Dissecting engineered cell types and enhancing cell fate conversion via CellNet.

Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells.

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 noncoding RNA mediates stroke-induced neurogenesis.

Neurogenesis contributes to poststroke recovery. Long noncoding RNAs (lncRNAs) participate in the regulation of stem cell self-renewal and differentiation. However, the role of lncRNAs in stroke-induced neurogenesis remains unknown. In this study, we found that H19 was the most highly upregulated lncRNA in neural stem cells (NSCs) of the subventricular zone (SVZ) of rats subjected to focal cerebral ischemia. Deletion of H19 suppressed cell proliferation, promoted cell death, and blocked NSC differentiation. RNA sequencing analysis revealed that genes deregulated by H19 knockdown were those that are involved in transcription, apoptosis, proliferation, cell cycle, and response to hypoxia. H19 knockdown significantly increased the transcription of cell cycle-related genes including p27, whereas overexpression of H19 substantially reduced expression of these genes through the interaction with chromatin remodeling proteins EZH2 and SUZ12. Moreover, H19 regulated neurogenesis-related miRNAs. Inactivation of H19 in NSCs of ischemic rats attenuated spontaneous functional recovery after stroke. Collectively, our data provide novel insights into the epigenetic regulation of lncRNAs in stroke-induced neurogenesis.

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.

Patient Satisfaction With Human Papillomavirus Self-Sampling in a Cohort of Ethnically Diverse and Rural Women in Yunnan Province, China.

OBJECTIVE: Rural Yunnan Province is one of the most ethnically, culturally, and religiously diverse regions in China. The majority of its women have never been screened for cervical cancer. It is not known whether women would feel comfortable and ultimately even prefer using a human papillomavirus (HPV) self-swabbing method. METHODS: In a 6-day period, 3,600 women were taught the role of HPV in cervical cancer. They were then given self-swabbing instructions. After obtaining their specimens, 600 women were interviewed about their experience with HPV self-testing. The women were of the Yi, Hui, Dai, and Han ethnicities. RESULTS: The overwhelming majority of the women surveyed understood the self-sampling instructions (588/600, 98%) and felt comfortable carrying out the self-sampling procedure (584/600, 97%). Significantly more women (389/600, 64.8%) preferred self-sampling to having the provider (211/600, 35.2%) obtain the sample (χ = 105.61, p < .05). Women who preferred self-sampling did so primarily because they felt capable of obtaining the specimens (n = 80) or that it was a more convenient way to be tested (n = 79). The medical expertise of the provider (n = 74) and concerns over the accuracy of the test (n = 88) shifted some women's preference toward a provider-obtained sample. CONCLUSIONS: There are 400+ million Chinese women who have never had a cervical cancer screening. Self-testing has the potential to significantly increase the number of women tested. Despite the diversity of the women screened, the majority felt comfortable self-sampling and preferred self-swabbing to provider testing.

Ring finger protein 31-mediated atypical ubiquitination stabilizes forkhead box P3 and thereby stimulates regulatory T-cell function.

The CD4+CD25+FOXP3+ regulatory T (Treg) cells are critical for maintaining immune tolerance in healthy individuals and are reported to restrict anti-inflammatory responses and thereby promote tumor progression, suggesting them as a target in the development of antitumor immunotherapy. Forkhead box P3 (FOXP3) is a key transcription factor governing Treg lineage differentiation and their immune-suppressive function. Here, using Treg cells, as well as HEK-293T and Jurkat T cells, we report that the stability of FOXP3 is directly and positively regulated by the E3 ubiquitin ligase ring finger protein 31 (RNF31), which catalyzes the conjugation of atypical ubiquitin chains to the FOXP3 protein. We observed that shRNA-mediated RNF31 knockdown in human Treg cells decreases FOXP3 protein levels and increases levels of interferon-γ, resulting in a Th1 helper cell-like phenotype. Human Treg cells that ectopically expressed RNF31 displayed stronger immune-suppressive capacity, suggesting that RNF31 positively regulates both FOXP3 stability and Treg cell function. Moreover, we found that RNF31 is up-regulated in Treg cells that infiltrate human gastric tumor tissues compared with their counterparts residing in peripheral and normal tissue. We also found that elevated RNF31 expression in intratumoral Treg cells is associated with poor survival of gastric cancer patients, suggesting that RNF31 supports the immune-suppressive functions of Treg cells. Our results suggest that RNF31 could be a potential therapeutic target in immunity-based interventions against human gastric cancer.

Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

Preeclampsia (PE), a hypertensive disorder of pregnancy, is a leading cause of maternal and fetal morbidity and mortality. Although the etiology is unknown, PE is thought to be caused by defective implantation and decidualization in pregnancy. Pregnant blood pressure high (BPH)/5 mice spontaneously develop placentopathies and maternal features of human PE. We hypothesized that BPH/5 implantation sites have transcriptomic alterations. Next-generation RNA sequencing of implantation sites at peak decidualization, embryonic day (E)7.5, revealed complement gene up-regulation in BPH/5 vs. controls. In BPH/5, expression of complement factor 3 was increased around the decidual vasculature of E7.5 implantation sites and in the trophoblast giant cell layer of E10.5 placentae. Altered expression of VEGF pathway genes in E5.5 BPH/5 implantation sites preceded complement dysregulation, which correlated with abnormal vasculature and increased placental growth factor mRNA and VEGF164 expression at E7.5. By E10.5, proangiogenic genes were down-regulated, whereas antiangiogenic sFlt-1 was up-regulated in BPH/5 placentae. We found that early local misexpression of VEGF genes and abnormal decidual vasculature preceded sFlt-1 overexpression and increased complement deposition in BPH/5 placentae. Our findings suggest that abnormal decidual angiogenesis precedes complement activation, which in turn contributes to the aberrant trophoblast invasion and poor placentation that underlie PE.-Sones, J. L., Merriam, A. A., Seffens, A., Brown-Grant, D.-A., Butler, S. D., Zhao, A. M., Xu, X., Shawber, C. J., Grenier, J. K., Douglas, N. C. Angiogenic factor imbalance precedes complement deposition in placentae of the BPH/5 model of preeclampsia.

Celecoxib restores angiogenic factor expression at the maternal-fetal interface in the BPH/5 mouse model of preeclampsia.

Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface. We have previously described improvement in maternal hypertension and fetal growth restriction in this model after treatment with the anti-inflammatory cyclooxygenase-2 (Cox2) specific inhibitor celecoxib. To further characterize the mechanisms by which celecoxib improves poor pregnancy outcomes in BPH/5 mice, we determined expression of angiogenic factors and complement pathway components after celecoxib. In BPH/5 implantation sites there was increased hypoxia inducible factor-1α ( Hif1α), heme oxygenase-1 ( Ho-1), and stem cell factor ( Scf) mRNA concomitant with elevated prostaglandin synthase 2 ( Ptgs2), encoding Cox2, and elevated VEGF protein. Angiopoietin 1 ( Ang1), tunica interna endothelial cell kinase-2 receptor ( Tie2), complement factor 3 ( C3), and complement factor B ( CfB) were increased in midgestation BPH/5 placentae. Whereas BPH/5 expression levels of VEGF, Ang1, and Tie2 normalized after celecoxib, placental C3 and CfB mRNA remained unchanged. However, celecoxib did reduce the pregnancy-specific circulating soluble fms-like tyrosine kinase-1 (sFlt-1) rise in BPH/5 mice at midgestation. These data show that elevated Cox2 during implantation contributes to placental angiogenic factor imbalances in the BPH/5 mouse model of PE.

[Treatment of Idiopathic Thrombocytopenic Purpura by Xiaoban Decoction: a Case Observation of 119 Patients].

Objective To observe the clinical effect of Xiaoban Decoction (XBD) in treating idio- pathic thrombocytopenic purpura (ITP). Methods Totally 119 ITP patients were treated by XBD. The he- mogram, bleeding symptoms, effective rate, and adverse reactions were observed before and after treatment. Patient condition was observed while taking XBD but with other treatment program withdrawal (including glucocorticoids). Results After 6 -18 months of treatment, WBC count, hemoglobin concen- tration, and platelet count were all increased, as compared before treatment. Complete relief (CR) oc- curred in 57 cases (platelet count≥100 x109/L) , response(R) in 27 cases (platelet count≥50 x109/L) , no relief (NR) in 35 cases (platelet count <50 x109/L). The total effective rate was 70. 6%. Bleeding symptoms were improved after one-month treatment. There were 70 patients using glucocorticoids before taking XBD. No withdrawal crisis occurred after rapid withdrawal. No adverse reaction occurred, except increased times of passing stool. Seven patients were pregnant during follow-up and gave birth safely lat- er. Conclusions XBD, independent of glucocorticoids, could rapidly improve bleeding symptoms and steadily elevate platelet count. It was an effectively long-lasting treatment of Chinese medicine.

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.

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 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.

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.

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.

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.

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.

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.

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.