Neural Network Structure Optimization by Simulated Annealing.

A critical problem in large neural networks is over parameterization with a large number of weight parameters, which limits their use on edge devices due to prohibitive computational power and memory/storage requirements. To make neural networks more practical on edge devices and real-time industrial applications, they need to be compressed in advance. Since edge devices cannot train or access trained networks when internet resources are scarce, the preloading of smaller networks is essential. Various works in the literature have shown that the redundant branches can be pruned strategically in a fully connected network without sacrificing the performance significantly. However, majority of these methodologies need high computational resources to integrate weight training via the back-propagation algorithm during the process of network compression. In this work, we draw attention to the optimization of the network structure for preserving performance despite compression by pruning aggressively. The structure optimization is performed using the simulated annealing algorithm only, without utilizing back-propagation for branch weight training. Being a heuristic-based, non-convex optimization method, simulated annealing provides a globally near-optimal solution to this NP-hard problem for a given percentage of branch pruning. Our simulation results have shown that simulated annealing can significantly reduce the complexity of a fully connected network while maintaining the performance without the help of back-propagation.

Estrogen can abolish oxytocin-induced spinal anti-hyperalgesia.

Our previous study verified a sex difference of anti-hyperalgesia in rats and anti-allodynia in mice induced by intrathecal oxytocin (OT). In the model of intraplantar carrageenan-induced inflammatory hyperalgesia, intrathecal OT injection induced a substantial anti-hyperalgesia in male rats even at a low dose (0.125 nmol). In contrast, female rats only responded to an extremely high dose (1.25 nmol). This sex difference concurs with a lower expression of OT receptors and higher expression of insulin-regulated aminopeptidase (IRAP; OT degrading enzyme) in the spinal cords of female rats. In this study, we further determined the role of female hormones in this sex difference by using ovariectomized rats. Our results show that a low dose of intrathecal OT caused a significant anti-hyperalgesia effect in ovariectomized female rats, similar to that seen in male rats. Ovariectomy did not cause any change of paw edema except at the late stage of convalescence when compared with the sham-operated group. Ovariectomy-induced faster recovery from edema but did not affect the severity of hyperalgesia. Moreover, there was a similar amount of IRAP expression in ovariectomized and sham rats. When estradiol (E2) was given together with OT, OT-induced anti-hyperalgesia was abolished at the developmental stage of hyperalgesia in ovariectomized rats. These results show an inhibitory role of female hormones generated from ovaries (mainly estrogen) in the sex difference of anti-hyperalgesia induced by OT. This study suggests the feasibility of a novel OT-based remedy to treat hyperalgesia in men and in menopausal women no receiving hormonal supplements.

Case Report: In Situ Vaccination by Autologous CD16+ Dendritic Cells and Anti-PD-L 1 Antibody Synergized With Radiotherapy To Boost T Cells-Mediated Antitumor Efficacy In A Psoriatic Patient With Cutaneous Squamous Cell Carcinoma.

The combination of radiotherapy and immunotherapy improves the survival rate of patients with malignancies developed through escape from T-cell-mediated immune surveillance. Immune checkpoint inhibitors, such as anti-programmed cell death protein-ligand 1 (anti-PD-L1) antibody, are used to rescue exhausted T cells. Simultaneously, dendritic cells (DCs) which are antigen-presenting cells that can initiate T-cell activation, are used to induce a tumor-specific immune response. However, the synergistic antitumor efficacy of the aforementioned combinational immunotherapy with intratumoral injection of low-dose DCs has not been reported, and the underlying therapeutic mechanism requires further investigation. Herein, we present the special case of a psoriatic patient with cutaneous squamous cell carcinoma (cSCC) in the right inguinal region, these two diseases characterized by opposing contradiction, further complicating treatments and side-effect management efforts. To treat the intractable SCC without exaggerating psoriasis, we developed the triple-regimen therapy (TRT) with the intratumoral injection of low-dose autologous DCs and anti-PD-L1 combined with radiotherapy. The injected DCs were obtained simply through leukapheresis without prior G-CSF administration for mobilization nor tumor-antigen loading for expansion. The patient received three radiation doses (24, 18, and 18 Gy) combined with three intratumoral injections of anti-PD-L1 antibody (40, 60, and 120 mg) plus autologous DCs (80% of the DC subpopulation being CD16+ myeloid DC with approximate amounts of 7.3 × 104, 2.5 × 106, and 1.7 × 107) within 10 weeks. The efficacy of the TRT was encouraging in shrinking tumor mass with remarkable SUVmax reduction (approximately 42%) on FDG PET-Scan despite relatively low-dose DCs were available. The low-dose intratumoral immunotherapy induced mild cutaneous side effects as expected. The transcriptomes were compared between pre-TRT and post-TRT biopsies to analyze underlying mechanical pathways of the TRT protocol. Over 10 highly significantly enriched T-cell-related pathways (P <0.0001) were identified in post-TRT biopsies. In addition, the activation of both innate and adaptive immunity was significantly enriched in post-TRT peripheral blood samples. We develop the easily accessible TRT which produces both local anti-tumor T-cell responses and systemic antitumor immunity for treating cSCC patients, especially for those with autoimmune disease.

The antitumor properties of metformin and phenformin reflect their ability to inhibit the actions of differentiated embryo chondrocyte 1.

BACKGROUND: Differentiated embryo chondrocyte 1 (DEC1) is a helix-loop-helix transcription factor that directly binds to the class B E-box in target genes. DEC1 exerts both pro-survival and pro-apoptotic effects in a cell- and tissue-dependent manner. Its actions play role the progression of cancer remains unclear. METHODS: We first examined the functional roles of DEC1 using the transient promoter reporter assay. Then, the knockdown of DEC1 expression was performed with the short hairpin RNA strategy in HeLa and A2058 cancer cell lines to check the cell cycle and mitochondrial function profile using the flow cytometry and Seahorse assays. We later clarified the role of DEC1 in the tumorigenesis using the colony formation, anchorage-independent growth assay, and cellular proliferation analysis. RESULTS: In the present study, we tested two guanide-containing drugs, metformin and phenformin, and found that both exhibit cytotoxicity against HeLa cervical carcinoma and A2058 melanoma cells. This effect was mediated, at least in part, through activation of the AMPK pathway; degradation of important cellular proteins, such as DEC1 and p53; and suppression of mitochondrial function, colony formation, and anchorage-independent cell proliferation. Our results further suggest that the cytotoxicity of metformin and phenformin reflect the impact of the repressive actions of DEC1 on gene expression, including DEC1 itself. This in turn suppresses both anchorage-independent growth and cell proliferation. CONCLUSION: These findings provide several lines of evidence suggesting that DEC1 activity contributes to tumorigenicity and that the antitumor properties of biguanides reflect their ability to inhibit DEC1 functions.

The aberrant systemic-pulmonary artery communication: three-dimensional image simulation.

BACKGROUND: Congenital arterial abnormalities are unusual causes of hemoptysis in elder patients. Appropriate image examination and recognition of the variant vessels are crucial in achieving precise diagnosis and successful treatment. CASE PRESENTATION: We report a case of 70-year-old female presenting with hemoptysis. Computed tomography angiography showed hypervascular lesions in the lingula of the left lung abutting the pericardium. Three-dimensional reconstruction image revealed an aberrant systemic arterial supply communicating with the left pulmonary artery and co-supplying the pulmonary parenchyma of the left upper. Single-port video-assisted thoracoscopic surgery with anomalous vessel ligation and lingual segmentectomy were performed smoothly. The symptom of hemoptysis subsided after operation with 2-year follow up. CONCLUSION: An anomalous systemic arterial supply to the left upper lobe of the lung with an aberrant systemic system draining into the left pulmonary artery and co-supplying the lung parenchyma is extremely rare. Preoperative simulation with three-dimensional reconstruction image provides a clear spatial anatomy that allows clinicians to identify the orientation of the vessels more precisely when deciding on intervention.

Woman with recurrent vomiting.

CLINICAL INTRODUCTION: A 69-year-old woman presented to the ED with a chief complaint of recurrent vomiting for 3 weeks. She was afebrile, blood pressure was 100/67 mm Hg, HR was 114/min, RR was 19/min and oxygen saturation was 98%. On physical examination, she had mild epigastric tenderness without guarding. Blood tests were normal except for hyponatraemia of 128 mmol/L and hypokalaemia of 2.7 mmol/L. The ECG demonstrated sinus tachycardia with first-degree atrioventricular block. Chest radiograph posteroanterior view (CXR) was performed (figure 1).emermed;35/11/691/F1F1F1Figure 1Chest radiograph posteroanterior view. The patient presented to the ED with a complaint of recurrent vomiting for 3 weeks. QUESTION: Due to continuous vomiting of this patient, which of the following is the most appropriate management?Abdominal ultrasonography.Chest and abdominal CT.Barium swallow.Oesophagogastroduodenoscopy (EGD). For answer see page 02 For question see page 01.

Zac1 regulates IL-11 expression in osteoarthritis.

Interleukin (IL)-11, a member of the IL-6 family of cytokines, exerts pleiotropic effects under normal and various disease conditions. We assessed IL-11 expression regulation and the IL-11/IL-6 ratio in osteoarthritis (OA) to better guide clinical therapeutic decision-making. Our findings suggest that Zac1, a zinc finger protein that regulates apoptosis and cell cycle arrest, is a transcription factor regulating IL-11 expression. Zac1 overexpression or knockdown respectively induced or suppressed IL-11 expression in HeLa cells. Zac1 acted synergistically with AP-1, human papillomavirus E2, and hypoxia inducible factor 1 alpha (HIF1α). IL-11 expression under various conditions, including hypoxia or treatment with phorbol 12-myristate 13-acetate or copper sulfate. Recombinant IL-11-induced phosphorylation of signal transducer and activator of transcription 3 at tyrosine 705 was reduced in a dose-dependent manner in HeLa cells. Cross-talk between Zac1, IL-11, p53, and suppressor of cytokine signaling 3 was differentially affected by copper sulfate, digoxin, and caffeine. Finally, aggressive vs. conventional treatment of OA patients was primarily determined by IL-6 levels. However, we suggest that OA patients with higher IL-11 levels may respond well to conventional treatments, even in the presence of high IL-6.

Modified Essex-Lopresti procedure with percutaneous calcaneoplasty for comminuted intra-articular calcaneal fractures: a retrospective case analysis.

BACKGROUND: The ideal treatment for comminuted intraarticular calcaneal fractures is still debated. Open reduction and internal fixation (ORIF) is the most popular surgical procedure; however, wound complications, implant choice, and infection remain major concerns. This study aimed to demonstrate the results of an innovative, minimally invasive surgical procedure, namely, a closed reduction technique using large-diameter Steinmann pins and percutaneous calcaneoplasty using injectable calcium sulfate cement (MIIG X3, Wright Medical Technology, Inc., Arlington, TN), in patients with comminuted calcaneal fractures. METHODS: From January 2012 to January 2014, 20 patients (three women, 17 men) with comminuted calcaneus fractures (Sanders classification type III and Essex-Lopresti classification joint-depression type fracture) were included. Plain films and CT scans were obtained preoperatively in all patients. The operation was performed within three days post-injury, and patients were not allowed to bear weight until three months postoperatively. During this period, the patients were educated on how to perform bed exercises for joints above the surgical site, including muscle strengthening and body conditioning. Early active range of motion exercises for the ankle and forefoot began 3 to 6 weeks postoperatively. All patients were followed up regularly. The results were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle score and Böhler's angle of the calcaneus. RESULTS: After an average follow-up of two years, none of the patients required further surgery or experienced soft tissue complications. The clinical results were rated good to excellent on the AOFAS scale in 80% of the cases (16 of 20 patients), and most patients had pain relief and returned to their former daily activities at the same level as before the injury. CONCLUSIONS: A modified Essex-Lopresti procedure with percutaneous calcaneoplasty appears to be a safe and effective procedure to treat comminuted calcaneal fractures with acceptable functional results. Long-term outcomes and additional cases using this technique are required to support our conclusion.

Results of infected total knee arthroplasty treated with arthroscopic debridement and continuous antibiotic irrigation system.

BACKGROUND: Arthroscopic debridement with continuous irrigation system was used with success in treating infective arthritis. We evaluated the effectiveness of arthroscopic debridement coupled with antibiotic continuous irrigation system in acute presentation of late infected total knee arthroplasty. MATERIALS AND METHODS: We performed a retrospective review of medical record of patients with acute presentation of late infected total knee arthroplasty who were treated by arthroscopic debridement coupled with continuous postoperative antibiotic irrigation system. RESULTS: Seventeen patients were included in our study. 15 (88%) patients preserved their total knee prosthesis at mean of followup of 27.5 months (range, 14-28 months). Two (12%) patients failed arthroscopic protocol and finally needed two stages revision. Our study showed an 88% prosthesis retention rate in patients with acute presentation of late prosthetic knee infection. No complication was associated with use of antibiotic irrigation system. CONCLUSION: Arthroscopic debridement combined with continuous antibiotic irrigation and suction is an effective treatment for patients with acute presentation of late infected total knee arthroplasty.

Redisplacement of diaphyseal fractures of the forearm after closed reduction in children: a retrospective analysis of risk factors.

OBJECTIVES: Manipulation and plaster fixation is the primary management for diaphyseal fractures of the radius and/or ulna in children. This study was designed to evaluate risk factors of fracture redisplacement after closed reduction and cast immobilization. DESIGN: Retrospective study. SETTING: Tertiary hospital. PATIENTS: Fifty-seven children with fractures of the radius were included. INTERVENTION: The medical records of patients with/without ulna treated with closed reduction and casting were reviewed. MAIN OUTCOME MEASURES: Data analyzed were age, sex, dominant hand, fracture pattern, reduction quality, experience of the surgeon, and type of anesthesia. Logistic regression was used for multivariate analysis. RESULTS: There were 41 (71.9%) males and 16 (28.1%) females with a mean age of 9.74 ± 3.07 years. There were 53 radius fractures and 54 ulna fractures, and 22 subjects experienced redisplacement. The redisplacement rate of radius fractures was 34% and of ulnar fractures was 27.8%. Multivariate analysis showed that the factors associated with redisplacement of radius fractures were fair reduction quality [odds ratio (OR), 8.45] and complete fracture (OR 9.62) and those for redisplacement of ulna fractures were fair reduction quality (OR 8.10) and complete fracture (OR 8.43). CONCLUSIONS: Poorer reduction and complete fracture are more likely to result in redisplacement, and surgical management may be considered in these cases.

Treatment of septic knee arthritis: comparison of arthroscopic debridement alone or combined with continuous closed irrigation-suction system.

BACKGROUND: Arthroscopic debridement has been widely adapted as initial treatment for septic knee arthritis. Although isolated cases of arthroscopic debridement combined with irrigation-suction systems have been reported, a comparison of two techniques has not been performed, to our knowledge. The purpose of this study was to compare the two methods of treatment. METHODS: From January 1996 to December 2008, 39 patients with 39 septic knee arthritis treated in our institution were retrospectively analyzed. Nineteen knees were initially treated with arthroscopic debridement alone (group I), and 20 knees were initially treated with arthroscopic debridement combined with continuous closed irrigation-suction system (group II). The clinical presentation, laboratory and microbiologic findings, hospital course, and clinical outcomes were compared between the two groups. RESULTS: The mean delay between the onset of the symptoms and treatment had a significant effect on the clinical outcomes. When the comparison included all the patients in the series, no significant difference between the two groups was found with regard to the number of operation procedures required or the length of the hospital stay. However, when the comparison was separated from the initial stage of infection, it was found that in stage II infection, patients had fewer reoperations and in stages II and III infection, a shorter hospital stay in group II than in group I (p < 0.05). There was no significant difference in the functional results between the two groups. CONCLUSIONS: The early diagnosis and aggressive initiation of treatment carried the success of therapy in septic knee arthritis. Arthroscopic debridement combined with continuous closed irrigation-suction system is an effective treatment for patients with septic knee arthritis; these patients had fewer operations and a shorter hospital stay than did patients who had received arthroscopic debridement alone.

Prevalence of flexible flatfoot in Taiwanese school-aged children in relation to obesity, gender, and age.

The objective of this study was to determine the prevalence of flexible flatfoot in elementary school children in Taiwan and evaluate the relationship between flatfoot and obesity, gender, and age. A sample of 2,083 children, between 7 and 12 years of age from public elementary schools in northern Taiwan was analyzed. Children were stratified into groups according to age: 7, 8, 9, 10, 11, or 12 years old. Demographic information was obtained, and the presence of flatfoot determined by footprint analysis and grading according to Denis flatfoot staging. A total of 1,222 (59%) children were documented with flatfoot. The incidence percentages of flatfoot were: 67% of males, 49% of females, and 75%, 65%, 57%, and 48% of obese, overweight, normal weight, and underweight children, respectively. A preponderance of flatfoot was observed among 8-year-olds. Multivariate analyses indicated that 8- and 9-year-olds were 1.52 and 0.72 times more likely to have flatfoot than 7-year-olds. Males were twice as likely to have flatfoot as females. Children who were obese or overweight were 2.66 and 1.39 times more likely to have flatfoot than those of average weight. The results of this study indicate that the prevalence of flexible flatfoot is highest among males who are obese and overweight, particularly in the age range of 7 to 8 years.

Biomechanical comparison of Cross-pin and Endobutton-CL femoral fixation of a flexor tendon graft for anterior cruciate ligament reconstruction--a porcine femur-graft-tibia complex study.

BACKGROUND: A stable fixation of the graft is imperative for early aggressive rehabilitation after anterior cruciate ligament (ACL) reconstruction. The suspension devices such as Endobutton-CL and Cross-pin system are common techniques of femoral fixation for the hamstring tendon graft and provide superior initial biomechanical properties than the screws system. It remains unclear how such implants perform under cyclic loading and initial pull-out strength. MATERIALS AND METHODS: Cross-pin and Endobutton-CL femoral fixation devices were tested for initial fixation strength in porcine knee joints by cyclic loads following a load-to-failure test. The Cross-pin and Endobutton-CL were used for femoral fixation of a porcine profundus flexor digitorum tendon autograft in 20 porcine knees. Ten specimens of femoral-graft-tibia complex in each group were loaded cyclically to between 0 and 150 N at 1 Hz for 1000 cycles following a load-to-failure test at a rate of 150 mm/min. RESULTS: The amount of total femur-graft-tibia complex graft displacement was significantly lower in the Cross-pin fixation group (5.37 +/- 0.28 mm) than in Endobutton-CL fixation group (6.08 +/- 0.61 mm: P < 0.05). There were no significant differences in the maximal failure load, yield load, and stiffness between the Cross-pin and Endobutton-CL fixation groups. CONCLUSIONS: This biomechanical study reveals that the Endobutton-CL and Cross-pin femoral fixation devices have an equally strong and safe fixation for ACL reconstruction. However, the Cross-pin fixation has significantly less displacement of femur-graft-tibia complex than that of Endobutton-CL fixation in response to the cyclic loading test. It indicates that the Cross-pin fixation is more suitable for early aggressive rehabilitation following ACL reconstruction.

Stress fractures of forearm bones in military recruits of rifle drill training.

BACKGROUND: Stress fractures rarely occur in the forearms. These injuries usually occur in healthy young patients, which are usually neglected by patients or physicians. Early diagnosis and treatment are important to avoid late complications of these fractures. The purpose of this study was to analyze a case series of military recruits who participated in rifle drill training and presented with forearm stress fractures at our institution. METHODS: We evaluated 216 military recruits of rifle drill training. Twelve patients were diagnosed with forearm stress fractures by typical history, physical examination, laboratory studies, serial radiographs, and bone scan examinations. RESULTS: Eighteen fractures were found in 12 patients. On initial radiographs, 11 had periosteal reactions, 4 had callus formation with complete fracture lines, and 3 were normal. All 18 fractures had increase radioactivity in the involved middle (15 of 18) or distal (2 of 18) ulnae and one middle radius (1 of 18). CONCLUSIONS: Stress fractures of the forearms in military rifle drill training usually occur in middle ulnae. Fifty percent of them were bilateral fractures. A high index of suspicion is the key to diagnosis. Early diagnosis with conservative treatment can achieve satisfactory results and avoid late complications of stress fractures.

Arthroscopic elimination of monosodium urate deposition of the first metatarsophalangeal joint reduces the recurrence of gout.

PURPOSE: To determine if the arthroscopic removal of gouty crystal deposits from the first metatarsophalangeal (MTP) joint will reduce the recurrence rate and improve foot function compared to medical treatment alone. METHODS: Twenty-eight male patients with hyperuricemia (>7.0 mg/dL) and repeated attacks of gouty arthritis of the first MTP joint were included in this study. Arthroscopic intervention of the first MTP joint was performed on 15 patients (group 1), while the other 13 patients were treated with medication alone (group 2). The follow-up period (mean +/- standard deviation) was 3.9 +/- 1.1 years in group 1 and 2.4 +/- 0.3 years in group 2. RESULTS: After treatment, both groups showed a significant improvement in the number of acute attacks of gouty arthritis and in their functional scores on the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale. On both measures, the results for group 1 were significantly better than those for group 2. CONCLUSIONS: Arthroscopic removal of gouty crystals from the first MTP joint can reduce the rate of acute repeated attacks of gouty arthritis and increase foot and ankle function.

Stress fracture of the ulna in a break-dancer.

Break dancing is a popular activity in teenagers and is associated with severe trauma to bones and tissues. We report the first known case of a break dancer with an ulnar stress fracture. Such injuries occur in a variety of sports due to substantial stress on the ulna and repetitive excessive rotation of the forearm. In this study we describe a patient who experienced an ulnar stress fracture during break dancing training. The diagnosis was established by history and physical examination. Initial radiographic findings were negative. However, radiographs taken 3 months after initial presented revealed callus formation over the ulnar shaft. This suggested that readjustment is required in break dancing training protocols. It is important to increase awareness of this injury among physicians to expedite the diagnosis and to prevent the possibility of conversion to an overt fracture in the future. Key pointsStress fractures should not be ignored when the patient changes exercise loading.A thoroughly detailed clinical history, physical examination, and plain radiographs were used diagnostically in this clinical case.The best methods for the treatment of stress fractures include readjustment training protocols to prevent conversion to overt fractures.