Precessing jet nozzle connecting to a spinning black hole in M87.

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.

Pleomorphic dermal sarcoma presenting in a child with Li-Fraumeni syndrome: A case report and review of the literature.

Pleomorphic dermal sarcoma (PDS) is an uncommon malignant soft-tissue tumor that occurs mostly in elderly patients, with only 5% of cases occurring in children. However, pediatric patients with Li-Fraumeni syndrome (LFS) can develop several types of cancer, particularly sarcomas. Here, we describe a young LFS patient who presented with early-onset PDS and review the literature.

Clinical characteristics and survival analysis of cutaneous metastases in a single tertiary centre in Korea.

BACKGROUND: Cutaneous metastasis (CM) refers to the spread of malignancy to the skin. CM is perceived as an advanced stage. It might be the first sign of a primary cancer or an indicator of recurrence. OBJECTIVES: To identify primary cancers associated with CMs and perform a survival analysis according to advanced stage of cutaneous metastasis at a single tertiary centre in Korea. METHODS: A total of 219 patients from Samsung Medical Center from January 2009 to April 2020 were retrospectively analysed to identify cases with biopsy-proven CMs. According to advanced stage of metastasis, patients were divided into three stages, CM only (CMO), CM with lymph node metastasis (CM/LM) and CM with distant metastasis (CM/DM), to analyse clinical characteristics and survival rate. RESULTS: The most common CM from primary cancer was breast cancer, followed by lung cancer, stomach cancer, colorectal cancer and others. When all primary cancers were included, the median survival period was 4.82 years for the CMO stage, 2.15 years for the CM/LM stage and 0.80 years for the CM/DM stage, with a tendency to deteriorate with advancing stage. At 1- and 3-year after occurrence of CM, the CM/DM stage showed a significantly poorer survival rate than the other two stages. CONCLUSIONS: This study showed a median survival period of 22 months for CM patients overall. Breast cancer has greater accessibility to the skin than other cancers. Therefore, breast cancer can metastasize to the skin without involving lymph nodes or other sites.

Analyzing the contribution of gully erosion to land degradation in the upper Blue Nile basin, Ethiopia.

Soil erosion has become a worldwide problem that threatens the environment and the future of economic and social development. The purpose of this study is to investigate the contribution of steep slopes and gullies to erosion in high precipitation tropical areas of the Ethiopian highlands. A trapezoidal weir was installed at the head and tail of the gully to monitor the discharge and sediment concentration from 2017 to 2020. Sediment yield and runoff are heavily influenced by the amount and timing of precipitation. The coefficients of variation for total sediment loads ranged from 65.1 to 96.1% at the head and 17.1-78.1% at the tail; the lowest coefficients were found in 2018 and the highest in 2020. Furthermore, 85% of the sediment at the tail comes from the gully, according to the four-year sediment budget. Further, a hysteretic analysis of suspended sediment concentration and runoff revealed that hilly sediment sources are limited (clockwise), then sediment can be transported through the gully via bank failures (counterclockwise). Study findings contributed to a classification of runoff patterns and an investigation of suspended sediment dynamics. In the gully tail, sediment yield was higher than in the head, suggesting gully sediment contributed more to sediment yield than large upland catchments. As a result of the study, we have been able to develop practical recommendations for managing gully erosion in the future.

Distribution of cellular remnants of melanocytes in the nail plate: Clue to the diagnosis of subungual melanoma.

BACKGROUND: Previous studies reported that cellular remnants in the nail plate could be a diagnostic clue for subungual melanoma (SUM). We sought to characterize the histopathologic features of cellular remnants in the nail plates of SUM patients. METHODS: A retrospective case-control study was conducted in a single tertiary center from 2012 to 2019. Twenty-three patients with pathologically diagnosed SUM and eight nail matrix nevi (NMN) patients were recruited. The analysis of the nail plate specimens focused on large cellular remnants of melanocytes (LCRMs). Longitudinal linear density and vertical distribution pattern of the LCRMs were scrutinized for possible features distinguishing SUM from NMN. RESULTS: The median linear density of the LCRMs was significantly higher in the SUM samples than in the NMN samples. LCRMs in the SUM samples were more dorsally distributed than those in the NMN samples. In invasive SUM, LCRMs were more likely to be found in the dorsal part of the nail plate compared to SUM in situ. CONCLUSION: Nail plate specimens should not be overlooked in the histopathological examination of melanonychia. High-density LCRMs with more dispersion to the dorsal side might be suggestive of SUM.

Magnesium microneedle patches for under-eye wrinkles.

Microneedling is a common cosmetic procedure for improvement of wrinkles, acne, scars, and other conditions. Various microneedle (MN) patches have been developed as home care therapy for wrinkles and skin texture. Most of them are made of soluble and absorbable needles. To evaluate the efficacy and safety of non-absorbable magnesium (Mg) MN patches on under-eye wrinkles. A total of 20 subjects aged 27-58 years was enrolled in the study. The subjects applied Mg MN patches on the under-eye wrinkle area for 1-2 h every other night for 12 weeks. The evaluation comprised grading by clinicians, measuring the wrinkle index with a facial analyzer, and measuring the dermal thickness of the under-eye area with ultrasonography. Any adverse events and discomfort were addressed during the study. The application of Mg MN patches on under-eye areas showed improvements in under-eye grading scale, wrinkle index, and dermal thickness after 12 weeks. The mean grading scale significantly improved after 8 weeks of application (p < 0.01). The wrinkle index showed significant improvement after 12 weeks on the right under-eye area (p < 0.05). The dermal thickness of the under-eye area tended to increase, but no statistically significant changes were observed. Non-absorbable Mg MN patches can be used for under-eye wrinkles with minimal discomfort.

Hutchinson Sign: Biopsy May Assist in Diagnosis of Subungual Melanoma in Situ.

BACKGROUND: Early and accurate diagnosis of subungual melanoma (SUM) through histopathologic examination is critical, but lack of clinical suspicion leads to delays in diagnosis. Hutchinson sign (HS) can be one of the important clinical indicators for diagnosing SUM. OBJECTIVE: To evaluate the diagnostic value of small biopsies of HS for detecting SUM in situ. METHODS: We retrospectively evaluated 12 patients who were diagnosed as SUM in situ and underwent punch biopsy at HS areas. Clinical features, dermoscopic findings, and histopathologic findings in HS regions were analyzed. RESULTS: In most cases, HS was seen in hyponychium (11/12, 91.7%) with 1 case found in proximal nail fold, and 1 case in both the hyponychium and proximal nail fold. Dermoscopic features of HS showed irregular diffuse pigmentation (12/12, 100%) and parallel ridge pattern (7/12, 58.3%). Histopathologically, all cases showed irregularly scattered atypical melanocytes with hyperchromatic nuclei. Two cases showed subtle changes in melanocytes with little nuclear atypia, but additional section specimen showed more definitive findings of SUM in situ. CONCLUSION: We present a supplementary biopsy technique for diagnosing SUM. Biopsy of HS may help in the diagnosis of SUM.

Regulation of mRNA export through API5 and nuclear FGF2 interaction.

API5 (APoptosis Inhibitor 5) and nuclear FGF2 (Fibroblast Growth Factor 2) are upregulated in various human cancers and are correlated with poor prognosis. Although their physical interaction has been identified, the function related to the resulting complex is unknown. Here, we determined the crystal structure of the API5-FGF2 complex and identified critical residues driving the protein interaction. These findings provided a structural basis for the nuclear localization of the FGF2 isoform lacking a canonical nuclear localization signal and identified a cryptic nuclear localization sequence in FGF2. The interaction between API5 and FGF2 was important for mRNA nuclear export through both the TREX and eIF4E/LRPPRC mRNA export complexes, thus regulating the export of bulk mRNA and specific mRNAs containing eIF4E sensitivity elements, such as c-MYC and cyclin D1. These data show the newly identified molecular function of API5 and nuclear FGF2, and provide a clue to understanding the dynamic regulation of mRNA export.

Perioperative risk factors for new-onset postoperative atrial fibrillation among patients after isolated coronary artery bypass grafting: A retrospective study.

AIMS: Incidence of atrial fibrillation is considerably high after open heart surgery, which may prolong hospitalization and increase mortality. The aim of the present study is to investigate the perioperative risk factors for the occurrence of new-onset atrial fibrillation following isolated coronary artery bypass grafting. DESIGN: A retrospective study. METHODS: A total of 327 Korean patients recorded to have undergone first-time isolated coronary artery bypass grafting and no preoperative history of atrial fibrillation were included. The data were obtained from electronic health record from January 2010 to December 2019 at a tertiary care hospital. Predictors of new-onset atrial fibrillation after the surgery were identified by multivariate logistic regression analysis. RESULTS: The incidence rate of new-onset atrial fibrillation after coronary artery bypass grafting was approximately 28.4%, and the highest occurrence rate was 44.1% on postoperative day 2. Our main finding showed that advanced age was the strongest predictor of atrial fibrillation after coronary artery bypass grafting. In addition, history of stroke and depression, chronic obstructive pulmonary disease and intraoperative use of intra-aortic balloon pump were shown to be the risk factors. CONCLUSION: Our findings showed that approximately 28% patients had new-onset atrial fibrillation after the surgery. Healthcare professionals should proactively assess risk factors for postoperative atrial fibrillation and focus more on older adults with pre-existing comorbidities, such as stroke, depression and chronic obstructive pulmonary disease. IMPACT: Older adults with history of stroke, depression and comorbid chronic obstructive pulmonary disease should be carefully monitored closely during perioperative period. The study highlights that early assessment of new-onset postoperative atrial fibrillation can contribute to promote the quality of nursing care and frontline nurses may be a vital role in timely detection of atrial fibrillation after surgery. Prospective studies are required to identify the mechanisms connecting perioperative risk factors for atrial fibrillation after cardiac surgery.

The teamwork structure, process, and context of a paediatric cardiac surgery team in Mongolia: A mixed-methods approach.

INTRODUCTION: Effective teamwork in paediatric cardiac surgery is known to improve team performance and surgical outcomes. However, teamwork in low- and middle-income countries (LMICs), including Mongolia, is understudied. We examined multiple dimensions of teamwork to inform a team-based training programme to strengthen paediatric cardiac surgical care in Mongolia. METHODS: We used a mixed-methods approach, combining social network analysis and in-depth interviews with medical staff, to explore the structure, process, quality, and context of teamwork at a single medical centre. We conceptualised the team's structure based on communication frequency among the members (n = 24) and explored the process, quality, and context of teamwork via in-depth interviews with select medical staff (n = 9). RESULTS: The team structure was highly dense and decentralised, but the intensive care unit nurses showed high betweenness-centrality. In the quality and process domain of teamwork, we did not find a regular joint decision-making process, leading to the absence of common goals among the team members. Although role assignment among the medical staff was explicit, those strictly defined roles hindered active communication about patient information and responsibility-sharing. Most interviewees did not agree with the organisational policies that limited discussions among team members; therefore, medical staff continued to share training and work experiences with each other, leading to strong and trustworthy relationships. CONCLUSION: The findings of this study underscore the importance of well-structured and goal-oriented communication between medical staff, as well as the management of the quality of collaboration within a team to increase teamwork effectiveness in paediatric cardiac surgery teams in LMICs.

Anti-pollution skincare: Research on effective ways to protect skin from particulate matter.

While there is increasing interest in anti-pollution care to particulate matter (PM), there has been no research evaluating the efficacy of skin care products in a real-world setting. Our objective was to find effective ways to protect skin from PM. In total, 64 volunteers whose skin was classified as reactive to PM concentration in the previous study were enrolled. Through split-face study, different combinations of skin care products (barrier cream, barrier cream/micellar water, antioxidant, and antioxidant/micellar water) were applied for 4 weeks during the high-PM period. The biophysical properties were measured, and a facial analysis system was used to evaluate skin condition at days 0, 14, and 28. The concentrations of PM and daily events that may affect skin conditions were also recorded. The mean concentration levels of PM10 and PM2.5 from days 0 to 14 were higher in the barrier cream group than in the antioxidant group. For each group, aside from skin tone in the antioxidant/micellar water group, there were no statistically significant differences in skin measurements before and after the application, which reflects no aggravation in skin condition during high-PM periods. Intergroup analysis showed no differences in skin measurements among the four groups from day 0 to day 14, from day 14 to day 28, and from day 0 to 28. For anti-pollution care, maintaining skin barrier function using barrier cream seems to be sufficient in individuals sensitive to PM.

Duration of Oral Antibiotics Administration for Cetuximab-Induced Acneiform Eruption.

BACKGROUND: Acneiform eruption is the most common cutaneous adverse event associated with cetuximab. As it can affect quality of life and adversely affect chemotherapy schedule, additional medical care is required. OBJECTIVES: To investigate the adherence to and the duration of antibiotic administration to treat cetuximab-induced acneiform eruption. METHODS: Medical data of patients who were referred to the Department of Dermatology were reviewed from January 2013 to June 2018. Dermatologists assessed the severity of acneiform eruption and prescribed tetracycline-class antibiotics according to the severity every 2 or 4 weeks. We investigated the duration and amount of oral antibiotic administration and analyzed the factors that may affect the control of acneiform eruption statistically. RESULTS: A total of 207 of 267 patients referred to the Department of Dermatology showed acneiform eruption; 124 patients were treated with minocycline, 34 patients with doxycycline, 27 patients with both, and 22 patients with topical agents. The mean duration of oral antibiotic medication was 82.7 days. A statistical analysis of the factors that prolonged the use of antibiotics for more than 90 days showed that male and younger age were risk factors. Shorter time interval from starting cetuximab to starting antibiotics was associated with longer duration of antibiotic use, statistically. CONCLUSIONS: Cetuximab-induced acneiform eruption can be well controlled with tetracycline-class antibiotics in about 3 months. It can last longer in male and younger patients. The sooner and the more severe it appears, the longer it can last.

Effect of photobiomodulation therapy on radiodermatitis in a mouse model: an experimental animal study.

This study aimed to evaluate the effect of photobiomodulation (PBM) for prevention of radiodermatitis in an irradiated mouse model and compare the efficacy of PBM using 633- or 830-nm wavelengths. Irradiated mice were randomly distributed into three groups: A (633 nm), B (830 nm), and C (without PBM). On post-irradiation days 7 and 21, we compared acute damage and recovery in treated skin samples to non-irradiated skin using H&E, Masson's trichrome, anti-CD45 and PCNA immunohistochemistry, and a TUNEL assay. Grade 3 radiodermatitis was evident only in group C. Compared with that in group C, the skin in groups A and B had significantly less epidermal hyperplasia, inflammatory cell infiltration, and thinner dermis on day 7 and less inflammatory cell infiltration, fewer apoptotic cells, and thinner dermis on day 21. However, there was no significant difference between groups A and B. This study indicates PBM could prevent severe radiodermatitis by reducing epidermal and dermal damage, inflammation, and apoptosis. There was no difference in PBM efficacy between the 633- and 830-nm wavelengths.

Interaction between SCP3 and JAB1 Confers Cancer Therapeutic Resistance and Stem-like Properties through EGF Expression.

Synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, has been implicated in cancer progression, and therapeutic resistance, as well as cancer stem cell (CSC)-like properties. Previously, we demonstrated that SCP3 promotes these aggressive phenotypes via hyperactivation of the AKT signaling pathway; however, the underlying mechanisms responsible for SCP3-induced AKT activation remain to be elucidated. In this study, we demonstrated that the EGF-EGFR axis is the primary route through which SCP3 acts to activate AKT signaling. SCP3 triggers the EGFR-AKT pathway through transcriptional activation of EGF. Notably, neutralization of secreted EGF by its specific monoclonal antibody reversed SCP3-mediated aggressive phenotypes with a concomitant reversal of EGFR-AKT activation. In an effort to elucidate the molecular mechanisms underlying SCP3-induced transcriptional activation of EGF, we identified Jun activation domain-binding protein 1 (JAB1) as a binding partner of SCP3 using a yeast two-hybrid (Y2H) assay system, and we demonstrated that SCP3 induces EGF transcription through physical interaction with JAB1. Thus, our findings establish a firm molecular link among SCP3, EGFR, and AKT by identifying the novel roles of SCP3 in transcriptional regulation. We believe that these findings hold important implications for controlling SCP3high therapeutic-refractory cancer.

Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease.

BACKGROUND: The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. METHODS: Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n = 20), surgical endarterectomy (n = 9), or bypass surgery (n = 19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). RESULTS: Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4 ± 13.9 vs. 47.2 ± 13.6 U/L, P = 0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. CONCLUSIONS: Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.

The concept of nail matrix onychodermis (onychomatricodermis) in the nail unit: Histology and elastin immunohistochemistry.

BACKGROUNDS: We previously demonstrated the presence of onychodermis below nail matrix and nail bed. Because nail matrix is a producer of nail plate, we hypothesized that onychodermis below nail matrix could be the nail counterpart of follicular dermal papilla. In this study, we sought to further characterize histologic, histochemical, and immunohistochemical features of nail matrix onychodermis. METHODS AND RESULTS: Hematoxylin and eosin slides of 10 polydactyly nail units and 10 nail matrix biopsies from children and adults were reviewed. In polydactyly nail units, the onychodermis beneath nail matrix was characterized by onychofibroblasts showing abundant cytoplasm, and this area was slightly separated from the undersurface of the nail matrix. Nail matrix biopsy specimens also showed similar histology in the nail matrix onychodermis. Alcian blue stain demonstrated mucin deposition in onychofibroblasts within the nail matrix onychodermis. Immunohistochemically, elastin was rarely expressed in the nail matrix onychodermis while it was strongly expressed in the dermis of other areas of polydactyly nail units. Elastin was not expressed in follicular dermal papilla of terminal hair follicles of the scalp. CONCLUSION: Our findings demonstrate the presence and localization of nail matrix onychodermis (onychomatricodermis). Our study also demonstrates similar elastin expression patterns in the onychomatricodermis and follicular dermal papilla.

Stabilization of HDAC1 via TCL1-pAKT-CHFR axis is a key element for NANOG-mediated multi-resistance and stem-like phenotype in immune-edited tumor cells.

Cancer immunoediting enriches NANOG expression in tumor cells, resulting in multi-drug resistance and stem-like phenotypes. We previously demonstrated that these NANOG-associated phenotypes are promoted through HDAC1 transcriptional upregulation. In this study, we identified that NANOG also contributes to the stabilization of HDAC1 protein through the AKT signaling pathway. NANOG-AKT axis leads to phosphor-dependent inactivation of CHFR, an E3 ligase for HDAC1 protein, and thereby inhibiting the ubiquitin-mediated degradation of HDAC1. Furthermore, AKT inhibition disrupts HDAC1 WT-mediated phenotypes but had no effect on the phenotypes mediated by HDAC1 FM, a mutant that is unable to interact with CHFR. Critically, we applied a catalytic dead mutant, HDAC1-H141A, to uncover that HDAC1 confers immune-resistance, drug-resistance and stem-like phenotype in tumor cells through its catalytic activity. Collectively, our results establish a firm molecular link in immune-edited tumor cells among NANOG, AKT, CHFR, and HDAC1, identifying HDAC1 as a molecular target in controlling NANOGHIGH immune-refractory cancer.

Cardiac Magnetic Resonance Predictor of Ventricular Function after Surgical Coronary Revascularization.

We evaluated echocardiographic changes of left ventricular (LV) function in coronary artery bypass grafting (CABG) patients with LV dysfunction, and examined cardiac magnetic resonance (CMR) parameters associated with improved LV function. Seventy-seven CABG patients presenting with decreased LV ejection fraction (LVEF, ≤ 35%) and who underwent preoperative gadolinium-enhanced CMR were enrolled. A 16-segment model was used to analyze CMR imaging. A viable myocardial segment was defined as ≤ 50% transmural extent of late gadolinium enhancement. Serial echocardiographic examinations were performed preoperatively, pre-discharge (median 6 days), and during postoperative year 1 (median 11 months) in 70 patients. Predictors of absolute increase in LVEF (≥ 5%) and proportional changes in LVEF were analyzed. Serial echocardiography demonstrated that LVEF measured 28.6% ± 5.4% preoperatively, 31.5% ± 8.0% median 6 days, and 42.1% ± 10.5% median 11 months postoperatively. Absolute increase of LVEF was observed in 27 patients at pre-discharge and in 24 patients by median 11 months. Proportional changes in LVEF at postoperative median 6 days and 11 months were 14% ± 28% and 57% ± 45%, respectively. The median number of viable myocardial segments was 14 (range, 9-16) in the 16 segment CMR model. Multivariable models demonstrated that the median number of overall viable myocardial segments (≥ 14) in preoperative CMR was associated with absolute increase (P = 0.046) and proportional changes (P = 0.005) in LVEF. In conclusion, the number of viable myocardial segments (≥ 14) in preoperative CMR predicted LV function improvement after CABG in patients with LV dysfunction.