Enantioselective Synthesis of Chiral 2-Nitroallylic Amines via Cooperative Cation-Binding Catalysis.

Chiral allylic amines are valuable building blocks for biologically important compounds and natural products. In this study, we present the use of cooperative cation-binding catalysis as an efficient method for synthesizing chiral allylic amines. By utilizing a chiral oligoEG and potassium fluoride as a cation-binding catalyst and base, respectively, a wide range of biologically relevant chiral 2-nitroallylic amines are obtained with excellent enantioselectivities (up to >99 % ee) through the organocatalytic asymmetric aza-Henry-like reaction of ß-monosubstituted and ß,ß-disubstituted nitroalkenes with α-amidosulfones as imine precursors. Extensive experimental studies are presented to illustrate plausible mechanisms. Preliminary use of a chiral 2-nitroallylic amine as a Michael acceptor demonstrated its potential application for diversity-oriented synthesis of bioactive compounds.

Clinical outcomes after incomplete cycles of R-CHOP for diffuse large B-cell lymphoma: 10 years' real-world experience in a single institute.

Although the current standard of care for diffuse large B-cell lymphoma (DLBCL) is six cycles of rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone combination chemotherapy (R-CHOP), a larger than expected number of patients cannot complete planned six cycles for various reasons in the real world. We aimed to evaluate the prognosis of patients with DLBCL after incomplete treatment by analyzing the chemotherapy response and survival according to the cause of discontinuation and the number of cycles. We analyzed a retrospective cohort of patients diagnosed with DLBCL who underwent incomplete cycles of R-CHOP at Seoul National University Hospital and Boramae Medical Center from January 2010 to April 2019. A total of 1183 patients were diagnosed with DLBCL, of which 260 (22%) did not complete six cycles of R-CHOP. The most common cause of discontinuation of chemotherapy was life-threatening infection, and the most common pathogen was Pneumocystis jirovecii. Overall survival (OS) and progression-free survival (PFS) were significantly better in patients who achieved complete response (CR) or partial response (PR) at the first response evaluation. Patients underwent three or more cycles of chemotherapy had a longer OS than those who did not. In patients with limited-stage disease, consolidative radiotherapy showed a significant improvement in OS and PFS. Advanced stage, high comorbidity score, and poor primary response to chemotherapy were poor prognostic factors in patients with unplanned treatment shortening. This study provides real-world outcomes for patients who could not complete the planned six cycles of R-CHOP.

Prognostic roles of leptin-signaling proteins, PD-L1, and tumor-infiltrating lymphocytes in surgically-resected biliary tract cancers.

BACKGROUND: Biliary tract cancers are rare, with a poor patient prognosis. Leptin and programmed death-ligand 1 (PD-L1) influence CD8+ and forkhead box P3 (FOXP3)+ lymphocytes, and thus, cancer cell growth. We aimed to define the prognostic implications of these variables and the clinicopathological features of biliary tract cancers. METHODS: Immunohistochemistry for leptin signaling-related proteins (leptin, leptin receptor, pSTAT3, extracellular-regulated kinase, mammalian target of rapamycin), PD-L1, CD8, and FOXP3 and in situ hybridization for Epstein-Barr virus-encoded small RNAs were performed in 147 cases of surgically-resected biliary tract cancers. RESULTS: Immune cell PD-L1-positivity, tumor size < 3 cm, adjuvant chemotherapy, no recurrence, and early-stage tumors were correlated with better 5-year survival in the tumoral PD-L1(-) and leptin(-) subgroups, and extrahepatic cholangiocarcinoma through multivariate analysis (all p < 0.05). Immune cell PD-L1 and adjuvant chemotherapy lost its prognostic significance in the tumoral PD-L1+ and leptin+ subgroups. CONCLUSIONS: The prognostic implication of the variables may depend upon tumoral protein expression and the anatomical site. Immune cell PD-L1-positivity and the administration of adjuvant chemotherapy may indicate the favorable survival of patients with surgically-resected biliary tract cancers, specifically, in the tumoral PD-L1(-) or tumor leptin(-) subgroups and extrahepatic cholangiocarcinoma. PD-L1- or leptin-targeted therapy combined with conventional chemotherapy may benefit the tumoral PD-L1+ or leptin+ subgroups.

Differences in time-to-fusion based on "absence of peri-graft radiolucency" and "trabecular bone bridging" criteria after transforaminal lumbar interbody fusion in patients with low and normal bone density.

OBJECTIVE: To investigate the difference in time-to-fusion between two sets of interbody fusion criteria (absence of peri-graft radiolucency vs. trabecular bone bridging), and to determine the effect of osteoporosis on time-to-fusion. MATERIALS AND METHODS: This retrospective study enrolled 79 patients treated for degenerative disease with one-level transforaminal lumbar interbody fusion from February 2012 to December 2018, and who had both pre- and post-operative CTs. Patients were divided into osteoporosis, osteopenia, and normal groups based on L1 vertebral body attenuation values in pre-operative CT with cutoff of 90 Hounsfield units (HU) and 120 HU. The osteoporosis, osteopenia, and normal groups included 36 patients (mean age: 69.9 years; 8 men and 28 women), 18 patients (mean age: 62.6 years; 7 men and 11 women), and 25 patients (mean age: 56.6 years; 15 men and 10 women), respectively. Fusion was assessed annually on post-operative CT images using absence of peri-graft radiolucency and trabecular bone bridging criteria. Time-to-fusion was estimated using the Kaplan-Meier method, and differences between the groups were examined using the log-rank test. Cox proportional hazards regression was performed. RESULTS: Time-to-fusion took significantly longer in the osteoporosis group in both fusion criteria (0.5 years in normal vs. 2 years in osteopenia vs. 3 years in osteoporosis for absence of peri-graft radiolucency; p = 0.003, and 3 years vs. 4 years vs. 5 years for trabecular bone bridging; p = 0.001). Only osteoporosis grouping was independent risk factor for slow trabecular bone fusion (hazard ratio:0.339; p = 0.003). CONCLUSION: The median time to fusion was significantly longer when using trabecular bone bridging criteria than absence of peri-graft radiolucency criteria.

Characteristics of Sweet syndrome in patients with or without malignancy.

Sweet syndrome is a neutrophilic dermatosis occasionally associated with malignancies. Due to its rarity, the clinical features of Sweet syndrome are still unclear. Thus, we aimed to analyze clinical features, treatment, and outcomes of these patients according to associated disease. We conducted a retrospective, longitudinal cohort study from January 2000 to August 2020. We reviewed the medical records of 52 patients with Sweet syndrome. The median age of patients was 57.5 years old (range, 17-84), and 48.1% were female. Of the 52 patients analyzed, 27 patients (51.9%) had malignancy-associated Sweet syndrome. Sweet syndrome was diagnosed concurrently with (N = 8), before (N = 5), and after (N = 14) the diagnosis of malignancy. The idiopathic Sweet syndrome was most common in the non-malignancy group (56.0%). Myelodysplastic syndrome was the most common malignancy associated with Sweet syndrome (47.6%). Leukopenia (p = 0.005), anemia (p < 0.001), and thrombocytopenia (p = 0.008) were significantly associated with malignancy. The majority of patients showed rapid improvement of symptoms after steroid administration. The symptoms of some patients with malignancy did not improve with steroid alone; however, their symptoms often improved when steroids were combined with a treatment for the associated malignancy. Relapse and aggravation of Sweet syndrome were common in the malignancy group. Sweet syndrome showed a broad spectrum of clinical features related to various diseases. Sweet syndrome often occurred as a paraneoplastic feature. Therefore, active systemic evaluation is needed in the first diagnosis of Sweet syndrome without clear etiology.

Long-term prognostic effect of hormone receptor subtype on breast cancer.

PURPOSE: To determine the long-term prognostic role of hormone receptor subtype in breast cancer using surveillance, epidemiology, and end results (SEER) database. METHODS: Data of 810,587 female operable invasive breast cancer patients from SEER database with a mean follow-up period of 94.2 months (range, 0-311 months) were analyzed. Hormone receptor subtype was classified into four groups based on estrogen receptor (ER) and progesterone receptor (PR) statuses: ER(+)/PR(+), ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-). RESULTS: Numbers of subjects with ER(+)/PR(+), ER(+)/PR(-), ER(-)/PR(+), ER(-)/PR(-), and unknown were 496,279 (61.2%), 86,858 (10.7%), 11,545 (1.4%), 135,441 (16.7%), and 80,464 (9.9%), respectively. The ER(+)/PR(+) subtype showed the best breast-cancer-specific survival, followed by ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) subtypes in the respective order (all p < 0.001). Survival difference among hormone receptor subtypes was maintained in subgroup analysis according to anatomic stage, race, age group, and year of diagnosis. Hormone receptor subtype was a significant independent prognostic factor in multivariable analyses (p < 0.001). Hazard ratios of ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) for breast-cancer-specific mortality risk were 1.419 (95% confidence interval [CI] 1.383-1.456), 1.630 (95% CI 1.537-1.729), and 1.811 (95% CI 1.773-1.848), respectively, with ER(+)/PR(+) as reference. CONCLUSION: Hormone receptor subtype is a significant independent prognostic factor in female operable invasive breast cancer patients with long-term effect. The ER(+)/PR(+) subtype shows the most favorable prognosis, followed by ER(+)/PR(-), ER(-)/PR(+), and ER(-)/PR(-) subtypes in the respective order. Prognostic impacts of hormone receptor subtypes are also maintained in subgroup analysis according to anatomic stage, race, age, and year of diagnosis.

Comparison of quality of life and health behaviors in survivors of acute leukemia and the general population.

We aimed to compare the health-related quality of life and health behaviors of acute leukemia (AL) survivors with that of the general population from two cohorts. AL survivors (n = 149) completed a set of questionnaires to evaluate quality of life, mental status, and health behaviors. AL survivors had more physical and mental difficulties (problems with usual activities, 15% vs. 5%, p < 0.001; anxiety or depression, 24% vs. 9%, p < 0.001; pain, 35% vs. 20%, p = 0.002) and more financial difficulties (p < 0.001) than the general population. Survivors who received stem cell transplantation (SCT) had significantly worse problems with role functioning, fatigue, pain, dyspnea, and insomnia, and had higher depression scores than chemotherapy group (p = 0.024). In terms of health behaviors, AL survivors had lower rates of smoking and drinking and higher influenza vaccination rates than the general population. However, only 17% of survivors had been recommended to receive screening for other cancers from health-care providers, and 67% thought their risk for other cancers was equal or lower than that of the general population. Cancer screening rates were even lower in the SCT group than in the chemotherapy group (p = 0.041). Our study indicates that clinicians should establish more appropriate survivorship care plans.

Quality-by-design approach for the development of telmisartan potassium tablets.

A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis® (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis® tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs. To determine the exact range and cause of risks, we used the risk assessment (RA) tools, preliminary hazard analysis and failure mode and effect analysis to determine the parameters affecting drug dissolution, impurities, and formulation. The range of the design space was optimized using the face-centered central composite design among the design of experiment (DOE) methods. The binder, disintegrant, and kneading time in the wet granulation were identified as X values affecting Y values (disintegration, hardness, friability, dissolution, and impurities). After determining the design space with the desired Y values, the TP tablets were formulated and their dissolution pattern was compared with that of the reference tablet. The selected TP tablet formulated using design space showed a similar dissolution to that of Micardis® tablets at pH 7.5. The QbD approach TP tablet was bioequivalent to Micardis® tablets in beagle dogs.

Pleural Effusion in Multiple Myeloma: Characteristics and Practice Patterns.

In many Asian countries battling with the double burden of increasing noninfectious diseases on top of infectious diseases, multiple myeloma (MM) patients presenting with pleural effusion (PE) pose a great diagnostic challenge. Thus, we aimed to analyze the clinical features and practice patterns of such patients. This is a multicenter retrospective study of newly diagnosed MM patients between January 2011 and December 2015. Among 575 MM patients diagnosed during the study period, 80 (13.9%) that were associated with PE were identified and analyzed. The most common cause of PE was parapneumonic (25%), followed by reactive (18.8%). Higher CRP levels and leukocytosis were indicators of parapneumonic PE. There were 7 (8.8%) with myelomatous PE and 2 (2.5%) with tuberculosis. Fifty-six patients underwent additional examinations to determine the exact cause of effusion; 28 patients received computed tomography (CT) of the chest, 5 patients underwent thoracentesis/biopsy, and 23 patients underwent both CT and thoracentesis/biopsy. On the other hand, 24 patients did not undergo additional analyses but were treated empirically. Real-world analyses of practice patterns in MM patients with PE showed the suboptimal use of invasive procedures to determine the exact cause of PE. Since reversible causes and tuberculosis pleurisy are not uncommon, invasive procedures should be actively incorporated as needed.

The effects of dual-task gait training on foot pressure in elderly women.

[Purpose] The purpose of this study was to evaluate the effect of dual-task gait training on foot pressure in elderly women. [Subjects and Methods] Twenty elderly people in local communities performed dual-task gait training for 20 minutes three times per week for 8 weeks. Foot pressure was measured using an F-scan System (Tekscan, South Boston, MA, USA) before the intervention and in the 4th and 8th weeks of the intervention. [Results] Foot pressure increased significantly between the 4th and 8th weeks of the intervention in the CFF (central forefoot); between before the intervention and the 4th week, between the 4th and 8th weeks, and between before the intervention and the 8th week in the MF (midfoot); and between before the intervention and the 4th and 8th weeks in the HL (heel). [Conclusion] The results of this study indicate that dual-task gait training may improve the gait ability of elderly persons residing in the community.

Comparison of the effectiveness of balance training using a reaching task between a sitting position and a standing position in the elderly.

[Purpose] The purpose of this study was to compare the effectiveness of balance training using a reaching task between a sitting position and a standing position in the elderly. [Subjects and Methods] The study included 30 elderly women from D city. The subjects were divided into the following two groups, according to the training position: the sitting group (n = 15) and standing group (n = 15). Both groups performed training for 20 min, thrice a week for 8 weeks. The short form of the berg balance scale (SFBBS), timed 10-m walk test (10MWT), timed up & go test (TUG), and falls efficacy scale (FES) were used before and after training. [Results] SFBBS, 10MWT, and TUG values were significantly different between before and after training in both groups. However, FES values were significantly different in only the standing group. [Conclusion] Balance training in a standing position is helpful for improving activities that mainly use the lower extremities, such as gait, and training in a sitting position is somewhat helpful for improving balance ability. In addition, balance training in both positions can help overcome the fear of falling.

Protective mechanisms of acacetin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.

This study examined the hepatoprotective effects of acacetin (1), a flavonoid isolated from Agastache rugosa, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were given an intraperitoneal injection of 1 (25, 50, and 100 mg/kg), or the vehicle alone (5% dimethyl sulfoxide-saline), 1 h before GalN (800 mg/kg)/LPS (40 µg/kg) treatment and sacrificed at 6 h after GalN/LPS injection. GalN/LPS markedly increased mortality and serum aminotransferase activity, and these increases were attenuated by 1. GalN/LPS increased serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, while 1 attenuated TNF-α levels and further increased IL-6 levels. GalN/LPS increased protein expression of toll-like receptor 4, phosphorylation of extracellular signal-related kinase, and p38 and c-Jun N-terminal kinase and increased nuclear protein expression of nuclear factor κB; these increases were attenuated by 1. GalN/LPS increased Atg5 and Atg7 protein expressions, and these increases were augmented by 1. GalN/LPS activated autophagic flux as indicated by decreased microtubule-associated protein 1 light chain 3-II and sequestosome1/p62 protein expression. This activation was enhanced by 1. These findings suggest that 1 protects against GalN/LPS-induced liver injury by suppressing TLR4 signaling and enhancing autophagic flux.

The risk factors for discrepancy after endoscopic submucosal dissection of gastric category 3 lesion (low grade dysplasia).

BACKGROUND: Treatment with endoscopic submucosal dissection (ESD) for gastric category 3 lesion (low grade dysplasia, LGD) diagnosed by endoscopic forceps biopsy (EFB) is controversial. AIMS: The purpose of the present study was to validate the use of ESD for gastric LGD diagnosed by EFB and to evaluate predictable factors for pathologic upgrade diagnosis to category 4 (high grade dysplasia, HGD) or 5 (early gastric cancer, EGC) lesions. METHODS: Between November 2008 and October 2011, a retrospective analysis of a prospective database was conducted at a single tertiary referral center. A total of 218 ESD procedures were carried out for gastric LGD lesions identified by EFB. The under-diagnosis rate by EFB and the predictable factors for upgrade diagnosis to category 4 or 5 lesions were analyzed. RESULTS: Pathologic discrepancy between EFB and surgical resection was 20.1 % (44/218). Thirty eight lesions (17.4 %) were diagnosed HGD or EGC by ESD. Gastric HGD lesions were 14 cases (6.4 %) and EGC lesions were 24 cases (23 mucosal and 1 submucosal cancer) (11.0 %). Multivariate analysis revealed that lesion diameter more than 1 cm (OR 3.496 [95 % CI 1.375-8.849]), surface redness (OR 6.493 [95 % CI 2.557-16.666]) and nodular surface (OR 2.762 [95 % CI 1.237-6.172]) were significant risk factors. CONCLUSIONS: Endoscopic resection can be recommended if a LGD lesion has risk factors such as a size of 1 cm or greater, surface redness or surface nodulariy. For lesions without the risk factors, follow-up endoscopy may be recommended.

Rare and complex mutations of epidermal growth factor receptor, and efficacy of tyrosine kinase inhibitor in patients with non-small cell lung cancer.

BACKGROUND: There are many complex and rare mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) other than the two classical mutations of L858R and exon 19 deletional mutation. The purpose of this study was to investigate the clinical significance of rare and complex mutations, and the efficacy of EGFR tyrosine kinase inhibitors (TKIs). METHODS: We analyzed 1,431 NSCLC patients who were treated with either gefitinib or erlotinib. Exons 18 to 21 of EGFR were analyzed by PCR and subjected to direct sequencing methods. RESULTS: Of 306 patients who had EGFR mutation, 24 patients (7.3 %) had complex mutations. The frequency of rare mutations was 10.3 %. Four groups were categorized [group A (N = 269): classical mutation alone; group B (N = 16): complex mutation with classical mutation; group C (N = 16): rare mutation alone or complex mutation with rare mutation; group D (N = 5); classical mutation with T790M]; the response rate (RR) to TKI was significantly different between each group (RR = 74.8 % in group A vs. 68.8 % in group B vs. 25.0 % in group C vs. 80.0 % in group D, P < 0.001). Progression-free survival (PFS) was also poorer in rare mutations (median PFS: 11.9 vs. 8.1 vs. 1.4 vs. 8.0 months, respectively, P < 0.001). CONCLUSIONS: NSCLC patients harboring rare mutations did not show consistent and favorable responses to EGFR TKI compared with those harboring classical mutations. However, complex mutations with classical mutations showed similar treatment efficacy toward EGFR TKI to that with classical mutations alone.

Detection of sulfur mustard simulant by trisaryl phosphoric triamide-based resin using a quartz crystal microbalance sensor.

Chemical warfare agents (CWAs) pose a persistent threat to human safety, and bis(2-chloroethyl) sulfide, or sulfur mustard (SM) is one of the most dangerous substances and is able to cause serious harm. Detecting SM gas is vital, but current methods have high-temperature requirements and limited selectivity, mainly because of the lack of CWA receptor development, and this makes them challenging to use. To address this issue, we present a trisaryl phosphoric triamide-based resin receptor that preferentially interacts with a SM simulant 2-chloroethyl ethyl sulfide (2-CEES) through dipole interactions. The receptor was synthesized through a facile process using an amine and a triethyl phosphate and the properties of its coating were enhanced using epoxy chemistry. The receptor's superior triamide structure was evaluated using a quartz crystal microbalance and reactivity was confirmed by observing the variations in reactivity according to the number of phosphoramides. The receptor showed better reactivity to 2-CEES vapor than to the known poly(epichlorohydrin) and showed selectivity to other volatile organic compounds. Moreover, its durability was evident even 30 days post-coating. The applicability of this receptor extends to array sensors, sound acoustic wave sensors, and chemo-resistive and chemo-capacitive sensors, and it promises advances in chemical warfare agent detection.

Estimating vegetation index for outdoor free-range pig production using YOLO.

The objective of this study was to quantitatively estimate the level of grazing area damage in outdoor free-range pig production using a Unmanned Aerial Vehicles (UAV) with an RGB image sensor. Ten corn field images were captured by a UAV over approximately two weeks, during which gestating sows were allowed to graze freely on the corn field measuring 100 × 50 m2. The images were corrected to a bird's-eye view, and then divided into 32 segments and sequentially inputted into the YOLOv4 detector to detect the corn images according to their condition. The 43 raw training images selected randomly out of 320 segmented images were flipped to create 86 images, and then these images were further augmented by rotating them in 5-degree increments to create a total of 6,192 images. The increased 6,192 images are further augmented by applying three random color transformations to each image, resulting in 24,768 datasets. The occupancy rate of corn in the field was estimated efficiently using You Only Look Once (YOLO). As of the first day of observation (day 2), it was evident that almost all the corn had disappeared by the ninth day. When grazing 20 sows in a 50 × 100 m2 cornfield (250 m2/sow), it appears that the animals should be rotated to other grazing areas to protect the cover crop after at least five days. In agricultural technology, most of the research using machine and deep learning is related to the detection of fruits and pests, and research on other application fields is needed. In addition, large-scale image data collected by experts in the field are required as training data to apply deep learning. If the data required for deep learning is insufficient, a large number of data augmentation is required.

Comparison of estimating vegetation index for outdoor free-range pig production using convolutional neural networks.

This study aims to predict the change in corn share according to the grazing of 20 gestational sows in a mature corn field by taking images with a camera-equipped unmanned air vehicle (UAV). Deep learning based on convolutional neural networks (CNNs) has been verified for its performance in various areas. It has also demonstrated high recognition accuracy and detection time in agricultural applications such as pest and disease diagnosis and prediction. A large amount of data is required to train CNNs effectively. Still, since UAVs capture only a limited number of images, we propose a data augmentation method that can effectively increase data. And most occupancy prediction predicts occupancy by designing a CNN-based object detector for an image and counting the number of recognized objects or calculating the number of pixels occupied by an object. These methods require complex occupancy rate calculations; the accuracy depends on whether the object features of interest are visible in the image. However, in this study, CNN is not approached as a corn object detection and classification problem but as a function approximation and regression problem so that the occupancy rate of corn objects in an image can be represented as the CNN output. The proposed method effectively estimates occupancy for a limited number of cornfield photos, shows excellent prediction accuracy, and confirms the potential and scalability of deep learning.

Alkyl Sulfonyl Fluorides Incorporating Geminal Dithioesters as SuFEx Click Hubs via Water-Accelerated Organosuperbase Catalysis.

Sulfur(VI) fluoride exchange (SuFEx) is recognized as another emerging tool for click chemistry. The preparation of the functionalized alkyl sulfonyl fluorides as key SuFEx hubs via C(sp3)-C(sp3) bond formation is exceptionally challenging. We report herein a new efficient method for accessing alkyl sulfonyl fluorides incorporating γ-geminal dithioester via phosphazene catalysis. The aqueous, neutral organosuperbase catalytic system amplifies the reactivity by taking advantage of the hydrophobic amplification. SuFEx-active products are applied to the click connection of bioactive molecules. Density functional theory studies show that the selective outcome of the product is guided by an ion-pair organosuperbase catalyst assembly that is potentially stabilized by a hydrogen-bonding interaction between the catalyst and the DTM in the C(sp3)-C(sp3) bond-forming transition structure.

Biomimetic Catalytic Retro-Aldol Reaction Using a Cation-Binding Catalyst: A Promising Route to Axially Chiral Biaryl Aldehydes.

Here we describe a biomimetic catalytic retro-aldol reaction of racemic α-substituted ß-hydroxy ketones utilizing a chiral oligoEG cation-binding catalyst as a type-II aldolase mimic. Our investigation of various aldol substrates has demonstrated that our biomimetic retro-aldol protocol enables rapid access to highly enantiomerically enriched aldols with a selectivity factor (s) of up to 70. Additionally, we have demonstrated the synthetic strategy's feasibility for accessing diverse and valuable axially chiral aldehydes.

Prognostic Implication of Focal Breast Edema on Preoperative Breast Magnetic Resonance Imaging in Breast Cancer Patients.

PURPOSE: In this study, we investigated the prognostic implications of focal breast edema on preoperative breast magnetic resonance imaging (MRI) in patients with breast cancer. METHODS: Data of 899 patients with breast cancer at a single institution were retrospectively analyzed. The patients were divided into an edema-positive group (EPG) and an edema-negative group (ENG) based on the presence of peritumoral, prepectoral, or subcutaneous edema. Two radiologists evaluated the presence or absence of focal edema and its subtypes on preoperative breast MRI. Clinicopathologic characteristics and survival outcomes were compared between the two groups and among the three subtypes using Pearson's χ² test, Kaplan-Meier estimator, and Cox proportional hazards model. RESULTS: There were 399 (44.4%) and 500 (55.6%) patients in the EPG and ENG, respectively. The EPG showed significantly higher rates of axillary lymph node metastasis (55.6% vs. 19.2%, p < 0.001) and lymphovascular invasion (LVI) (57.9% vs. 12.6%, p < 0.001) than the ENG. Patients in the EPG showed significantly worse overall survival (OS) rate (log-rank p < 0.001; hazard ratio [HR], 4.83; 95% confidence interval [CI], 2.56-9.11) and recurrence-free survival rate (log-rank p < 0.001; HR, 3.00; 95% CI, 1.94-4.63) than those in the ENG. After adjusting for other variables, focal breast edema remained a significant factor affecting the OS rate, regardless of the edema type. Specifically, the presence of subcutaneous edema emerged as the strongest predictor for OS with the highest HR (p < 0.001; HR, 9.10; 95% CI, 3.05-27.15). CONCLUSION: Focal breast edema on preoperative breast MRI implies a higher possibility of LVI and axillary lymph node metastasis, which can lead to a poor prognosis. A detailed description of focal breast edema, especially subcutaneous edema, on preoperative breast MRI may provide prognostic predictions. More intensive surveillance is required for patients with breast cancer and focal preoperative breast edema.