Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease.

BACKGROUND: Hypertension adds to the pressure overload on the left ventricle (LV) in combination with aortic valve (AV) disease, but the optimal blood pressure (BP) targets for patients with AV disease remain unclear. We tried to investigate whether intensive BP control reduces LV hypertrophy in asymptomatic patients with aortic stenosis (AS) or aortic regurgitation (AR). METHODS: A total of 128 hypertensive patients with mild to moderate AS (n = 93) or AR (n = 35) were randomly assigned to intensive therapy, targeting a systolic BP <130 mm Hg, or standard therapy, targeting a systolic BP <140 mm Hg. The primary end point was the change in LV mass from baseline to the 24-month follow-up. Secondary end points included changes in severity of AV disease, LV volumes, ejection fraction and global longitudinal strain (GLS). RESULTS: The treatment groups were generally well balanced regarding the baseline characteristics. The mean (±SD) age of the patients was 68 ± 8 years and 48% were men. The mean BP was 145 ± 12/81 ± 10 mm Hg at baseline. Medication at baseline was similar between the 2 groups. The 2 treatment strategies resulted in a rapid and sustained difference in systolic BP (P < .05). At 24-month, the mean systolic BP was 129 ± 12 mm Hg in the intensive therapy group and 135 ± 14 mm Hg in the standard therapy group. No patient died or underwent AV surgery during follow-up in either of the groups. LV mass was changed from 189.5 ± 41.3 to 185.6 ± 41.5 g in the intensive therapy group (P = .19) and from 183.8 ± 38.3 to 194.0 ± 46.4 g in the standard therapy group (P < .01). The primary end point of change in LV mass was significantly different between the intensive therapy and the standard therapy group (-3.9 ± 20.2 g vs 10.3 ± 20.4 g; P = .0007). The increase in LV mass index was also significantly greater in the standard therapy group (P = .01). No significant differences in secondary end points (changes in severity of AV disease, LV volumes, ejection fraction and GLS) were observed between the treatment groups. CONCLUSIONS: Among hypertensive patients with AV disease, intensive hypertensive therapy resulted in a significant reduction in LV hypertrophy, although progression of AV disease was similar between the treatment groups. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov (Number NCT03666351).

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Computational optical sensing and imaging: introduction to the feature issue.

This joint feature issue of Optics Express and Applied Optics showcases technical innovations by participants of the 2023 topical meeting on Computational Optical Sensing and Imaging and the computational imaging community. The articles included in the feature issue highlight advances in imaging science that emphasize synergistic activities in optics, signal processing and machine learning. The issue features 26 contributed articles that cover multiple themes including non line-of-sight imaging, imaging through scattering media, compressed sensing, lensless imaging, ptychography, computational microscopy, spectroscopy and optical metrology.

Tailored Planning of Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease characterized by abnormal thickening of the myocardium caused by myocardial disarray and interstitial fibrosis. HCM is associated with sudden cardiac-related events, such as ventricular fibrillation, tachycardia, and syncope. Moreover, left ventricular or midcavity obstruction due to the thickened myocardium can result in severe heart failure and mortality in patients with HCM. Surgical myectomy is a standard treatment option for patients with symptomatic obstructive HCM; however, it is a complex procedure that requires careful planning and execution to avoid complications, such as residual flow obstruction, persistent obliteration of the left ventricular cavity in systole, or iatrogenic ventricular septal defects. Therefore, a thorough understanding of the mechanics of HCM and precise evaluation of the location and extent of the hypertrophic myocardium to be removed are crucial for preoperative planning. Multiphase cardiac CT postprocessing is important for preoperative evaluation and planning of surgical myectomy in patients with HCM. In this review, the authors highlight use of multiphase cardiac CT with step-by-step postprocessing methods to simulate successful surgical myectomy. The transaortic surgeon's view on end-diastolic phase images accurately represents the surgical field. Moreover, myocardial segmentation can be used to generate volume-rendered images and three-dimensional printing. CT evaluation can also assist in identifying concurrent abnormalities, such as mitral valve or papillary muscle abnormalities. In addition to CT, other imaging modalities for preoperative evaluation of HCM and postmyectomy evaluation methods are presented. ©RSNA, 2023 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis.

BACKGROUND: The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial. METHODS: In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up. RESULTS: In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years. CONCLUSIONS: Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).

Impact of new-onset arrhythmia on cardiac reverse remodeling following transcatheter aortic valve replacement: computed tomography-derived left ventricular and atrial strains.

OBJECTIVE: Patients who undergo transcatheter aortic valve replacement (TAVR) are at risk for new-onset arrhythmia (NOA) that may require permanent pacemaker (PPM) implantation, resulting in decreased cardiac function. We aimed to investigate the factors that are associated with NOA after TAVR and to compare pre- and post-TAVR cardiac functions between patients with and without NOA using CT-derived strain analyses. METHODS: We included consecutive patients who underwent pre- and post-TAVR cardiac CT scans six months after TAVR. New-onset left bundle branch block, atrioventricular block, and atrial fibrillation/flutter lasting over 30 days after the procedure and/or the need for PPM diagnosed within 1 year after TAVR were regarded as NOA. Implant depth and left heart function and strains were analyzed using multi-phase CT images and compared between patients with and without NOA. RESULTS: Of 211 patients (41.7% men; median 81 years), 52 (24.6%) presented with NOA after TAVR, and 24 (11.4%) implanted PPM. Implant depth was significantly deeper in the NOA group than in the non-NOA group (- 6.7 ± 2.4 vs. - 5.6 ± 2.6 mm; p = 0.009). Left ventricular global longitudinal strain (LV GLS) and left atrial (LA) reservoir strain were significantly improved only in the non-NOA group (LV GLS, - 15.5 ± 4.0 to - 17.3 ± 2.9%; p < 0.001; LA reservoir strain, 22.3 ± 8.9 to 26.5 ± 7.6%; p < 0.001). The mean percent change of the LV GLS and LA reservoir strains was evident in the non-NOA group (p = 0.019 and p = 0.035, respectively). CONCLUSIONS: A quarter of patients presented with NOA after TAVR. Deep implant depth on post-TAVR CT scans was associated with NOA. Patients with NOA after TAVR had impaired LV reserve remodeling assessed by CT-derived strains. CLINICAL RELEVANCE STATEMENT: New-onset arrhythmia (NOA) following transcatheter aortic valve replacement (TAVR) impairs cardiac reverse remodeling. CT-derived strain analysis reveals that patients with NOA do not show improvement in left heart function and strains, highlighting the importance of managing NOA for optimal outcomes. KEY POINTS: • New-onset arrhythmia following transcatheter aortic valve replacement (TAVR) is a concern that interferes with cardiac reverse remodeling. • Comparison of pre-and post-TAVR CT-derived left heart strain provides insight into the impaired cardiac reverse remodeling in patients with new-onset arrhythmia following TAVR. • The expected reverse remodeling was not observed in patients with new-onset arrhythmia following TAVR, given that CT-derived left heart function and strains did not improve.

Relationship between Preoperative Echocardiographic Parameters and the Incidence of Postoperative Complications in Patients Undergoing Clipping of Unruptured Intracranial Aneurysms: A Retrospective Cohort Study.

Background and Objectives: Preoperative echocardiography is widely performed in patients undergoing major surgeries to evaluate cardiac functions and detect structural abnormalities. However, studies on the clinical usefulness of preoperative echocardiography in patients undergoing cerebral aneurysm clipping are limited. Therefore, this study aimed to investigate the correlation between preoperative echocardiographic parameters and the incidence of postoperative complications in patients undergoing clipping of unruptured intracranial aneurysms. Materials and Methods: Electronic medical records of patients who underwent clipping of an unruptured intracranial aneurysm from September 2018 to April 2020 were retrospectively reviewed. Data on baseline characteristics, laboratory variables, echocardiographic parameters, postoperative complications, and hospital stays were obtained. Univariable and multivariable logistic regression analyses were performed to identify independent variables related to the occurrence of postoperative complications and prolonged hospital stay (≥8 d). Results: Among 531 patients included in the final analysis, 27 (5.1%) had postoperative complications. In multivariable logistic regression, the total amount of crystalloids infused (1.002 (1.001-1.003), p = 0.001) and E/e' ratio (1.17 (1.01-1.35), p = 0.031) were significant independent factors associated with the occurrence of a postoperative complication. Additionally, the maximal diameter of a cerebral aneurysm (1.13 (1.02-1.25), p = 0.024), total amount of crystalloids infused (1.001 (1.000-1.002), p = 0.031), E/A ratio (0.22 (0.05-0.95), p = 0.042), and E/e' ratio (1.16 (1.04-1.31), p = 0.011) were independent factors related to prolonged hospitalization. Conclusions: Echocardiographic parameters related to diastolic function might be associated with postoperative complications in patients undergoing clipping of unruptured intracranial aneurysms.

Impact of Brain MRI on the Diagnosis of Infective Endocarditis and Treatment Decisions: Systematic Review and Meta-Analysis.

BACKGROUND. Despite increasing use of brain MRI to evaluate patients with suspected infective endocarditis, the clinical impact of brain MRI in this setting has not yet been systematically reviewed. OBJECTIVE. The purpose of this study was to evaluate the frequency of brain MRI findings in patients with suspected or confirmed infective endocarditis and to determine the impact of such findings on clinical decisions. EVIDENCE ACQUISITION. A systematic search of the PubMed, Embase, and Cochrane databases was performed from January 1, 1990, to December 31, 2020, to identify original research investigations of brain MRI in patients with suspected or confirmed infective endocarditis. Study quality was assessed with QUADAS-2. Study endpoints included the frequency of brain MRI findings and the frequency of diagnostic modifications, modification of therapeutic plan, and modification of valve surgery plan resulting from MRI findings. Frequencies were pooled by means of the inverse variance method. Subgroup analysis was performed. EVIDENCE SYNTHESIS. A total of 21 studies with 2133 patients were included. Overall study quality was considered moderate. In terms of brain MRI findings, the pooled frequency of acute ischemic lesions was 61.9% (95% CI, 50.7-71.9%); of cerebral microbleeds, 52.9% (95% CI, 41.6-63.9%); hemorrhagic lesions, 24.7% (95% CI, 15.1-37.9%); abscess or meningitis, 9.5% (95% CI, 5.6-15.6%); and intracranial mycotic aneurysm, 6.2% (95% CI, 4.0-9.4%). Subgroup analysis after exclusion of three studies in which neurologic findings were the indication for all brain MRI examinations yielded similar frequencies of these findings. Six studies included results on the impact of brain MRI findings on clinical decisions. The frequencies of diagnostic modifications in two studies were 5.4% and 32.1%. The pooled frequency of therapeutic plan modification in six studies was 12.8% (95% CI, 6.5-23.7%) and of surgical plan modification in five studies was 14.2% (95% CI, 8.2-23.4%). CONCLUSION. In patients with suspected or confirmed infective endocarditis, brain MRI examinations commonly show relevant abnormalities that affect diagnostic and therapeutic clinical decisions. CLINICAL IMPACT. The findings support a potential role for screening brain MRI in the evaluation of patients with suspected or confirmed infective endocarditis, regardless of the presence or absence of neurologic symptoms.

Timing of Intervention in Asymptomatic Aortic Stenosis.

The decision to perform an intervention for asymptomatic severe aortic stenosis (AS) requires careful weighing of the risks of early intervention against those of watchful observation, and the optimal timing of intervention remains controversial. With improvements in surgical and postoperative care, long-term survival after surgical aortic valve (AV) replacement (AVR) is excellent in low-risk patients, and the emergence of transcatheter AVR may change the thresholds for early preemptive intervention, although a durability issue has to be resolved. A watchful observation strategy also has a risk of sudden death, irreversible myocardial damage, and increase in operative risk while waiting for symptoms to develop. We have been waiting for a prospective randomized trial to solve the intense debate between early AVR and watchful observation, and the RECOVERY (Randomized Comparison of Early Surgery versus Conventional Treatment in Very Severe Aortic Stenosis) trial provides the evidence to support early AVR for asymptomatic severe AS. Risk assessment with severity of AS and staging classification may help to facilitate the identification of patients who may benefit from early intervention. Based on the results of the RECOVERY trial, early surgical AVR is reasonable for asymptomatic patients with very severe AS (aortic jet velocity ≥4.5 m/s) and low surgical risk. Further evidence is required to extend the indications of surgical AVR and to consider transcatheter AVR in asymptomatic patients with severe AS.

Central obesity is associated with lower prevalence of sarcopenia in older women, but not in men: a cross-sectional study.

BACKGROUND: Obesity is a chronic disease that causes various medical health problems, increases morbidity, and reduces the quality of life. Obesity (especially central obesity) in older adults is expected to act with the development of sarcopenia. However, the relationship between obesity, central obesity, and sarcopenia remains controversial. This study aimed to investigate the impact of obesity on sarcopenia. METHODS: In this cross-sectional study, we used data from the Korean Frailty and Aging Cohort Study; 1,827 community-dwelling older adults (883 men and 944 women) aged 70-84 years were recruited. The Asian Working Group for Sarcopenia (AWGS) criteria were used to evaluate sarcopenia. Subjects with a low appendicular skeletal muscle mass index (ASMI; men: < 7.0 kg/m2, women: < 5.4 kg/m2) and either low handgrip strength (HGS; men: < 28 kg, women: < 18 kg) or low Short Physical Performance Battery (SPPB; ≤ 9) were diagnosed with sarcopenia. Obesity was defined as a body mass index (BMI) of ≥ 25 kg/m2, while central obesity was defined as WC measurements of ≥ 90 cm in men and ≥ 85 cm in women. Logistic regression analyses were performed to evaluate the impact of obesity and central obesity on sarcopenia and the parameters of sacropenia. RESULTS: In both sexes, the obese group, defined based on the BMI, had a significantly low prevalence of low ASMI (odds ratio [OR] = 0.14, 95% confidence interval CI = 0.10-0.20 in men, OR = 0.17, 95% CI = 0.12-0.25 in women) and sarcopenia (OR = 0.28, 95% CI = 0.16-0.50 in men, OR = 0.17, 95% CI = 0.08-0.35 in women) in the multivariable logistic regression analysis. In women, the central obese group had a low prevalence of sarcopenia (OR = 0.46, 95% CI = 0.27-0.77) in the multivariable logistic regression analysis. Meanwhile, the obese group had a significantly higher prevalence of low SPPB in women (OR = 1.75, 95% CI = 1.18-2.59). CONCLUSIONS: Obesity may have a protective effect on low ASMI and sarcopenia, as defined by the AWGS criteria. Central obesity was associated with a low prevalence of sarcopenia in women only. However, obesity did not have a positive impact on functional parameters of sarcopenia including muscle strength and physical performance.

Noniterative sub-pixel shifting super-resolution lensless digital holography.

Lensless digital holography (LDH) is gaining considerable attention lately due to a simple experimental setup, wide field-of-view, and three-dimensional (3D) imaging capability. Since the resolution of LDH is limited by the Nyquist frequency of a detector array, the major drawback of LDH is resolution, and a lot of efforts were made to enhance the resolution of LDH. Here we propose and demonstrate a fast noniterative sub-pixel shifting super-resolution technique that can effectively enhance the resolution of LDH by a factor of two. We provide detailed frequency-domain formulae for our noniterative frequency-domain super-resolution method. The validity of our proposed method is experimentally demonstrated both for scattering and phase objects.

Machine learning-based leaky momentum prediction of plasmonic random nanosubstrate.

In this work, we explore the use of machine learning for constructing the leakage radiation characteristics of the bright-field images of nanoislands from surface plasmon polariton based on the plasmonic random nanosubstrate. The leakage radiation refers to a leaky wave of surface plasmon polariton (SPP) modes through a dielectric substrate which has drawn interest due to its possibility of direct visualization and analysis of SPP propagation. A fast-learning two-layer neural network has been deployed to learn and predict the relationship between the leakage radiation characteristics and the bright-field images of nanoislands utilizing a limited number of training samples. The proposed learning framework is expected to significantly simplify the process of leaky radiation image construction without the need of sophisticated equipment. Moreover, a wide range of application extensions can be anticipated for the proposed image-to-image prediction.

Clinical impact of mild to moderate pulmonary hypertension in living-donor liver transplantation.

Severe pulmonary hypertension (PHT) is a contraindication to liver transplantation (LT); however, the prognostic implication of mild to moderate PHT in living-donor LT (LDLT) is unknown. The study cohort retrospectively included 1307 patients with liver cirrhosis who underwent LDLT. PHT was defined as a mean pulmonary artery pressure (PAP) of ≥25 mmHg, measured intraoperatively just before surgery. The primary endpoint was graft failure within 1 year after LDLT, including retransplantation or death from any cause. The secondary endpoints were in-hospital adverse events. In the overall cohort, the median Model for End-stage Liver Disease-Sodium (MELD-Na) score was 19, and 100 patients (7.7%) showed PHT. During 1-year follow-up, graft failure occurred in 94 patients (7.2%). Patients with PHT had lower 1-year graft survival (86% vs. 93.4%, P = 0.005) and survival rates (87% vs. 93.6%, P = 0.011). Mean PAP was associated with a high risk of in-hospital adverse events and 1-year graft failure. Adding the mean PAP to the clinical risk model improved the risk prediction. In conclusion, mild to moderate PHT was associated with higher risks of 1-year graft failure and in-hospital events, including mortality after LDLT in patients with liver cirrhosis. Intraoperative mean PAP can help predict the early clinical outcomes after LDLT.

Surface Plasmon Localization-Based Super-resolved Raman Microscopy.

We investigate label-free measurement of molecular distribution by super-resolved Raman microscopy using surface plasmon (SP) localization. Localized SP was formed with plasmonic nanopost arrays (PNAs) for measurement of the molecular distribution in HeLa cells. Compared with conventional Raman microscopy on gold thin films, PNAs induce a localized near-field, which allows for the enhancement of the peak signal-to-noise ratio by as much as 4.5 dB in the Raman shifts. Super-resolved distributions of aromatic amino acids and lipids (C-C stretching and C-H2 twist mode) as targets in HeLa cells were obtained after image reconstruction. Results show almost 4-fold improvement on average in the lateral precision over conventional diffraction-limited Raman microscopy images. Combined with axial imaging in an evanescent field, the results suggest an improvement in optical resolution due to superlocalized light volume by more than an order of magnitude over that of conventional diffraction-limited Raman microscopy.

Mice lacking the epidermal retinol dehydrogenases SDR16C5 and SDR16C6 display accelerated hair growth and enlarged meibomian glands.

Retinol dehydrogenases catalyze the rate-limiting step in the biosynthesis of retinoic acid, a bioactive lipid molecule that regulates the expression of hundreds of genes by binding to nuclear transcription factors, the retinoic acid receptors. Several enzymes exhibit retinol dehydrogenase activities in vitro; however, their physiological relevance for retinoic acid biosynthesis in vivo remains unclear. Here, we present evidence that two murine epidermal retinol dehydrogenases, short-chain dehydrogenase/reductase family 16C member 5 (SDR16C5) and SDR16C6, contribute to retinoic acid biosynthesis in living cells and are also essential for the oxidation of retinol to retinaldehyde in vivo Mice with targeted knockout of the more catalytically active SDR16C6 enzyme have no obvious phenotype, possibly due to functional redundancy, because Sdr16c5 and Sdr16c6 exhibit an overlapping expression pattern during later developmental stages and in adulthood. Mice that lack both enzymes are viable and fertile but display accelerated hair growth after shaving and also enlarged meibomian glands, consistent with a nearly 80% reduction in the retinol dehydrogenase activities of skin membrane fractions from the Sdr16c5/Sdr16c6 double-knockout mice. The up-regulation of hair-follicle stem cell genes is consistent with reduced retinoic acid signaling in the skin of the double-knockout mice. These results indicate that the retinol dehydrogenase activities of murine SDR16C5 and SDR16C6 enzymes are not critical for survival but are responsible for most of the retinol dehydrogenase activity in skin, essential for the regulation of the hair-follicle cycle, and required for the maintenance of both sebaceous and meibomian glands.

A nomogram constructed using intraoperative ex vivo shear-wave elastography precisely predicts metastasis of sentinel lymph nodes in breast cancer.

OBJECTIVE: To develop a nomogram and validate its use for the intraoperative evaluation of nodal metastasis using shear-wave elastography (SWE) elasticity values and nodal size METHODS: We constructed a nomogram to predict metastasis using ex vivo SWE values and ultrasound features of 228 axillary LNs from fifty-five patients. We validated its use in an independent cohort comprising 80 patients. In the validation cohort, a total of 217 sentinel LNs were included. RESULTS: We developed the nomogram using the nodal size and elasticity values of the development cohort to predict LN metastasis; the area under the curve (AUC) was 0.856 (95% confidence interval (CI), 0.783-0.929). In the validation cohort, 15 (7%) LNs were metastatic, and 202 (93%) were non-metastatic. The mean stiffness (23.54 and 10.41 kPa, p = 0.005) and elasticity ratio (3.24 and 1.49, p = 0.028) were significantly higher in the metastatic LNs than those in the non-metastatic LNs. However, the mean size of the metastatic LNs was not significantly larger than that of the non-metastatic LNs (8.70 mm vs 7.20 mm, respectively; p = 0.123). The AUC was 0.791 (95% CI, 0.668-0.915) in the validation cohort, and the calibration plots of the nomogram showed good agreement. CONCLUSIONS: We developed a well-validated nomogram to predict LN metastasis. This nomogram, mainly based on ex vivo SWE values, can help evaluate nodal metastasis during surgery. KEY POINTS: • A nomogram was developed based on axillary LN size and ex vivo SWE values such as mean stiffness and elasticity ratio to easily predict axillary LN metastasis during breast cancer surgery. • The constructed nomogram presented high predictive performance of sentinel LN metastasis with an independent cohort. • This nomogram can reduce unnecessary intraoperative frozen section which increases the surgical time and costs in breast cancer patients.

STDD: Short-Term Depression Detection with Passive Sensing.

It has recently been reported that identifying the depression severity of a person requires involvement of mental health professionals who use traditional methods like interviews and self-reports, which results in spending time and money. In this work we made solid contributions on short-term depression detection using every-day mobile devices. To improve the accuracy of depression detection, we extracted five factors influencing depression (symptom clusters) from the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders), namely, physical activity, mood, social activity, sleep, and food intake and extracted features related to each symptom cluster from mobile devices' sensors. We conducted an experiment, where we recruited 20 participants from four different depression groups based on PHQ-9 (the Patient Health Questionnaire-9, the 9-item depression module from the full PHQ), which are normal, mildly depressed, moderately depressed, and severely depressed and built a machine learning model for automatic classification of depression category in a short period of time. To achieve the aim of short-term depression classification, we developed Short-Term Depression Detector (STDD), a framework that consisted of a smartphone and a wearable device that constantly reported the metrics (sensor data and self-reports) to perform depression group classification. The result of this pilot study revealed high correlations between participants` Ecological Momentary Assessment (EMA) self-reports and passive sensing (sensor data) in physical activity, mood, and sleep levels; STDD demonstrated the feasibility of group classification with an accuracy of 96.00% (standard deviation (SD) = 2.76).

Effects of probiotic bacterium Weissella cibaria CMU on periodontal health and microbiota: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Weissella cibaria CMU (oraCMU) has been commercially available in the market for several years as oral care probiotics. The present study aimed to evaluate the effects of oraCMU-containing tablets on periodontal health and oral microbiota. METHODS: A randomised, double-blind, placebo-controlled trial was conducted in 92 adults without periodontitis (20-39 years of age). All subjects received dental scaling and root planing, and were randomly assigned to either probiotic or placebo groups. The tablets were administered once daily for 8 weeks. Periodontal clinical parameters included bleeding on probing (BOP), probing depth (PD), gingival index (GI), and plaque index (PI). In addition, microbiota in the gingival sulcus were analysed. RESULTS: BOP improved more in the probiotic group over 8 weeks. There were statistically significant differences in BOP of the maxilla buccal and lingual sites between the groups during the intervention (P < 0.05). No significant inter-group differences in PD, GI, and PI were observed during the intervention. Oral bacteria were observed to be fewer in the probiotic group. There was a significant change in levels of Fusobacterium nucleatum at four and 8 weeks between the two groups. Besides, there were significant differences at 8 weeks in levels of Staphylococcus aureus. CONCLUSIONS: We reported an improvement in BOP and microbial environment and demonstrated the antimicrobial activity of oraCMU against F. nucleatum. Thus, its supplementation may contribute to overall oral health. TRIAL REGISTRATION: Ethical issues approved by the Kangwon National University Institutional Review Board with a number of KWNUIRB-2018-05-003-005 and CRIS code Number of KCT0005078 were retrospectively registered on 06/02/2020. This study was conducted in the period of July to November 2018.

Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review.

Deregulation of the cyclin D-CDK4/6-INK4-RB pathway leading to uncontrolled cell proliferation, is frequently observed in breast cancer. Currently, three selective CDK4/6 inhibitors have been FDA approved: palbociclib, ribociclib and abemaciclib. Despite promising clinical outcomes, intrinsic or acquired resistance to CDK4/6 inhibitors has limited the success of these treatments; therefore, the development of various strategies to overcome this resistance is of great importance. We highlight the various mechanisms that are directly or indirectly responsible for resistance to CDK4/6 inhibitors, categorizing them into two broad groups; cell cycle-specific mechanisms and cell cycle-nonspecific mechanisms. Elucidation of the diverse mechanisms through which resistance to CDK4/6 inhibitors occurs, may aid in the design of novel therapeutic strategies to improve patient outcomes. This review summarizes the currently available knowledge regarding mechanisms of resistance to CDK4/6 inhibitors, and possible therapeutic strategies that may overcome this resistance as well.