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The retina is an important organ of the human body, with a crucial function in the vision mechanism. A minor disturbance in the retina can cause various abnormalities in the eye, as well as complex retinal diseases such as diabetic retinopathy. To diagnose such diseases in early stages, many researchers are incorporating machine learning (ML) technique. The combination of medical science with ML improves the healthcare diagnosis systems of hospitals, clinics, and other providers. Recently, AI-based healthcare diagnosis systems assist clinicians in handling more patients in less time and improves diagnosis accuracy. In this paper, we review cutting-edge AI-based retinal diagnosis technologies. This article also briefly describes the potential of the latest densely connected convolutional networks (DenseNets) to improve the performance of diagnosis systems. Moreover, this paper focuses on state-of-the-art results from comprehensive investigations in retinal diagnosis and the development of AI-based retinal healthcare diagnosis approaches with deep-learning models.

Many therapies have been developed for patients with mass rotator cuff tears. Partial repair is often performed in patients with partially repairable massive rotator cuff tears because it is simpler to perform than superior capsule reconstruction. It may, however, result in rotator cuff retears frequently. This article presents our modified technique of arthroscopic partial reconstruction of the superior capsule using the long head of the biceps tendon with a biceps interposition.

Rheumatoid arthritis (RA) is a highly inflammatory autoimmune disease. Although proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-6, play a key role in the pathogenesis of RA, the causes of chronic inflammation are not fully understood. Here, we report that protein phosphatase magnesium-dependent 1A (PPM1A) levels were increased in RA synovial fluid compared with osteoarthritis (OA) synovial fluid and positively correlated with TNF levels. In addition, PPM1A expression was increased in synovial tissue from RA patients and joint tissue from a mouse model of arthritis. Finally, extracellular PPM1A induced inflammation by stimulating macrophages to produce TNF through toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein 88 (MyD88) signaling pathway. Our findings suggest that extracellular PPM1A may contribute to the pathogenesis of RA by functioning as a damage-associated molecular pattern (DAMP) to induce inflammation.

Introduction Ilio-sacral screw fixation has been used for sacral fractures and sacroiliac joint dislocations. However, it is associated with significant complications including screw loosening with backing-out and loss of reduction. Trans-sacral screw fixation is indicated for rigid fixation in specific circumstances including bilateral posterior ring injuries, osteoporotic bone, or to supplement other types of posterior ring fixation. Hypothesis The reformatting the CT scanning plane may distinguish sacral dysmorphism and predict the possibility of trans-sacral screw fixation by introducing the new indicator. Material and methods The CT data of 112 adult cadavers (61 males and 51 females) were imported into Mimics® software and a 7.0 mm-sized trans-sacral screw was virtually placed in the ideal position of S1. The osseous widths around screw in the axial images (AxWS1) were measured. By reformatting the CT scanning plane parallel to the superior endplate of S1, the AxWRS1 was measured and the height of elevated segment in the upper sacrum (elevated height) was assessed as a new preoperative indicator. Results Cortical violation around screw was detected in 26 models and was considered as sacral dysmorphism. The average AxWS1 was measured as 13.70 ± 2.76 mm in the non-dysmorphism group, and 5.81 ± 2.19 mm in the dysmorphism group, with statistical difference (p Discussion By reformatting the CT scanning plane, the osseous width around screw was widened, and the new preoperative indicator of elevated height could be introduced to predict the possibility of trans-sacral screw fixation into S1. If the elevated height exceeded 13 mm, the pelvis was assigned to sacral dysmorphism and thus, could not apply the trans-sacral screw fixation into S1. Level of evidence III, controlled laboratory study.

Despite enduring diverse insults, mitochondria maintain normal functions through mitochondrial quality control. However, the failure of mitochondrial quality control resulting from excess damage and mechanical defects causes mitochondrial dysfunction, leading to various human diseases. Recent studies have reported that mitochondrial defects are found in Alzheimer's disease (AD) and worsen AD symptoms. In AD pathogenesis, mitochondrial dysfunction-driven generation of reactive oxygen species (ROS) and their contribution to neuronal damage has been widely studied. In contrast, studies on mitochondrial dysfunction-associated inflammatory responses have been relatively scarce. Moreover, ROS produced upon failure of mitochondrial quality control may be linked to the inflammatory response and influence the progression of AD. Thus, this review will focus on inflammatory pathways that are associated with and initiated through defective mitochondria and will summarize recent progress on the role of mitochondria-mediated inflammation in AD. We will also discuss how reducing mitochondrial dysfunction-mediated inflammation could affect AD. [BMB Reports 2020; 53(1): 35-46].

Speaker Change Detection (SCD) is the process that detects speaker changes during a conversation. The conversation can be divided into homogeneous segments using a typical SCD system or speaker diarization system in which the segments are partitioned according to a speaker identity. When the d-vectors are used to identify or verify the speakers with deep neural network model, they are often considered insufficient to train model for detecting the speaker changes by using only acoustic information. There are few dedicated datasets for system training, so the progress of the SCD study is slow and the performance is poor. Therefore, we presented data augmentation method based on TIMIT dataset to suit for the system, and we also proposed several methods to represent d-vectors for SCD systems and their preliminary results. In the proposed data augmentation method, the boundary information of speakers is transformed into probability according to the offset in a given frame and collected in the segment. To model the boundaries of the speakers, we concatenate two random speech sentences dedicated to speech recognition system. The preliminary experimental results, specifically recall percentage, shows the possibility of the proposed approaches. In the future, we will add linguistic information to the proposed classification system, or improve the system to use hybrid system of d-vector and frame vectors, or convolutional networks.

Proteinopathy in neurodegenerative diseases is typically characterized by deteriorating activity of specific protein aggregates. In tauopathies, including Alzheimer’s disease (AD), tau protein abnormally accumulates and induces dysfunction of the affected neurons. Despite active identification of tau modifications responsible for tau aggregation, a critical modulator inducing tau proteinopathy by affecting its protein degradation flux is not known. Here, we report that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase, is crucial for the tau-mediated AD pathology. ALK caused abnormal accumulation of highly phosphorylated tau in the somatodendritic region of neurons through its tyrosine kinase activity. ALK-induced LC3-positive axon swelling and loss of spine density, leading to tau-dependent neuronal degeneration. Notably, ALK activation in neurons impaired Stx17-dependent autophagosome maturation and this defect was reversed by a dominant-negative Grb2. In a Drosophila melanogaster model, transgenic flies neuronally expressing active Drosophila Alk exhibited the aggravated tau rough eye phenotype with retinal degeneration and shortened lifespan. In contrast, expression of kinase-dead Alk blocked these phenotypes. Consistent with the previous RNAseq analysis showing upregulation of ALK expression in AD [1], ALK levels were significantly elevated in the brains of AD patients showing autophagosomal defects. Injection of an ALK.Fc-lentivirus exacerbated memory impairment in 3xTg-AD mice. Conversely, pharmacologic inhibition of ALK activity with inhibitors reversed the memory impairment and tau accumulation in both 3xTg-AD and tauC3 (caspase-cleaved tau) transgenic mice. Together, we propose that aberrantly activated ALK is a bona fide mediator of tau proteinopathy that disrupts autophagosome maturation and causes tau accumulation and aggregation, leading to neuronal dysfunction in AD.

Background This study aimed to determine the prevalence of excessive lateral pressure syndrome (ELPS) in potential candidates for high tibial osteotomy (HTO) using single-photon emission computed tomography–computed tomography (SPECT–CT). We also sought to identify risk factors related to the presence of ELPS. Methods This retrospective study included 150 patients (216 knees) who were candidates for HTO from an initial screening of 3579 patients (7158 knees). There were 183 female and 33 male knees with a mean age of 58 years. The presence of ELPS was defined as a grade 3 uptake on the SPECT–CT at the lateral PF joint. To determine the risk factors related to the ELPS, multivariate regression analysis was performed with independent demographic and radiographic variables. Results Increased uptake on the lateral side of the PF joints was detected in 120 knees (56% of total subjects). Of these, 34 (16%) knees presented with a grade 3 uptake, which indicated the presence of ELPS. No single risk factor had significant associations with the presence of ELPS. Conclusions A considerable number of the knees that were candidates for HTO had ELPS. Nonetheless, we did not find any risk factor related to the presence of ELPS. These results suggest that surgeons should be cautious when diagnosing concomitant ELPS despite acceptable radiographic findings from patellofemoral joints when performing HTO.

Mangosteen (Garcinia mangostana) pericarp waste extract was used to synthesize gold and silver nanoparticles by a green strategy. The extract was both a reducing and stabilizing agent during synthesis. Phytochemical screening of the extract was conducted to obtain information regarding the presence/absence of primary and secondary metabolites in the extract. The in vitro antioxidant activity results demonstrated that the extract had excellent antioxidant activity, which was comparable to a standard (butylated hydroxy toluene). Spherical gold nanoparticles (gold nanoparticles green synthesized by mangosteen pericarp extract [GM-AuNPs]) with an average size of 15.37±3.99 to 44.20±16.99 nm were observed in high-resolution transmission electron microscopy (HR-TEM) images. Most interestingly, the silver nanoparticles (silver nanoparticles green synthesized by mangosteen pericarp extract [GM-AgNPs]) had asymmetric nanodumbbell shapes where one tail grew from a spherical head. The average head size was measured to be 13.65±5.07 to 31.08±3.99 nm from HR-TEM images. The hydrodynamic size of both nanoparticles tended to increase with increasing extract concentration. Large negative zeta potentials (-18.92 to -34.77 mV) suggested that each nanoparticle solution possessed excellent colloidal stability. The reaction yields were 99.7% for GM-AuNPs and 82.8% for GM-AgNPs, which were assessed by inductively coupled plasma optical emission spectroscopy. A high-resolution X-ray diffraction pattern confirmed the face-centered cubic structure of both nanoparticles. Based on phytochemical screening and Fourier transform infrared spectra, the hydroxyl functional groups of carbohydrates, flavonoids, glycosides, and phenolic compounds were most likely involved in a reduction reaction of gold or silver salts to their corresponding nanoparticles. The in vitro cytotoxicity (based on a water-soluble tetrazolium assay) demonstrated that GM-AgNPs were toxic to both A549 (a human lung cancer cell) and NIH3T3 (a mouse fibroblast cell). The cytotoxicity of GM-AgNPs on A549 cells was related to apoptotic cell death. However, GM-AuNPs did not show any significant cytotoxicity to either cell. These results suggest that GM-AuNPs have the potential to be drug delivery vehicles or carriers for pharmaceutical and biomedical applications.

Many options have been developed to treat irreparable massive cuff tears. Superior capsular reconstruction has been reported as one of the treatment options for relatively young patients with irreparable massive cuff tear. However, this original technique has a disadvantage of requiring a tensor facia lata autograft. It requires another incision at the lateral thigh and can be a cause of thigh pain. This article describes our modified technique for arthroscopic superior capsule reconstruction using the biceps autograft to preserve the long head of the biceps tendon anchors to the glenoid labrum (the snake technique).

Vanillin is a value added compound used in wide range of areas including food, beverage, fragrance and pharmaceutical. It can be produced by reduction of vanillic acid, a by-product in lignin degradation processes or a competing component in the metabolic pathways in biological vanillin production. The reduction process is energetically disadvantageous due to the high activation energy in the reaction coordinates, but can be overcome by an enzymatic strategy using carboxylic acid reductases (CARs). In this study, fourteen CARs heterologously expressed in Escherichia coli were tested for vanillic acid reduction, of which a CAR from Mycobacterium abscessus B1MLD7 gene, as a result, was selected for the highest activity. The selected CAR exhibited 8.6-fold higher in vitro activity than that of the CAR from Nocardia iowensis Q6RKB1, previously reported to have the highest activity in vanillic acid reduction. The effect of substrate concentration and reducing power supply on the biocatalytic reaction has been investigated to enhance the yield while minimizing the by-product formation, resulting in 2.86 g L−1 of vanillin production in the whole cell biocatalytic reaction. The sequential and structural analyses of the enzyme with molecular modeling also have been carried out to discuss the catalytic characteristics of the enzyme.

Distal ulnar fractures are commonly accompanied by distal radial fractures, and several treatment options such as plate osteosynthesis and pinning with Kirschner's wires are used. In this study, we present a technique using headless compression screws to achieve bony union of distal ulnar fractures. From November 2016 to November 2018, we treated 11 patients with distal ulnar fractures combined with distal radial fractures with headless compression screws (DePuy Synthes). Patients were instructed to maintain a short-arm splint for less than two weeks after the treatment. The mean time to bony union was 6.5 weeks, mean Quick Disabilities of the Arm, Shoulder, and Hand score was 14.6 points, and mean visual analog scale score was 1.09 points. Full range of motion was possible in all directions after surgery and no specific complications were observed. The suggested technique allows minimal incision and minimally invasive intramedullary fixation and can promote bony union in a simple way without specific complications.

2-Hydroxy acid dehydrogenases (2-HADHs) have been implicated in the synthesis of 2-hydroxy acids from 2-oxo acids that are used in wide areas of industry. d -lactate dehydrogenases ( d -LDHs), a subfamily of 2-HADH, have been utilized to this purpose, yet they exhibited relatively low catalytic activity to the 2-oxo acids with large functional groups at C3. In this report, four putative 2-HADHs from Oenococcus oeni, Weissella confusa, Weissella koreensis and Pediococcus claussenii were examined for activity on phenylpyruvate (PPA), a substrate to 3-phenyllactic acid (PLA) with a C3 phenyl group. The 2-HADH from P. claussenii was found to have the highest kcat/Km on PPA with 1,348.03 s−1 mM−1 among the four enzymes with higher substrate preference for PPA than pyruvate. Sequential, structural and mutational analysis of the enzyme revealed that it belonged to the d -LDH family, and phenylalanine at the position 51 was the key residue for the PPA binding to the active site via hydrophobic interaction, whereas in the 2-HADHs from O. oeni and W. confusa the hydrophilic tyrosine undermined the interaction. Because phenyllactate is a potential precursor for pharmaceutical compounds, antibiotics and biopolymers, the enzyme could increase the efficiency of bio-production of valuable chemicals. This study suggests a structural basis for the high substrate preference of the 2-HADH, and further engineering possibilities to synthesize versatile 2-hydroxy acids.

SRC-family kinases (SFKs) have been implicated in Alzheimer's disease (AD), but their mode of action was scarcely understood. Here, we show that LYN plays an essential role in amyloid β (Aβ)-triggered neurotoxicity and tau hyperphosphorylation by phosphorylating Fcγ receptor IIb2 (FcγRIIb2). We found that enzyme activity of LYN was increased in the brain of AD patients and was promoted in neuronal cells exposed to Aβ 1-42 (Aβ1-42). Knockdown of LYN expression inhibited Aβ1-42-induced neuronal cell death. Of note, LYN interacted with FcγRIIb2 upon exposure to Aβ1-42 and phosphorylated FcγRIIb2 at Tyr273 within immunoreceptor tyrosine-based inhibitory motif in neuronal cells. With the use of the structure-based drug design, we isolated KICG2576, an ATP-competitive inhibitor of LYN. Determination of cocrystal structure illustrated that KICG2576 bound to the cleft in the LYN kinase domain and inhibited LYN with a half-maximal inhibitory concentration value of 0.15 μM. KICG2576 inhibited Aβ- or FcγRIIb2-induced cell death, and this effect was better than pyrazolopyrimidine 1, a widely used inhibitor of SFK. Upon exposure to Aβ, KICG2576 blocked the phosphorylation of FcγRIIb2 and translocation of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2, a binding protein to the phosphorylated FcγRIIb2, to the plasma membrane, resulting in the inhibition of tau hyperphosphorylation, the downstream event of Aβ1-42-FcγRIIb2 binding. Furthermore, intracerebroventricular injection of KICG2576 into mice ameliorated Aβ-induced memory impairment. These results suggest that LYN plays a crucial role in Aβ1-42-mediated neurotoxicity and tau pathology, providing a therapeutic potential of LYN in AD.-Gwon, Y., Kim, S.-H., Kim, H. T., Kam, T.-I., Park, J., Lim, B., Cha, H., Chang, H.-J., Hong, Y. R., Jung, Y.-K. Amelioration of amyloid β-FcγRIIb neurotoxicity and tau pathologies by targeting LYN.

Convolution neural network (CNN) was only consider their input images. It was only limitation of this technique for prediction of therapeutic response or patients outcome. The purpose of this study was to development of chemotherapy response prediction model using advanced deep learning techniques. 18F-FDG PET image was acquired in osteosarcoma patients (n=54) before the chemotherapy. The osteosarcoma patients was binary classification between responder (n=28) and non-responder (n=26). Radiomics feature was calculated using texture analysis method in 18F-FDG PET image. To improvement the deep learning model prediction accuracy, we performed the feature selection of information gain (IG) method. Deep learning models were define of CNN with radiomics features and without radiomics feature model. CNN was consist of 2 convolution layer and max pooling layers. Convolution and max pooling layers were generate the feature map. Advanced deep learning technique was input PET image as well as radiomics features. Radiomics features were concatenate with PET image feature map before the fully connected layer. Total 70 radiomics feature were extracted in 18F-FDG PET image of osteosarcoma patients before the chemotherapy. Total 9 radiomics features were selected by the above of the IG value 0.1. The prediction accuracy without radiomics feature model was 80%, On the other hand, the number of radiomics features , seventy, three, nine was 81, 82, 85% when they were worked with deep learning. mode. Nine radiomics features with deep learning model has better prediction accuracy than seventy radiomics feature. In this study, prediction accuracy of the selected radiomics features co-worked with deep learning model was higher than those of all features and only CNN model. Our developed prediction model will help to consider the radiomics feature as well as disease related feature such as genomics data.

Three aqueous plant extracts (Artemisia capillaris, Portulaca oleracea, and Prunella vulgaris) were selected for the biofabrication of gold nanoparticles. The antioxidant activities (i.e., free radical scavenging activity, total phenolic content, and reducing power) of the extracts and how these activities affected the biofabrication of gold nanoparticles were investigated. P. vulgaris exerted the highest antioxidant activity, followed by A. capillaris and then P. oleracea. P. vulgaris was the most efficient reducing agent in the biofabrication process. Gold nanoparticles biofabricated by P. vulgaris (PV-AuNPs) had a maximum surface plasmon resonance of 530 nm with diverse shapes. High-resolution X-ray diffraction analysis showed that the PV-AuNPs had a face-centered cubic structure. The reaction yield was estimated to be 99.3% by inductively coupled plasma optical emission spectroscopy. The hydrodynamic size was determined to be 45 ± 2 nm with a zeta potential of − 13.99 mV. The PV-AuNPs exerted a dose-dependent antioxidant activity. Remarkably, the highest cytotoxicity of the PV-AuNPs was observed against human colorectal adenocarcinoma cells in the absence of fetal bovine serum, while for human pancreas ductal adenocarcinoma cells, the highest cytotoxicity was observed in the presence of fetal bovine serum. This result demonstrates that P. vulgaris extract was an efficient reducing agent for biofabrication of gold nanoparticles exerting cytotoxicity against cancer cells.

This paper introduces a wearable robotic orthosis with spring-assist actuators, which is designed to assist people who have difficulty in walking. The spring-assist actuator consists of an electrical motor and a spring, which are attached to a rotational axis in parallel to each other. The spring-assist actuator is developed based on the analysis on the stiffness of the knee and hip joints during walking. “COWALK-Mobile,” which is a wearable robotic orthosis, is developed using the spring-assist actuators to reduce the required motor torque during walking. The COWALK-Mobile has active hip and knee joints and passive ankle joints to provide assistive torque to the wearer. The required joint torque is generated by the spring as well as the electrical motor, which results in a decrease of maximum required torque for the motor. In order to evaluate the performance of the spring-assist actuator, experiments are carried out. The experiments show that the spring-assist actuators reduced the required motor torque during walking.

Background It is difficult for surgeons to reconstruct soft tissue defects of the great toe. This report aims to evaluate the utility and efficacy of innervated distally based first dorsal metatarsal artery (FDMA) flap with a wide pedicle for reconstruction of soft tissue defects of the great toe. Methods This is a retrospective report. Between January 2015 and December 2017, six cases of skin defect of the great toe were reconstructed with an innervated distally based FDMA flap with a wide pedicle. One case was excluded in this report because of chronic pain on the metatarsophalangeal joint due to osteoarthritis before the injury. A total of five cases were evaluated for flap survival and sensory recovery. The sensory recovery was investigated by two-point discrimination and Semmes-Weinstein monofilament tests. The average age of the selected patients was 40 years (range, 36 to 56 years), and the average size of the defect in the toe was 8.3 cm2 (range, 4 to 13.8 cm2). The average follow-up period was 29.4 months (range, 18 to 38 months). Results All patients survived without any complications. The average two-point discrimination test value was 8.0 ± 0.89 mm (range, 7 to 9 mm), and the average value obtained from the Semmes-Weinstein monofilament test was 4.53 ± 0.33 (range, 4.17 to 4.93). The average residual pain score evaluated with a visual analog scale was 1 (range, 0 to 2). Two patients complained of stiffness in the great toe below 30° of total range of motion during the early stages after surgery, but this stiffness gradually improved after rehabilitation. The average range of motion of three patients with a remaining metatarsophalangeal joint after surgery was 80° (range, 70° to 90°). All five cases could walk regularly without any unique footwear at the final follow-up. Conclusions The innervated distally based FDMA flap with a wide pedicle could be a good alternative method for repair of soft tissue defects of the great toe.