Intracellular delivery of nuclear localization sequence peptide mitigates COVID-19 by inhibiting nuclear transport of inflammation-associated transcription factors.

The novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), can trigger dysregulated immune responses known as the cytokine release syndrome (CRS), leading to severe organ dysfunction and respiratory distress. Our study focuses on developing an improved cell-permeable nuclear import inhibitor (iCP-NI), capable of blocking the nuclear transport of inflammation-associated transcription factors, specifically nuclear factor kappa B (NF-κB). By fusing advanced macromolecule transduction domains and nuclear localization sequences from human NF-κB, iCP-NI selectively interacts with importin α5, effectively reducing the expression of proinflammatory cytokines. In mouse models mimic SARS-CoV-2-induced pneumonitis, iCP-NI treatment demonstrated a significant decrease in mortality rates by suppressing proinflammatory cytokine production and immune cell infiltration in the lungs. Similarly, in hamsters infected with SARS-CoV-2, iCP-NI effectively protected the lung from inflammatory damage by reducing tumor necrosis factor-α, interleukin-6 (IL-6), and IL-17 levels. These promising results highlight the potential of iCP-NI as a therapeutic approach for COVID-19-related lung complications and other inflammatory lung diseases.

Cyclic Carbaporphyrin Arrays.

Two cyclic carbaporphyrin arrays (trimer 6 and tetramer 7) were synthesized from a dibrominated carbaporphyrin precursor (5) via a one-pot Yamamoto-type coupling. Single-crystal X-ray diffraction analyses revealed that 6 and 7 contain three and four covalently linked carbaporphyrin (formally dicarbacorrole) units, respectively. Trimer 6 adopts a roughly planar conformation and tetramer 7 adopts an up-and-down zig-zag conformation. Both 6 and 7 contain a [n]cyclo-meta-phenylene ([n]CMP) core, namely, [6]- and [8]CMP for 6 and 7, respectively. Transient absorption (TA) anisotropy and pump-power-dependent excited-state decay studies provided evidence for excitation energy transfer (EET) within both trimer 6 and tetramer 7. The exciton energy hopping (EEH) times were estimated to be 18 and 35 ps for 6 and 7, respectively, as inferred from pump-power-dependent TA measurements. Since the center-to-center distances between adjacent carbaporphyrin units are similar in 6 and 7, the different EEH times are attributed to differences in the orientation of the transition dipoles in these two congeneric arrays. The orientation factor κ2, the key parameter defining the Förster resonance energy transfer efficiency, was calculated to be 2.15 and 1.03 for 6 and 7, respectively, a finding that supports the shorter excitation energy hopping time seen in the case of trimer 6. To our knowledge, this is the first time that covalently linked cyclic carbaporphyrin arrays were synthesized using a single carbaporphyrin as the starting point and that EET between carbaporphyrin subunits constrained within a well-defined polycyclic framework has been correlated with structural differences.

Xanthene-Separated 24 π-Electron Antiaromatic Rosarin Dimer.

Antiaromatic molecules have recently received attention because of their intrinsic properties, such as high reactivity and their narrow HOMO-LUMO gaps. Stacking of antiaromatic molecules has been predicted to induce three-dimensional aromaticity via frontier orbital interactions. Here, we report a covalently linked π-π stacked rosarin dimer that has been examined experimentally by steady-state absorption and transient absorption measurements and theoretically by quantum chemical calculations, including time-dependent density functional theory, anisotropy of induced current density, and nucleus-independent chemical shift calculations. Relative to the corresponding monomer, the dimer exhibits diminished antiaromaticity upon lowering the temperature to 77 K, a finding ascribed to intramolecular interactions between the macrocyclic rosarin subunits.

Assessment of Pulmonary Ventilation Using 3D Ventilation Flow-Weighted and Ventilation-Weighted Maps From 3D Ultrashort Echo Time (UTE) MRI.

BACKGROUND: Three-dimensional (3D) ventilation flow-weighted (VFW) maps together with 3D ventilation-weighted (VW) maps may help to better assess pulmonary function. PURPOSE: To investigate the use of 3D VFW and VW maps for evaluating pulmonary ventilation function. STUDY TYPE: Prospective. POPULATION: Two patients (one male, 85 years old; one female, 64 years old) with chronic obstructive pulmonary disease (COPD) and nine healthy subjects (all male; 23-27 years). FIELD STRENGTH/SEQUENCE: 3-T, 3D radial UTE imaging. ASSESSMENT: 3D VFW and VW maps were calculated from 3D UTE MRI by voxel-wise subtraction of respiratory phase images. Their validation was tested in nine healthy volunteers using slow/deep and fast/shallow breathing conditions. Additional validation was performed by comparison with single photon emission computed tomography (SPECT) ventilation maps of one healthy participant. For comparison, gravity dependence of anterior-posterior regional ventilation was assessed by one-dimensional plot of the mean signal intensity for each coronal slice. Structural similarity index measure was also calculated. Finally, VW maps and VFW maps of two COPD patients were evaluated for emphysema lesions with reference to CT images. STATISTICAL TESTS: Wilcoxon sign-rank tests for regional Ventilation and Ventilation flow, analysis of variance, post-hoc t-tests and Bonferroni correction, coefficient of variation, Kullback-Liebler divergence. A P-value <0.05 was considered statistically significant. RESULTS: The validation of 3D VFW and VW maps was shown by statistically significant differences in ventilation flow and ventilation between the breathing conditions. Additionally, UTE-MRI and SPECT-based ventilation maps showed gravitational dependence in the anteroposterior direction. When applied to patients with COPD, the use of 3D VFW and VW maps was able to differentiate between two patients with different phenotypes. DATA CONCLUSION: The use of 3D VFW and VW maps can provide regional information on ventilation function and potentially contribute to assessment of COPD subtypes and disease progression. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Provenance-Based Trust-Aware Requirements Engineering Framework for Self-Adaptive Systems.

With the development of artificial intelligence technology, systems that can actively adapt to their surroundings and cooperate with other systems have become increasingly important. One of the most important factors to consider during the process of cooperation among systems is trust. Trust is a social concept that assumes that cooperation with an object will produce positive results in the direction we intend. Our objectives are to propose a method for defining trust during the requirements engineering phase in the process of developing self-adaptive systems and to define the trust evidence models required to evaluate the defined trust at runtime. To achieve this objective, we propose in this study a provenance-based trust-aware requirement engineering framework for self-adaptive systems. The framework helps system engineers derive the user's requirements as a trust-aware goal model through analysis of the trust concept in the requirements engineering process. We also propose a provenance-based trust evidence model to evaluate trust and provide a method for defining this model for the target domain. Through the proposed framework, a system engineer can treat trust as a factor emerging from the requirements engineering phase for the self-adaptive system and understand the factors affecting trust using the standardized format.

Multi-Domain Rapid Enhancement Networks for Underwater Images.

Images captured during marine engineering operations suffer from color distortion and low contrast. Underwater image enhancement helps to alleviate these problems. Many deep learning models can infer multi-source data, where images with different perspectives exist from multiple sources. To this end, we propose a multichannel deep convolutional neural network (MDCNN) linked to a VGG that can target multi-source (multi-domain) underwater image enhancement. The designed MDCNN feeds data from different domains into separate channels and implements parameters by linking VGGs, which improves the domain adaptation of the model. In addition, to optimize performance, multi-domain image perception loss functions, multilabel soft edge loss for specific image enhancement tasks, pixel-level loss, and external monitoring loss for edge sharpness preprocessing are proposed. These loss functions are set to effectively enhance the structural and textural similarity of underwater images. A series of qualitative and quantitative experiments demonstrate that our model is superior to the state-of-the-art Shallow UWnet in terms of UIQM, and the performance evaluation conducted on different datasets increased by 0.11 on average.

Philanthropic conference-based requirements engineering in time of pandemic and beyond.

As software engineering (SE) practitioners, we can help society by using our communities of experts to address a software need of a socially conscious organization. Doing so can benefit society in the locale of a SE conference and provide access to international experts for local organizations. Furthermore, established SE researchers as well as practitioners and students have the opportunity for a unique learning experience. While the SE community has already realized the importance of addressing human values and promoting social good objectives in software development, we are unaware of previous attempts to leverage SE conferences for this activity. Conferences present an opportunity to enjoy the assembly of SE practitioners, researchers, and students for the purpose of a philanthropic endeavor. Over the past four years of running a "Requirements Engineering for Social Good" event called RE Cares, co-located with the International Conference on Requirements Engineering, we worked with the stakeholders local to the conference venue. We selected stakeholders who would not necessarily have ready access to requirements engineering, software design, and development expertise otherwise, to build software targeting "good causes." In the last two years, this event was altered to adapt to the constraints induced by COVID-19, moving to a hybrid mode and changing many of its practices accordingly. This paper summarizes and generalizes our experiences, discussing our lessons learned in the context of the pandemic and beyond and providing a framework for conducting similar social contribution in any SE conferences in general.

Pyrene-Bridged Expanded Carbaporphyrin Nanobelts.

Two belt-like expanded carbaporphyrins (NB1 and NB2) were prepared via a one-pot procedure that involves a [6 + 3] condensation between a pyrene-bearing tetrapyrrole precursor (2) and pentafluorobenzaldehyde, followed by oxidation. Single crystal X-ray diffraction analyses revealed that NB1 and NB2 both contain six dipyrromethene moieties and three bridging pyrene units. In the structure of NB1, there are two vertically orientated pyrene units and one transverse orientated pyrene unit; however, in NB2 all three pyrene units are vertically orientated. The structural differences between NB1 and NB2 are reflected in their respective physical properties as revealed by proton NMR, UV-vis, and fluorescence spectroscopies. In contrast to all-carbon nanobelts, NB1 and NB2 contain multiple pyrrolic nitrogen donors that could serve as potential metal coordination sites. As a test of this possibility, NB2 was used to prepare an unprecedented Zn complex containing 7 Zn2+ metal centers connected by a network of bridging atoms, as confirmed by a single crystal X-ray diffraction analysis. To the best of our knowledge, this is the first example of a belt-like molecular system that can coordinate multiple metal ions both along the backbone and within its central cavity.

Impact of the ACOSOG Z0011 trial on surgical practice in Asian patients: trends in axillary surgery for breast cancer from a Korean Breast Cancer Registry analysis.

BACKGROUND: Since the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer from a Korean Breast Cancer Registry to understand the impact of the Z0011 trial in Asian patients. METHODS: We collected prospectively constructed data from the nationwide Korean Breast Cancer Registry (KBCR). We identified patients who underwent sentinel node biopsy followed by breast-conserving surgery from 2011 to 2018 and were found to have pathological stage T1-2N1-3M0 disease. Regression analyses were performed to compare the downward trend of axillary lymph node dissection (ALND) in Korean cohort with that previously reported in a Dutch cohort. RESULTS: From KBCR data, 7478 patients met the inclusion criteria. The proportion of ALND significantly decreased from 2011 (76.6%) to 2018 (47.5%). Multivariate analysis revealed that earlier years at diagnosis, larger tumor size, and lymphatic invasion were associated with a higher odds ratio of performing ALND. Compared to the Dutch cohort, the downward trend of ALND in Korea was significantly more gradual (annual percent change: 37.2 vs. 5.8%, p < 0.001). CONCLUSIONS: This study demonstrated a downward trend of ALND in Korean patients with breast cancer. However, the rate of decrease was significantly slower than that in the Dutch cohort.

SRE_BBC: A Self-Adaptive Security Enabled Requirements Engineering Approach for SLA Smart Contracts in Blockchain-Based Cloud Systems.

Current blockchain-based cloud (BBC) systems have several security vulnerabilities regarding smart contracts (SC), and several attacks have been reported recently. The SC development lacks standard design processes that follow software lifecycle principles to model secure SC. Secondly, the security mechanisms in the SC are not constantly evolved to resist evolving adversary attacks. BBC systems lack self-adaptive security capability to make spontaneous decisions when adversarial attacks are encountered. To build a self-adaptive secure BBC system that follows standard software development lifecycle principles to model secure SC, we propose the so-called self-adaptive security RE_BBC framework. The framework would utilize the MAPE-BBC adaptation loop to make decisions internally based on the threat models, goal models, and service level agreement (SLA) SC security specifications. The framework identifies vulnerabilities and threats and takes precautionary measures using self-adaptive SC agents. We validated the proposed methodology theoretically and empirically, and statistically proved the research questions and hypothesis using the t-test and Mann-Whitney U test. Subsequently, we compare our proposed approach with the Security Quality Requirements Engineering approach (SQUARE). The feasibility results and the replicated study results indicate that the proposed approach outperformed the SQUARE approach in terms of artifacts quality, self-adaptive security evaluation quality, efficiency in response time, complexity, and usefulness of the proposed approach for the Healthcare Data Management (HDM) system. SC security developers can immensely benefit from our proposed methodology. They need not reengineer SC from scratch; depending on their security needs and plan, the contract can be adapted to execute a new plan.

Effect of GNWs/NiO-WO3/GNWs Heterostructure for NO2 Gas Sensing at Room Temperature.

Recently, as air pollution and particulate matter worsen, the importance of a platform that can monitor the air environment is emerging. Especially, among air pollutants, nitrogen dioxide (NO2) is a toxic gas that can not only generate secondary particulate matter, but can also derive numerous toxic gases. To detect such NO2 gas at low concentration, we fabricated a GNWs/NiO-WO3/GNWs heterostructure-based gas sensor using microwave plasma-enhanced chemical vapor deposition (MPECVD) and sputter, and we confirmed the NO2 detection characteristics between 10 and 50 ppm at room temperature. The morphology and carbon lattice characteristics of the sensing layer were investigated using field emission scanning electron microscopy (FESEM) and Raman spectroscopy. In the gas detection measurement, the resistance negative change according to the NO2 gas concentration was recorded. Moreover, it reacted even at low concentrations such as 5-7 ppm, and showed excellent recovery characteristics of more than 98%. Furthermore, it also showed a change in which the reactivity decreased with respect to humidity of 33% and 66%.

Architecture Exploration of a Backprojection Algorithm for Real-Time Video SAR.

This paper explores novel architectures for fast backprojection based video synthetic aperture radar (BP-VISAR) with multiple GPUs. The video SAR frame rate is analyzed for non-overlapped and overlapped aperture modes. For the parallelization of the backprojection process, a processing data unit is defined as the phase history data or range profile data from partial synthetic-apertures divided from the full resolution target data. Considering whether full-aperture processing is performed and range compression or backprojection are parallelized on a GPU basis, we propose six distinct architectures, each having a single-stream pipeline with a single GPU. The performance of these architectures is evaluated in both non-overlapped and overlapped modes. The efficiency of the BP-VISAR architecture with sub-aperture processing in the overlapped mode is accelerated further by filling the processing gap from the idling GPU resources with multi-stream based backprojection on multiple GPUs. The frame rate of the proposed BP-VISAR architecture with sub-aperture processing is scalable with the number of GPU devices for large pixel resolution. It can generate 4096 × 4096 video SAR frames of 0.5 m cross-range resolution in 23.0 Hz on a single GPU and 73.5 Hz on quad GPUs.

Preparation of Carbon Nanowall and Carbon Nanotube for Anode Material of Lithium-Ion Battery.

Carbon nanowall (CNW) and carbon nanotube (CNT) were prepared as anode materials of lithium-ion batteries. To fabricate a lithium-ion battery, copper (Cu) foil was cleaned using an ultrasonic cleaner in a solvent such as trichloroethylene (TCE) and used as a substrate. CNW and CNT were synthesized on Cu foil using plasma-enhanced chemical vapor deposition (PECVD) and water dispersion, respectively. CNW and CNT were used as anode materials for the lithium-ion battery, while lithium hexafluorophosphate (LiPF6) was used as an electrolyte to fabricate another lithium-ion battery. For the structural analysis of CNW and CNT, field emission scanning electron microscope (FE-SEM) and Raman spectroscopy analysis were performed. The Raman analysis showed that the carbon nanotube in composite material can compensate for the defects of the carbon nanowall. Cyclic voltammetry (CV) was employed for the electrochemical properties of lithium-ion batteries, fabricated by CNW and CNT, respectively. The specific capacity of CNW and CNT were calculated as 62.4 mAh/g and 49.54 mAh/g. The composite material with CNW and CNT having a specific capacity measured at 64.94 mAh/g, delivered the optimal performance.

Dermoglandular rotation flap with subaxillary advancement flap as an oncoplastic technique for breast cancer.

We propose a novel oncoplastic surgical technique, dermoglandular rotation flap with subaxillary advancement flap, as a feasible one-stage operation. Breast conserving surgery, incorporating the dermoglandular rotation flap with subaxillary advancement flap, was performed in 49 female patients with breast cancer, between January and December 2015. After a full-thickness fibroglandular resection including the tumor, an inferior- or a superior-based rotation flap was performed according to the location of the defect. The subaxillary flap consisted of skin, dermis, and subcutaneous fat tissue and was mobilized from the chest wall musculature. Since subaxillary skin has greater redundancy, it can be easily moved to reach the lateral aspect of the breast. Approximation of the subaxillary flap to the lateral side of rotated dermoglandular flap served to relieve skin tension and avoid displacement of the nipple-areola complex (NAC). Consequently, there was wider dermoglandular tissue rotation and efficient filling of defect without any significant postoperative deformity. The mean follow-up period was 46.5 ± 3.1 months (range, 42.4-52.1 months). Mean tumor size, on pathology, was 2.1 cm (range, 0.4-6.0). Mean excised breast tissue weight was 78.4 g (range, 28.6-195.0). More than half of the patients (51%) studied had excised breast tissue weighing more than 80 g. None of the included patients had positive surgical margins in final pathologic reports. Most patients answered excellent or good for self-estimated cosmetic outcomes including symmetry of the breast and NAC, breast shape, scarring, and overall satisfaction. A modified dermoglandular rotation flap technique along with subaxillary advancement flap is a feasible and effective oncoplastic technique for breast cancers.

Clinical subtypes and prognosis in breast cancer according to parity: a nationwide study in Korean Breast Cancer Society.

PURPOSE: We explored the association between parity and the risk of developing a specific subtype of breast cancer. We also assessed the association between parity and prognosis according to subtypes. METHODS: A total of 158,189 patients were enrolled in the Korean Breast Cancer Society Registry database between 1996 and 2015 in Korea. The database provided information on sex, age, number of parity, surgical method, stage, histological findings, presence of biologic markers, adjuvant therapy, and date and cause of death. RESULTS: The patients with higher parity showed a higher ratio of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) subtypes. In univariate analysis, women with TNBC who had more than three children had a worse prognosis compared to other groups (HR 1.83; 95% CI 1.34-2.49; P < 0.001). This association was also observed in women younger than 50 years (HR 1.63; 95% CI 1.07-2.48; P = 0.021). In multivariate analysis stratified by subtypes, women who had more than three children were associated with a worse prognosis in TNBC in the total population (HR 1.53; 95% CI 1.11-2.12; P = 0.011). This association was also observed in patients younger than 50 years of age (HR 1.53; 95% CI 1.09-2.61; P = 0.017). CONCLUSION: Women who had more than three children were more likely to develop hormone receptor-negative (HR-) subtypes. Women who had more than three children were associated with worse prognosis in patients younger than 50 years of age and in patients with TNBC.

Is the high proportion of young age at breast cancer onset a unique feature of Asian breast cancer?

PURPOSE: Women with breast cancer in Asian and Western countries are similar in many respects, but there are also differences, such as in the age at onset and the proportion of breast cancer occurring at younger ages. There is controversy as to whether these differences are due to inter-racial genetic differences or to environmental or other factors. METHODS: Using the Korean Breast Cancer Society's large breast cancer registry, we investigated the causes of Koreans' unique breast cancer characteristics by examining the changes in the incidence and proportion of young-onset breast cancer (YBC) in Korea over time. We analyzed data from 108,894 patients to compare characteristics between patients with YBC and non-YBC. For a subtype analysis, we analyzed data from 85,691 patients from 2000. RESULTS: Among the 108,894 patients, 17,877 (15.5%) had YBC. The tumors associated with YBC showed aggressive clinicopathologic features. The incidence of breast cancer in Korea has increased over time, and while both YBC and non-YBC increased each year, the increase in non-YBC was more pronounced; thus, the proportion of YBC has decreased over time. By 2020, it appears that the ratio of YBC in Korea will be similar to that in Western countries. The increase in YBC was mainly due to an increase in the luminal A subtype. The incidence of other YBC subtypes did not change over time. CONCLUSIONS: Our data suggest that the current high proportion of YBC is probably not a unique feature of breast cancer in Asia but rather a transient phenomenon. Additionally, our results indirectly suggest that there were different causes for breast cancer in different age groups, suggesting the importance of using different approaches for different age groups to establish policies for preventing breast cancer.

A Prospective Longitudinal Study about Change of Sleep, Anxiety, Depression, and Quality of Life in Each Step of Breast Cancer Patients.

PURPOSE: Quality of sleep (QoS), anxiety, depression, and quality of life (QoL) are common issues among breast cancer patients. Prospective longitudinal studies of QoS, anxiety, depression, and QoL in breast cancer patients are lacking. The aim of this study was to find out whether there is a proper treatment point associated with QoS, anxiety, depression, and QoL during early treatment of breast cancer patients. METHODS: We used 4 self-report questionnaires about QoS, anxiety, depression, and QoL. QoS was measured using the Pittsburgh Sleep Quality Index, anxiety was measured with the Beck Anxiety Inventory, depression was measured with the Beck Depression Inventory, and QoL was measured with the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form. Patients were assessed at the time of surgery, at the beginning of chemotherapy, and at the end of chemotherapy. Clinicopathological information was collected for analysis. RESULTS: Fifty-two patients were enrolled in this study, and 29 completed 3 self-report questionnaires. QoS, anxiety, and depression showed no differences during the early treatment period. However, QoL changed during that period (p = 0.004). Type of breast surgery (total mastectomy vs. breast-conserving surgery) showed a relationship with QoS during the entire treatment period, but with anxiety only at the time of surgery (p = 0.002). Although the sample size was too small, the total mastectomy group showed better results. CONCLUSION: Breast cancer patients experience sleep disturbance, anxiety, depression, and loss of QoL. During the period of treatment, these do not change significantly, but these symptoms are often overlooked. Providing sufficient explanations about the treatment and prognosis of breast cancer and mental support for breast cancer patients prior to treatment will help to improve patients' QoS, anxiety, depression, and QoL.

Tamoxifen therapy improves overall survival in luminal A subtype of ductal carcinoma in situ: a study based on nationwide Korean Breast Cancer Registry database.

PURPOSE: To determine the prognostic role of tamoxifen therapy for patients with ductal carcinoma in situ (DCIS) according to molecular subtypes. METHODS: Data of 14,944 patients with DCIS were analyzed. Molecular subtypes were classified into four categories based on expression of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Kaplan-Meier estimator was used for overall survival analysis while Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS: Luminal A subtype (ER/PR+, HER2-) showed higher (P = .009) survival rate than triple-negative (TN) subtype. Tamoxifen therapy group showed superior (P < .001) survival than no-tamoxifen therapy group. It had survival benefit only for luminal A subtype (P = .001). Tamoxifen therapy resulted in higher survival rate in subgroups with positive ER (P = .006), positive PR (P = .009), and negative HER2 (P < .001). In luminal A subtype, tamoxifen therapy showed lower hazard ratio (HR) compared to no-tamoxifen therapy (HR, 0.420; 95% CI 0.250-0.705; P = .001). Tamoxifen therapy was a significant independent factor by multivariate analysis (HR, 0.538; 95% CI 0.306-0.946; P = .031) as well as univariate analysis. CONCLUSION: Tamoxifen therapy group showed superior prognosis than the no-tamoxifen therapy group. Its prognostic influence was only effective for luminal A subtype. Patients with luminal A subtype showed higher survival rate than those with TN subtype. Active tamoxifen therapy is recommended for DCIS patients with luminal A subtype, and routine tests for ER, PR, and HER2 should be considered for DCIS.

Immediate chest wall reconstruction using an external oblique myocutaneous flap for large skin defects after mastectomy in advanced or recurrent breast cancer patients: A single center experience.

BACKGROUND AND OBJECTIVES: We report 75 single-stage chest-wall reconstructions using ipsilateral external oblique myocutaneous flap (EOMCF) to cover the extensive skin defects following resection of advanced or recurrent breast tumours at the Pusan National University Hospital. METHODS: Between January 2007 and October 2015, 75 women with advanced or recurred breast cancer who underwent extensive mastectomy with immediate chest wall reconstruction using EOMCF were reviewed retrospectively. RESULTS: Mean age was 50.5 ± 9.8 years and mean follow-up period was 36.7 ± 25.1 months. A total of 59 patients (78.7%) had stage III disease and the remaining 16 patients (21.3%) had stage IV. Mean excised breast tissue weight was 687.6 ± 416.5 g (range, 120.3-2797.1 g). The mean chest wall skin defect covered with an EOMCF was 228.3 ± 168.1 cm2 and corresponded to an approximately 15 × 15 cm defect. Average operative time for reconstruction was <2 h. There were no major complications such as flap loss, full thickness skin necrosis, or surgical site infections. With respect to loco-regional recurrence, nine patients (12%) experienced recurrence. Among the 59 non-stage IV patients, loco-regional relapse occurred in five patients (8.5%). CONCLUSIONS: EOMCF can effectively cover large chest wall defects with a few minor complications and reliable local disease control.

Spatiotemporal expression patterns of clusterin in the mouse inner ear.

Clusterin (CLU) is an extracellular chaperone protein that is implicated in diverse physiological and pathophysiological cellular processes. CLU expression is upregulated in response to cellular stress and under certain conditions, such as neurodegenerative disease and cancer. CLU primarily functions as a chaperone that exerts cytoprotective effects by removing cellular debris and misfolded proteins and also acts as a signaling molecule that regulates pro-survival pathways. Deafness is caused by genetic factors and various extrinsic insults, including ototoxic drugs, exposure to loud sounds and aging. Considering its cytoprotectivity, CLU may also mediate cellular defense mechanisms against hearing loss due to cellular stresses. To understand the function of CLU in the inner ear, we analyze CLU expression patterns in the mouse inner ear during development and in the adult stage. Results of quantitative real-time polymerase chain reaction analysis showed that Clu mRNA levels in the inner ear were increased during embryogenesis and were constantly expressed in the adult. Detailed spatial expression patterns of Clu both in the mRNA and protein levels were analyzed throughout various developmental stages via in situ hybridization and immunofluorescence staining. Clu expression was found in specific domains of developing inner ear starting from the otocyst stage, mainly adjacent to the prosensory domain of the cochlear epithelium. In the mature inner ear, Clu expression was observed in Deiter's cells and pillar cells of the organ of Corti, outer sulcus and in basal cells of the stria vascularis in the cochlea. These specific spatiotemporal expression patterns suggest the possible roles of CLU in inner ear development and in maintaining proper hearing function.