Design, implementation, and evaluation of the computer-aided clinical decision support system based on learning-to-rank: collaboration between physicians and machine learning in the differential diagnosis process.

BACKGROUND: We are researching, developing, and publishing the clinical decision support system based on learning-to-rank. The main objectives are (1) To support for differential diagnoses performed by internists and general practitioners and (2) To prevent diagnostic errors made by physicians. The main features are that "A physician inputs a patient's symptoms, findings, and test results to the system, and the system outputs a ranking list of possible diseases". METHOD: The software libraries for machine learning and artificial intelligence are TensorFlow and TensorFlow Ranking. The prediction algorithm is Learning-to-Rank with the listwise approach. The ranking metric is normalized discounted cumulative gain (NDCG). The loss functions are Approximate NDCG (A-NDCG). We evaluated the machine learning performance on k-fold cross-validation. We evaluated the differential diagnosis performance with validated cases. RESULTS: The machine learning performance of our system was much higher than that of the conventional system. The differential diagnosis performance of our system was much higher than that of the conventional system. We have shown that the clinical decision support system prevents physicians' diagnostic errors due to confirmation bias. CONCLUSIONS: We have demonstrated that the clinical decision support system is useful for supporting differential diagnoses and preventing diagnostic errors. We propose that differential diagnosis by physicians and learning-to-rank by machine has a high affinity. We found that information retrieval and clinical decision support systems have much in common (Target data, learning-to-rank, etc.). We propose that Clinical Decision Support Systems have the potential to support: (1) recall of rare diseases, (2) differential diagnoses for difficult-to-diagnoses cases, and (3) prevention of diagnostic errors. Our system can potentially evolve into an explainable clinical decision support system.

Radiographic analysis of the angle in the lateromedial projection of the metacarpophalangeal joint and the distal interphalangeal joint in metacarpophalangeal flexural deformities in calves.

The bone alignment of the metacarpophalangeal joint (MPJ) of the distal interphalangeal joint (DIPJ) in metacarpophalangeal flexural deformity (MPFD) in calves was evaluated by radiography. This study was designed by retrospective study of radiographs. Lateral to medial radiographs of distal forelimbs were taken from 19 MPFD affected calves (35 forelimbs) and 21 normal calves (42 forelimbs). Based on the radiographs, the lateral angles of MPJ were measured from the metacarpal bone axis and proximal phalanx axis, and lateral angles of DIPJ were measured from the middle phalanx axis and distal phalanx axis. Mean lateral angle of MPJ in the normal limbs was 175.9 (95% CI 174.5 to 177.4). Mean lateral angles of MPJ in MPFD were as follows: mild: 167.1 (158.9-175.2), moderate: 165.1 (158.5-171.7) and severe: 150.6 (146-155.1). MPJ angle in MPFD limbs was narrower than that in the normal limbs (mild, moderate and severe: P=0.017, P=0.003 and P<0.001, respectively). Mean lateral angle of DIPJ in the normal limbs was 211.9 (210.7-213.2). Mean lateral angles of DIPJ in moderate: 200.6 (195.2-206.1) and severe: 204.9 (203.3-206.5) MPFD were narrower than that in the normal limbs (both P<0.001). There was no significant difference between the normal limbs and mild: 210.3 (206.9-213.7) MPFD limbs (P=0.7). The clinical severity of MPFD corresponded well with the lateral angle of MPJ. The flexion of DIPJ in moderate and severe MPFD was similar to the flexion of MPJ in MPFD. This suggested that the lateral to medial radiographs accurately reflected the MPJ flexion and the DIPJ in MPFD in calves, providing useful information for the treatment of MPFD.

[A case of MRSA infection in multiple artificial joints successfully treated with conservative medical treatment].

We report herein on a case with multiple MRSA prosthetic arthritis and osteomyelitis successfully treated medically. Our patient was a 64-year-old Japanese woman with a previous medical history of malignant rheumatoid arthritis and multiple surgical interventions with an atlantoaxial fixation in 2003, artificial joint replacement of both knee joints in 2006, and of the right hip joint in September, 2007. She was initially hospitalized due to MRSA arthritis in the right hip in October, 2007. Thereafter, multiple joint infections occurred sequentially in the right knee joint in January 2008 and the left hip joint in June 2008. More recently, the patient was re-admitted in January 2009 due to cervical osteomyelitis with MRSA infection. The patient had been treated with a combination of vancomycin and rifampin for 17 weeks and followed by sulfamethoxazole/trimetoprim in the out-patient setting up to the present. Although the complete resolution of multiple deep MRSA infections with prosthetic arthritis and osteomyelitis is not expected without removing the infectious sources, our patient was successfully treated with chronic antibiotic suppressive therapy. Therefore, we report on our case with a literature review.

Efficacy of MK615 for the treatment of patients with liver disorders.

AIM: To investigate the hepatoprotective effect of MK615, a Japanese apricot extract, in an animal model, and its clinical therapeutic effect. METHODS: Wistar rats were administered physiological saline (4 mL/kg) or MK615 solution (4 mL/kg) for 7 d. On the sixth d, acute hepatic injury was induced by administering a single intraperitoneal injection (ip) of D-galactosamine hydrochloride (D-GalN) (600 mg/kg). Plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined, and liver tissues were used for histopathological analysis. Fifty-eight patients with liver disorders [hepatitis C (n = 40), non-alcoholic fatty liver disease (n = 15), and autoimmune liver disease (n = 3)] were orally administered commercially available Misatol ME-containing MK615 (13 g/d) daily for 12 wk. Blood and urine were sampled immediately before and 6 wk, 12 wk, and 16 wk after the start of intake to measure various biochemical parameters. The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint. RESULTS: D-GalN effectively induced acute hepatic injury in the rats. At 48 h after the ip injection of D-GalN, the plasma levels of ALT (475.6 ± 191.5 IU/L vs 225.3 ± 194.2 IU/L, P < 0.05) and AST (1253.9 ± 223.4 IU/L vs 621.9 ± 478.2 IU/L, P < 0.05) in the MK615 group were significantly lower than the control group. Scattered single cell necrosis, loss of hepatocytes, and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group. However, these findings were less pronounced in the group receiving MK615. At the end of the clinical study, serum ALT and AST levels were significantly decreased compared with pre-intake baseline levels from 103.5 ± 58.8 IU/L to 71.8 ± 39.3 IU/L (P < 0.05) and from 93.5 ± 55.6 IU/L to 65.5 ± 34.8 IU/L (P < 0.05), respectively. A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 26 (45%) of the 58 patients, while 25 (43%) patients exhibited similar AST level reductions. The chronic hepatitis C group exhibited significant ALT and AST level reductions from 93.4 ± 51.1 IU/L to 64.6 ± 35.1 IU/L (P < 0.05) and from 94.2 ± 55.5 IU/L to 67.2 ± 35.6 IU/L (P < 0.05), respectively. A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 20 (50%) of the 40 patients. ALT levels in both the combined ursodeoxycholic acid (UDCA) treatment and the UDCA uncombined groups were significantly lower after Misatol ME administration. MK615 protected hepatocytes from D-GalN-induced cytotoxicity in rats. Misatol ME decreased elevated ALT and AST levels in patients with liver disorders. CONCLUSION: These results suggest that MK615 and Misatol ME are promising hepatoprotective agents for patients with liver disorders.

The value of dynamic imaging for standardization of abdominal ultrasonography.

PURPOSE: Digital video recording of dynamic images is a potential way to improve the reproducibility of abdominal ultrasonography (US). Static US and dynamic US were compared using contrast-enhanced computed tomography (CE-CT) as a reference standard, and the value of stored video images was verified. METHODS: The subjects were 120 individuals who had undergone CE-CT ≤1 month before undergoing US. After static US, dynamic US was carried out according to the Scanning Procedure for Abdominal Ultrasonography described in this paper, and records of 30 separate scans were saved on digital video discs (DVD) as individual video files for interpretation. The findings from static US and dynamic US were compared. RESULTS: With respect to the abdominal US signs covered in this evaluation, dynamic US achieved a detection rate equivalent to or better than that of static US. Detection rates were significantly more frequent on dynamic US for: enlarged hepatic hilum lymph nodes (P < 0.001); gallbladder wall thickness (P < 0.01); cystic lesions of the liver, bright liver, and splenomegaly (P < 0.05). CONCLUSION: Dynamic US is a valuable tool because it enables repeated evaluation of target organs with playback speed adjustment.

[A case of acute septic osteomyelitis onset due to Streptococcus dysgalactiae subsp. equisimilis in an elderly diabetic patient].

Group C streptococci are increasingly causing invasive infections such as that we report here. A 70-year-old man being treated for diabetes and seen at the emergency room for neck pain and fever was hospitalized for possible sepsis. His temperature was 39.8 degrees C, regular pulse 101 bpm, and pain reinforced in flexing and cervical rotation. Streptococcus dysgalactiae subsp. equisimilis (SDSE) was cultured from blood. Neck pain gradually decreased with of 2 million units PCG 6 times/day. Magnetic resonance imaging (MRI) of the cervical spine showed high-intensity areas in fat-suppression imaging at C7, Thl and intervertebral disks plus enhancement around the vertebral body, yielding a diagnosis of cervicothoracic vertebral osteomyelitis. Antimicrobial intravenous therapy continuede 6 weeks. The man was discharged after 45 days without relapse.

High-power direct green laser oscillation of 598 mW in Pr(3+)-doped waterproof fluoroaluminate glass fiber excited by two-polarization-combined GaN laser diodes.

We demonstrated a high-power and highly efficient Pr-doped waterproof fluoride glass fiber laser at 522.2 nm excited by two-polarization-combined GaN laser diodes and achieved a subwatt output power of 598 mW and slope efficiency of 43.0%. This system will enable us to make a vivid laser display, a photocoagulation laser for eye surgery, a color confocal scanning laser microscope, and an effective laser for material processing. Direct visible ultrashort pulse generation is also expected.

Development of an ex vivo cellular model of rheumatoid arthritis: critical role of CD14-positive monocyte/macrophages in the development of pannus tissue.

OBJECTIVE: To establish an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue (ST). METHODS: Inflammatory cells that infiltrated pannus tissue from patients with rheumatoid arthritis (RA) were collected without enzyme digestion, and designated as ST-derived inflammatory cells. Single-cell suspensions of ST-derived inflammatory cells were cultured in medium alone. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. ST-derived inflammatory cells were transferred into the joints of immunodeficient mice to explore whether these cells could develop pannus. CD14 and CD2 cells were depleted by negative selection. RESULTS: Culture of ST-derived inflammatory cells from 92 of 111 patients with RA resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks. Ex vivo tissue contained fibroblasts, macrophages, T cells, and tartrate-resistant acid phosphatase-positive multinucleated cells. On calcium phosphate-coated slides, ST-derived inflammatory cell cultures showed numerous resorption pits. ST-derived inflammatory cell cultures continuously produced matrix metalloproteinase 9 and proinflammatory cytokines associated with osteoclastogenesis, such as tumor necrosis factor alpha, interleukin-8, and macrophage colony-stimulating factor. More importantly, transferring ST-derived inflammatory cells into the joints of immunodeficient mice resulted in the development of pannus tissue and erosive joint lesions. Both in vitro development and in vivo development of pannus tissue by ST-derived inflammatory cells were inhibited by depleting CD14-positive, but not CD2-positive, cells from ST-derived inflammatory cells. CONCLUSION: These findings suggest that overgrowth of inflammatory cells from human rheumatoid synovium simulates the development of pannus. This may prove informative in the screening of potential antirheumatic drugs.

In vitro tissue engineering of a cardiac graft using a degradable scaffold with an extracellular matrix-like topography.

OBJECTIVE: Cardiac tissue engineering has been proposed as a treatment to repair impaired hearts. Bioengineered cardiac grafts are created by combining autologous cell transplantation with a degradable scaffold as a temporary extracellular matrix. Here we present a system for engineered myocardium combining cultured cardiomyocytes and a novel biodegradable scaffold with a unique extracellular matrix-like topography. METHODS: Cardiomyocytes were harvested from neonatal rats and cultured in vitro on biodegradable electrospun nanofibrous poly(epsilon-caprolactone) meshes. Between days 5 and 7, the meshes were overlaid to construct 3-dimensional cardiac grafts. On day 14 of in vitro culture, the engineered cardiac grafts were analyzed by means of histology, immunohistochemistry, and scanning electron microscopy. RESULTS: The cultured cardiomyocytes attached well to the meshes, and strong beating was observed throughout the experimental period. The average fiber diameter of the scaffold is about 250 nm, well below the size of an individual cardiomyocyte. Hence the number of cell-cell contacts is maximized. Constructs with up to 5 layers could be formed without any incidence of core ischemia. The individual layers adhered intimately. Morphologic and electrical communication between the layers was established, as verified by means of histology and immunohistochemistry. Synchronized beating was also observed. CONCLUSIONS: This report demonstrates the formation of thick cardiac grafts in vitro and the versatility of biodegradable electrospun meshes for cardiac tissue engineering. It is envisioned that cardiac grafts with clinically relevant dimensions can be created by using this approach and combining it with new technologies to induce vascularization.

Endothelialized networks with a vascular geometry in microfabricated poly(dimethyl siloxane).

One key challenge in regenerating vital organs is the survival of transplanted cells. To meet their metabolic requirements, transport by diffusion is insufficient, and a convective pathway, i.e., a vasculature, is required. Our laboratory pioneered the concept of engineering a vasculature using microfabrication in silicon and Pyrex. Here we report the extension of this concept and the development of a methodology to create an endothelialized network with a vascular geometry in a biocompatible polymer, poly(dimethyl siloxane) (PDMS). High-resolution PDMS templates were produced by replica-molding from micromachined silicon wafers. Closed channels were formed by bonding the patterned PDMS templates to flat PDMS sheets using an oxygen plasma. Human microvascular endothelial cells (HMEC-1) were cultured for 2 weeks in PDMS networks under dynamic flow. The HMEC-1 cells proliferated well in these confined geometries (channel widths ranging from 35 mum to 5 mm) and became confluent after four days. The HMEC-1 cells lined the channels as a monolayer and expressed markers for CD31 and von Willebrand factor (vWF). These results demonstrate that endothelial cells can be cultured in confined geometries, which is an important step towards developing an in vitro vasculature for tissue-engineered organs.

Initial assessment of a tissue engineered stomach derived from syngeneic donors in a rat model.

The objective of this study is to assess the feasibility of creating a tissue engineered stomach using isolated stomach epithelium organoid unit from syngeneic adult donors and a biodegradable polymer scaffold in a rat model. Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. As an alternative treatment, a tissue engineered stomach that replaces the mechanical and metabolic functions of a normal stomach is proposed. Stomach epithelium organoid units were isolated from syngeneic adult rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of recipient adult rats. All constructs were harvested for histologic and immunohistochemical examination at designated time points. Cyst-like structures were formed that showed the development of vascularized tissue with a neomucosa. Immunohistochemical staining for alpha-actin smooth muscle, gastric mucin, and proton pump indicated the presence of a smooth muscle layer and gastric epithelium, as well as the existence of parietal cells of the stomach mucosa, respectively. Epithelium derived stomach organoid units seeded on biodegradable polymers were transplanted in donor rats and have been shown to vascularize, survive, and regenerate into complex tissue resembling a native stomach. These initial results are encouraging, and studies are currently underway to further assess this approach.