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Open and comminuted mid-distal fractures often result from high-energy trauma, and a concomitant poor blood supply often leads to skin necrosis, infection, and bone union. To circumvent such complications, we used limited-reduction and bilateral-external fixators to treat open and comminuted mid-distal tibial fractures with compromised soft tissue. A retrospective series of 34 patients who had open and comminuted mid-distal tibial fractures and treated by bilateral-external fixators with limited-internal fixation were analyzed. Patients were followed for 10-25 months (mean: 12 months) post-treatment and osseous union was achieved in each case. The average union time was 16.3 weeks. Based on the Johner- Wruhs criteria, the retrospective series consisted of 21 ‘excellent’ cases, 8 ‘good’ cases, 4 ‘fair’ cases, and a ‘poor’ case. The total percentage of ‘excellent’ and ‘good’ cases of fracture recovery was 85.29%. Bilateral-external and limited-internal fixators pro- vided high bone union rate and excellent ankle-joint motion. Hence, it is an appropriate surgical approach for treating open and comminuted mid-distal tibial fractures with compromised soft tissue.

This paper develops an artificial intelligence based automated valuation model (AI-AVM) using the boosting tree ensemble technique to predict housing prices in Singapore. We use more than 300,000 private and public housing transactions in Singapore for the period from 1995 to 2017 in the training of the AI-AVM models. The boosting model is the best predictive model that produce the most robust and accurate predictions for housing prices compared to the decision tree and multiple regression analysis (MRA) models. The boosting AI-AVM models explain 91.33% and 94.28% of the price variances, and keep the mean absolute percentage errors at 8.55% and 5.34% for the public housing market and the private housing market, respectively. When subject the AI-AVM to the out-of-sample forecasting using the 2018 housing sale samples, the prediction errors remain within a narrow range of between 5% and 9%.

Objectives The objectives of this study were to describe trajectories of pelvic floor symptoms and support from the third trimester to 1 year postpartum in primiparous women after vaginal delivery and to explore factors associated with their resolution between 8 weeks postpartum and 1 year postpartum. Methods Five hundred ninety-seven nulliparous women 18 years or older who gave birth vaginally at term completed the Epidemiology of Prolapse and Incontinence Questionnaire and the Pelvic Organ Prolapse Quantification examination at the third trimester, 8 weeks postpartum, and 1 year postpartum. Results At 1 year postpartum, 41%, 32%, and 23% of participants reported stress urinary incontinence, nocturia, and flatus incontinence, respectively, and 9% demonstrated maximal vaginal descent (MVD) ≥ 0 cm. For more common symptoms, incidence rates between the third trimester and 8 weeks postpartum ranged from 6% for urinary frequency to 22% for difficult bowel movements, and resolution rates between 8 weeks postpartum and 1 year postpartum ranged from 23% for stress urinary incontinence to 73% for pain. Between the third trimester and 8 weeks postpartum, 13% demonstrated de novo MVD ≥ 0 cm. For most symptoms, the presence of the same symptom before delivery decreased the probability of resolution between 8 weeks postpartum and 1 year. However, the sensitivities of predelivery vaginal bulge and MVD of 0 cm or greater for those outcomes at 1 year postpartum was overall low (10-12%). Conclusions One year postpartum, urinary and bowel symptoms are common in primiparous women who gave birth vaginally. A substantial portion of this burden is represented by symptoms present before delivery, while most of the prevalence of worse anatomic support is accounted for by de novo changes after delivery.

OBJECTIVE: To determine whether oxytocin for induction or augmentation of labor impacts the incidence or persistence of pelvic floor symptoms and support 5–10 weeks after first vaginal delivery. METHODS: Participants in this prospective cohort study were nulliparous women ≥ 18 years that delivered vaginally at ≥ 37 weeks gestation, completed the Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ) and the Pelvic Organ Prolapse Quantification examination (POP-Q) in third trimester and 5–10 weeks postpartum. We compared the incidence and persistence of symptomatic EPIQ domains and worse vaginal support (maximal vaginal descent ≥ 0 cm) between women who received oxytocin to those that did not (with or without prostaglandin or mechanical methods in both groups). We performed modified binomial regression to calculate adjusted relative risks of each outcome with 95% confidence intervals. RESULTS: Mean age of the 722 participants was 28.3 (SD 5.2) years; 20% were Hispanic. There were no significant differences according to oxytocin exposure in either incidence or persistence of symptomatic EPIQ domains or worse vaginal support. We found similar results in sensitivity analyses comparing women who received oxytocin as the sole pharmacologic agent to women who received no pharmacologic agent. After adjusting for demographic and obstetric factors associated with incidence and persistence of symptoms and support, oxytocin exposure continued to have no effect. CONCLUSIONS: Oxytocin during labor does not significantly increase the risks for the incidence or persistence of pelvic floor symptoms or worse vaginal support in the early postpartum period, though power for less frequent outcomes was limited. SINGLE SENTENCE SUMMARY: Oxytocin during labor does not significantly increase the risks for the incidence or persistence of pelvic floor symptoms or worse vaginal support in the early postpartum period.

BACKGROUND Minocycline blocks microglial TNF signaling and downstream NF-κB activation, which reduces the mesenchymal phenotype in preclinical models of GBM. Primary analysis of the D-TERMINED trial identified a maximal tolerated dose (MTD) of oral minocycline at 150 mg BID in combination with temozolomide and radiation. In the overall population, the secondary objective of improved PFS was not met. Here, response is further stratified by biomarkers delineating mesenchymal subtype (OLIG2, CD44), microglial activation (IBA-1), and NF-κB signaling (P-p65). METHODS Patients with newly diagnosed high-grade glioma received continuous oral minocycline during concurrent chemoradiation and adjuvant temozolomide. Twenty patients were included in the MTD efficacy population. Within this cohort, immunohistochemistry for OLIG2, CD44, IBA-1, and P-p65 was performed on nineteen patient tumor samples. For each biomarker, the mean percent positivity or number/HPF was compared between patients who exceeded or did not exceed expected PFS. Spearman correlation coefficients were also generated for pairwise comparison of these biomarkers. RESULTS In patients with high PFS, 12.7% of tumor cells were positive for OLIG-2, 36.5% for CD44, and 23.9% for P-p65, with 41.7 cells/HPF positive for IBA-1. Comparatively, in patients with low PFS, 9.4% of tumor cells were positive for OLIG-2 (p = 0.59), 34.1% for CD44 (p = 0.77), and 22.3% for P-p65 (p = 0.85), with 31.1 cells/HPF positive for IBA-1 per HPF (p = 0.38). The only biomarkers demonstrating significant relationship were P-p65 and IBA-1, with a rank correlation of 0.637 (p = 0.007). CONCLUSIONS Exploratory analysis of D-TERMINED concludes that OLIG-2, CD44, IBA-1, and P-p65 are not predictive of improved PFS within high-grade glioma patients treated with SOC and minocycline. Concurrent use of minocycline with chemoradiation is therefore not indicated in these or unselected populations. Significant correlation is seen between IBA-1 and P-p65, biomarkers of microglial activation and NF-κB signaling. SPONSORSHIP: Funding provided by the Musella Foundation and NIH grant P30CA042014.

This study primarily aims to evaluate the cooling and heating characteristics and provide a performance comparison of CO2, R41, and several CO2/R41 blends for applications in automobile air-conditioning and heat pump systems. Experiments were conducted to reveal the effects of the refrigerant charge, compositions, ambient temperatures, and compressor speeds among the trans-critical and subcritical cycles. The performance merits of the environmental friendliness, energy efficiency, and safety of using CO2/R41 blends are emphasized. The results demonstrate that, at an optimum charge amount, the coefficient of performance of pure CO2 in the heating and cooling modes can be improved up to a maximum of 14.5% and 25.7%, respectively, by increasing the R41 mass fraction. The heating and cooling capacities were both decreased with an increasing R41 mass fraction, as the system mass flow rates decreased owing to the reduction in suction density. The overall system operation pressure, gas cooler outlet temperature, and high- and low-side pressure drops in both the heating and cooling modes were reduced significantly when the mass fraction of R41 increased from 0% to 100%. Furthermore, the effect of the CO2 mass fraction on the flammability of CO2/R41 blends was studied to discuss the advantages of its safety application. Finally, based on the experimental data, a correlation of the optimum high-side pressure for the trans-critical CO2/R41 cycle was developed, showing a deviation of ±5% from the data.

Background: Venous thromboembolism events (VTEs) continue to be of the most widespread severe complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, there are no optimal accurate monitoring methods to assess the changes in coagulability after anticoagulation and anti-fibrinolysis during the perioperative period. Therefore, the objective of this study is to determine changes in coagulability as measured by thromboelastography (TEG) following revision total hip arthroplasty when the patients received rivaroxaban and tranexamic acid in perioperative period during enhanced recovery after surgery (ERAS). Methods: We retrospectively reviewed 70 revision TKA patients (mean age 63.69±10.17 years). Perioperative management of each patient was conducted in accordance with ERAS. The patients received tranexamic (TXA) to control perioperative bleeding. TEG was performed pre-operatively and on post-operative days (POD) 1, 3, 5 and 7. TEG-hypercoagulability was classified into three types: enzymatic hypercoagulability, platelet hypercoagulability and mixed hypercoagulability. Screening for coagulation-related complications at three months of follow-up. Results: The mean duration of surgery was 2.91±0.99 h. the mean intraoperative blood loss of patients was 486.43±346.92 ml. And 55.71% (39) patients received transfusion, the mean blood transfusion volume was 482.86 ± 458.79 ml. There only were 4 (5.71%) patients who suffered postoperative coagulation-related complications. 1 patient with hypercoagulable on preoperative developed intramuscular venous thrombosis at 1 month postoperatively. 1 patient with hypercoagulability at POD5 and POD7 suffered melena at POD5. 2 patients with hypocoagulability developed ecchymosis at POD3. The proportion of postoperative hypercoagulable state is gradually increasing. The distribution of different hypercoagulable states on the postoperative day (POD) 5 and 7 were significantly different from that pre-operation (Pre) and POD1 (POD5 vs Pre: p=0.011; POD5 vs POD1: p=0.001; POD7 vs Pre: p=0.001; POD7 vs POD5: p

The whole-life ratchetting and fatigue failure, as well as the ratchetting-fatigue interaction, of polyamide-6 (PA6) were investigated by performing a set of uniaxial stress-controlled cyclic tests at room temperature and with different stress levels. The effects of mean stress, stress amplitude and stress ratio on the evolution of ratchetting strain and the fatigue life of PA6 are discussed. Simultaneously, the evolution of damage variable, which is defined as a function of equivalent modulus, is summarized to reflect the interaction of ratchetting and fatigue damage. The experimental results show that the uniaxial whole-life ratchetting and fatigue life of PA6 are sensitive to the mean stress, stress amplitude and stress ratio. The evolution of damage variable and its dependence on the stress level are similar to that of whole-life ratchetting, and present a tri-phased feature with respect to the damage rate. By comparing the fatigue lives obtained in the asymmetrical and symmetrical tests, a detrimental effect of ratchetting deformation on the fatigue life of PA6 is found.

Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor. The Group 3 molecular subgroup of Medulloblastoma (Group 3 MB) is the deadliest with only 30% long term survival. Irradiation for Group 3 Medulloblastoma is required for long term survival of children. Methods to enhance the effect of irradiation against Group 3 MB are an active area of investigation. Immunotherapy using the anti-CD47 treatment has shown promise in treating Group 3 MB. We recently demonstrated that irradiation significantly enhanced anti-CD47-mediated phagocytosis of high-grade glioma cells in vitro. Furthermore, mice engrafted with human high-grade glioma that received anti-CD47 combined with irradiation showed a significant increase in the survival rate and a significant decrease in tumor growth than those that received a single treatment. We have now extended these studies to demonstrate the enhancement of anti-CD47-dependent phagocytosis of human Group 3 MB with irradiation. We also analyzed normal human neural stem cells exposed to the same treatments to assess for the potential toxicity that uniquely exists with this treatment combination.

Objective: Most studies about truncal pain during and after pregnancy focus on low back pain, few prospectively define change in pain, and even fewer evaluate pain in all three major truncal areas: upper back, lower back, and pelvic girdle. Thus, the objective of this prospective cohort study was to describe, in primiparous women delivered vaginally, prevalence rates and severities of upper back, lower back, and pelvic girdle pain during pregnancy and 6–10 weeks postpartum and to describe the trajectory of pain constellations between time points. Study design: Participants completed questionnaires at each time point. Pain intensity was rated on a visual analogue scale ranging from 0 to 100. Results: Of the 288 participants, 94% reported truncal pain during pregnancy, while 75% did so postpartum. Prevalence rates of upper back, lower back, and pelvic girdle pain with or without other types of pain during pregnancy were 42%, 77%, and 74% and postpartum were 43%, 52%, and 41%, respectively. Pain severity was highest for women endorsing pain in three locations (median 55–60). Of women with the most common pain constellation during pregnancy, lower back and pelvic girdle (32%), 18% had persistent low back and pelvic girdle pain postpartum, 20% had no pain, and the remainder had pain in a different location. Of women with pain in all three locations during pregnancy (27%), 34% had persistent pain in three locations postpartum, 13% had no pain, and the remainder had pain in at least one location. Conclusion: More women experience pain in a constellation of locations than in a single location. Severity increases as number of pain sites increase. Women with pain in three sites during pregnancy are least likely to have pain resolve. Interventions should focus on the entire trunk and not simply one site of pain.

Mesenchymal stem cells (MSCs) possess tumor-tropic properties and consequently have been used to deliver therapeutic agents for cancer treatment. Their potential in cancer therapy highlights the need for a consistent and renewable source for the production of uniform human MSCs suitable for clinical applications. In this study, we seek to investigate whether human embryonic stem cells can be used as a cell source to fulfill this goal. We generated MSC-like cells from two human embryonic stem cell lines, HuES9 and H1, and observed that MSC-like cells derived from human embryonic stem cells were able to migrate into human glioma intracranial xenografts after being injected into the cerebral hemisphere contralateral to the tumor inoculation site. We engineered these cells with baculoviral and lentiviral vectors, respectively, for transient and stable expression of the herpes simplex virus thymidine kinase gene. In tumor-bearing mice the engineered MSC-like cells were capable of inhibiting tumor growth and prolonging survival in the presence of ganciclovir after they were injected either directly into the xenografts or into the opposite hemisphere. Our findings suggest that human embryonic stem cell-derived MSCs may be a viable and attractive alternative for large-scale derivation of targeting vehicles for cancer therapy.

Yeast cells, like mammalian cells, enlarge steadily as they age. Unabated cell growth can promote cellular senescence; however, the significance of the relationship between size and cellular lifespan is not well understood. Herein, we report a genetic link between cell size, growth rate and lifespan. Mutations that increase cell size concomitantly increase growth rate and decrease lifespan. As a result, large cells grow, divide and age dramatically faster than small cells. Conversely, small cell mutants age slowly and are long-lived. Investigation of the mechanisms involved suggests that attainment of a maximal size modulates lifespan. Indeed, cumulative results revealed that life expectancy is size-dependent, and that the rate at which cells age is determined in large part by the amount of cell growth per generation.

Adult stem cells may serve as powerful cellular vehicles to deliver therapeutic genes for cancer therapy. In such applications, effective and safe transduction to load stem cells with genes of interest is essential. To examine whether baculovirus can be used to fulfill this task, we tested a range of baculoviral vectors in human bone marrow mesenchymal stem cells (MSCs). A vector using the human cytomegalovirus immediate-early gene promoter to drive transgene expression and the woodchuck hepatitis virus posttranscriptional regulatory element to enhance translation was able to transduce MSCs with efficiency close to 80%. Following the observation that baculoviral transduction did not significantly affect surface marker expression of the stem cells, we tested the feasibility of using baculovirus-transduced MSCs for targeted cancer therapy. We transduced cells with a baculoviral vector harboring the herpes simplex virus thymidine kinase gene, and performed tail vein injection of the transduced cells into mice preinoculated subcutaneously with human U87 glioma cells. After ganciclovir prodrug injection, we observed inhibition of tumor growth and significantly prolonged survival of tumor-inoculated animals. Our findings suggest that baculoviral transduction of MSCs is an attractive option to generate targeting vehicles for systemic cancer therapy.

Large, multisubunit Ccr4-Not complexes are evolutionarily conserved global regulators of gene expression. Deletion of CCR4 or several components of Ccr4-Not complexes results in abnormally large cells. Since yeast must attain a critical cell size at Start to commit to division, the large size of ccr4Δ cells implies that they may have a size-specific proliferation defect. Overexpression of CLN1, CLN2, CLN3, and SWI4 reduces the size of ccr4Δ cells, suggesting that ccr4Δ cells have a G1-phase cyclin deficiency. In support of this, we find that CLN1 and CLN2 expression and budding are delayed in ccr4Δ cells. Moreover, overexpression of CCR4 advances the timing of CLN1 expression, promotes premature budding, and reduces cell size. Genetic analyses suggest that Ccr4 functions independently of Cln3 and downstream of Bck2. Thus, like cln3Δbck2Δ double deletions, cln3Δccr4Δ cells are also inviable. However, deletion of Whi5, a transcriptional repressor of CLN1 and CLN2, restores viability. We find that Ccr4 negatively regulates the half-life of WHI5 mRNAs, and we conclude that, by modulating the stability of WHI5 mRNAs, Ccr4 influences the size-dependent timing of G1-phase cyclin transcription.

Mammalian target of rapamycin (mTOR) integrates multiple signals, including nutrient status, growth factor availability, and stress, to regulate cellular and organismal growth. How mTOR regulates transcriptional programs in response to these diverse stimuli is poorly understood. MondoA and its obligate transcription partner Mlx are basic helix-loop-helix leucine zipper (bHLHZip) transcription factors that sense and execute a glucose-responsive transcriptional program. MondoA-Mlx complexes activate expression of thioredoxin-interacting protein (TXNIP), which is a potent inhibitor of cellular glucose uptake and aerobic glycolysis. Both mTOR and MondoA are central regulators of glucose metabolism, yet whether they interact physically or functionally is unknown. We show that inhibition of mTOR induces MondoA-dependent expression of TXNIP, coinciding with reduced glucose uptake. Mechanistically, mTOR binds to MondoA in the cytoplasm and prevents MondoA-Mlx complex formation, restricting MondoA's nuclear entry and reducing TXNIP expression. Further, we show that mTOR inhibitors and reactive oxygen species (ROS) regulate interaction between MondoA and mTOR in an opposing manner. Like mTOR's suppression of the MondoA-TXNIP axis, MondoA can also suppress mTOR complex 1 (mTORC1) activity via its direct transcriptional regulation of TXNIP. Collectively, these studies reveal a regulatory relationship between mTOR and the MondoA-TXNIP axis that we propose contributes to glucose homeostasis.

This study applies an artificial intelligence (AI) based model to predict the infection rate of coronavirus disease 2019 (COVID-19). The results provide information for managing public and global health risks regarding pandemic controls, disease diagnosis, vaccine development, and socio-economic responses. The machine learning algorithm is developed with the Python program to analyze pathways and evolutions of infection. The finding is robust in predicting the virus spread situation. The machine learning algorithms predict the rate of spread of COVID -19 with an accuracy of nearly 90%. The algorithms simulate the virus spread distance and coverage. We find that self-isolation for suspected cases plays an important role in containing the pandemic. The COVID-19 virus could spread asymptotically (silent spreader); therefore, earlier doctor consultation and testing of the virus could reduce its spread in local communities.

Recombinant baculoviral vectors efficiently transduce many types of mammalian cells. However, their in vivo applications are hampered by the sensitivity of the virus to complement-mediated inactivation. Based on our observation that the surface charge of baculovirus is negative at neutral pH, we developed a procedure to coat baculoviral vectors with positively charged polyethylenimine 25 kDa, a commonly tested non-viral gene delivery vector, through electrostatic interaction. This coating was effective in protecting baculoviral vectors against human and rat serum-mediated inactivation in vitro, providing transduction efficiencies comparable with that generated by the control virus used under a serum-free condition. Enhanced in vivo gene expression in the liver and spleen was observed after tail vein injection of the coated viruses into mice. When injected directly into human tumor xenografts in nude mice, the coated viruses suppressed tumor development more effectively than uncoated viral vectors. These findings demonstrated the usefulness of using a simple coating method to circumvent a major obstacle to in vivo application of baculoviral vectors. The method may also serve as a flexible platform technology for improved use of the vectors, for example introducing a targeting ligand and minimizing immune responses.