The HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15-HISTONE DEACETYLASE9 complex associates with HYPONASTIC LEAVES 1 to modulate microRNA expression in response to abscisic acid signaling.

The regulation of microRNA (miRNA) biogenesis is crucial for maintaining plant homeostasis under biotic and abiotic stress. The crosstalk between the RNA polymerase II (Pol-II) complex and the miRNA processing machinery has emerged as a central hub modulating transcription and cotranscriptional processing of primary miRNA transcripts (pri-miRNAs). However, it remains unclear how miRNA-specific transcriptional regulators recognize MIRNA loci. Here, we show that the Arabidopsis (Arabidopsis thaliana) HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15 (HOS15)-HISTONE DEACETYLASE9 (HDA9) complex is a conditional suppressor of miRNA biogenesis, particularly in response to abscisic acid (ABA). When treated with ABA, hos15/hda9 mutants show enhanced transcription of pri-miRNAs that is accompanied by increased processing, leading to overaccumulation of a set of mature miRNAs. Moreover, upon recognition of the nascent pri-miRNAs, the ABA-induced recruitment of the HOS15-HDA9 complex to MIRNA loci is guided by HYPONASTIC LEAVES 1 (HYL1). The HYL1-dependent recruitment of the HOS15-HDA9 complex to MIRNA loci suppresses expression of MIRNAs and processing of pri-miRNA. Most importantly, our findings indicate that nascent pri-miRNAs serve as scaffolds for recruiting transcriptional regulators, specifically to MIRNA loci. This indicates that RNA molecules can act as regulators of their own expression by causing a negative feedback loop that turns off their transcription, providing a self-buffering system.

ABA INSENSITIVE 2 promotes flowering by inhibiting OST1/ABI5-dependent FLOWERING LOCUS C transcription in Arabidopsis.

The plant hormone abscisic acid (ABA) is an important regulator of plant growth and development and plays a crucial role in both biotic and abiotic stress responses. ABA modulates flowering time, but the precise molecular mechanism remains poorly understood. Here we report that ABA INSENSITIVE 2 (ABI2) is the only phosphatase from the ABA-signaling core that positively regulates the transition to flowering in Arabidopsis. Loss-of-function abi2-2 mutant shows significantly delayed flowering both under long day and short day conditions. Expression of floral repressor genes such as FLOWERING LOCUS C (FLC) and CYCLING DOF FACTOR 1 (CDF1) was significantly up-regulated in abi2-2 plants while expression of the flowering promoting genes FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) was down-regulated. Through genetic interactions we further found that ost1-3 and abi5-1 mutations are epistatic to abi2-2, as both of them individually rescued the late flowering phenotype of abi2-2. Interestingly, phosphorylation and protein stability of ABA INSENSITIVE 5 (ABI5) were enhanced in abi2-2 plants suggesting that ABI2 dephosphorylates ABI5, thereby reducing protein stability and the capacity to induce FLC expression. Our findings uncovered the unexpected role of ABI2 in promoting flowering by inhibiting ABI5-mediated FLC expression in Arabidopsis.

Reference-free in situ rapid regional calibration of phase-only spatial light modulators.

Spatial light modulators (SLMs) have become an indispensable element in modern optics for their versatile performance in many applications. Among various types of SLMs, such as digital micromirror devices (DMD), liquid crystal-based phase-only spatial light modulators (LC-SLMs), and deformable mirrors (DM), LC-SLMs are often the method of choice due to their high efficiency, precise phase modulation, and abundant number of effective pixels. In general, for research grade applications, an additional SLM calibration step is required due to fabrication imperfection resulting in non-flat liquid crystal panels and varying phase responses over the SLM area. Here, we demonstrate a straightforward approach for reference-free orthogonal calibration of an arbitrary number of SLM subregions which only requires the same measurement time as global calibration. The proposed method requires minimal optical elements and can be applied to any optical setup as is. As a benchmark performance test, we achieved a 2.2-fold enhancement in correction efficiency for wavefront shaping through scattering media utilizing the calibrated 2160 subregions of the SLM, in comparison with a single global look-up table (LUT).

Novel self-expandable stent-based endobiliary radiofrequency ablation for unresectable malignant biliary obstruction.

BACKGROUND AND AIMS: Endobiliary radiofrequency ablation (RFA) is an emerging endoscopic palliative adjunctive therapy used for the local treatment of unresectable malignant biliary obstruction (MBO). However, irregular ablation ranges caused by insufficient electrode-to-bile duct contact pose a significant obstacle. We investigated the feasibility of a self-expandable stent (SES)-based electrode with a customized RFA generator in the porcine liver and common bile duct (CBD). METHODS: An SES-RFA system with polarity switching was developed to perform endobiliary RFA. The ablation ranges of 20 ablation protocols were evaluated to validate the feasibility of the newly developed RFA system in the porcine liver. Nine of 20 ablation protocols were selected for evaluation in the porcine CBD with cholangiography, endoscopy, and histologic and immunohistochemical analysis. RESULTS: The SES-RFA system with polarity switching was successfully constructed and demonstrated high accuracy and reproducibility. The ablation area was clearly identified between the 2 SESs. The ablation ranges and degree of mucosal damage, including terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling-positive and heat shock protein 70-positive depositions, increased proportionally with ablation protocols in the porcine liver and CBD (all P < .05). Ablation length and depth linearly increased with ablation protocols from 8.74 ± .25 to 31.25 ± .67 mm and 1.61 ± .09 to 11.94 ± .44 mm, respectively. CONCLUSIONS: The SES-RFA system with polarity switching between electrodes provided an even circumferential area of ablation and enhanced ablation depth between the electrodes. This novel endobiliary RFA system is a promising modality for local ablation in patients with unresectable MBO.

The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy.

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

Balloon neck-plasty to create a wide-necked aneurysm in the elastase-induced rabbit model.

PURPOSE: The elastase-induced aneurysm (EIA) model in rabbits has been proposed for translational research; however, the adjustment of aneurysm neck size remains challenging. In this study, the technical feasibility and safety of balloon neck-plasty to create a wide-necked aneurysm in rabbit EIA model were investigated. METHODS: Male New Zealand White rabbits (N = 15) were randomly assigned to three groups: group A, EIA creation without neck-plasty; group B, neck-plasty immediately after EIA creation; group C, neck-plasty 4 weeks after EIA creation. The diameter of balloon used for neck-plasty was determined 1 mm larger than origin carotid artery diameter. All rabbits were euthanized 4 weeks after their final surgery. Aneurysm neck, height, dome-to-neck (D/N) ratio, and histologic parameters were compared among the groups. RESULTS: Aneurysm creation was technically successful in 14 out of 15 rabbits (93.3%), with one rabbit experiencing mortality due to an adverse anesthetic event during the surgery. Saccular and wide-necked aneurysms were successfully created in all rabbits. Aneurysm neck was significantly greater in groups B and C compared to group A (all P < .05). D/N ratio was significantly lower in groups B and C compared to group A (all P < .05). Additionally, tunica media thickness, vessel area, and luminal area were significantly greater in groups B and C compared to group A (all P < .05). These variables were found to be significantly greater in group B compared to group C (all P < .05). CONCLUSION: The creation of a wide-necked aneurysm using balloon neck-plasty after elastase induction in rabbits has been determined to be technically feasible and safe.

Maternal age at birth and child attention-deficit hyperactivity disorder: causal association or familial confounding?

BACKGROUND: Causal explanations for the association of young motherhood with increased risk for child attention-deficit hyperactivity disorder (ADHD) remain unclear. METHODS: The ABCD Study recruited 11,878 youth from 22 sites across the United States between June 1, 2016 and October 15, 2018. This cross-sectional analysis of 8,514 children aged 8-11 years excluded 2,260 twins/triplets, 265 adopted children, and 839 younger siblings. We examined associations of maternal age with ADHD clinical range diagnoses based on the Child Behavior Checklist and NIH Toolbox Flanker Attention Scores using mixed logistic and linear regression models, respectively. We conducted confounding and causal mediation analyses using genotype array, demographic, socioeconomic, and prenatal environment data to investigate which genetic and environmental variables may explain the association between young maternal age and child ADHD. RESULTS: In crude models, each 10-year increase in maternal age was associated with 32% decreased odds of ADHD clinical range diagnosis (OR = 0.68; 95% CI [0.59, 0.78]) and 1.09-points increased NIH Flanker Attention Scores (ß = 1.09; 95% CI [0.76, 1.41]), indicating better child visual selective attention. However, adjustment for confounders weakened these associations. The strongest confounders were family income, caregiver education, and ADHD polygenic risk score for ADHD clinical range diagnoses, and family income, caregiver education, and race/ethnicity for NIH Flanker Attention Scores. Breastfeeding duration, prenatal alcohol exposure, and prenatal tobacco exposure were responsible for up to 18%, 6%, and 4% mediation, respectively. CONCLUSIONS: Socioeconomic disadvantages were likely the primary explanation for the association of young maternal age with child ADHD, although genetics and modifiable environmental factors also played a role. Public policies aimed at reducing the burden of ADHD associated with young motherhood should target socioeconomic inequalities and support young pregnant women by advocating for reduced prenatal tobacco exposure and healthy breastfeeding practices after childbirth.

HOS15 is a transcriptional corepressor of NPR1-mediated gene activation of plant immunity.

Transcriptional regulation is a complex and pivotal process in living cells. HOS15 is a transcriptional corepressor. Although transcriptional repressors generally have been associated with inactive genes, increasing evidence indicates that, through poorly understood mechanisms, transcriptional corepressors also associate with actively transcribed genes. Here, we show that HOS15 is the substrate receptor for an SCF/CUL1 E3 ubiquitin ligase complex (SCFHOS15) that negatively regulates plant immunity by destabilizing transcriptional activation complexes containing NPR1 and associated transcriptional activators. In unchallenged conditions, HOS15 continuously eliminates NPR1 to prevent inappropriate defense gene expression. Upon defense activation, HOS15 preferentially associates with phosphorylated NPR1 to stimulate rapid degradation of transcriptionally active NPR1 and thus limit the extent of defense gene expression. Our findings indicate that HOS15-mediated ubiquitination and elimination of NPR1 produce effects contrary to those of CUL3-containing ubiquitin ligase that coactivate defense gene expression. Thus, HOS15 plays a key role in the dynamic regulation of pre- and postactivation host defense.

Combination of Metal-Phenolic Network-Based Immunoactive Nanoparticles and Bipolar Irreversible Electroporation for Effective Cancer Immunotherapy.

To circumvent the limitations of conventional cancer immunotherapy, it is critical to prime antigen-presenting cells (APCs) to initiate the cancer-immune cycle. Here, the authors develop a metal-phenolic network (MPN)-based immunoactive nanoparticle in combination with irreversible electroporation (IRE) for an effective cancer immunotherapy. The MPN nanoparticles are synthesized by coordinating tannic acid with manganese (Mn) ions, and subsequent coating with CpG-oligodeoxynucleotides (CpG-ODNs) via hydrogen bonding. The CpG-ODN-coated Mn-phenolic network (CMP) nanoparticles are effectively internalized into macrophages, a type of APCs, and successfully trigger M1 polarization to promote release of proinflammatory cytokines. Notably, the CMP nanoparticles demonstrate an extended retention time period than the free CpG-ODN in the tumor. The tumor microenvironment tailored bipolar IRE, enhances the therapeutic efficacy by significantly broadening the ablation zone, which further increases immunogenic cell death (ICD). Ultimately, the simultaneous CMP nanoparticles and IRE treatment successfully inhibit tumor growth and prolong survival in a mouse tumor model. Thus, CMP nanoparticles are empowered with Mn and CpG-ODN immunomodulators and the tumor microenvironment tailored bipolar IRE will be a new tool for effective cancer immunotherapy to treat intractable malignancies.

Dynamic multimodal holograms of conjugated organogels via dithering mask lithography.

Polymeric materials have been used to realize optical systems that, through periodic variations of their structural or optical properties, interact with light-generating holographic signals. Complex holographic systems can also be dynamically controlled through exposure to external stimuli, yet they usually contain only a single type of holographic mode. Here, we report a conjugated organogel that reversibly displays three modes of holograms in a single architecture. Using dithering mask lithography, we realized two-dimensional patterns with varying cross-linking densities on a conjugated polydiacetylene. In protic solvents, the organogel contracts anisotropically to develop optical and structural heterogeneities along the third dimension, displaying holograms in the form of three-dimensional full parallax signals, both in fluorescence and bright-field microscopy imaging. In aprotic solvents, these heterogeneities diminish as organogels expand, recovering the two-dimensional periodicity to display a third hologram mode based on iridescent structural colours. Our study presents a next-generation hologram manufacturing method for multilevel encryption technologies.

The Histone-Modifying Complex PWR/HOS15/HD2C Epigenetically Regulates Cold Tolerance.

Cold stress is a major environmental stress that severely affects plant growth and crop productivity. Arabidopsis (Arabidopsis thaliana) HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15 (HOS15) is a substrate receptor of the CULLIN4-based CLR4 ubiquitin E3 ligase complex, which epigenetically regulates cold tolerance by degrading HISTONE DEACETYLASE2C (HD2C) to switch from repressive to permissive chromatin structure in response to cold stress. In this study, we characterized a HOS15-binding protein, POWERDRESS (PWR), and analyzed its function in the cold stress response. PWR loss-of-function plants (pwr) showed lower expression of cold-regulated (COR) genes and sensitivity to freezing. PWR interacts with HD2C through HOS15, and cold-induced HD2C degradation by HOS15 is diminished in the pwr mutant. The association of HOS15 and HD2C to promoters of cold-responsive COR genes was dependent on PWR. Consistent with these observations, the high acetylation levels of histone H3 by cold-induced and HOS15-mediated HD2C degradation were significantly reduced in pwr under cold stress. PWR also interacts with C-repeat element-binding factor transcription factors to modulate their cold-induced binding to the promoter of COR genes. Collectively, our data signify that the PWR-HOS15-HD2C histone-modifying complex regulates the expression of COR genes and the freezing tolerance of plants.

The GIGANTEA-ENHANCED EM LEVEL Complex Enhances Drought Tolerance via Regulation of Abscisic Acid Synthesis.

Drought is one of the most critical environmental stresses limiting plant growth and crop productivity. The synthesis and signaling of abscisic acid (ABA), a key phytohormone in the drought stress response, is under photoperiodic control. GIGANTEA (GI), a key regulator of photoperiod-dependent flowering and the circadian rhythm, is also involved in the signaling pathways for various abiotic stresses. In this study, we isolated ENHANCED EM LEVEL (EEL)/basic Leu zipper 12, a transcription factor involved in ABA signal responses, as a GI interactor in Arabidopsis (Arabidopsis thaliana). The diurnal expression of 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3), a rate-limiting ABA biosynthetic enzyme, was reduced in the eel, gi-1, and eel gi-1 mutants under normal growth conditions. Chromatin immunoprecipitation and electrophoretic mobility shift assays revealed that EEL and GI bind directly to the ABA-responsive element motif in the NCED3 promoter. Furthermore, the eel, gi-1, and eel gi-1 mutants were hypersensitive to drought stress due to uncontrolled water loss. The transcript of NCED3, endogenous ABA levels, and stomatal closure were all reduced in the eel, gi-1, and eel gi-1 mutants under drought stress. Our results suggest that the EEL-GI complex positively regulates diurnal ABA synthesis by affecting the expression of NCED3, and contributes to the drought tolerance of Arabidopsis.

Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-analysis.

BACKGROUND: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave's syndrome (BS). METHODS: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. RESULTS: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8-5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2-7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2-6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1-3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1-3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD. CONCLUSIONS: This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.

Temporary percutaneous radiologic gastrojejunostomy with single gastropexy.

BACKGROUND: Although the effectiveness of percutaneous radiologic gastrojejunostomy (PRGJ) has been reported, a detailed description of the indications and clinical effectiveness of temporary PRGJ is still limited. PURPOSE: To evaluate the clinical effectiveness and technical feasibility of temporary PRGJ using the modified Chiba-needle technique with single gastropexy. MATERIAL AND METHODS: Temporary PRGJ using the modified Chiba-needle technique with single gastropexy was performed in 27 consecutive patients (19 men, 8 women; mean age = 61 years; age range = 32-77 years) for esophageal perforation (n = 18) or postoperative gastroparesis (n = 9). Outcomes analyzed included the technical and clinical success, procedure-related complications, and the tube indwelling period. RESULTS: Technical and clinical success was achieved in all 27 patients. All the tubes were electively removed 19-364 days (mean indwelling period = 104 days) after confirmation of the possibility of oral intake. Asymptomatic pneumoperitoneum occurred in 2/27 (7.4%) patients as minor complications and was resolved spontaneously by the time of the one-week follow-up. There were no major complications. During the follow-up period, a total of 11 tube changes were performed in seven patients for an elective tube change within a six-month interval (n = 5) or because of tube occlusion (n = 6). CONCLUSION: Temporary PRGJ using the modified Chiba-needle technique with a single gastropexy was clinically effective and technically feasible in patients with esophageal perforation or gastroparesis. It can provide adequate enteral nutrition during its temporary placement.

Percutaneous antegrade removal of foreign bodies in the urinary tract: a 20-year, single-center experience.

BACKGROUND: While removing urinary tract foreign bodies is mostly performed through retrograde cystoscopy, antegrade removal using interventional procedures is reported less frequently. PURPOSE: To evaluate the safety and effectiveness of percutaneous antegrade removal of urinary tract foreign bodies. MATERIAL AND METHODS: A total of 14 consecutive patients (age range 9-80 years) who percutaneous antegrade removal of urinary tract foreign bodies between January 2001 and March 2020 were reviewed. Detailed removal procedures and complications were reviewed retrospectively. RESULTS: Types of foreign bodies were sheared percutaneous nephrostomy (PCN) catheters (n = 5), sheared double J stents (n = 3), migrated ureteral catheters (n = 3), embolization coils (n = 2), and a 0.018-inch guide wire (n = 1). The mean and median indwelling times (range 0-306 days) of the foreign bodies were 58.3 and 1.5 days, respectively. Computed tomography (CT) scans were conducted in six patients, and the extent and nature of the foreign bodies were well-visualized on CT scans. The removal access was new PCN access (n = 8), the tract missing PCN catheter (n = 3), pre-existing PCN access (n = 2), and percutaneous dissection (n = 1). The removal success rate was 92.9% (13/14) with either a simple (n = 8) or modified (n = 4; combination of a snare and guide wire is used) snare technique or a direct forceps grasp (n = 1). The mean procedure time for successful cases was 14.2 min (range 7-25 min). Procedure-related hematoma with (n = 2) or without (n = 1) renal pelvis injury occurred in three patients, which were all self-limited within one week. CONCLUSION: Percutaneous antegrade removal is safe and effective for urinary tract foreign bodies.

Epigenetic switch from repressive to permissive chromatin in response to cold stress.

Switching from repressed to active status in chromatin regulation is part of the critical responses that plants deploy to survive in an ever-changing environment. We previously reported that HOS15, a WD40-repeat protein, is involved in histone deacetylation and cold tolerance in Arabidopsis However, it remained unknown how HOS15 regulates cold responsive genes to affect cold tolerance. Here, we show that HOS15 interacts with histone deacetylase 2C (HD2C) and both proteins together associate with the promoters of cold-responsive COR genes, COR15A and COR47 Cold induced HD2C degradation is mediated by the CULLIN4 (CUL4)-based E3 ubiquitin ligase complex in which HOS15 acts as a substrate receptor. Interference with the association of HD2C and the COR gene promoters by HOS15 correlates with increased acetylation levels of histone H3. HOS15 also interacts with CBF transcription factors to modulate cold-induced binding to the COR gene promoters. Our results here demonstrate that cold induces HOS15-mediated chromatin modifications by degrading HD2C. This switches the chromatin structure status and facilitates recruitment of CBFs to the COR gene promoters. This is an apparent requirement to acquire cold tolerance.

Large-field-of-view imaging by multi-pupil adaptive optics.

Adaptive optics can correct for optical aberrations. We developed multi-pupil adaptive optics (MPAO), which enables simultaneous wavefront correction over a field of view of 450 × 450 µm2 and expands the correction area to nine times that of conventional methods. MPAO's ability to perform spatially independent wavefront control further enables 3D nonplanar imaging. We applied MPAO to in vivo structural and functional imaging in the mouse brain.

Increasing the enhancement factor for DMD-based wavefront shaping.

Focusing through scattering media is a subject of great interest due to its direct impact in the field of biomedical optics. However, the greatest barrier currently limiting direct applications is the fact that most scattering media that we wish to deliver light through are dynamic. To focus or deliver light through dynamic scattering media, using a digital micromirror device (DMD) has been demonstrated to be a potential solution, as it enables fast modulation speeds. However, since a DMD is a binary amplitude modulator, the large number of controlled modes needed to acquire adequate focus enhancement has limited optimal usage. Here we demonstrate a novel (to the best of our knowledge) scheme to use the "thrown-away" components of light to effectively use a binary amplitude DMD as a binary phase modulator, thereby increasing the correction efficiency by a factor of two. Our concept can be applied to any iterative optimization algorithm and can speed up the iterative optimization process by increasing the enhancement factor, rather than the measurement or modulation speeds.

Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea.

PURPOSE: Triple-negative breast cancer (TNBC) accounts for 10-20% of all diagnosed BCs and it is enriched in BRCA1 mutation. Guidelines for Western countries suggest that BRCA 1/2 genetic testing should be done for patients with TNBC diagnosed less than 60 years, but there is lack of evidence supporting genetic testing in Asian populations. We determined the prevalence of germline BRCA 1/2 mutations among unselected Korean patients with TNBC and analyzed oncologic outcomes. METHODS: From among 1628 women with TNBC who underwent surgery at Samsung Medical Center (SMC) between Jul 2008 and Jan 2016, 999 samples were available in the SMC biobank for testing germline BRCA 1/2 mutations using next-generation DNA sequencing. RESULTS: Overall, 131 Korean patients (13.1%) had BRCA 1/2 mutations: 97 (9.7%) were in BRCA 1, and 35 (3.5%) were in BRCA 2. One patient had both BRCA 1 and BRCA 2 mutations. Overall, 68 distinct pathologic or likely pathogenic variants (43 BRCA1 and 25 BRCA2) were found. Among those diagnosed at ≤ 60 years, the prevalence of BRCA 1/2 mutation was 14.5%. The mean age of diagnosis of BRCA1/2 mutation carriers was significantly younger than that of non-carriers (45.6 vs. 50.1 years, p < 0.0001). The median follow-up duration was 53.6 months. There were no significant differences in disease-free survival, overall survival, or breast cancer-specific survival (p = 0.799, 0.092, and 0.124, respectively) between BRCA 1/2 carriers and non-carriers, although BRCA 1/2 carriers showed significantly worse contralateral breast cancer-free survival (p < 0.0001) than non-carriers. CONCLUSION: In unselected TNBC patients, we found BRCA 1/2 mutations in 13.1% of overall patients and 14.5% of patients ≤ 60 years. We suggest that Korean women with TNBC diagnosed at ≤ 60 years should be tested for BRCA1/2 mutation.

Fast diffraction-limited image recovery through turbulence via subsampled bispectrum analysis.

Imaging through temporally changing aberrations is a common challenge that can be found in many different fields such as astronomy, long-range surveillance, and deep tissue bioimaging. Based on the notions originally developed in speckle interferometry, time-varying aberrations can be used to our advantage to obtain diffraction-limited resolution images through turbulence via bispectrum analysis. However, due to the heavy computational load brought on by the triple correlation and the phase extraction process, widespread use has been limited. Here, we demonstrate a Fourier domain subsampling scheme that can accelerate the speed of bispectrum analysis by more than 2 orders of magnitude. In contrast to other approaches for parallelization such as those based on Radon transform or image segmentation, our proposed method enables diffraction-limited imaging without suffering from resolution loss or image artifacts.