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Kyung Jae Ryu,1 Seunghoon Kim,2 Mee Kum Kim,3 Hae Jung Paik,1 Dong Hyun Kim1 1Department of Ophthalmology, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea; 2RudaCure Co., LTD, Incheon, Korea; 3Department of Ophthalmology, Seoul National University College of Medicine, Seoul, KoreaCorrespondence: Dong Hyun KimDepartment of Ophthalmology, Gachon University College of Medicine, Gil Medical Center, 1198, Guwol-dong, Namdong-Gu, Incheon, 21565, KoreaEmail amidfree@gmail.comPurpose: To compare the short-term therapeutic effects of topical corticosteroids in patients with refractory dry eye disease (DED) according to the tear matrix metalloproteinase 9 (MMP-9) point-of-care positivity.Methods: This study was conducted on 137 patients who were referred from other eye clinics, complaining of irresponsive DED or acute DED flares despite routine treatment with topical cyclosporin or diquafosol. The patients received treatment with topical corticosteroids for 1 month. DED was evaluated by SANDE (Symptom Assessment in Dry Eye) questionnaire, tear film breakup time, ocular surface staining score, and meibomian gland dysfunction stage. The InflammaDry MMP-9 immunoassay was conducted in more symptomatic eyes of all patients. The changes in the subjective symptoms were additionally surveyed as symptom improvement score.Results: The mean age of the patients was 57.8± 13.4 years, and the tear MMP-9 positivity was 73.0%. Topical corticosteroids treatment showed significant improvement of symptoms and signs in the patients with refractory DED irrespective of the positivity of MMP-9 (each p< 0.001). The changes in SANDE score and OSS, and symptom improvement score were higher in the MMP-9 positive group than in the MMP-9 negative group (p=0.002/0.010/0.011). The overall rates of subjective symptoms improvement and SANDE reduction were 73.0% and 90.6% after topical corticosteroids treatment, respectively.Conclusion: Short-term topical corticosteroids had excellent therapeutic effects in patients with refractory DED or acute DED flares, irrespective of the tear MMP-9 level. Tear MMP-9 positivity may serve as a reliable response predictor of topical corticosteroids treatment in DED.Keywords: dry eye disease, ocular surface inflammation, tear MMP-9 positivity, corticosteroid

Periodontitis is a widespread chronic inflammatory disease caused by interactions between periodontal bacteria and homeostasis in the host. We aimed to investigate the performance and reliability of machine learning models in predicting the severity of chronic periodontitis. Mouthwash samples from 692 subjects (144 healthy controls and 548 generalized chronic periodontitis patients) were collected, the genomic DNA was isolated, and the copy numbers of nine pathogens were measured using multiplex qPCR. The nine pathogens are as follows: Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn), Campylobacter rectus (Cr), Aggregatibacter actinomycetemcomitans (Aa), Peptostreptococcus anaerobius (Pa), and Eikenella corrodens (Ec). By adding the species one by one in order of high accuracy to find the optimal combination of input features, we developed an algorithm that predicts the severity of periodontitis using four machine learning techniques. The accuracy was the highest when the models classified “healthy” and “moderate or severe” periodontitis (H vs. M-S, average accuracy of four models: 0.93, AUC = 0.96, sensitivity of 0.96, specificity of 0.81, and diagnostic odds ratio = 112.75). One or two red complex pathogens were used in three models to distinguish slight chronic periodontitis patients from healthy controls (average accuracy of 0.78, AUC = 0.82, sensitivity of 0.71, and specificity of 0.84, diagnostic odds ratio = 12.85). Although the overall accuracy was slightly reduced, the models showed reliability in predicting the severity of chronic periodontitis from 45 newly obtained samples. Our results suggest that a well-designed combination of salivary bacteria can be used as a biomarker for classifying between a periodontally healthy group and a chronic periodontitis group.

Background Papillary renal cell carcinoma type 2 (PRCC2) is refractory to systemic treatment and has a dismal prognosis. Previous studies showed that genetic alterations in PRCC2 were heterogeneous regardless of germline or somatic mutations. In this study, we aimed to perform precision treatment of PRCC2 based on genetic information. Methods We performed exome and genome sequencing of tumor tissues and matched normal samples. Based on sequencing data, we treated patients with metastatic PRCC2 using precision oncology. Results Four patients underwent curative surgery of PRCC2 and three patients had metastatic PRCC2. All PRCC2 heterogeneously harbored own driver mutations. Two out of the three patients with metastatic disease had fumarate hydratase (FH) germline mutations. One patient with a germline FH mutation was diagnosed with hereditary leiomyomatosis RCC. He was treated with bevacizumab and erlotinib combination and showed a durable response. The other metastatic PRCC2 patient harboring a germline FH mutation had an additional somatic FH mutation and was durably controlled with pazopanib. Other metastatic PRCC2 patient with somatic PBRM1 and SETD2 mutations had over 5 years of overall survival with axitinib treatment. Conclusions We performed precision systemic treatment based on genetic information. Genome sequencing could help identify candidates for targeted therapy in PRCC2, a genetically heterogeneous disease.

In this letter, new two-way and four-way power dividers are proposed using quarter-wave long multi-conductor coupled lines. The design equations for a two-way power divider are derived by analyzing a three-conductor coupled line. Then, the structure is extended to propose a planar four-way power divider with compact size. The fabricated two-way and four-way power dividers at 2.0 GHz show an excellent performance in the insertion loss, impedance matching at all ports and isolation between output ports.

A cyclic 10-bit D/A converter based on a Johnson counter and a capacitor swapping technique is described. To reduce capacitor mismatching errors, two capacitors are alternately swapped according to input data. Further, a half differential architecture to reduce offset errors and a Johnson counter to improve the digital logic performance are proposed. With a 0.35μm Samsung CMOS technology, the measured SFDR is about 65dB, when the input frequency is 1MHz at a clock frequency of 2MHz. The power consumption is only 310μW at 3.3V power supply. The measured INL and DNL are within ±0.7LSB and ±0.75LSB, respectively.

In battery-powered embedded systems, dedicated circuitry is used to convert stored energy into a form that can be directly used by processors. These power regulation devices seek to mask non-ideal aspects of the battery and present an ideal, fixed-voltage power source to the processor. However, this comes at a high price in terms of form factor, component cost, and energy efficiency. We describe and evaluate a new method for eliminating voltage regulation circuitry from battery-powered embedded systems. This method makes use of power gating, frequency scaling, and thread migration in chip-level multiprocessors to dynamically adjust to varying battery voltage. The key advantages of this approach are reduction in printed circuit board area (by 1/3 in many embedded applications) and the elimination of bulky unreliable discrete components such as electrolytic capacitors while maintaining similar battery lifespan. We have evaluated the power consumption, performance, and reliability implications of the proposed method using analytical techniques, power models, and detailed full-system simulation of numerous benchmarks from the ALPBench and Me-diaBench benchmark suites. For a number of battery technologies, the proposed technique holds the potential to eliminate power regulation circuitry and maintain battery lifespan while maintaining the same performance as systems using Buck-Boost voltage regulators.