Efficient Spin-to-Charge Conversion via Altermagnetic Spin Splitting Effect in Antiferromagnet RuO_{2}.

The relativistic spin Hall effect and inverse spin Hall effect enable the efficient generation and detection of spin current. Recently, a nonrelativistic altermagnetic spin splitting effect (ASSE) has been theoretically and experimentally reported to generate time-reversal-odd spin current with controllable spin polarization in antiferromagnet RuO_{2}. The inverse effect, electrical detection of spin current via ASSE, still remains elusive. Here we show the spin-to-charge conversion stemming from ASSE in RuO_{2} by the spin Seebeck effect measurements. Unconventionally, the spin Seebeck voltage can be detected even when the injected spin current is polarized along the directions of either the voltage channel or the thermal gradient, indicating the successful conversion of x- and z-spin polarizations into the charge current. The crystal axes-dependent conversion efficiency further demonstrates that the nontrivial spin-to-charge conversion in RuO_{2} is ascribed to ASSE, which is distinct from the magnetic or antiferromagnetic inverse spin Hall effects. Our finding not only advances the emerging research landscape of altermagnetism, but also provides a promising pathway for the spin detection.

Semi-automatic artifact quantification in thermal ablation probe and algorithms for the evaluation of metal artifact reduction.

OBJECTIVES: To compare metal artifacts and evaluation of metal artifact reduction algorithms during probe positioning in computed tomography (CT)-guided microwave ablation (MWA), cryoablation (CRYO), and radiofrequency ablation (RFA). MATERIALS AND METHODS: Using CT guidance, individual MWA, CRYO, and RFA ablation probes were placed into the livers of 15 pigs. CT imaging was then performed to determine the probe's position within the test subject's liver. Filtered back projection (B30f) and iterative reconstructions (I30-1) were both used with and without dedicated iterative metal artifact reduction (iMAR) to generate images from the initial data sets. Semi-automatic segmentation-based quantitative evaluation was conducted to estimate artifact percentage within the liver, while qualitative evaluation of metal artifact extent and overall image quality was performed by two observers using a 5-point Likert scale: 1-none, 2-mild, 3-moderate, 4-severe, 5-non-diagnostic. RESULTS: Among MWA, RFA, and CRYO, compared with non-iMAR in B30f reconstruction, the largest extent of artifact volume percentages were observed for CRYO (11.5-17.9%), followed by MWA (4.7-6.6%) and lastly in RFA (5.5-6.2%). iMAR significantly reduces metal artifacts for CRYO and MWA quantitatively (p = 0.0020; p = 0.0036, respectively) and qualitatively (p = 0.0001, p = 0.0005), but not for RFA. No significant reduction in metal artifact percentage was seen after applying iterative reconstructions (p > 0.05). Noise, contrast-to-noise-ratio, or overall image quality did not differ between probe types, irrespective of the application of iterative reconstruction and iMAR. CONCLUSION: A dedicated metal artifact algorithm may decrease metal artifacts and improves image quality significantly for MWA and CRYO probes. Their application alongside with dedicated metal artifact algorithm should be considered during CT-guided positioning.

[Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial].

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

[Clinical features of IgG4-related lung disease].

Objective: To explore the clinical features of IgG4-related lung disease. Methods: The clinical data of 60 patients diagnosed with IgG4-related lung disease in Peking University People's Hospital from February 2012 to May 2021 were retrospectively collected. Analysis was made to explore the features of clinical manifestation, laboratory, imaging, prognosis and other characteristics of the disease. Results: A total of 60 patients were included, with 40 males, age of (58.2±12.9) years, an age of onset of (57.1±13.2) years, and 31.7% (19 cases) of the patients had a history of allergic disease. 36.7% (22 cases) of the patients had respiratory symptoms during the disease. 94.6% (53/56) of patients had serum IgG4>1.35 g/L, 24.1% (14/58) of patients had increased eosinophils, 79.2% (38/48) of patients had increased IgE level, and 53.7% (29/54) of patients had decreased C3 or C4. Common imaging findings included nodular changes (38 cases, 63.3%), mediastinal and/or hilar lymphadenopathy (34 cases, 56.7%), and ground glass opacities (31 cases, 51.7%). Fifty-three cases (88.3%) showed two or more imaging changes. The pathological examination of the patient was mainly characterized by lymphoplasmacytic infiltration and fibrosis, with only one case of phlebitis obliterans. Compared with the asymptomatic group (38 cases), patients with respiratory symptoms (22 cases) showed higher level of serum total IgG and eosinophils (43.2 vs 17.8 g/L, 0.30×109/L vs 0.14×109/L, P<0.05), lower proportion of allergic diseases, and higher proportion of consolidation shadows on chest CT (P<0.05). There were no significant differences in serum IgG4, IgE, complement levels, and imaging outcomes after treatment between the two groups (P>0.05). Conclusions: The clinical manifestations of IgG4-related lung disease are atypical, and asymptomatic patients account for a high proportion. The imaging of the disease is highly heterogeneous, and patients are prone to show coexisted multiple imaging changes. The main clinical features and imaging outcomes of patients with and without respiratory symptoms are not significantly different.

[Clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis].

Objective: To present efficacy of clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis (DLS). Methods: A case series study. Clinical data of 61 cases (8 males, 53 females) who underwent posterior correction surgery for DLS from January 2019 to January 2021 were retrospectively analyzed. The mean age was (71.7±6.2) years (ranged 60-82 years). According to the direction of C7 plumb line (C7PL) deviated from central sacral vertical line (CSVL) and orientation of L4 coronal tilt, the author determined which one was the crucial curve. If C7PL deviated from CSVL in the same direction as concave side of the thoracolumbar curve and L4 coronally tilts opposite direction of C7PL deviates from CSVL, then the crucial curve was thoracolumbar curve (type 1). On the contrary, if C7PL deviated from CSVL in the same direction as concave side of the lumbosacral curve and L4 coronally tilts consist with direction of C7PL deviates from CSVL, then the crucial curve was lumbosacral curve (type 2). According to absolute value of coronal balance distance (|CBD|), each type of patients was divided into two groups, respectively, namely coronal balance (CB) (|CBD|≤3 cm) and coronal imbalance (CIB) (|CBD|>3 cm). Changes of Cobb angles of thoracolumbar curve and lumbosacral curve and CBD were recorded and analyzed. Results: The rate of preoperative CIB was 55.7% (34/61) in all the patients. Of the patients, 23 cases were classified as type 1 and 38 cases as type 2. The rate of preoperative CIB was 34.8% (8/23) in type 1 patients and 68.4% (26/38) in type 2. The rate of postoperative CIB was 27.9% (17/61) in all the patients, with 13.0% (3/23) in type 1 and 36.8% (14/38) in type 2. The |CBD| of CB group in type 1 patients decreased from (2.6±1.4) cm before the operation to (1.5±1.0) cm after (P=0.015); and the correction rate of thoracolumbar curve (68.8%±18.4%) was significantly higher than that of lumbosacral curve (34.5%±23.9%) (P=0.005). The |CBD| of CB group in type 2 patients decreased from (2.6±3.0) cm before the operation to (1.6±1.2) cm after (P=0.027); the correction rate of lumbosacral curve (71.3%±18.6%) was higher than that of thoracolumbar curve (57.3%±21.1%), but the difference was not statistically significant (P=0.546). There was no significant difference in |CBD| of CIB group in type 2 patients before and after the operation (P=0.222); the correction rate of lumbosacral curve (38.3%±14.8%) was significantly lower than that of thoracolumbar curve (53.6%±16.0%) (P=0.001). There was a correlation between the change of CBD (3.8±1.5) cm and the difference in correction rate between thoracolumbar and lumbosacral curve (32.3%±19.6%) in CB group in type 1 patients after surgery (r=0.904, P<0.001). There was a correlation between the change of CBD (1.9±2.2) cm and the difference in correction rate between lumbosacral and thoracolumbar curve (14.0%±26.2%) in CB group in type 2 patients after surgery (r=0.960, P<0.001). Conclusion: Clinical application of a classification based on crucial curvature of coronal imbalance in DLS is satisfactory, and its combination with matching correction can effectively prevent the occurrence of coronal imbalance after spinal correction surgery.

Joint synovial macrophages as a potential target for intra-articular treatment of osteoarthritis-related pain.

Osteoarthritis is the most common form of joint disease and is one of the leading causes of chronic pain. Given the multi-factorial nature, numerous efforts have been made to clarify the multiple factors impacting the pain symptoms and joint pathology, including synovial macrophages in particular. Accumulating evidence from studies involving human participants and experimental animal models suggests that accumulating macrophages in synovial tissue are implicated in peripherally mediated pain sensitization of affected joints in osteoarthritis. Crosstalk between synovial macrophages and the innervating primary nociceptive neurons is thought to contribute to this facilitated pain processing by the peripheral nervous system. Due to high plasticity and complexity of synovial macrophages in the joint, safe therapies targeting single cells or molecules are currently lacking. Using advanced technologies (such as single-cell RNA sequencing and mass cytometry), studies have shown that diverse subpopulations of synovial macrophages exist in the distinct synovial microenvironments of specific osteoarthritis subtypes. Considerable progress has been made in delineating the molecular mechanisms of various subsets of synovial macrophages in the development of osteoarthritis. To develop a novel intra-articular treatment paradigm targeting synovial macrophages, we have summarized in this review the recent advances in identifying the functional consequences of synovial macrophage sub-populations and understanding of the molecular mechanisms driving macrophage-mediated remodeling.

Knee symptom but not radiographic knee osteoarthritis increases the risk of falls and fractures: results from the Osteoarthritis Initiative.

OBJECTIVE: To describe the effect of knee symptoms and radiographic osteoarthritis (ROA) on the risk of falls, recurrent falls, and fractures. DESIGN: Participants from the Osteoarthritis Initiative were classified as having 'no', 'unilateral' or 'bilateral' knee symptoms (≥19 on a 0-96 Western Ontario and McMaster Universities Osteoarthritis Index) and ROA (Kellgren-Lawrence grade ≥2) for each visit. Self-reported falls and fractures in the past 12 months were extracted at baseline and follow-up visits until month 96. Recurrent falls were defined as having ≥2 falls in the past 12 months. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using mixed-effects complementary log-log regression. RESULTS: Of 4465 participants, 3145 (70%), 1681 (38%), and 806 (18%) experienced at least one fall, recurrent fall, and fracture, respectively, over 96 months. Compared to participants without symptomatic knee, unilateral and bilateral knee symptoms were associated with a 17% increased risk of falls and a 36-46% increased risk of recurrent falls, and bilateral knee symptoms increased the risk of fractures (HR 1.45, 95%CI 1.17 to 1.81). Compared to participants with no ROA in either knee, bilateral ROA was associated with a reduced risk of falls (HR 0.87, 95%CI 0.77 to 0.99) and fractures (HR 0.78, 95%CI 0.64 to 0.96). No statistically significant interactions between knee symptoms and ROA were observed. CONCLUSIONS: This large population-based study showed that knee symptoms but not ROA increased the risk of falls, recurrent falls, and fractures, and that adults with bilateral ROA may have a lower risk of falls and fractures.

Observation of Spin Splitting Torque in a Collinear Antiferromagnet RuO_{2}.

Current-induced spin torques provide efficient data writing approaches for magnetic memories. Recently, the spin splitting torque (SST) was theoretically predicted, which combines advantages of conventional spin transfer torque (STT) and spin-orbit torque (SOT) as well as enables controllable spin polarization. Here we provide the experimental evidence of SST in collinear antiferromagnet RuO_{2} films. The spin current direction is found to be correlated to the crystal orientation of RuO_{2} and the spin polarization direction is dependent on (parallel to) the Néel vector. These features are quite characteristic for the predicted SST. Our finding not only presents a new member for the spin torques besides traditional STT and SOT, but also proposes a promising spin source RuO_{2} for spintronics.

[Quality of life and risk factors in patients with herpes zoster].

Objective: To evaluate the quality of life and influencing factors of patients with herpes zoster (HZ) seen in hospitals. Methods: Based on Zoster Brief Pain Inventory (ZBPI) and Five-level EuroQol Five-dimensional Questionnaire (EQ-5D-5L), a cross-sectional survey was conducted to evaluate the pain severity and quality of life of 332 HZ cases seen in 22 hospitals of Lu'an City (Anhui Province), Zibo City (Shandong Province) and Tongchuan City (Shaanxi Province) from October to December 2021. The censored least absolute deviations (CLAD) model was used to analyze the related factors affecting the changes of patients' health utility values. Results: The 45.5% of 332 HZ cases were male. The median (Q1,Q3) age was 59 (50, 68) years. 59.64% of them assessed by ZBPI had moderate to severe pain in the past 24 hours (worst pain score≥5), and that of PHN cases was 84.8%(39/46). 77.7% (258/332), 77.4% (257/332) and 74.1% (246/332) of all patients reported that pain interfered with sleep, mood and general activities, respectively. Aging [ß40-49y (95%CI)=-0.11 (-0.15, -0.08); ß50-59y (95%CI)=-0.03 (-0.05, 0.00); ß60-69y (95%CI)=-0.09 (-0.12, -0.06); ß70-90y(95%CI)=-0.16 (-0.19, -0.12)], working status (unemployed) [ßfarmer (95%CI)=0.15 (0.13, 0.18); ßretirees(95%CI)=0.21 (0.18, 0.24); ßemployee (95%CI)=0.13 (0.10, 0.16) ], complications[ßPHN (95%CI)=-0.08 (-0.13, -0.04); ßother complications (95%CI)=-0.12 (-0.15, -0.08)], within 30 days after onset [ß(95%CI)=-0.01 (-0.03, 0.01)] and treatment [ßother complications (95%CI)=-0.09 (-0.11, -0.06)] were related factors for the decline of health utility value (all P values <0.05). Conclusions: More than half of the patients with HZ had moderate to severe pain in the past 24 hours, which had a serious negative impact on the physical and mental health of the patients. Elderly patients, acute patients and patients with complications had lower health utility values and worse health status. We suggest that eligible people be vaccinated with HZ vaccine as soon as possible.

Elevated expression of CDT1 in childhood acute lymphoblastic leukemia promotes cell proliferation, invasion and migration through activation of EMT.

Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematopoietic system. At present, the mechanism and pathogenesis of ALL have not been fully clarified. This study aimed to illustrate the roles of Cdc10 protein-dependent transcript 1 (CDT1) in ALL. Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) was performed to examine serum levels of CDT1 in childhood ALL patients and healthy volunteers. The interaction between CDT1 expression and prognosis of childhood ALL was analyzed. Meanwhile, expressions of CDT1 in ALL cell lines were determined. Furthermore, CDT1 knockdown model was constructed in ALL cells, and Cell Counting Kit-8 (CCK-8), and Transwell assays were conducted to analyze the effect of CDT1 on the biological functions of ALL cells. Potential mechanism was further explored through detecting the expressions of Epithelial-to-mesenchymal transition (EMT)-related genes. RT-qPCR results indicated that serum level of CDT1 in childhood ALL patients was remarkably higher than that of healthy volunteers. Childhood ALL patients with high expression of CDT1 had lower overall survival rate compared with those expressing low expression of CDT1. CDT1 knockdown remarkably decreased the proliferation and metastasis abilities of pediatric ALL cells. Results of western blot showed that CDT1 might contribute to the malignant progression of childhood ALL via activating EMT. The findings showed that elevated CDT1 facilitated ALL metastasis by promoting EMT, suggesting that CDT1 played a pivotal role in ALL metastasis and may serve as a novel prognostic biomarker and therapeutic target.

Radiological management of postoperative lymphorrhea.

PURPOSE: Postoperative lymphorrhea can occur after different surgical procedures and may prolong the hospital stay due to the need for specific treatment. In this work, the therapeutic significance of the radiological management of postoperative lymphorrhea was assessed and illustrated. METHOD: A standardized search of the literature was performed in PubMed applying the Medical Subject Headings (MeSH) term "lymphangiography." For the review, the inclusion criterion was "studies with original data on Lipiodol-based Conventional Lymphangiography (CL) with subsequent Percutaneous Lymphatic Intervention (PLI)." Different exclusion criteria were defined (e.g., studies with <15 patients). The collected data comprised of clinical background and indications, procedural aspects and types of PLI, and outcomes. In the form of a pictorial essay, each author illustrated a clinical case with CL and/or PLI. RESULTS: Seven studies (corresponding to evidence level 4 [Oxford Centre for Evidence-Based Medicine]) accounting for 196 patients were included in the synthesis and analysis of data. Preceding surgery resulting in postoperative lymphorrhea included different surgical procedures such as extended oncologic surgery or vascular surgery. Central (e.g., chylothorax) and peripheral (e.g., lymphocele) types of postoperative lymphorrhea with a drainage volume of 100-4000 ml/day underwent CL with subsequent PLI. The intervals between "preceding surgery and CL" and between "CL and PLI" were 2-330 days and 0-5 days, respectively. CL was performed before PLI to visualize the lymphatic pathology (e.g., leakage point or inflow lymph ducts), applying fluoroscopy, radiography, and/or computed tomography (CT). In total, seven different types of PLI were identified: (1) thoracic duct (or thoracic inflow lymph duct) embolization, (2) thoracic duct (or thoracic inflow lymph duct) maceration, (3) leakage point direct embolization, (4) inflow lymph node interstitial embolization, (5) inflow lymph duct (other than thoracic) embolization, (6) inflow lymph duct (other than thoracic) maceration, and (7) transvenous retrograde lymph duct embolization. CL-associated and PLI-associated technical success rates were 97-100% and 89-100%, respectively. The clinical success rate of CL and PLI was 73-95%. CL-associated and PLI-associated major complication rates were 0-3% and 0-5%, respectively. The combined CL- and PLI-associated 30-day mortality rate was 0%, and the overall mortality rate was 3% (corresponding to six patients). In the pictorial essay, the spectrum of CL and/or PLI was illustrated. CONCLUSION: The radiological management of postoperative lymphorrhea is feasible, safe, and effective. Standardized radiological treatments embedded in an interdisciplinary concept are a step towards improving outcomes.

[Efficacy and safety of prophylactic intravenous administration of tranexamic acid in abdominal aorta balloon-assisted pelvic tumor surgery].

Objective: To investigate the efficacy and safety of prophylactic intravenous (IV) administration of tranexamic acid (TXA) in abdominal aorta balloon-assisted pelvic tumor surgery. Methods: The data of patients who underwent abdominal aorta balloon-assisted pelvic tumor surgery in Peking University People's Hospital from January 1, 2015 to December 31, 2019 were retrospectively collected. According to whether receiving the prophylactic use of TXA, the patients were divided into two groups: TXA group and control group. After propensity score matching based on age, gender and surgeon, 51 patients in TXA group and 51 patients in control group were allocated. The baseline, intraoperative and postoperative clinical data of the two groups were compared to explore the efficacy and safety of TXA. Results: A total of 525 cases undergoing abdominal aorta balloon-assisted pelvic surgery were enrolled from 2015 to 2019, of which 51 cases received prophylactic use of TXA, with a utilization rate of 9.7%. There were no significant differences in age [(40.7±15.1) years vs (38.2±14.5) years, P=0.393], gender (male: 51.0% vs 49.0%, P=0.843), body weight, body mass index (BMI), complications, American Society of Anesthesiologists (ASA) classification, hemoglobin, hemocrit (Hct), platelet, coagulation function-related indexes and tumor pathological types between the two groups (all P>0.05). Likewise, there were no significant differences in operation time, anesthesia time, cumulative time of balloon occlusion, intraoperative blood loss, intravenous fluid volume and blood transfusion volume between the two groups (all P>0.05). Additionally, there were no significant differences in postoperative ICU admission rate and length of hospital stay between the two groups (all P>0.05), and no venous thromboembolism (VTE) or death was reported. Compared with the control group, the rate of blood transfusion at 24 hours after operation in the TXA group was lower (41.2% vs 70.6%, P=0.003). The level of fibrinogen degradation products was lower [10.4 (6.1, 22.6) mg/L vs 13.2 (7.0, 24.7) mg/L], but the difference was not statistically significant (P=0.326). Conclusions: Prophylactic IV use of TXA does not reduce intraoperative bleeding in abdominal aorta balloon-assisted pelvic tumor surgery, but can decrease the rate of postoperative blood transfusion. No increased risk of postoperative TXA-related VTE was observed.

Metabolic syndrome and trajectory of knee pain in older adults.

OBJECTIVES: To examine the association of metabolic syndrome (MetS) and its components with knee pain severity trajectories. METHODS: Data from a population-based cohort study were utilised. Baseline blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) cholesterol were measured. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. Radiographic knee osteoarthritis (ROA) was assessed by X-ray. Pain severity was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain questionnaire at each time-point. Group-based trajectory modelling was used to identify pain trajectories and multi-nominal logistic regression was used for analysis. Mediation analysis was performed to assess whether body mass index (BMI)/central obesity mediated the association between MetS, its components and pain trajectories. RESULTS: Among 985 participants (Mean ± SD age: 62.9 ± 7.4, 50% female), 32% had MetS and 60% had ROA. Three pain trajectories were identified: 'Minimal pain' (52%), 'Mild pain' (33%) and 'Moderate pain' (15%). After adjustment for potential confounders, central obesity increased risk of belonging to both 'Mild pain' and 'Moderate pain' trajectories as compared to the 'Minimal pain' trajectory group, but MetS [relative risk ratio (RRR): 2.26, 95%CI 1.50-3.39], hypertriglyceridemia (RRR: 1.75, 95%CI 1.16-2.62) and low HDL (RRR: 1.67, 95%CI 1.10-2.52) were only associated with 'Moderate pain' trajectory. BMI/central obesity explained 37-70% of these associations. Results were similar in those with ROA. CONCLUSION: MetS and its components are predominantly associated with worse pain trajectories through central obesity, suggesting that the development and maintenance of worse pain trajectories may be caused by MetS.

Value of contrast-enhanced ultrasound in the diagnosis of breast US-BI-RADS 3 and 4 lesions with calcifications.

AIM: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) for Breast Imaging-Reporting and Data System for Ultrasound (US-BI-RADS) 3 and 4 lesions with calcifications. MATERIALS AND METHODS: A retrospective study of 168 breast lesions with calcifications detected on both mammography and conventional ultrasonography (US) in 152 patients were categorised as US-BI-RADS 3-4 at US between June 2009 and June 2018. CEUS scores were obtained based on a CEUS five-point scoring system. The combination of US-BI-RADS and CEUS scores created the Rerated BI-RADS (referred to as CEUS-BI-RADS). All results were compared with the histological findings. The diagnostic performances of US and CEUS-BI-RADS were compared. RESULTS: The diagnostic sensitivity, specificity, and accuracy of US were 81.8% (95% confidence interval [CI]: 71.6%, 92%), 85% (95% CI: 78.4%, 91.5%), and 83.9% (95% CI: 78.4%, 89.5%), respectively, while those for CEUS-BI-RADS were 98.2% (95% CI: 94.7%, 100%), 90.3% (95% CI: 84.8%, 95.7%), and 92.9% (95% CI: 89%, 96.8%), respectively. The diagnostic sensitivity and accuracy values of CEUS-BI-RADS greatly improved compared with those of US (p=0.003 and p=0.004, respectively). The areas under the receiver operating characteristic (ROC) curves for US and CEUS-BI-RADS were 0.888 (95% CI: 0.840, 0.936) and 0.963 (95% CI: 0.936, 0.989), respectively. The diagnostic efficacy of CEUS-BI-RADS was significantly higher than that of US alone (p=0.004). CONCLUSION: CEUS-BI-RADS significantly improves the diagnostic accuracy for breast US-BI-RADS 3 and 4 lesions with calcifications compared with US.

Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes with DNA gyrase.

A paucity of novel acting antibacterials is in development to treat the rising threat of antimicrobial resistance, particularly in Gram-negative hospital pathogens, which has led to renewed efforts in antibiotic drug discovery. Fluoroquinolones are broad-spectrum antibacterials that target DNA gyrase by stabilizing DNA-cleavage complexes, but their clinical utility has been compromised by resistance. We have identified a class of antibacterial thiophenes that target DNA gyrase with a unique mechanism of action and have activity against a range of bacterial pathogens, including strains resistant to fluoroquinolones. Although fluoroquinolones stabilize double-stranded DNA breaks, the antibacterial thiophenes stabilize gyrase-mediated DNA-cleavage complexes in either one DNA strand or both DNA strands. X-ray crystallography of DNA gyrase-DNA complexes shows the compounds binding to a protein pocket between the winged helix domain and topoisomerase-primase domain, remote from the DNA. Mutations of conserved residues around this pocket affect activity of the thiophene inhibitors, consistent with allosteric inhibition of DNA gyrase. This druggable pocket provides potentially complementary opportunities for targeting bacterial topoisomerases for antibiotic development.

Bimodal Actions of a Naphthyridone/Aminopiperidine-Based Antibacterial That Targets Gyrase and Topoisomerase IV.

Gyrase and topoisomerase IV are the targets of fluoroquinolone antibacterials. However, the rise in antimicrobial resistance has undermined the clinical use of this important drug class. Therefore, it is critical to identify new agents that maintain activity against fluoroquinolone-resistant strains. One approach is to develop non-fluoroquinolone drugs that also target gyrase and topoisomerase IV but interact differently with the enzymes. This has led to the development of the "novel bacterial topoisomerase inhibitor" (NBTI) class of antibacterials. Despite the clinical potential of NBTIs, there is a relative paucity of data describing their mechanism of action against bacterial type II topoisomerases. Consequently, we characterized the activity of GSK126, a naphthyridone/aminopiperidine-based NBTI, against a variety of Gram-positive and Gram-negative bacterial type II topoisomerases, including gyrase from Mycobacterium tuberculosis and gyrase and topoisomerase IV from Bacillus anthracis and Escherichia coli. GSK126 enhanced single-stranded DNA cleavage and suppressed double-stranded cleavage mediated by these enzymes. It was also a potent inhibitor of gyrase-catalyzed DNA supercoiling and topoisomerase IV-catalyzed decatenation. Thus, GSK126 displays a similar bimodal mechanism of action across a variety of species. In contrast, GSK126 displayed a variable ability to overcome fluoroquinolone resistance mutations across these same species. Our results suggest that NBTIs elicit their antibacterial effects by two different mechanisms: inhibition of gyrase/topoisomerase IV catalytic activity or enhancement of enzyme-mediated DNA cleavage. Furthermore, the relative importance of these two mechanisms appears to differ from species to species. Therefore, we propose that the mechanistic basis for the antibacterial properties of NBTIs is bimodal in nature.

Structure-guided design of antibacterials that allosterically inhibit DNA gyrase.

A series of DNA gyrase inhibitors were designed based on the X-ray structure of a parent thiophene scaffold with the objective to improve biochemical and whole-cell antibacterial activity, while reducing cardiac ion channel activity. The binding mode and overall design hypothesis of one series was confirmed with a co-crystal structure with DNA gyrase. Although some analogs retained both biochemical activity and whole-cell antibacterial activity, we were unable to significantly improve the activity of the series and analogs retained activity against the cardiac ion channels, therefore we stopped optimization efforts.

Predictors of pain severity trajectory in older adults: a 10.7-year follow-up study.

OBJECTIVES: To identify distinct pain trajectories over 10.7 years and to examine predictors of identified pain trajectories in an older population and those with radiographic knee osteoarthritis (ROA). METHODS: 963 participants (aged 50-80 years) from a population-based cohort had baseline demographic, psychological, lifestyle and comorbidities data collected. T1-and T2-weighted magnetic resonance imaging (MRI) of the right knee was performed to measure knee structural pathology-cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis. Group-based trajectory modelling (GBTM) was applied to identify trajectories of knee pain over 10.7 years measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Three distinct pain trajectories were defined: 'Minimal pain' (n = 501, 52%), 'Mild pain' (n = 329, 34%) and 'Moderate pain' (n = 165, 14%). In multivariable analysis, having cartilage defects, BMLs and effusion-synovitis were associated with an increased risk of being in the 'Mild pain' (relative risk [RR]: 1.40 to 1.92) and 'Moderate pain' trajectory (RR: 1.72 to 2.26), compared with the 'Minimal pain' trajectory. Being obese and having more painful sites were associated with 'Mild pain' and 'Moderate pain' trajectories, while unemployment, lower education level and presence of emotional problems were associated with 'Moderate pain' trajectory group. Similar results were found for those with ROA. CONCLUSION: Distinct pain trajectories identified suggest that homogeneous subgroups exist, which might be useful for phenotypic assessment for pain management, particularly in knee osteoarthritis. Structural pathology was associated with worse pain trajectories, suggesting that peripheral stimuli are critical for the development and maintenance of pain severity. Environmental and psychological factors may exacerbate pain perception.

A randomised double-blind placebo-controlled crossover trial of HUMira (adalimumab) for erosive hand OsteoaRthritis - the HUMOR trial.

OBJECTIVE: To assess the efficacy of adalimumab in patients with erosive hand osteoarthritis (OA). METHOD: Patients >50 years old, meeting the American College of Rheumatology (ACR) criteria for hand OA, with pain >50 on 100 mm visual analogue scale (VAS), morning stiffness >30 min and ≥1 erosive joint on X-ray with synovitis present on magnetic resonance imaging (MRI) were included in a randomised double-blind placebo-controlled crossover trial. Patients were randomised to adalimumab (40 mg subcutaneous injections every other week) or identical placebo injections for 12 weeks followed by an 8-week washout and then crossed over treatment groups for another 12 weeks. The primary outcome was change in VAS hand pain over 12 weeks. Secondary outcomes included change in Australian/Canadian Hand OA Index (AUSCAN) pain, function and stiffness subscales from baseline to 4, 8 and 12 weeks, change in MRI-detected synovitis and bone marrow lesions (BMLs) from baseline to 12 weeks and change in VAS from baseline to 4 and 8 weeks. RESULTS: We recruited 51 patients and 43 were randomised to either Group 1 (N = 18, active then placebo) or Group 2 (N = 25, placebo then active). At 12 weeks there was no difference between the groups on the primary outcome measure (mean decrease in VAS pain of 3.2 mm standard deviation (SD 16.7) for adalimumab vs 0.8 mm (SD 29.6) for placebo). The adjusted treatment effect was -0.7 mm (95% confidence interval (CI) -9.3 to 8.0), P = 0.87. No statistically significant differences were found for any secondary outcomes. CONCLUSION: Adalimumab did not show any effect on pain, synovitis or BMLs in patients with erosive hand OA with MRI-detected synovitis as compared to placebo after 12 weeks. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12612000791831.

Antidamping-Torque-Induced Switching in Biaxial Antiferromagnetic Insulators.

We investigate the current-induced switching of the Néel order in NiO(001)/Pt heterostructures, which is manifested electrically via the spin Hall magnetoresistance. Significant reversible changes in the longitudinal and transverse resistances are found at room temperature for a current threshold lying in the range of 10^{7} A/cm^{2}. The order-parameter switching is ascribed to the antiferromagnetic dynamics triggered by the (current-induced) antidamping torque, which orients the Néel order towards the direction of the writing current. This is in stark contrast to the case of antiferromagnets such as Mn_{2}Au and CuMnAs, where fieldlike torques induced by the Edelstein effect drive the Néel switching, therefore resulting in an orthogonal alignment between the Néel order and the writing current. Our findings can be readily generalized to other biaxial antiferromagnets, providing broad opportunities for all-electrical writing and readout in antiferromagnetic spintronics.