent engagement (0.5%-3.6%) varied between subspecialty divisions, some submitting significantly fewer MLOs (P < .01). MLO proportion did not vary between peer learning categories. CONCLUSION: Educational value of a large-scale PLP, estimated through manual review of case submissions, is likely a more accurate measure of program impact. Incentives to enhance PLP use did not diminish the program's educational value.

Representing narrative evidence as clinical evidence logic statements.

Objective: Clinical evidence logic statements (CELS) are shareable knowledge artifacts in a semistructured "If-Then" format that can be used for clinical decision support systems. This project aimed to assess factors facilitating CELS representation. Materials and Methods: We described CELS representation of clinical evidence. We assessed factors that facilitate representation, including authoring instruction, evidence structure, and educational level of CELS authors. Five researchers were tasked with representing CELS from published evidence. Represented CELS were compared with the formal representation. After an authoring instruction intervention, the same researchers were asked to represent the same CELS and accuracy was compared with that preintervention using McNemar's test. Moreover, CELS representation accuracy was compared between evidence that is structured versus semistructured, and between CELS authored by specialty-trained versus nonspecialty-trained researchers, using χ2 analysis. Results: 261 CELS were represented from 10 different pieces of published evidence by the researchers pre- and postintervention. CELS representation accuracy significantly increased post-intervention, from 20/261 (8%) to 63/261 (24%, P value < .00001). More CELS were assigned for representation with 379 total CELS subsequently included in the analysis (278 structured and 101 semistructured) postintervention. Representing CELS from structured evidence was associated with significantly higher CELS representation accuracy (P = .002), as well as CELS representation by specialty-trained authors (P = .0004). Discussion: CELS represented from structured evidence had a higher representation accuracy compared with semistructured evidence. Similarly, specialty-trained authors had higher accuracy when representing structured evidence. Conclusion: Authoring instructions significantly improved CELS representation with a 3-fold increase in accuracy. However, CELS representation remains a challenging task.

AMSER Rad Path Case of the Month: Effect of Case-based Integration of Radiology and Pathology on Medical Student Education and Interdisciplinary Collaboration.

RATIONALE AND OBJECTIVES: Radiology and pathology are often underrepresented in undergraduate medical education. The Alliance of Medical Student Educators in Radiology (AMSER) hosts the AMSER Rad Path Case of the Month, an online archive of radiological case reports with pathology correlations submitted by medical students. The purpose of this study is to assess the value of preparing and submitting a case on medical students' educational experience. MATERIALS AND METHODS: Students who had cases accepted for publication in AMSER Rad Path Case of the Month from July 2018 to December 2019 were contacted by email to request their participation in a voluntary, anonymous 22-question survey. Surveys were sent to 35 students from seven institutions. RESULTS: Twenty three of the 35 students (65.7%) responded. Only five (21.7%) of respondents reported having previously followed a patient case through radiology and pathology during medical school, defined as interaction with a clinician in each specialty to discuss the case. When asked about their experience with AMSER Rad Path Case of the Month, most agreed or strongly agreed it was a valuable case-based learning experience (100%). Respondents also reported high satisfaction with improved understanding of disease process, increased understanding and ability to collaborate, and increased likelihood of participating in future academic work. CONCLUSION: AMSER Rad Path Case of the Month is a valuable case-based educational experience that deepens students' understanding of disease processes while affording them an opportunity for interdisciplinary and scholarly collaboration.

Use of a PACS Embedded System for Communicating Radiologist to Technologist Learning Opportunities and Patient Callbacks.

OBJECTIVE: This study aimed to determine effect of modality, care setting, and radiology subspecialty on frequency of diagnostic image quality issues identified by radiologists during image interpretation. METHODS: This Institutional Review Board-exempt retrospective study was performed 10/1/18-6/30/20 at an academic radiology practice performing 700,000+ examinations annually. A closed-loop communication tool integrated in PACS workflow enabled radiologists to alert technologists to image quality issues. Radiologists categorized communications as requiring patient callback, or as technologist learning opportunities if image quality was adequate to generate a diagnostic report. Fisher's exact test assessed impact of imaging modality, radiology subspecialty, and care setting on radiologist-identified image quality issues. RESULTS: 976,915 imaging examinations were performed during the study period. Radiologists generated 1,935 technologist learning opportunities (0.20%) and 208 callbacks (0.02%). Learning opportunity rates were highest for MRI (0.60%) when compared to CT (0.26%) and radiography (0.08%) (p<0.0001). The same was true for patient callbacks (MRI 0.13%, CT 0.02%, radiography 0.0006%; p<0.0001). Outpatient examinations generated more learning opportunities (1479/637,092; 0.23%) vs. inpatient (305/200,206; 0.15%) and Emergency Department (151/139,617; 0.11%) (p<0.0001). Abdominal subspecialists were most likely to generate learning opportunities when compared to other subspecialists and cardiovascular imagers were most likely to call a patient back. CONCLUSIONS: Image quality issues identified by radiologists during the interpretation process were rare and 10 times more commonly categorized as learning opportunities not interfering with a clinically adequate report than as requiring patient callback. Further work is necessary to determine if creating learning opportunities leads to fewer patients requiring repeat examinations.

Public health spending, primary care, and perceived risk promoted vaccination against H1N1.

The purpose of this study is to examine factors affecting the intent to vaccinate during the 2009 H1N1 pandemic and to leverage the results to inform public health policy decisions aimed at increasing vaccine uptake during the COVID-19 pandemic. Using the National 2009 H1N1 Flu Survey data and state-level administrative data, we employ logistic regression and mediation models to estimate the association between vaccine uptake and state level public health spending, political ideology, and H1N1 case and death rates as well as a set of individual and household characteristics. We find that higher public health spending can significantly increase the intent to vaccinate, mainly through raising concerns about the pandemic and promoting vaccine relevant doctor patient interactions. We conclude that physicians, especially primary care physicians, should play more important roles in the ongoing vaccination efforts against the COVID-19 virus.

Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics.

Background: Intrahepatic cholestasis (IC) is a disorder of bile production, secretion, and excretion with various causes. Crocin I (CR) is effective in the treatment of IC, but its underlying mechanisms need to be further explored. We aimed to reveal the therapeutic mechanism of crocin I for IC by combining an integrated strategy of metabolomics and transcriptomics. Methods: The hepatoprotective effect of CR against cholestasis liver injury induced by α-naphthylisothiocyanate (ANIT) was evaluated in rats. The serum biochemical indices, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß), as well as the liver oxidative stress indexes and the pathological characteristics of the liver were analyzed. In addition, we also performed a serum metabolomics study using UPLC-Q Exactive HF-X technology to investigate the effect of CR on the serum of rats with ANIT-induced IC and screened potential biomarkers. The enrichment analysis of differential expressed genes (DEGs) was performed by transcriptomics. Finally, the regulatory targets of CR on potential biomarkers were obtained by combined analysis, and the relevant key targets were verified by western blotting. Results: CR improved serum and liver homogenate indexes and alleviated liver histological injury. Compared with ANIT group, the CR group had 76 differential metabolites, and 10 metabolic pathways were enriched. There were 473 DEGs significantly changed after CR treatment, most of which were enriched in the retinol metabolism, calcium signaling pathway, PPAR signaling pathway, circadian rhythm, chemokine signaling pathway, arachidonic acid metabolism, bile secretion, primary bile acid biosynthesis, and other pathways. By constructing the "compound-reaction-enzyme-gene" interaction network, three potential key-target regulation biomarkers were obtained, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), ATP-binding cassette transporter G5 (ABCG5), and sulfotransferase2A1(SULT2A1), which were further verified by western blotting. Compared with the ANIT group, the CR group significantly increased the expression of ABCG5 and SULT2A1, and the expression of HMGCR significantly decreased. Conclusion: Combined metabolomic and transcriptomic analyses show that CR has a therapeutic effect on IC through regulation of the biosynthesis of bile acids and bilirubin in the bile secretion pathway and regulation of the expression of HMGCR, ABCG5, and SULT2A1.

Peer Learning in Radiology: Effect of a Pay-for-Performance Initiative on Clinical Impact and Usage.

OBJECTIVE. The purpose of this article is to assess the effects of a pay-for-performance (PFP) initiative on clinical impact and usage of a radiology peer learning tool. MATERIALS AND METHODS. This retrospective study was performed at a large academic hospital. On May 1, 2017, a peer learning tool was implemented to facilitate radiologist peer feedback including clinical follow-up, positive feedback, and consultation. Subsequently, PFP target numbers for peer learning tool alerts by subspecialty divisions (October 1, 2017) and individual radiologists (October 1, 2018) were set. The primary outcome was report addendum rate (percent of clinical follow-up alerts with addenda), which was a proxy for peer learning tool clinical impact. Secondary outcomes were peer learning tool usage rate (number of peer learning tool alerts per 1000 radiology reports) and proportion of clinical follow-up alerts (percent of clinical follow-ups among all peer learning tool alerts). Outcomes were assessed biweekly using ANOVA and statistical process control analyses. RESULTS. Among 1,265,839 radiology reports from May 1, 2017, to September 29, 2019, a total of 20,902 peer learning tool alerts were generated. The clinical follow-up alert addendum rate was not significantly different between the period before the PFP initiative (9.9%) and the periods including division-wide (8.3%) and individual (7.9%) PFP initiatives (p = .55; ANOVA). Peer learning tool usage increased from 2.2 alerts per 1000 reports before the PFP initiative to 12.6 per 1000 during the division-wide PFP period (5.7-fold increase; 12.6/2.2), to 25.2 in the individual PFP period (11.5-fold increase vs before PFP; twofold increase vs division-wide) (p < .001). The clinical follow-up alert proportion decreased from 37.5% before the PFP initiative, to 34.4% in the division-wide period, to 31.3% in the individual PFP period. CONCLUSION. A PFP initiative improved radiologist engagement in peer learning by marked increase in peer learning tool usage rate without a change in report addendum rate as a proxy for clinical impact.

Improving the completeness of structured MRI reports for rectal cancer staging.

PURPOSE: Assess the impact of a multifaceted intervention to improve the completeness of structured MRI reports for patients undergoing initial staging for rectal cancer. METHODS: This Institutional Review Board-approved retrospective study was performed at a large academic hospital. MRI reports for initial staging of rectal cancer in 2017 and 2019 were analyzed pre- and post-implementation of multiple quality improvement interventions in 2018, including harmonizing MRI protocols across the institution, educational conferences and modules, and requiring second opinion consultation for all MRI rectal cancer examinations. The primary outcome measure was the completeness of rectal cancer staging MRI reports, classified as optimal, satisfactory, or unsatisfactory based on the inclusion of 15 quality measures pre-defined by a consensus of abdominal and cancer imaging subspecialists, colorectal surgeons, and radiation oncologists at our institution, based on published recommendations. Fisher's exact test was used to evaluate changes in report quality and documentation of each quality measure. RESULTS: The study included 138 MRI reports, of which 72 (52%) were completed in 2017 pre-intervention. Post intervention, the proportion of optimal reports increased significantly from 52.8% (38/72) to 71.2% (47/66) (p = 0.035). Documentation of 1 quality measure (N stage) increased post intervention from 91.7% (66/72) to 100% (66/66) (p = 0.029). Documentation of 7 quality measures was 100% post intervention, with a documentation rate of > 95% for all quality measures except radial location of tumor. CONCLUSION: A combination of educational and system-wide interventions was associated with an improvement in the completeness of structured MRI reports for rectal cancer staging.

Medical Student Patient Outreach to Ensure Continuity of Care During the COVID-19 Pandemic.

Background: In response to the COVID-19 pandemic, the Yale New Haven Health System began rescheduling nonurgent outpatient appointments as virtual visits in March 2020. While Yale New Haven Health expanded its telemedicine infrastructure to accommodate this shift, many appointments were delayed and patients faced considerable uncertainty. Objective: Medical students created the Medical Student Task Force (MSTF) to help ensure continuity of care by calling patients whose appointments were delayed during this transition to telemedicine. Methods: Eighty-five student volunteers called 3765 internal medicine patients with canceled appointments, completing screening for 2197 patients. Volunteers screened for health care needs, assessed preferences for future appointments, and offered emotional support and information about COVID-19. Urgent or emergent patient concerns were triaged and escalated to providers. In this analysis, we used a mixed-methods approach: call information and provider responses were analyzed quantitatively, and patient feedback was analyzed qualitatively via thematic analysis. Results: Ninety-one percent of patients screened found the MSTF calls helpful. Twenty-one percent of patients reported health concerns, with 1% reporting urgent concerns escalated to and addressed by providers. Themes of patient comments included gratitude for outreach and social contact, utility of calls, and well-wishes for health care workers. Conclusions: By calling patients whose appointments had been canceled during a rapid transition to telemedicine, the MSTF helped bridge a potential gap in care by offering patients communication with their care teams, information, and support. We propose that this model could be used in other care systems urgently transitioning to outpatient telemedicine, whether during ongoing outbreaks of COVID-19 or other public health emergencies.

An induced pluripotent stem cell model of Fanconi anemia reveals mechanisms of p53-driven progenitor cell differentiation.

Fanconi anemia (FA) is a disorder of DNA repair that manifests as bone marrow (BM) failure. The lack of accurate murine models of FA has refocused efforts toward differentiation of patient-derived induced pluripotent stem cells (IPSCs) to hematopoietic progenitor cells (HPCs). However, an intact FA DNA repair pathway is required for efficient IPSC derivation, hindering these efforts. To overcome this barrier, we used inducible complementation of FANCA-deficient IPSCs, which permitted robust maintenance of IPSCs. Modulation of FANCA during directed differentiation to HPCs enabled the production of FANCA-deficient human HPCs that recapitulated FA genotoxicity and hematopoietic phenotypes relative to isogenic FANCA-expressing HPCs. FANCA-deficient human HPCs underwent accelerated terminal differentiation driven by activation of p53/p21. We identified growth arrest specific 6 (GAS6) as a novel target of activated p53 in FANCA-deficient HPCs and modulate GAS6 signaling to rescue hematopoiesis in FANCA-deficient cells. This study validates our strategy to derive a sustainable, highly faithful human model of FA, uncovers a mechanism of HPC exhaustion in FA, and advances toward future cell therapy in FA.