Accelerated Musculoskeletal Magnetic Resonance Imaging.

With a substantial growth in the use of musculoskeletal MRI, there has been a growing need to improve MRI workflow, and faster imaging has been suggested as one of the solutions for a more efficient examination process. Consequently, there have been considerable advances in accelerated MRI scanning methods. This article aims to review the basic principles and applications of accelerated musculoskeletal MRI techniques including widely used conventional acceleration methods, more advanced deep learning-based techniques, and new approaches to reduce scan time. Specifically, conventional accelerated MRI techniques, including parallel imaging, compressed sensing, and simultaneous multislice imaging, and deep learning-based accelerated MRI techniques, including undersampled MR image reconstruction, super-resolution imaging, artifact correction, and generation of unacquired contrast images, are discussed. Finally, new approaches to reduce scan time, including synthetic MRI, novel sequences, and new coil setups and designs, are also reviewed. We believe that a deep understanding of these fast MRI techniques and proper use of combined acceleration methods will synergistically improve scan time and MRI workflow in daily practice. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Ulnar neuropathy at the elbow: associations of pre-operative DTI parameters with clinical outcomes after cubital tunnel decompression.

OBJECTIVES: To evaluate whether DTI parameters of the ulnar nerve at the elbow are associated with clinical outcomes in patients receiving cubital tunnel decompression (CTD) surgery for ulnar neuropathy. METHODS: This retrospective study included 21 patients with cubital tunnel syndrome who received CTD surgery between January 2019 and November 2020. All patients underwent pre-operative elbow MRI, including DTI. Region-of-interest analysis was performed on the ulnar nerve at three levels around the elbow: above (level 1), cubital tunnel (level 2), and below (level 3). Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated on three sections at each level. Clinical data on symptom improvement in respect to pain and tingling sensation after CTD were recorded. Logistic regression analysis was used to compare DTI parameters of the nerve at three levels and the entire nerve course between patients with and without symptom improvement after CTD. RESULTS: After CTD, 16 patients showed improvement in symptoms, but five did not. ROC analysis of DTI parameters showed that AUCs of FA, AD, and MD were higher at level 1 than at levels 2 and 3, with FA showing the highest AUC (level 1: FA, 0.7104 [95% CI, 0.5206-0.9002] vs AD, 0.6521 [95% CI, 0.4900-0.8142] vs MD, 0.6153 [95% CI, 0.4187-0.8119]). CONCLUSION: In patients who underwent CTD surgery for ulnar neuropathy at the elbow, the DTI parameters of FA, AD, and MD above the cubital tunnel level were associated with clinical outcomes, with FA showing the strongest associations. KEY POINTS: • After CTD surgery for ulnar neuropathy at the elbow, persistent symptoms may be observed, depending on symptom severity. • DTI parameters of the ulnar nerve at the elbow showed differences in their capacity for discriminating between patients with and without symptom improvement following CTD surgery, with this capacity depending on the nerve level at the elbow. • FA, AD, and MD measured above the cubital tunnel on pre-operative DTI may be associated with surgical outcomes, with FA showing the strongest association (AUC at level 1, 0.7104 [95% CI, 0.5206-0.9002]).

Survival of children with trisomy 18 associated with the presence of congenital heart disease and intervention in the Republic of Korea.

BACKGROUND: Trisomy 18 syndrome (T18) is the second most common autosomal trisomy and has a high risk of fetal loss and stillbirth. Aggressive surgical treatments for the respiratory, cardiac, or digestive systems of patients with T18 were previously futile, while the results of recent studies are controversial. Over the past decade, there have been approximately 300,000 to 400,000 births annually in the Republic of Korea; however, there have been no nationwide studies on T18. This nationwide retrospective cohort study aimed to determine the prevalence of T18 in Korea and its prognosis according to the presence of congenital heart disease and relevant interventions. METHODS: This study utilized NHIS-registered data between 2008 and 2017. A child was defined as having T18 if the ICD-10 revision code Q91.0-3 was reported. Subgroup analysis was performed for children with congenital heart diseases, and survival rates were compared based on the history of cardiac surgical or catheter interventions. The primary outcomes in this study were the survival rate during the first hospitalization period and the 1-year survival rate. RESULTS: Of the children born between 2008 and 2017, 193 were diagnosed with T18. Of these, 86 died, with a median survival of 127 days. The 1-year survival rate for children with T18 was 63.2%. The survival rate in the first admission of children with T18 who did and did not have congenital heart disease was 58.3% and 94.1%, respectively. Children with heart disease who underwent surgical or catheter intervention had a longer survival time than those who did not. CONCLUSIONS: We suggest these data could be used in ante- and postnatal counseling. Ethical concerns about the prolonged survival of children with T18 remain; however, the potential benefits of interventions for congenital heart disease in this population need further study.

Small (≤5 cm) soft tissue tumors of the extremity and superficial trunk: MRI features and demographic characteristics associated with malignancy.

BACKGROUND: Although a substantial proportion of small soft tissue tumors are malignant, magnetic resonance imaging (MRI) features and demographic characteristics associated with these tumors have not been well described. PURPOSE: To investigate the MRI features and demographic characteristics associated with small (≤5 cm) malignant soft tissue tumors, and to identify independent predictors that allow differentiation of small benign and malignant soft tissue tumors. MATERIAL AND METHODS: This retrospective study evaluated patients who underwent surgical excision of small soft tissue tumors of the extremities and superficial trunk, and preoperative contrast-enhanced MRI. Seven MRI findings (tumor depth, tumor-fascia relationship, heterogeneity of signal intensity, necrosis, peritumoral edema, peritumoral enhancement, and margin) and two demographic parameters (age and sex) were included in univariate and multivariate logistic regression analyses to identify independent predictors of small malignant soft tissue tumors. RESULTS: A total of 221 patients (102 men; mean age=45.6 ± 17.6 years) with 72 malignant and 149 benign tumors were included. In the univariate analysis, peritumoral edema (odds ratio [OR] = 3.854; P < 0.001) and peritumoral enhancement (OR = 3.966; P < 0.001) and patient age (≥46 years) (OR = 2.154; P = 0.009) were significantly associated with malignancy. Multivariate analysis showed that peritumoral enhancement on MRI (OR = 3.728; P < 0.001) and patient age (≥46 years) (OR = 1.907; P = 0.036) were independent predictors of malignancy. The combination of these two parameters showed accuracy of 75.1%, sensitivity of 55.6%, and specificity of 84.6% to predict malignancy. CONCLUSION: Among several MRI and demographic features, the presence of peritumoral enhancement on MRI and patient age (≥46 years) were independent predictors of malignancy in small soft tissue tumors.

Dental students' perception of their educational environment in relation to their satisfaction with dentistry major: a cross-sectional study.

BACKGROUND: Students' perception of their educational environment and satisfaction with their major can reveal the extent of their readiness to practice their profession after graduation. This study aimed to evaluate dental students' perception of their educational environment and satisfaction with their major in dentistry, as well as the relationship between these two factors. METHODS: An online survey was conducted in 2022 among first- to fourth-year students across 11 dental schools in Korea. The Dundee Ready Education Environment Measure (DREEM) and Academic Major Satisfaction Scale (AMSS) were used to measure the students' perception of the educational environment and satisfaction with their major in dentistry, respectively. RESULTS: A total of 539 students participated in the survey (response rate = 18.1%). The overall mean scores of the DREEM and AMSS were 125.03 (maximum score 200) and 22.01 (maximum score 30), respectively. Fourth-year students had the lowest scores in the overall DREEM, DREEM subscales (excluding students' perceptions of atmosphere), and AMSS. The overall DREEM scores and all DREEM subscales showed statistically significant positive and moderate correlations with AMSS (p < 0.001). CONCLUSION: Using the DREEM, we identified areas that need improvement and the academic year (fourth year) that require proactive support. Considering the positive correlation between all DREEM subscales and the AMSS, measures to comprehensively improve the educational environment are needed to improve dental students' satisfaction with their major.

[Public health situation of CIDP patients in nine German centers-neuritis network Germany]. / Versorgungssituation von CIDP-Patienten in neun deutschen Zentren des Neuritis Netzes.

BACKGROUND: Diagnosis and treatment of patients with immune-mediated neuropathies is challenging due to the heterogeneity of the diseases. OBJECTIVES: To assess similarities and differences in the current care of patients with immune-mediated polyneuropathies in specialized centers in Germany within the German neuritis network "Neuritis Netz". MATERIAL AND METHODS: We conducted a cross-sectional survey of nine neurological departments in Germany that specialize in the care of patients with immune-mediated neuropathies. We assessed the diagnosis, the approach to diagnostic work-up and follow-up, typical symptoms at manifestation and progression of the disease, and treatment data. RESULTS: This report includes data from 1529 patients per year treated for immune-mediated neuropathies, of whom 1320 suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnostic work-up almost always included nerve conduction studies, electromyography, and lumbar puncture in accordance with current guidelines. The use of ultrasound, biopsy, and MRI varied. The most important clinical parameter for therapy monitoring in all centers was motor function in the clinical follow-up examinations. A wide range of different immunosuppressants was used for maintenance therapy in about 15% of patients. CONCLUSIONS: These data provide important epidemiological insights into the care of patients with immune-mediated neuropathies in Germany. The further development of specific recommendations for treatment and follow-up examinations is necessary to ensure a uniform standard of patient care. This effort is greatly facilitated by a structured collaboration between expert centers such as Neuritis Netz.

Concept map-based learning in an oral radiographic interpretation course: Dental students' perceptions of its role as a learning tool.

OBJECTIVES: Concept mapping is used to promote critical thinking and meaningful learning in health professions education. This study aimed to evaluate dental undergraduates' perceptions of concept mapping as a learning tool for oral radiographic interpretation competency. METHODS: A total of 39 third-year undergraduates at a dental college participated in the oral radiological interpretation session. The students received 1 hour of instruction before creating their concept map (CM). Participants were provided an assignment of four relevant clinical cases to draw an individualised CM. The students' draft and final CM were submitted. The instructor evaluated the CMs to identify whether students could analyse, connect and organise the information in a meaningful way. Among them, 37 completed the questionnaire about their experiences and responses to concept mapping. RESULTS: Students perceived concept mapping positively. The instructor's feedback helped them recognise their misconceptions and fostered greater motivation to learn. Students attempted to integrate basic biomedical knowledge and clinical features through cross-linking. However, they also expressed negative attitudes toward concept mapping regarding time consumption and heavy burden. CONCLUSIONS: Concept mapping motivated students' directed learning and gave them the opportunity to recognise their misconceptions. This study suggests the potential use of CMs as an adjunctive learning strategy in the oral radiographic interpretation class.

Endothelin 2: a key player in ovulation and fertility.

Ovulation is the fundamental biological process during which an oocyte is expelled from the ovary, and it is an essential step toward establishing a pregnancy. Understanding regulatory mechanisms governing the ovulation process is essential for diagnosing and treating causes of infertility, identifying contraceptive targets, and developing novel contraception methods. Endothelin-2 (EDN2) is a 21 amino acid-long peptide that is transiently synthesized by granulosa cells of the ovulatory follicle prior to ovulation and plays an essential role in ovulation via promoting contraction in the myofibroblast cells of the theca layer of the follicle. This review describes the organization of the endothelin system, summarizes recent findings on the expression and synthesis of the endothelin system in the ovary, illustrates the roles that EDN2 plays in regulating ovulation, and discusses EDN2 as a potential target of contraception.

Quality of recovery in patients administered remimazolam versus those administered an inhalant agent for the maintenance of general anesthesia: a randomized control trial.

BACKGROUND: Remimazolam is a novel intravenous benzodiazepine that is appropriate for the maintenance of anesthesia. Quality of recovery is an important component of health care quality, but there is no published randomized control trial focused on the quality of recovery in patients undergoing total intravenous anesthesia with remimazolam. METHODS: This parallel-group, single-blind randomized control trial at a tertiary care medical center in South Korea was conducted to determine the difference in the quality of recovery between the patients administered remimazolam and those administered an inhalant anesthetic agent. A total of 168 patients aged 19-65 years who underwent elective laparoscopic cholecystectomy or robotic gynecologic surgery were considered for enrollment. Randomization was performed using sealed envelopes containing computer-generated random allocation sequences. Remimazolam was administered for the maintenance of anesthesia in the remimazolam group (Group R), and desflurane was administered in the desflurane group (Group D). The induction protocol and the target value of the bispectral index were identical in both groups. Patients were blinded to the drug that was administered until they finished the postoperative questionnaire. The main outcome measure was the decrement of the QoR-40 score on postoperative day 1 compared to the QoR-40 score on the day before surgery. RESULTS: A total of 165 patients were analyzed. The preoperative and postoperative global QoR-40 scores were 183 and 152 (IQR 173-192 and 136-169), respectively. The perioperative decrement of the global QoR-40 score was 29.96 ± 22.49. The decrement of the QoR-40 score was smaller in Group R than in Group D (26.99 versus 32.90, respectively; mean difference 5.91, 95% confidence interval -0.96-12.79). After adjustment for sex, the type of surgery and surgical time, the administration of remimazolam resulted in a 7.03-point (95% CI 0.35-13.72) less decrement of the QoR-40 score than desflurane. There were no severe adverse events in either group. CONCLUSION: Total intravenous anesthesia maintained with remimazolam provides a better quality of recovery than anesthesia maintained with an inhalant agent in patients undergoing laparoscopic surgery. Additionally, postoperative nausea and vomiting were largely reduced with remimazolam. TRIAL REGISTRATION: KCT0006288 , Clinical Research Information Service (CRIS), Republic of Korea Registration date: 23/06/2021.

Assessment of central cartilaginous tumor of the appendicular bone: inter-observer and intermodality agreement and comparison of diagnostic performance of CT and MRI.

BACKGROUND: Diagnostic performance, inter-observer agreement, and intermodality agreement between computed tomography (CT) and magnetic resonance imaging (MRI) in the depiction of the major distinguishing imaging features of central cartilaginous tumors have not been investigated. PURPOSE: To determine the inter-observer and intermodality agreement of CT and MRI in the evaluation of central cartilaginous tumors of the appendicular bones, and to compare their diagnostic performance. MATERIAL AND METHODS: Two independent radiologists retrospectively reviewed preoperative CT and MRI. Inter-observer and intermodality agreement between CT and MRI in the assessment of distinguishing imaging features, including lesion size, deep endosteal scalloping, cortical expansion, cortical disruption, pathologic fracture, soft tissue extension, and peritumoral edema, were evaluated. The agreement with histopathology and the accuracy of the radiologic diagnoses made with CT and MRI were also analyzed. RESULTS: A total of 72 patients were included. CT and MRI showed high inter-observer and intermodality agreements with regard to size, deep endosteal scalloping, cortical expansion, cortical disruption, and soft tissue extension (ICC = 0.96-0.99, k = 0.60-0.90). However, for the evaluation of pathologic fracture, MRI showed only moderate inter-observer agreement (k = 0.47). Peritumoral edema showed only fair intermodality agreement (k = 0.28-0.33) and moderate inter-observer agreement (k = 0.46) on CT. Both CT and MRI showed excellent diagnostic performance, with high agreement with the histopathology (k = 0.89 and 0.87, respectively) and high accuracy (91.7% for both CT and MRI). CONCLUSION: CT and MRI showed high inter-observer and intermodality agreement in the assessment of several distinguishing imaging features of central cartilaginous tumors of the appendicular bones and demonstrated comparable diagnostic performance.

Diagnostic performance of computed tomography and diffusion-weighted imaging as first-line imaging modality according to the International Myeloma Working Group (IMWG) imaging algorithm for monoclonal plasma cell disorders.

BACKGROUND: The latest International Myeloma Working Group (IMWG) guideline recommends low-dose whole-body (WB) computed tomography (CT) as the first-line imaging technique for the initial diagnosis of plasma cell disorders. PURPOSE: To evaluate diagnostic performances of CT and diffusion-weighted imaging (DWI) as the first-line imaging modalities and assess misclassification rates obtained following the guideline. MATERIAL AND METHODS: Two independent radiologists analyzed CT (acquired as PET/CT) and DWI (3-T; b-values = 50 and 900 s/mm2) of patients newly diagnosed with plasma cell disorder, categorizing the number of bone lesions. Diagnostic performance of CT and DWI was compared using the McNemar test, and misclassification rates were calculated with a consensus WB-MRI reading as the reference standard. Differences in lesion number categories were assessed using marginal homogeneity and kappa statistics. RESULTS: Of 56 patients (36 men; mean age = 63.5 years), 39 had myeloma lesions. DWI showed slightly higher sensitivity for detecting myeloma lesions (97.4%) than CT (84.6%-92.3%; P > 0.05). CT showed significantly higher specificity (88.2%) than DWI (52.9%-58.8%; P<0.05). CT had a higher additional study requirement rate than DWI (7.7%-15.4% vs. 2.6%), but a lower unnecessary treatment rate (11.8% vs. 41.2%-47.1%). Both readers showed significant differences in categorization of the number of lesions on CT compared with the reference standard (P < 0.001), and one reader showed a significant difference on DWI (P = 0.006 and 0.098). CONCLUSION: CT interpreted according to the IMWG guideline is a diagnostically effective first-line modality with relatively high sensitivity and specificity. DWI alone may not be an acceptable first-line imaging modality because of low specificity.

Reconstruction of the coracoclavicular ligament with palmaris longus tendon and Mersilene tape for acromioclavicular dislocations.

BACKGROUND: Acromioclavicular (AC) joint dislocation is common among shoulder injuries, and various surgical methods have been introduced for effective ligament reconstruction. Reconstruction of the coracoclavicular (CC) ligament in the anatomical position using autologous tendons is a recent surgical trend. This study is to report clinical and radiologic results of reconstruction of the CC ligament using an autologous palmaris longus tendon interweaved with Mersilene tape (PLMT) with a minimum 2-year follow-up. METHODS: This retrospective study analyzed 76 patients (mean age, 43.4 ± 11.2 years) with AC joint dislocation treated by reconstruction of the CC ligament with PLMT, from March 2004 to February 2017. The mean follow-up period was 28 ± 6.7 months (range, 24-66 months). The Visual Analog Scale (VAS) for pain assessment, American Shoulder and Elbow Surgeons rating scale (ASES), and Constant Score (CS) were used to evaluate clinical outcomes at the preoperative and the final follow-ups. CC and AC distances were measured using anteroposterior (AP) X-ray preoperatively and at the final follow-up for radiologic outcomes. Complications were also assessed. RESULTS: The mean preoperative VAS for pain, ASES, CS were 5.7 ± 0.7, 77.1 ± 6.2, and 61.5 ± 5.2, respectively. These scores at the final follow-up improved to 2.1 ± 0.5, 90.9 ± 4.3, and 94 ± 7.0, respectively (p = 0.043, p <  0.001, p <  0.001). The mean preoperative CC and AC distances were 16.49 ± 3.73 mm and 13.84 ± 3.98 mm, respectively. The final follow-up CC and AC distances were 9.29 ± 2.72 mm and 5.30 ± 2.09 mm, respectively (p <  0.001, p <  0.001). Although a slight re-widening of the CC distance occurred in 10 patients (13.1%), most patients regained full range of motion of the affected shoulder at the final follow-up. CONCLUSION: The CC ligament reconstruction with PLMT for the treatment of AC joint dislocation showed good clinical and radiological results. This technique could be a good alternative treatment for AC dislocations.

Surface Properties of CVD-Grown Graphene Transferred by Wet and Dry Transfer Processes.

Graphene, an atomically thin material, has unique electrical, mechanical, and optical properties that can enhance the performance of thin film-based flexible and transparent devices, including gas sensors. Graphene synthesized on a metallic catalyst must first be transferred onto a target substrate using wet or dry transfer processes; however, the graphene surface is susceptible to chemical modification and mechanical damage during the transfer. Defects on the graphene surface deteriorate its excellent intrinsic properties, thus reducing device performance. In this study, the surface properties of transferred graphene were investigated according to the transfer method (wet vs. dry) and characterized using atomic force microscopy, Raman spectroscopy, and contact angle measurements. After the wet transfer process, the surface properties of graphene exhibited tendencies similar to the poly(methyl methacrylate) residue remaining after solvent etching. The dry-transferred graphene revealed a surface closer to that of pristine graphene, regardless of substrates. These results provide insight into the utilization of wet and dry transfer processes for various graphene applications.

A JUN N-terminal kinase inhibitor induces ectodomain shedding of the cancer-associated membrane protease Prss14/epithin via protein kinase CßII.

Serine protease 14 (Prss14)/epithin is a transmembrane serine protease that plays essential roles in tumor progression and metastasis and therefore is a promising target for managing cancer. Prss14/epithin shedding may underlie its activity in cancer and worsen outcomes; accordingly, a detailed understanding of the molecular mechanisms in Prss14/epithin shedding may inform the design of future cancer therapies. On the basis of our previous observation that an activator of PKC, phorbol 12-myristate 13-acetate (PMA), induces Prss14/epithin shedding, here we further investigated the intracellular signaling pathway involved in this process. While using mitogen-activated protein kinase inhibitors to investigate possible effectors of downstream PKC signaling, we unexpectedly found that an inhibitor of c-Jun N-terminal kinase (JNK), SP600125, induces Prss14/epithin shedding even in the absence of PMA. SP600125-induced shedding, like that stimulated by PMA, was mediated by tumor necrosis factor-α-converting enzyme. In contrast, a JNK activator, anisomycin, partially abolished the effects of SP600125 on Prss14/epithin shedding. Moreover, the results from loss-of-function experiments with specific inhibitors, short hairpin RNA-mediated knockdown, and overexpression of dominant-negative PKCßII variants indicated that PKCßII is a major player in JNK inhibition- and PMA-mediated Prss14/epithin shedding. SP600125 increased phosphorylation of PKCßII and tumor necrosis factor-α-converting enzyme and induced their translocation into the plasma membrane. Finally, in vitro cell invasion experiments and bioinformatics analysis of data in The Cancer Genome Atlas breast cancer database revealed that JNK and PKCßII are important for Prss14/epithin-mediated cancer progression. These results provide important information regarding strategies against tumor metastasis.

Three-dimensional microengineered vascularised endometrium-on-a-chip.

STUDY QUESTION: Can we reconstitute physiologically relevant 3-dimensional (3D) microengineered endometrium in-vitro model? SUMMARY ANSWER: Our representative microengineered vascularised endometrium on-a-chip closely recapitulates the endometrial microenvironment that consists of three distinct layers including epithelial cells, stromal fibroblasts and endothelial cells in a 3D extracellular matrix in a spatiotemporal manner. WHAT IS KNOWN ALREADY: Organ-on-a-chip, a multi-channel 3D microfluidic cell culture system, is widely used to investigate physiologically relevant responses of organ systems. STUDY DESIGN, SIZE, DURATION: The device consists of five microchannels that are arrayed in parallel and partitioned by array of micropost. Two central channels are for 3D culture and morphogenesis of stromal fibroblast and endothelial cells. In addition, the outermost channel is for the culture of additional endometrial stromal fibroblasts that secrete biochemical cues to induce directional pro-angiogenic responses of endothelial cells. To seed endometrial epithelial cells, on Day 8, Ishikawa cells were introduced to one of the two medium channels to adhere on the gel surface. After that, the microengineered endometrium was cultured for an additional 5-6 days (total ∼ 14 days) for the purpose of each experiment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Microfluidic 3D cultures were maintained in endothelial growth Medium 2 with or without oestradiol and progesterone. Some cultures additionally received exogenous pro-angiogenic factors. For the three distinct layers of microengineered endometrium-on-a-chip, the epithelium, stroma and blood vessel characteristics and drug response of each distinct layer in the microfluidic model were assessed morphologically and biochemically. The quantitative measurement of endometrial drug delivery was evaluated by the permeability coefficients. MAIN RESULTS AND THE ROLE OF CHANCE: We established microengineered vascularised endometrium-on-chip, which consists of three distinct layers: epithelium, stroma and blood vessels. Our endometrium model faithfully recapitulates in-vivo endometrial vasculo-angiogenesis and hormonal responses displaying key features of the proliferative and secretory phases of the menstrual cycle. Furthermore, the effect of the emergency contraception drug levonorgestrel was evaluated in our model demonstrating increased endometrial permeability and blood vessel regression in a dose-dependent manner. We finally provided a proof of concept of the multi-layered endometrium model for embryo implantation, which aids a better understanding of the molecular and cellular mechanisms underlying this process. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This report is largely an in-vitro study and it would be beneficial to validate our findings using human primary endometrial cells. WIDER IMPLICATIONS OF THE FINDINGS: Our 3D microengineered vascularised endometrium-on-a-chip provides a new in-vitro approach to drug screening and drug discovery by mimicking the complicated behaviours of human endometrium. Thus, we suggest our model as a tool for addressing critical challenges and unsolved problems in female diseases, such as endometriosis, uterine cancer and female infertility, in a personalised manner. STUDY FUNDING/COMPETING INTEREST(S): This work is supported by funding from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) to Y.J.K. (No. 2018R1C1B6003), to J.A. (No. 2020R1I1A1A01074136) and to H.S.K. (No. 2020R1C1C100787212). The authors report no conflicts of interest.

Combined radiomics-clinical model to predict malignancy of vertebral compression fractures on CT.

OBJECTIVES: To develop and validate a combined radiomics-clinical model to predict malignancy of vertebral compression fractures on CT. METHODS: One hundred sixty-five patients with vertebral compression fractures were allocated to training (n = 110 [62 acute benign and 48 malignant fractures]) and validation (n = 55 [30 acute benign and 25 malignant fractures]) cohorts. Radiomics features (n = 144) were extracted from non-contrast-enhanced CT images. Radiomics score was constructed by applying least absolute shrinkage and selection operator regression to reproducible features. A combined radiomics-clinical model was constructed by integrating significant clinical parameters with radiomics score using multivariate logistic regression analysis. Model performance was quantified in terms of discrimination and calibration. The model was internally validated on the independent data set. RESULTS: The combined radiomics-clinical model, composed of two significant clinical predictors (age and history of malignancy) and the radiomics score, showed good calibration (Hosmer-Lemeshow test, p > 0.05) and discrimination in both training (AUC, 0.970) and validation (AUC, 0.948) cohorts. Discrimination performance of the combined model was higher than that of either the radiomics score (AUC, 0.941 in training cohort and 0.852 in validation cohort) or the clinical predictor model (AUC, 0.924 in training cohort and 0.849 in validation cohort). The model stratified patients into groups with low and high risk of malignant fracture with an accuracy of 98.2% in the training cohort and 90.9% in the validation cohort. CONCLUSIONS: The combined radiomics-clinical model integrating clinical parameters with radiomics score could predict malignancy in vertebral compression fractures on CT with high discriminatory ability. KEY POINTS: • A combined radiomics-clinical model was constructed to predict malignancy of vertebral compression fractures on CT by combining clinical parameters and radiomics features. • The model showed good calibration and discrimination in both training and validation cohorts. • The model showed high accuracy in the stratification of patients into groups with low and high risk of malignant vertebral compression fractures.

Profilin-1; a novel regulator of DNA damage response and repair machinery in keratinocytes.

Profilin-1 (PFN1) regulates actin polymerization and cytoskeletal growth. Despite the essential roles of PFN1 in cell integration, its subcellular function in keratinocyte has not been elucidated yet. Here we characterize the specific regulation of PFN1 in DNA damage response and repair machinery. PFN1 depletion accelerated DNA damage-mediated apoptosis exhibiting PTEN loss of function instigated by increased phosphorylated inactivation followed by high levels of AKT activation. PFN1 changed its predominant cytoplasmic localization to the nucleus upon DNA damage and subsequently restored the cytoplasmic compartment during the recovery time. Even though γH2AX was recruited at the sites of DNA double strand breaks in response to DNA damage, PFN1-deficient cells failed to recruit DNA repair factors, whereas control cells exhibited significant increases of these genes. Additionally, PFN1 depletion resulted in disruption of PTEN-AKT cascade upon DNA damage and CHK1-mediated cell cycle arrest was not recovered even after the recovery time exhibiting γH2AX accumulation. This might suggest PFN1 roles in regulating DNA damage response and repair machinery to protect cells from DNA damage. Future studies addressing the crosstalk and regulation of PTEN-related DNA damage sensing and repair pathway choice by PFN1 may further aid to identify new mechanistic insights for various DNA repair disorders.

Diagnostic performance of plain radiography for sacroiliitis in patients with suspected axial spondyloarthritis: a systematic review and meta-analysis.

BACKGROUND: Plain radiography serves a pivotal role in diagnosing axial spondyloarthritis. However, a broad range of diagnostic performance of plain radiography has been reported. PURPOSE: To perform a systematic review and meta-analysis to measure the diagnostic performance of plain radiography for sacroiliitis in patients suspected of having axial spondyloarthritis using magnetic resonance imaging (MRI) findings as the reference standard. MATERIAL AND METHODS: Studies comparing radiography and MRI in the diagnosis of sacroiliitis in patients suspected of having axial spondyloarthritis were searched in PubMed and EMBASE. Additionally, studies analyzed SPondyloaArthritis Caught Early (SPACE), DEvenir des Spondylarthropathies Indifferenciées Récentes (DESIR), GErman Spondyloarthritis Inception Cohort (GESPIC), and South Swedish Arthritis Treatment Group (SSATG) cohorts were manually searched. Pooled sensitivity and specificity of radiography were calculated by using a bivariate random-effects model. Meta-regression analyses were performed to identify the sources of heterogeneity. RESULTS: Eight eligible studies with 1579 patients were included. The pooled sensitivity and specificity of radiography were 0.55 (95% confidence interval [CI] = 0.40-0.69) and 0.87 (95% CI = 0.72-0.95). The meta-regression analyses showed prospective study design and criteria for MRI positivity considering only active bone marrow edema were associated with lower sensitivity. CONCLUSION: The plain radiography showed low sensitivity and reasonable specificity in diagnosis of sacroiliitis in patients suspected of having axial spondyloarthritis.

New Approaches to Critical Illness Polyneuromyopathy: High-Resolution Neuromuscular Ultrasound Characteristics and Cytokine Profiling.

BACKGROUND: Diagnosis of intensive care unit acquired weakness (ICUAW) is challenging. Pathogenesis of underlying critical illness polyneuromyopathy (CIPNM) remains incompletely understood. This exploratory study investigated whether longitudinal neuromuscular ultrasound examinations and cytokine analyses in correlation to classical clinical and electrophysiological assessment contribute to the understanding of CIPNM. METHODS: Intensive care unit patients were examined every 7 days until discharge from hospital. Clinical status, nerve conduction studies, electromyography as well as ultrasound of peripheral nerves and tibial anterior muscle were performed. Cytokine levels were analyzed by a bead-based multiplex assay system. RESULTS: Of 248 screened patients, 35 patients were included at median of 6 days (IQR: 8) after admission to intensive care unit. Axonal damage was the main feature of CIPNM. At the peak of CIPNM (7 days after inclusion), nerve ultrasound showed cross-sectional area increase of tibial nerve as a sign of inflammatory edema as well as hypoechoic nerves as a possible sign of inflammation. Cytokine analyses showed signs of monocyte and macrophage activation at this stage. Fourteen days after inclusion, cytokines indicated systemic immune response as well as profiles associated to neovascularization and regeneration. CONCLUSIONS: Exploratory neuromuscular ultrasound and cytokine analyses showed signs of inflammation like macrophage and monocyte activation at the peak of CIPNM followed by a systemic immune response parallel to axonal damage. This underlines the role of both axonal damage and inflammation in pathogenesis of CIPNM.

Intramembrane proteolysis of an extracellular serine protease, epithin/PRSS14, enables its intracellular nuclear function.

BACKGROUND: Epithin/PRSS14, a type II transmembrane serine protease, is an emerging target of cancer therapy because of its critical roles in tumor progression and metastasis. In many circumstances, the protease, through its ectodomain shedding, exists as a soluble form and performs its proteolytic functions in extracellular environments increasing cellular invasiveness. The seemingly functional integrity of the soluble form raises the question of why the protease is initially made as a membrane-associated protein. RESULTS: In this report, we show that the epithin/PRSS14 intracellular domain (EICD) can be released from the membrane by the action of signal peptide peptidase-like 2b (SPPL2b) after ectodomain shedding. The EICD preferentially localizes in the nucleus and can enhance migration, invasion, and metastasis of epithelial cancer when heterologously expressed. Unbiased RNA-seq analysis and subsequent antibody arrays showed that EICD could control the gene expression of chemokines involved in cell motility, by increasing their promoter activities. Finally, bioinformatics analysis provided evidence for the clinical significance of the intramembrane proteolysis of epithin/PRSS14 by revealing that the poor survival of estrogen receptor (ER)-negative breast cancer patients with high epithin/PRSS14 expression is further worsened by high levels of SPPL2b. CONCLUSIONS: These results show that ectodomain shedding of epithin/PRSS14 can initiate a unique and synchronized bidirectional signal for cancer metastasis: extracellularly broadening proteolytic modification of the surrounding environment and intracellularly reprogramming the transcriptome for metastatic conversion. Clinically, this study also suggests that the intracellular function of epithin/PRSS14 should be considered for targeting this protease for anti-cancer treatment.