Enhanced charge density wave with mobile superconducting vortices in La1.885Sr0.115CuO4.

Superconductivity in the cuprates is found to be intertwined with charge and spin density waves. Determining the interactions between the different types of order is crucial for understanding these important materials. Here, we elucidate the role of the charge density wave (CDW) in the prototypical cuprate La1.885Sr0.115CuO4, by studying the effects of large magnetic fields (H) up to 24 Tesla. At low temperatures (T), the observed CDW peaks reveal two distinct regions in the material: a majority phase with short-range CDW coexisting with superconductivity, and a minority phase with longer-range CDW coexisting with static spin density wave (SDW). With increasing magnetic field, the CDW first grows smoothly in a manner similar to the SDW. However, at high fields we discover a sudden increase in the CDW amplitude upon entering the vortex-liquid state. Our results signify strong coupling of the CDW to mobile superconducting vortices and link enhanced CDW amplitude with local superconducting pairing across the H - T phase diagram.

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis.

BACKGROUND: First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival. PATIENTS AND METHODS: Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed. RESULTS: In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population. CONCLUSION: Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.

Enhanced charge density wave coherence in a light-quenched, high-temperature superconductor.

Superconductivity and charge density waves (CDWs) are competitive, yet coexisting, orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning their interaction on its natural length and time scale is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBa2Cu3O6+x after the quench of superconductivity by an infrared laser pulse. We observe a nonthermal response of the CDW order characterized by a near doubling of the correlation length within ≈1 picosecond of the superconducting quench. Our results are consistent with a model in which the interaction between superconductivity and CDWs manifests inhomogeneously through disruption of spatial coherence, with superconductivity playing the dominant role in stabilizing CDW topological defects, such as discommensurations.

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.

BACKGROUND: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation. METHODS: Patients with stage IV/recurrent NSCLC were randomized 1 : 1 : 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan. RESULTS: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified. CONCLUSIONS: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these data support the use of nivolumab plus ipilimumab as first-line treatment of Asian patients with advanced NSCLC.

Nivolumab with carboplatin, paclitaxel, and bevacizumab for first-line treatment of advanced nonsquamous non-small-cell lung cancer.

BACKGROUND: This international, randomized, double-blind phase III study (ONO-4538-52/TASUKI-52) evaluated nivolumab with bevacizumab and cytotoxic chemotherapy as first-line treatment for nonsquamous non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between June 2017 and July 2019, this study enrolled treatment-naïve patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations. They were randomly assigned in a 1 : 1 ratio to receive nivolumab or placebo in combination with carboplatin, paclitaxel, and bevacizumab every 3 weeks for up to six cycles, followed by nivolumab/placebo with bevacizumab until progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by an independent radiology review committee (IRRC). RESULTS: Overall, 550 patients from Japan, Korea, and Taiwan were randomized; of these patients, 273 and 275 received the nivolumab and placebo combinations, respectively. In the present preplanned interim analysis with a median follow up of 13.7 months, the IRRC-assessed median PFS was significantly longer in the nivolumab arm than in the placebo arm (12.1 versus 8.1 months; hazard ratio 0.56; 96.4% confidence interval 0.43-0.71; P < 0.0001). The PFS benefit was observed across all patients with any programmed death-ligand 1 (PD-L1) expression levels including PD-L1-negative patients. The IRRC-assessed objective response rates were 61.5% and 50.5% in the nivolumab and placebo arms, respectively. The incidence of treatment-related adverse events of grade 3 or 4 was comparable between the two arms; treatment-related adverse events leading to death were observed in five and four patients in the nivolumab and placebo arms, respectively. CONCLUSION: The TASUKI-52 regimen should be considered a viable new treatment strategy for treatment-naïve patients with advanced nonsquamous NSCLC.

Two-Dimensional Superconducting Fluctuations Associated with Charge-Density-Wave Stripes in La_{1.87}Sr_{0.13}Cu_{0.99}Fe_{0.01}O_{4}.

The presence of a small concentration of in-plane Fe dopants in La_{1.87}Sr_{0.13}Cu_{0.99}Fe_{0.01}O_{4} is known to enhance stripelike spin and charge density wave (SDW and CDW) order and suppress the superconducting T_{c}. Here, we show that it also induces highly two-dimensional superconducting correlations that have been argued to be the signatures of a new form of superconducting order, the so-called pair density wave (PDW) order. In addition, using resonant soft x-ray scattering, we find that the two-dimensional superconducting fluctuation is strongly associated with the CDW stripe. In particular, the PDW signature first appears when the correlation length of the CDW stripe grows over eight times the lattice unit (∼8a). These results provide critical conditions for the formation of the PDW order.

Association of low skeletal muscle mass with the presence of advanced colorectal neoplasm: integrative analysis using three skeletal muscle mass indices.

AIM: This study aimed to evaluate an association between colorectal neoplasm (CRN) and skeletal muscle mass using three widely accepted skeletal muscle mass indices (SMIs) in a large population at average risk. METHOD: We performed a cross-sectional study using a screening colonoscopy database of 33 958 asymptomatic subjects aged 40-75 years. Appendicular skeletal muscle mass (ASM) was measured using a bioelectrical impedance analyser. ASM adjusted for height squared (ASM/ht2 ), weight (ASM/wt) and body mass index (ASM/BMI) were used as indices for muscle mass. Logistic regression models were used to evaluate the association between SMIs and CRN. RESULTS: In a multivariable-adjusted model, the risk of an advanced CRN increased linearly with decreasing quartiles for all three SMIs. The adjusted odds ratios (ORs) for advanced CRN in quartiles 1, 2 and 3 of ASM/wt compared with that in quartile 4 were 1.279, 1.196 and 1.179, respectively (Ptrend  = 0.017); for ASM/BMI, ORs were 1.307, 1.144 and 1.091, respectively (Ptrend  = 0.002); and for ASM/ht2 , ORs were 1.342, 1.169 and 1.062, respectively (Ptrend  = 0.002). The risk of distally located advanced CRN was higher in quartile 1 than in quartile 4 for all three SMIs (ASM/wt, OR = 1.356; ASM/BMI, OR = 1.383; ASM/ht2 , OR = 1.430). CONCLUSION: Our study demonstrated that low skeletal muscle mass was consistently associated with the presence of advanced CRN in a population at average risk regardless of the operational definition of the SMI, and it was particularly associated with distal advanced CRN.

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial.

BACKGROUND: The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen. PATIENTS AND METHODS: Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-LC13. RESULTS: Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3-4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm. CONCLUSIONS: In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting. CLINICAL TRIALS NUMBER: NCT02763579.

Observation of two types of charge-density-wave orders in superconducting La2-xSrxCuO4.

The discovery of charge- and spin-density-wave (CDW/SDW) orders in superconducting cuprates has altered our perspective on the nature of high-temperature superconductivity (SC). However, it has proven difficult to fully elucidate the relationship between the density wave orders and SC. Here, using resonant soft X-ray scattering, we study the archetypal cuprate La2-xSrxCuO4 (LSCO) over a broad doping range. We reveal the existence of two types of CDW orders in LSCO, namely CDW stripe order and CDW short-range order (SRO). While the CDW-SRO is suppressed by SC, it is partially transformed into the CDW stripe order with developing SDW stripe order near the superconducting Tc. These findings indicate that the stripe orders and SC are inhomogeneously distributed in the superconducting CuO2 planes of LSCO. This further suggests a new perspective on the putative pair-density-wave order that coexists with SC, SDW, and CDW orders.

Oligonol prevented the relapse of dextran sulfate sodium-ulcerative colitis through enhancing NRF2-mediated antioxidative defense mechanism.

Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P < 0.05). Oligonol pretreatment significantly decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) as well as nuclear factor-κB (NF-κB), c-Fos, and c-Jun in affected colon tissues, but the expression of heme oxygenase-1 (HO-1) and NADH: quinone oxidoreductase-1(NQO-1) as well as total antioxidant concentration (P < 0.005) was significantly increased with oligonol. A relapse model established with repeated DSS administration led to high mortality. However, oligonol significantly ameliorated exacerbations of colitis, while sulfasalazine did not (P < 0.01). Significantly decreased expressions of cyclooxygenase-2 (COX-2), TNF-α, and macrophages inhibition were relapse preventing actions of oligonal, but significant action of oligonol relevant to relapse prevention was either significantly increased expressions of NQO-1 or significantly preserved mucin (P < 0.05). Concerted anti-inflammatory, antioxidative, and host defense enhancing actions of oligonol can be applied during maintenance therapy of IBD to prevent relapse of IBD.

Erythrocyte sedimentation rate measured using microhemagglutination is not elevated in monoclonal gammopathy compared with other diseases.

BACKGROUND: The erythrocyte sedimentation rate (ESR) as measured using the Westergren method is extremely elevated in patients with monoclonal gammopathy (MG) owing to the abundance of positively charged paraproteins. However, it has not been determined if the ESR is likewise high in patients with MG when measured using alternate ESR methods. METHODS: The ESR was measured using both the modified Westergren and microhemagglutination method (TEST1) in 36 patients with MG and in 159 individuals with other diseases. RESULTS: Erythrocyte sedimentation rates measured by the Westergren vs microhemagglutination methods showed substantial, but not remarkably high correlation. ESR measured using the Westergren method was higher in MG than in non-MG patients; however, ESR measured using microhemagglutination was not different in the 2 groups, resulting in a larger ΔESR (microhemagglutination ESR-Westergren ESR) in MG patients. When considered as continuous variables, none of the tested interfering plasma proteins (C-reactive protein, globulin, or fibrinogen) showed substantial correlations with Westergren or microhemagglutination ESRs. MG and low hematocrit were the only factors independently associated with ΔESR on multivariate analysis. CONCLUSION: We demonstrated, for the first time, that the ESR as measured by microhemagglutination is not elevated in patients with MG compared with those without. The ESR does not correlate with a particular plasma protein, showing that its measurement is multifactorial. The presence of MG is an independent factor for ΔESR.

A computational simulation study to determine the biomechanical influence of posterior condylar offset and tibial slope in cruciate retaining total knee arthroplasty.

OBJECTIVES: Posterior condylar offset (PCO) and posterior tibial slope (PTS) are critical factors in total knee arthroplasty (TKA). A computational simulation was performed to evaluate the biomechanical effect of PCO and PTS on cruciate retaining TKA. METHODS: We generated a subject-specific computational model followed by the development of ± 1 mm, ± 2 mm and ± 3 mm PCO models in the posterior direction, and -3°, 0°, 3° and 6° PTS models with each of the PCO models. Using a validated finite element (FE) model, we investigated the influence of the changes in PCO and PTS on the contact stress in the patellar button and the forces on the posterior cruciate ligament (PCL), patellar tendon and quadriceps muscles under the deep knee-bend loading conditions. RESULTS: Contact stress on the patellar button increased and decreased as PCO translated to the anterior and posterior directions, respectively. In addition, contact stress on the patellar button decreased as PTS increased. These trends were consistent in the FE models with altered PCO. Higher quadriceps muscle and patellar tendon force are required as PCO translated in the anterior direction with an equivalent flexion angle. However, as PTS increased, quadriceps muscle and patellar tendon force reduced in each PCO condition. The forces exerted on the PCL increased as PCO translated to the posterior direction and decreased as PTS increased. CONCLUSION: The change in PCO alternatively provided positive and negative biomechanical effects, but it led to a reduction in a negative biomechanical effect as PTS increased.Cite this article: K-T. Kang, Y-G. Koh, J. Son, O-R. Kwon, J-S. Lee, S. K. Kwon. A computational simulation study to determine the biomechanical influence of posterior condylar offset and tibial slope in cruciate retaining total knee arthroplasty. Bone Joint Res 2018;7:69-78. DOI: 10.1302/2046-3758.71.BJR-2017-0143.R1.

Changes in anti-müllerian hormone levels as a biomarker for ovarian reserve after ultrasound-guided high-intensity focused ultrasound treatment of adenomyosis and uterine fibroid.

OBJECTIVE: To assess the changes in antimüllerian hormone (AMH) levels after ablation for symptomatic uterine fibroids and adenomyosis using ultrasound-guided high-intensity focused ultrasound (USgHIFU). DESIGN: A prospective study. SETTING: Gynaecological department in multiple hospitals in South Korea. POPULATION: Patients with uterus fibroids and adenomyosis. METHODS: Seventy-nine women with symptomatic uterine fibroids and adenomyosis who met the inclusion criteria were enrolled in our study between January 2014 and December 2014. All patients underwent USgHIFU ablations. Each patient was examined before and after treatment, and at 6 and 12 months after treatment by T2-weighted MRI imaging (T2WI) and T1-weighted MRI imaging (T1WI) with gadolinium injection. Symptom severity scores (SSS), Uterine Fibroid Symptom Quality of Life (UFS-QOL) questionnaire subscales, and reductions of treated volume were assessed. AMH levels before and 6 months after HIFU ablation were compared to determine whether USgHIFU ablation affected ovarian reserve. MAIN OUTCOME MEASURES: HIFU treatment did not affect the ovarian function. RESULTS: HIFU treatment time (mean ± standard deviation), HIFU ablation time, and treatment energy were 73.5 ± 25.6 minutes, 9994.7 ± 386.8 seconds, and 364 713.8 ± 156 350.7 Joules, respectively. AMH levels before and 6 months after HIFU ablation were 2.11 ± 2.66 and 1.84 ± 2.57 µg/l, respectively. There was no significant difference in AMH level between the two time points (P > 0.05). CONCLUSIONS: USgHIFU ablation for uterine fibroid and adenomyosis was effective without affecting ovarian reserve. TWEETABLE ABSTRACT: HIFU ablation is a safe and effective treatment for patients with uterine fibroids and adenomyosis that does not affect ovarian function.

Femtosecond electron-phonon lock-in by photoemission and x-ray free-electron laser.

The interactions that lead to the emergence of superconductivity in iron-based materials remain a subject of debate. It has been suggested that electron-electron correlations enhance electron-phonon coupling in iron selenide (FeSe) and related pnictides, but direct experimental verification has been lacking. Here we show that the electron-phonon coupling strength in FeSe can be quantified by combining two time-domain experiments into a "coherent lock-in" measurement in the terahertz regime. X-ray diffraction tracks the light-induced femtosecond coherent lattice motion at a single phonon frequency, and photoemission monitors the subsequent coherent changes in the electronic band structure. Comparison with theory reveals a strong enhancement of the coupling strength in FeSe owing to correlation effects. Given that the electron-phonon coupling affects superconductivity exponentially, this enhancement highlights the importance of the cooperative interplay between electron-electron and electron-phonon interactions.

Comparison of the characteristics of Mycobacterium tuberculosis isolates from sputum and lung lesions in chronic tuberculosis patients.

Mycobacterium tuberculosis (Mtb) in sputum originates from lung cavities in tuberculosis (TB) patients. But drug susceptibility testing (DST) of sputum Mtb can not be conducted the same as in the lung because mutagenesis of bacilli may be happening in the lung during treatment and result in the possibility of the presence of heterogeneous drug-resistant subpopulations in the different lung lesions. This could be one of the reasons for low cure rates for multi-drug resistant (MDR)-TB. We studied the resected lungs of nine surgery patients with chronic TB. The isolates isolated from the sputum and different lung lesions of each patient were tested for phenotypic DST and genotyped using restriction fragment length polymorphism (RFLP) typing method. Genetic analysis to resistance to first and second line drugs was also performed. Five of nine patients were MDR-TB and three XDR-TB. DST results for ten anti-TB drugs were in accordance among different lung lesions in eight patients. However, only three of these eight patients showed the concordance of DST with sputum. Even though the isolates were heteroresistant, genotyping them by RFLP showed the clonal population in each individual patient. Six of eight followed-up patients achieved successful cure. In conclusion, the heteroresistance between sputum and lung lesions and a clonal population without mixed infection might provide useful information in establishing treatment regimen and surgery decision for MDR- and XDR-TB.

The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in cartilage damage.

OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats. METHODS: Rat OA was induced by performing meniscectomy surgery while cartilage samples were collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were determined by using enzyme-linked immunosorbent assay, while other proteins were assessed by using Western blot RESULTS: In the time course of the study, nitric oxide was increased seven and 14 days after OA induction. Pro-inflammatory cytokines including tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 were decreased. L-NG-Nitroarginine methyl ester (L-NAME, a non-specific nitric oxide synthase inhibitor) significantly decreased cartilage nitric oxide and blocked immune suppression. Further, L-NAME decreased Matrix metalloproteinase (MMPs) and increased tissue inhibitor of metalloproteinase (TIMP) expression in meniscectomised rats. CONCLUSION: Nitric oxide-dependent innate immune suppression protects cartilage from damage in the early stages of OA initiation in rats.Cite this article: C-C. Hsu, C-L. Lin, I-M. Jou, P-H. Wang, J-S. Lee. The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in ca rtilage da mage. Bone Joint Res 2017;6:253-258. DOI: 10.1302/2046-3758.64.BJJ-2016-0161.R1.

Three-dimensional analysis of mandibular condyle position in patients with deviated mandibular prognathism.

The purpose of this study was to evaluate the bilateral difference in condyle position in patients with deviated mandibular prognathism. Patients with asymmetrical (n=28) and symmetrical mandibular prognathism (n=23) were compared using the three-dimensional (3D) reformatted image from cone beam computed tomography. Significant positional differences in the condyle and subcondyle region (sigmoid notch) were found between the deviated and contralateral sides in the group with asymmetrical mandibular prognathism, but not in the control group. The lateral condyle was more laterally and inferiorly positioned on the contralateral side than on the deviated side (P<0.05). The sigmoid notch was more laterally, superiorly, and posteriorly positioned on the deviated side (P<0.01). Interestingly, condyle width and height on the deviated side was narrower and shorter than on the contralateral side and in the control group. Menton deviation was closely correlated with the bilateral difference in condyle height and 3D position of the sigmoid notch (P<0.01). The degree of asymmetry was more highly correlated with condyle height than with the spatial orientation of the condyle head. The results demonstrated that mandibular prognathism with asymmetry is associated with bilateral differences in 3D morphology and orientation of the condyle. Therefore, clinicians should consider these variations during surgical planning.

Targeting KRas-dependent tumour growth, circulating tumour cells and metastasis in vivo by clinically significant miR-193a-3p.

KRas is mutated in a significant number of human cancers and so there is an urgent therapeutic need to target KRas signalling. To target KRas in lung cancers we used a systems approach of integrating a genome-wide miRNA screen with patient-derived phospho-proteomic signatures of the KRas downstream pathway, and identified miR-193a-3p, which directly targets KRas. Unique aspects of miR-193a-3p biology include two functionally independent target sites in the KRas 3'UTR and clinically significant correlation between miR-193a-3p and KRas expression in patients. Rescue experiments with mutated KRas 3'UTR showed very significantly that the anti-tumour effect of miR-193a-3p is via specific direct targeting of KRas and not due to other targets. Ex vivo and in vivo studies utilizing nanoliposome packaged miR-193a-3p demonstrated significant inhibition of tumour growth, circulating tumour cell viability and decreased metastasis. These studies show the broader applicability of using miR-193a-3p as a therapeutic agent to target KRas-mutant cancer.

Ideal charge-density-wave order in the high-field state of superconducting YBCO.

The existence of charge-density-wave (CDW) correlations in cuprate superconductors has now been established. However, the nature of the CDW ground state has remained uncertain because disorder and the presence of superconductivity typically limit the CDW correlation lengths to only a dozen unit cells or less. Here we explore the field-induced 3D CDW correlations in extremely pure detwinned crystals of YBa2Cu3O2 (YBCO) ortho-II and ortho-VIII at magnetic fields in excess of the resistive upper critical field ([Formula: see text]) where superconductivity is heavily suppressed. We observe that the 3D CDW is unidirectional and possesses a long in-plane correlation length as well as significant correlations between neighboring CuO2 planes. It is significant that we observe only a single sharply defined transition at a critical field proportional to [Formula: see text], given that the field range used in this investigation overlaps with other high-field experiments including quantum oscillation measurements. The correlation volume is at least two to three orders of magnitude larger than that of the zero-field CDW. This is by far the largest CDW correlation volume observed in any cuprate crystal and so is presumably representative of the high-field ground state of an "ideal" disorder-free cuprate.