Microscopic observation of a liquid-liquid-(semi)solid phase in polluted PM2.5

Atmospheric aerosol particles are complex mixtures having various physicochemical properties. To predict the role and characteristics of such complex aerosol particles in air pollution and related atmospheric chemistry, our knowledge of the number and types of phases in complex aerosol particles should be improved. However, most studies on the phase behavior of aerosol particles have been conducted in the laboratory and have not used real-world aerosol particles. In this study, using a combination of optical microscopy and poke-and-flow technique, we investigated the number and types of phases of actual aerosol particles of particulate matter < 2.5 µm (PM2.5) collected on heavily polluted days in Seosan, South Korea in winter 2020–2021. From the microscopic observations at 293 K, it showed that the PM2.5 particles exist in a single liquid phase at relative humidity (RH) >∼85%, a liquid-liquid phase at ∼70% < RH <∼85%, a liquid-liquid-(semi)solid phase at ∼30% < RH <∼70%, and a (semi)solid phase at RH <∼30% upon dehydration. This reveals that three phases of atmospheric aerosol particles coexisting as liquid-liquid and liquid-liquid-(semi)solid would be the most common phases in the atmosphere considering ambient RH ranges. These observations provide fundamental properties necessary for improved predictions of air quality and aerosol chemistry such as reactive uptake of N2O5, size distributions, and mass concentrations of aerosol particles

Underestimation of atypical ductal hyperplasia at sonographically guided core biopsy of the breast

OBJECTIVE: The purpose of this study was to determine the rate of underestimation of atypical ductal hyperplasia (ADH) at sonographically guided core biopsy of the breast and to identify the factors involved. MATERIALS AND METHODS: We retrospectively reviewed 3,563 lesions con secutively evaluated with sonographically guided core biopsy between January 2002 and June 2006. Histologic analysis yielded ADH in 60 of the 3,563 lesions (1.7%). The rate of underestimation of ADH was determined by dividing the number of lesions that proved to be carcinoma at surgical excision by 44, the total number of lesions evaluated with excisional biopsy. Clinical, sonographic, and core biopsy features were analyzed to identify factors that affect the rate of underestimation of ADH. RESULTS: The rate of underestimation of ADH was found to be 48% (21 of 44 lesions). Underestimation of ADH was significantly less frequent for lesions evaluated with 11-gauge vacuum-assisted biopsy than for lesions evaluated with 14-gauge automated gun biopsy (22% [four of 18 lesions] vs 65% [17 of 26 lesions], p = 0.012). The other clinical, sonographic, and biopsy features examined did not affect the rate of underestimation of ADH. CONCLUSION: For sonographically guided core biopsy of the breast, the rate of underestimation of ADH was 48%. This rate was lower for lesions evaluated with 11-gauge vacuum-assisted biopsy (22%) than for those evaluated with 14-gauge automated gun biopsy (65%). This finding was particularly true of smaller lesions (< or = 2.0 cm) and for lesions of the mass-only type.Supported by grant A062260 from the Innovative Research Institute for Cell Therapy, Republic of Korea

Gut Microbial Metabolites Induce Changes in Circadian Oscillation of Clock Gene Expression in the Mouse Embryonic Fibroblasts

Circadian rhythm is an endogenous oscillation of about 24-h period in many physiological processes and behaviors. This daily oscillation is maintained by the molecular clock machinery with transcriptional-translational feedback loops mediated by clock genes including Period2 (Per2) and Bmal1. Recently, it was revealed that gut microbiome exerts a significant impact on the circadian physiology and behavior of its host; however, the mechanism through which it regulates the molecular clock has remained elusive. 3-(4-hydroxyphenyl)propionic acid (4-OH-PPA) and 3-phenylpropionic acid (PPA) are major metabolites exclusively produced by Clostridium sporogenes and may function as unique chemical messengers communicating with its host. In the present study, we examined if two C. sporogenes-derived metabolites can modulate the oscillation of mammalian molecular clock. Interestingly, 4-OH-PPA and PPA increased the amplitude of both PER2 and Bmal1 oscillation in a dosedependent manner following their administration immediately after the nadir or the peak of their rhythm. The phase of PER2 oscillation responded differently depending on the mode of administration of the metabolites. In addition, using an organotypic slice culture ex vivo, treatment with 4-OH-PPA increased the amplitude and lengthened the period of PER2 oscillation in the suprachiasmatic nucleus and other tissues. In summary, two C. sporogenes-derived metabolites are involved in the regulation of circadian oscillation of Per2 and Bmal1 clock genes in the host&apos;s peripheral and central clock machineries.1

Nonpalpable Breast Masses: Evaluation by US Elastography

OBJECTIVE: To compare the diagnostic performances of conventional ultrasound (US) and US elastography for the differentiation of nonpalpable breast masses, and to evaluate whether elastography is helpful at reducing the number of benign biopsies, using histological analysis as a reference standard. MATERIALS AND METHODS: Conventional US and real-time elastographic images were obtained for 100 women who had been scheduled for a US-guided core biopsy of 100 nonpalpable breast masses (83 benign, 17 malignant). Two experienced radiologists unaware of the biopsy and clinical findings analyzed conventional US and elastographic images by consensus, and classified lesions based on degree of suspicion regarding the probability of malignancy. Results were evaluated by receiver operating characteristic curve analysis. In addition, the authors investigated whether a subset of lesions was categorized as suspicious by conventional US, but as benign by elastography. RESULTS: Areas under the ROC curves (Az values) were 0.901 for conventional US and 0.916 for elastography (p = 0.808). For BI-RADS category 4a lesions, 44% (22 of 50) had an elasticity score of 1 and all were found to be benign. CONCLUSION: Elastography was found to have a diagnostic performance comparable to that of conventional US for the differentiation of nonpalpable breast masses. The authors conclude that BI-RADS category 4a lesions with an elasticity score of 1 probably do not require biopsy

Does Ultrasound-Guided Directional Vacuum-Assisted Removal Help Eliminate Abnormal Nipple Discharge in Patients with Benign Intraductal Single Mass?

Objective: To evaluate whether the removal of an intraductal mass using an ultrasound (US)-guided directional vacuum-assisted device can eliminate symptoms in patients presenting with abnormal nipple discharge. Materials and Methods: Between March 2004 and October 2006, 36 patients who presented with abnormal nipple discharge, underwent US-guided, 11-gauge vacuum-assisted biopsy for a benign intraductal single mass on US. The ability of the procedure to eliminate nipple discharge was evaluated by physical examination during follow-up US. Lesion characteristics, biopsy variables, and histologic features were analyzed to identify factors affecting symptom resolution. Results: Of the 36 lesions, 25 (69%) were intraductal papillomas, 10 (28%) were fibrocystic changes, and one (3%) was a fibroadenoma. The nipple discharge disappeared in 69% (25 of 36) of the women at a mean follow-up time of 25 months (range 12-42 month). There was no difference in the lesion characteristics, biopsy variables, and the histologic features between groups that eliminated the symptom compared those with persistent nipple discharge. Conclusion: US-guided directional vacuum-assisted removal of an intraductal mass appears to eliminate nipple discharge in only 69% of patients and thus, it should not be considered as an alternative to surgical excision.This study was supported by a grant (A070001) of the Korea Healthcare Technology R&D Project, Ministry for Realm, Welfare & Family Affairs, and the Republic of Korea

Computer-Aided Evaluation of Breast MRI for the Residual Tumor Extent and Response Monitoring in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Objective: To evaluate the accuracy of a computer-aided evaluation program (CAE) of breast MRI for the assessment of residual tumor extent and response monitoring in breast cancer patients receiving neoadjuvant chemotherapy. Materials and Methods: Fifty-seven patients with breast cancers who underwent neoadjuvant chemotherapy before surgery and dynamic contrast enhanced MRI before and after chemotherapy were included as part of this study. For the assessment of residual tumor extent after completion of chemotherapy, the mean tumor diameters measured by radiologists and CAE were compared to those on histopathology using a paired student t-test. Moreover, the agreement between unidimensional (1D) measurement by radiologist and histopathological size or 1D measurement by CAE and histopathological size was assessed using the Bland-Altman method. For chemotherapy monitoring, we evaluated tumor response through the change in the 1D diameter by a radiologist and CAE and three-dimensional (3D) volumetric change by CAE based on Response Evaluation Criteria in Solid Tumors (RECIST). Agreement between the 1D response by the radiologist versus the 1D response by CAE as well as by the 3D response by CAE were evaluated using weighted kappa (k) statistics. Results: For the assessment of residual tumor extent after chemotherapy, the mean tumor diameter measured by radiologists (2.0 &plusmn; 1.7 cm) was significantly smaller than the mean histological diameter (2.6 &plusmn; 2.3 cm) (p = 0.01), whereas, no significant difference was found between the CAE measurements (mean = 2.2 &plusmn; 2.0 cm) and histological diameter (p = 0.19). The mean difference between the 1D measurement by the radiologist and histopathology was 0.6 cm (95% confidence interval: -3.0, 4.3), whereas the difference between CAE and histopathology was 0.4 cm (95% confidence interval: -3.9, 4.7). For the monitoring of response to chemotherapy, the 1D measurement by the radiologist and CAE showed a fair agreement (k = 0.358), while the 1D measurement by the radiologist and 3D measurement by CAE showed poor agreement (k = 0.106). Conclusion: CAE for breast MRI is sufficiently accurate for the assessment of residual tumor extent in breast cancer patients receiving neoadjuvant chemotherapy. However, for the assessment of response to chemotherapy, the assessment by the radiologist and CAE showed a fair to poor agreement

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Mask Branch Network: Weakly Supervised Branch Network with a Template Mask for Classifying Masses in 3D Automated Breast Ultrasound

Automated breast ultrasound (ABUS) is being rapidly utilized for screening and diagnosing breast cancer. Breast masses, including cancers shown in ABUS scans, often appear as irregular hypoechoic areas that are hard to distinguish from background shadings. We propose a novel branch network architecture incorporating segmentation information of masses in the training process. The branch network is integrated into neural network, providing the spatial attention effect. The branch network boosts the performance of existing classifiers, helping to learn meaningful features around the target breast mass. For the segmentation information, we leverage the existing radiology reports without additional labeling efforts. The reports, which is generated in medical image reading process, should include the characteristics of breast masses, such as shape and orientation, and a template mask can be created in a rule-based manner. Experimental results show that the proposed branch network with a template mask significantly improves the performance of existing classifiers. We also provide qualitative interpretation of the proposed method by visualizing the attention effect on target objects