In Situ Engineering Multifunctional Active Sites of Ruthenium-Nickel Alloys for pH-Universal Ampere-Level Current-Density Hydrogen Evolution.

Developing robust non-platinum electrocatalysts with multifunctional active sites for pH-universal hydrogen evolution reaction (HER) is crucial for scalable hydrogen production through electrochemical water splitting. Here ultra-small ruthenium-nickel alloy nanoparticles steadily anchored on reduced graphene oxide papers (Ru-Ni/rGOPs) as versatile electrocatalytic materials for acidic and alkaline HER are reported. These Ru-Ni alloy nanoparticles serve as pH self-adaptive electroactive species by making use of in situ surface reconstruction, where surface Ni atoms are hydroxylated to produce bifunctional active sites of Ru-Ni(OH)2 for alkaline HER, and selectively etched to form monometallic Ru active sites for acidic HER, respectively. Owing to the presence of Ru-Ni(OH)2 multi-site surface, which not only accelerates water dissociation to generate reactive hydrogen intermediates but also facilitates their recombination into hydrogen molecules, the self-supported Ru90Ni10/rGOP hybrid electrode only takes overpotential of as low as ≈106 mV to deliver current density of 1000 mA cm-2, and maintains exceptional stability for over 1000 h in 1 m KOH. While in 0.5 m H2SO4, the Ru90Ni10/rGOP hybrid electrode exhibits acidic HER catalytic behavior comparable to commercially available Pt/C catalyst due to the formation of monometallic Ru shell. These electrochemical behaviors outperform some of the best Ru-based catalysts and make it attractive alternative to Pt-based catalysts toward highly efficient HER.

Management of anastomotic biliary stricture through utilizing percutaneous transhepatic cholangioscopy.

AIM: Occurrence of anastomotic biliary stricture (AS) remains an essential issue following hepatobiliary surgeries, and percutaneous transhepatic cholangioscopy (PTCS) has great therapeutic significance in handling refractory AS for patients with altered gastrointestinal anatomy after cholangio-jejunostomy. This present study aimed to investigate feasibility of PTCS procedures in AS patients for therapeutic indications. MATERIALS AND METHODS: This study was a single-center, retrospective cohort study with a total number of 124 consecutive patients who received therapeutic PTCS due to AS. Clinical success rate, required number, and adverse events of therapeutic PTCS procedures as well as patients survival state were reviewed. RESULTS: These 124 patients previously underwent choledochojejunostomy or hepatico-jejunostomy, and there was post-surgical altered gastrointestinal anatomy. Overall, 366 therapeutic PTCS procedures were performed for these patients through applying rigid choledochoscope, and the median time of PTCS procedures was 3 (1-11). Among these patients, there were 34 cases (27.32%) accompanied by biliary strictures and 100 cases (80.65%) were also combined with biliary calculi. After therapeutic PTCS, most patients presented with relieved clinical manifestations and improved liver functions. The median time of follow-up was 26 months (2-86 months), and AS was successfully managed through PTCS procedures in 104 patients (83.87%). During the follow-up period, adverse events occurred in 81 cases (65.32%), most of which were tackled through supportive treatment. CONCLUSION: PTCS was a feasible, safe and effective therapeutic modality for refractory AS, which may be a promising alternative approach in clinical cases where the gastrointestinal anatomy was changed after cholangio-jejunostomy.

Optimizing Skim Milk Yogurt Properties: Combined Impact of Trans-glutaminase and Protein-Glutaminase.

The lack of fat in yogurt can lead to alterations in taste and whey separation, reducing consumer acceptance. In this study, the feasibility of enhancing the quality of skim milk yogurt through a combination of transglutaminase (TG) and protein-glutaminase (PG) was investigated. The combination of TG and PG resulted in simultaneous cross-linking and deamidated of casein micelles, with PG deamidation taking priority over TG cross-linking, leading to higher solubility and lower turbidity of milk proteins compared with TG alone. When 0.06 U/mL TG and 0.03 U/mL PG were added, firmness and viscosity indexes significantly increased by 38.26 and 78.59%, respectively as compared with the control. Microscopic images revealed increased cross-linking with casein and filling of cavities by smaller sub-micelles in the combination of TG and PG treatment. Furthermore, the combination of TG and PG resolved issues of rough taste and whey separation, leading to improved overall liking. This study highlights the benefits of using both enzymes in dairy production and has important implication for future research.

Recent advances in early pregnancy loss diagnosis in dairy cows: New approaches.

Early pregnancy loss is a primary cause of low reproductive rates in dairy cows, posing severe economic losses to dairy farming. The accurate diagnosis of dairy cows with early pregnancy loss allows for oestrus synchronization, shortening day open, and increasing the overall conception rate of the herd. Several techniques are available for detecting early pregnancy loss in dairy cows, including rectal ultrasound, circulating blood progesterone, and pregnancy-associated glycoproteins (PAGs). Yet, there is a need to improve on existing techniques and develop novel strategies to identify cows with early pregnancy loss accurately. This manuscript reviews the applications of rectal ultrasound, circulating blood progesterone concentration, and PAGs in the diagnosis of pregnancy loss in dairy cows. The manuscript also discusses the recent progress of new technologies, including colour Doppler ultrasound (CDUS), interferon tau-induced genes (ISGs), and exosomal miRNA in diagnosing pregnancy loss in dairy cows. This study will provide an option for producers to re-breed cows with pregnancy loss, thereby reducing the calving interval and economic costs. Meanwhile, this manuscript might also act as a reference for exploring more economical and precise diagnostic technologies for early pregnancy loss in dairy cows.

Gram-level NH3 Electrosynthesis via NOx reduction on a Cu Activated Co Electrode.

Ambient electrochemical ammonia (NH3 ) synthesis is one promising alternative to the energy-intensive Haber-Bosch route. However, the industrial requirement for the electrochemical NH3 production with amperes current densities or gram-level NH3 yield remains a grand challenge. Herein, we report the high-rate NH3 production via NO2 - reduction using the Cu activated Co electrode in a bipolar membrane (BPM) assemble electrolyser, wherein BPM maintains the ion balance and the liquid level of electrolyte. Benefited from the abundant Co sites and optimal structure, the target modified Co foam electrode delivers a current density of 2.64 A cm-2 with the Faradaic efficiency of 96.45 % and the high NH3 yield rate of 279.44 mg h-1 cm-2 in H-type cell using alkaline electrolyte. Combined with in situ experiments and theoretical calculations, we found that Cu optimizes the adsorption behavior of NO2 - and facilitates the hydrogenation steps on Co sites toward a rapid NO2 - reduction process. Importantly, this activated Co electrode affords a large NH3 production up to 4.11 g h-1 in a homemade reactor, highlighting its large-scale practical feasibility.

The Predictive Value of NGF, TMAO, SIRT1 and apoA1 in Patients With Ischemic Heart Failure.

Objective: The present study aimed to explore the predictive value and prognosis of SYNTAX score, nerve growth factor (NGF), trimethylamino oxide (TMAO), silent information regulator 1 (SIRT1), and apolipoprotein A1 (apoA1) for ischemic heart failure (IHF) patients. Methods: From January 2020 to January 2021, 87 patients diagnosed with IHF in the Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, and 42 healthy people were included and analyzed retrospectively. The 87 patients were divided into 3 subgroups according to New York Heart Association (NYHA) heart function classification, as group 1 (n=9, classes I-II heart function), group 2 (n = 7, class III heart function), and group 3 (n = 31, class IV heart function). The levels of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left atrium diameter (LAD), NGF, TMAO, SIRT1, SYNTAX score, and apoA1 were compared among these groups. Results: The SIRT1 and apoA1 of patients with classes I-II, III, and IV heart function were significantly lower than that of healthy people in the control group, while TMAO and NGF were significantly higher than those of healthy people (all P < .05). The SYNTAX score of grade I-II, grade III, and grade IV groups was significantly lower than that of the healthy group (P < .05). The two groups had no significant difference in the number of coronary artery lesions (P > .05). The SIRT1 and apoA1 of patients with classes III and IV heart function were significantly lower than that of patients with classes I -II heart function, while TMAO and NGF were significantly higher than those of class I-II people (all P < .05). The SIRT1 and apoA1 of patients with class IV heart function were significantly lower than those of patients with class III heart function, while TMAO and NGF were significantly higher than those of patients with class III heart function (all P < .05). After 1 year follow-up of these IHF patients, 22 patients were readmission because of cardiac events, and 6 patients died in hospital or during follow-up. These 28 patients were allocated to the event group, while the rest 59 patients were allocated to the events-free group. The SIRT1 and apoA1 level in event group was significantly lower than those of event-free group, while the TMAO, SYNTAX score, and NGF level were significantly higher than those of the event-free group (all P < .001). Baseline characters and heart function with significant differences (LVEF, LAD and LVEDD) among these groups, and NGF, TMAO, SIRT1, SYNTAX score and apoA1 were enrolled into Logistic regression. SYNTAX score, NGF, TMAO, SIRT1 and apoA1 were independent risk factors for the prognosis of IHF patients (all P < .05). Conclusion: SIRT1, apoA1, TMAO and NGF serum levels in patients with IHF are abnormally expressed and closely related to cardiac function. The levels of SYNTAX score, NGF, TMAO, SIRT1, and apoA can effectively predict adverse events in patients with IHF.

Malignancy in giant cell tumor of bone: analysis of an open-label phase 2 study of denosumab.

BACKGROUND: Giant cell tumor of bone (GCTB) is a rare osteoclastogenic stromal tumor. GCTB can rarely undergo malignant transformation. This post hoc analysis evaluated and classified malignancies in patients with GCTB who received denosumab. METHODS: This analysis was conducted on patients with pathologically confirmed GCTB and measurable active disease treated with denosumab 120 mg subcutaneously once every 4 weeks, with loading doses on study days 8 and 15, as part of a phase 2, open-label, multicenter study. We identified potential cases of malignancy related to GCTB through an independent multidisciplinary review or medical history, associated imaging or histopathologic reports, and disease course. The findings were summarized and no statistical analysis was performed. RESULTS: Twenty of five hundred twenty-six patients (3.8%) who received at least one dose of denosumab were misdiagnosed with GCTB that was later discovered to be malignancies: five primary malignant GCTB, five secondary malignant GCTB, four sarcomatous transformations, and six patients with other malignancies (giant cell-rich osteosarcoma, undifferentiated pleomorphic sarcoma, spindle cell sarcoma, osteogenic sarcoma, phosphaturic mesenchymal tumor of mixed connective tissue type, and fibrosarcoma/malignant fibrous histiocytoma). Many malignancies were present before denosumab was initiated (8 definitive cases, 7 likely cases), excluding potential involvement of denosumab in these cases. Signs associated with potential misdiagnoses of GCTB included poor mineralization with denosumab treatment, rapid relapse in pain, or a failure of the typical dramatic improvement in pain normally observed with denosumab. CONCLUSIONS: Although rare, GCTB can undergo malignant transformation, and rates in this study were consistent with previous reports. Signs of poor mineralization or lack of response to denosumab treatment may warrant close monitoring. TRIAL REGISTRATION: clinicaltrials.gov , ( NCT00680992 ). Registered May 20, 2008.

KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPß transcription.

BACKGROUND: As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored. METHODS: The expression of KDM6B in human ESCC tissues and cell lines was examined using RT-qPCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC. RESULTS: We show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPß, leading to the promotion of C/EBPß transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells. CONCLUSIONS: The present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPß depending on its H3K27 demethylase activity.

Pseudoaneurysm of Ascending Aorta induced by Brucella Endocarditis In bicuspid Aortic Valve.

Brucellosis is endemic in the Mediterranean region, South American countries, and Asia. In China, it is frequently diagnosed in herdsmen who often have contact with livestock. Brucella endocarditis (BE) is a rare complication, but it is the leading reason for mortality. We report a rare case of BE of bicuspid aortic valve with consequent pseudoaneurysm of ascending aorta, which has never been reported before. The major educational value lies in acknowledging a novel presentation of BE which happened in a patient in remission of BE and appreciation of the role of echocardiography in early diagnosis and definitive surgical therapy.

Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Denosumab is a fully human monoclonal antibody that binds to, and inhibits, the receptor activator of RANKL (TNFSF11) and might affect breast cancer biology, as shown by preclinical evidence. We aimed to assess whether denosumab combined with standard-of-care adjuvant or neoadjuvant systemic therapy and locoregional treatments would increase bone metastasis-free survival in women with breast cancer. METHOD: In this international, double-blind, randomised, placebo-controlled, phase 3 study (D-CARE), patients were recruited from 389 centres in 39 countries. We enrolled women (aged ≥ 18 years) with histologically confirmed stage II or III breast cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1. On eligibility confirmation, investigators at each site telephoned an interactive voice response system to centrally randomly assign patients (1:1) based on a fixed stratified permuted block randomisation list (block size 4) to receive either denosumab (120 mg) or matching placebo subcutaneously every 3-4 weeks, starting with neoadjuvant or adjuvant chemotherapy, for about 6 months and then every 12 weeks for a total duration of 5 years. Stratification factors were breast cancer therapy, lymph node status, hormone receptor and HER2 status, age, and geographical region. The primary endpoint was the composite endpoint of bone metastasis-free survival. This trial is registered with ClinicalTrials.gov, NCT01077154. FINDINGS: Between June 2, 2010, and Aug 24, 2012, 4509 women were randomly assigned to receive denosumab (n=2256) or placebo (n=2253) and included in the intention-to-treat analysis. The primary analysis of the study was done when all patients had the opportunity to complete 5 years of follow-up with an analysis data cutoff date of Aug 31, 2017. The primary endpoint of bone metastasis-free survival was not significantly different between the groups (median not reached in either group; hazard ratio 0·97, 95% CI 0·82-1·14; p=0·70). The most common grade 3 or worse treatment-emergent adverse events, reported in patients who had at least one dose of the investigational product (2241 patients with denosumab vs 2218 patients with placebo), were neutropenia (340 [15%] vs 328 [15%]), febrile neutropenia (112 [5%] vs 142 [6%]), and leucopenia (62 [3%] vs 61 [3%]). Positively adjudicated osteonecrosis of the jaw occurred in 122 (5%) of 2241 patients treated with denosumab versus four (<1%) of 2218 patients treated with placebo; treatment-emergent hypocalcaemia occurred in 152 (7%) versus 82 (4%). Two treatment-related deaths occurred in the placebo group due to acute myeloid leukaemia and depressed level of consciousness. INTERPRETATION: Despite preclinical evidence suggesting RANKL inhibition might delay bone metastasis or disease recurrence in patients with early-stage breast cancer, in this study, denosumab did not improve disease-related outcomes for women with high-risk early breast cancer. FUNDING: Amgen.

Nonparametric estimation of broad sense agreement between ordinal and censored continuous outcomes.

The concept of broad sense agreement (BSA) has recently been proposed for studying the relationship between a continuous measurement and an ordinal measurement. They developed a nonparametric procedure for estimating the BSA index, which is only applicable to completely observed data. In this work, we consider the problem of evaluating BSA index when the continuous measurement is subject to censoring. We propose a nonparametric estimation method built upon a derivation of a new functional representation of the BSA index, which allows for accommodating censoring by plugging in the nonparametric survival function estimators. We establish the consistency and asymptotic normality for the proposed BSA estimator. We also investigate an alternative approach based on the strategy of multiple imputation, which is shown to have better empirical performance with small sample sizes than the plug-in method. Extensive simulation studies are conducted to evaluate our proposals. We illustrate our methods via an application to a Surgical Intensive Care Unit study.

Vibrio parahaemolyticus infection impaired intestinal barrier function and nutrient absorption in Litopenaeus vannamei.

The intestine is the primary target of pathogenic microbes during invasion. However, the interaction of Vibrio parahaemolyticus (V. parahaemolyticus) with intestinal epithelial cells and its effects on the intestinal function of Litopenaeus vannamei (L. vannamei) are poorly studied. Therefore, the aim of this study was to investigate the influence of V. parahaemolyticus infection on intestinal barrier function and nutrient absorption in L. vannamei. In the present study, a total of 90 shrimp were randomly divided into two groups including the control group and V. parahaemolyticus infection group (final concentration of 1 × 105 CFU/mL), with three replicates per group. The result showed that compared with the control group, V. parahaemolyticus infection increased (P < 0.05) serum diamine oxidase activity and endotoxin quantification, and down-regulated (P < 0.05) the mRNA levels of intestinal peroxinectin, integrin, midline fasciclin at 48 h and 72 h; V. parahaemolyticus infection decreased (P < 0.05) the mRNA expression of intestinal amino acid transporter (CAT1, EAAT3 and ASCT1) and glucose transporter (SGLT-1, GLUT) at 24 h, 48 h and 72 h, and increased (P < 0.05) serum glucose and amino acid (Asp, Thr, Ser, Glu, Gly, Ala, Val, Ile, Leu, Tyr, Phe, Lys, His and Arg) concentration at 24 h. The results indicated that V. parahaemolyticus infection increased intestinal permeability, inhibited absorption of glucose and amino acid in L. vannamei.

Association between ambient particulate matter (PM10) and incidence of diabetes in northwest of China: A prospective cohort study.

OBJECTIVES: We aimed to assess the association between long-term exposure to ambient PM10 and risk of diabetes incidence, based on the "Jinchang Cohort" platform in the Northwest of China. METHODS: We selected 19884 subjects who had not yet developed diabetes in the baseline and had completed survey information from "Jinchang Cohort". The residential address was used to match the nearest pollution monitoring station for each subject, and the average concentration of PM10 from baseline to follow-up were used as an estimate of individual exposure level. Cox regression model and restricted cubic splines functions were used to evaluate the effects of PM10 on the incidence of diabetes and the dose-response relationship after adjusting for confounding covariates. RESULTS: We observed 791 new-onset diabetics with a total follow-up of 45254.16 person-years (incidence rate of 17.48 per 1000 person-years). The risk of diabetes incidence increased by 17% (HR = 1.17, 95%CI: 1.08-1.26) per 10µg/m3 increase in environmental PM10, and the risk rises gradually with the rise of PM10 concentration. Comparing with the first quartile of PM10, the fully adjusted HRs (95%CI) for incident diabetes from the second to the fourth quartile of PM10 were 1.15 (95%CI: 0.93-1.43), 1.50 (95%CI: 1.22-1.84) and 1.44 (95%CI: 1.15-1.79), respectively (P for trend<0.001). Stratified analyses suggested that the risk of diabetes incidence associated with ambient PM10 was higher in female, young to middle-aged people, overweight and obese subjects, and subjects with FPG level at baseline lower than 5.6 mmol/L. CONCLUSIONS: Long-term exposure to ambient PM10 significantly associated with a higher risk of diabetes development. Some urgent strategies may be advocated to reduce air pollution that can aid in preventing the prevalence of diabetes in the population.

Glyceraldehyde-3-Phosphate Dehydrogenase Increases the Adhesion of Lactobacillus reuteri to Host Mucin to Enhance Probiotic Effects.

The ability to adhere to the intestinal mucus layer is an important property of probiotic bacteria. Lactobacillus reuteri strains ZJ615 and ZJ617 show low and high adhesion, respectively, to intestinal epithelial cells. In this study, we quantified bacterial cell wall-associated glyceraldehyde-3-phosphate dehydrogenases (cw-GAPDH) and bacterial cell membrane permeability in both strains using immunoblotting and flow cytometry, respectively. Highly adhesive L. reuteri ZJ617 possessed significantly more cw-GAPDH, higher cell membrane permeability, and significantly higher adhesive ability toward mucin compared with low-adhesive L. reuteri ZJ615. In vitro adhesion studies and analysis of interaction kinetics using the Octet, the system revealed significantly decreased interaction between L. reuteri and mucin when mucin was oxidized when bacterial surface proteins were removed when bacteria were heat-inactivated at 80 °C for 30 min, and when the interaction was blocked with an anti-GAPDH antibody. SWISS-MODEL analysis suggested intensive interactions between mucin glycans (GalNAcα1-O-Ser, GalNAcαSer, and Galß3GalNAc) and GAPDH. Furthermore, in vivo studies revealed significantly higher numbers of bacteria adhering to the jejunum, ileum, and colon of piglets orally inoculated with L. reuteri ZJ617 compared with those inoculated with L. reuteri ZJ615; this led to a significantly decreased rate of diarrhea in piglets inoculated with L. reuteri ZJ617. In conclusion, there are strong correlations among the abundance of cw-GAPDH in L. reuteri, the ability of the bacterium to adhere to the host, and the health benefits of this probiotic.

Nasal Pressure Injuries Due to Nasal Continuous Positive Airway Pressure Treatment in Newborns: A Prospective Observational Study.

PURPOSE: The purpose of this study was to calculate incidence, severity, and risk factors of nasal pressure injuries due to nasal continuous positive airway pressure (NCPAP) treatment in newborns. DESIGN: A prospective observational study. SUBJECTS AND SETTING: Newborns admitted between March 2017 and February 2018 to the neonatal intensive care unit of the First Affiliated Hospital of Xiamen University, Xiamen, China. METHODS: All newborns' noses were examined during NCPAP application. Every NCPAP-related nasal pressure injury including occurrence date, injury severity, outcomes, and pressure injury treatment methods was recorded. These data were collected twice a week by a research nurse. Nasal pressure injuries were classified using the National Pressure Ulcer Advisory Panel/European Pressure Ulcer Advisory Panel pressure injury classification system. RESULTS: During the study period, 429 newborns received NCPAP treatment via nasal prongs. Nasal pressure injuries were observed in 149 (34.7%); 99 (66.44%) were classified as Stage 1, 48 (32.31%) were Stage 2, and 2 (1.25%) cases were classified as deep tissue injury. The risk of nasal pressure injury was significantly higher when gestational age was less than 32 weeks (odds ratio [OR], 3.728; 95% confidence interval [CI], 1.18-11.77; P ≤ .025) and in those who received NCPAP treatment for more than 6 days (OR, 0.262; 95% CI, 0.087-0.787; P ≤ .017). The mean interval between the application of NCPAP and onset of nasal pressure injury was 4.72 days (SD, 4.78; range, 0-30 days). CONCLUSIONS: Nasal pressure injuries are a prevalent complication of NCPAP use, especially in preterm newborns. Our results identified a gestational age of less than 32 weeks and longer use of NCPAP are important factors associated with nasal pressure injuries. Methods to prevent the development of injuries such as the use of a prophylactic dressing along and replacement of binasal prongs with nasal masks are advocated.

A New Functional Representation of Broad Sense Agreement.

We derive a new functional representation of Broad Sense Agreement (BSA) index that evaluates the agreement/alignment between a continuous measurement and an ordinary measurement. Using this result, we develop an alternative BSA estimator, which can offer significant numerical advantages.

[Clinical analysis of suspected COVID-19 patients with anxiety and depression].

OBJECTIVE: To explore the risk factors of anxiety and depression in patients with suspected coronavirus disease 2019 (COVID-19) so as to achieve early intervention and better clinical prognosis. METHODS: Seventy-six patients with suspected COVID-19 in fever isolation wards of Second Hospital of Lanzhou University were enrolled From January 31, 2020 to February 22, 2020. Their clinical baseline data were collected. The anxiety of patients was assessed by Hamilton Anxiety Scale, and the depression of patients was assessed by Hamilton Depression Scale. Multivariate Logistic regression analysis was performed to explore the risk factors of anxiety and depression in these patients. RESULTS: Female patients are more likely to have anxiety (OR=3.206, 95%CI: 1.073-9.583, P<0.05) and depression (OR=9.111, 95%CI: 2.143-38.729, P<0.01) than male patients; patients with known contact history of epidemic area and personnel in epidemic area are more likely to have depression (OR=3.267, 95%CI: 1.082-9.597, P<0.05). CONCLUSIONS: During the isolation treatment of suspected COVID-19 patients, early psychological intervention should be carried out for the female patients with known contact history of epidemic area and personnel in epidemic area, and drug treatment should be given in advance if necessary.

Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study.

BACKGROUND: Giant-cell tumour of bone (GCTB) is a rare, locally aggressive osteoclastogenic stromal tumour of the bone. This phase 2 study aimed to assess the safety and activity of denosumab in patients with surgically salvageable or unsalvageable GCTB. METHODS: In this multicentre, open-label, phase 2 study done at 30 sites in 12 countries we enrolled adults and skeletally mature adolescents (aged ≥12 years) weighing at least 45 kg with histologically confirmed and radiographically measurable GCTB, Karnofsky performance status 50% or higher (Eastern Cooperative Oncology Group status 0, 1, or 2), and measurable active disease within 1 year of study enrolment. Patients had surgically unsalvageable GCTB (cohort 1), had surgically salvageable GCTB with planned surgery expected to result in severe morbidity (cohort 2), or were enrolled from a previous study of denosumab for GCTB (cohort 3). Patients received 120 mg subcutaneous denosumab once every 4 weeks during the treatment phase, with loading doses (120 mg subcutaneously) administered on study days 8 and 15 to patients in cohorts 1 and 2 (patients in cohort 3 did not receive loading doses). The primary endpoint was safety in terms of the type, frequency, and severity of adverse events; secondary endpoints included time to disease progression from cohort 1 and the proportion of patients without surgery at month 6 for cohort 2. The safety analysis set included all enrolled patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, number NCT00680992, and has been completed. FINDINGS: Between Sept 9, 2008, and Feb 25, 2016, 532 patients were enrolled: 267 in cohort 1, 253 in cohort 2, and 12 in cohort 3. At data cutoff on Feb 24, 2017, median follow-up was 58·1 months (IQR 34·0-74·4) in the overall patient population, and 65·8 months (40·9-82·4) in cohort 1, 53·4 months (28·2-64·1) in cohort 2, and 76·4 months (61·2-76·5) in cohort 3. During the treatment phase, the most common grade 3 or worse adverse events were hypophosphataemia (24 [5%] of 526 patients), osteonecrosis of the jaw (17 [3%], pain in extremity (12 [2%]), and anaemia (11 [2%]). Serious adverse events were reported in 138 (26%) of 526 patients; the most common were osteonecrosis of the jaw (17 [3%]), anaemia (6 [1%]), bone giant cell tumour (6 [1%]), and back pain (5 [1%]). 28 (5%) patients had positively adjudicated osteonecrosis of the jaw, four (1%) had atypical femur fracture, and four (1%) had hypercalcaemia occurring 30 days after denosumab discontinuation. There were four cases (1%) of sarcomatous transformation, consistent with historical data. Ten (2%) treatment-emergent deaths occurred (two of which were considered treatment-related; bone sarcoma in cohort 2 and sarcoma in cohort 1). Median time to progression or recurrence for patients in cohort 1 during the first treatment phase was not reached (28 [11%] of 262 patients had progression or recurrence). 227 (92%; 95% CI 87-95) of 248 patients who received at least one dose of denosumab in cohort 2 had no surgery in the first 6 months of the study. INTERPRETATION: The types and frequencies of adverse events were consistent with the known safety profile of denosumab, which showed long-term disease control for patients with GCTB with unresectable and resectable tumours. Our results suggest that the overall risk to benefit ratio for denosumab treatment in patients with GCTB remains favourable. FUNDING: Amgen.

Therapeutic Plasma Exchange in Children With Thrombocytopenia-Associated Multiple Organ Failure: The Thrombocytopenia-Associated Multiple Organ Failure Network Prospective Experience.

OBJECTIVE: The objective was to compare the resolution of organ dysfunction, 28-day mortality, and biochemical markers in children with thrombocytopenia-associated multiple organ failure who received therapeutic plasma exchange versus no therapeutic plasma exchange. DESIGN: Observational longitudinal cohort study. SETTING: Nine U.S. PICUs. PATIENTS: Eighty-one children with sepsis-induced thrombocytopenia-associated multiple organ failure. INTERVENTIONS: Therapeutic plasma exchange. MEASUREMENTS AND MAIN RESULTS: Adjusted relative risk for 28-day mortality was modeled using standard multivariate regression with propensity score weighting to reduce covariate confounding. Change from baseline Pediatric Logistic Organ Dysfunction scores between therapeutic plasma exchange and no therapeutic plasma exchange differed in temporal pattern during the first week (p = 0.009). By day 4, mean Pediatric Logistic Organ Dysfunction score declined by 7.9 points (95% CI, -10.8 to -5.1) in the therapeutic plasma exchange-treated group compared with no change with no therapeutic plasma exchange. Use of therapeutic plasma exchange was associated with reduced 28-day mortality by multivariate analysis (adjusted relative risk, 0.45; 95% CI, 0.23-0.90; p = 0.02) and by propensity score weighting (adjusted relative risk, 0.46; 95% CI, 0.22-0.97; p = 0.04). CONCLUSIONS: Therapeutic plasma exchange use in thrombocytopenia-associated multiple organ failure was associated with a decrease in organ dysfunction. After accounting for several risk factors, 28-day all-cause mortality was lower in children treated with therapeutic plasma exchange compared with those receiving no therapeutic plasma exchange. A multicenter randomized clinical trial is necessary to determine a causal relationship.

A Real-Time Mismatch Detection Method for Underwater Database-Referenced Navigation.

Database-referenced navigation (DBRN) using geophysical information is often implemented on autonomous underwater vehicles (AUVs) to correct the positional errors of the inertial navigation system (INS). The matching algorithm is a pivotal technique in DBRN. However, it is impossible to completely eliminate mismatches in practical application. Therefore, it is necessary to perform a mismatch detection method on the outputs of DBRN. In this paper, we propose a real-time triple constraint mismatch detection method. The proposed detection method is divided into three modules: the model fitting detection module, the spatial structure detection module, and the distance ratio detection module. In the model fitting detection module, the navigation characteristics of AUVs are used to select the fitting model. In the spatial structure detection module, the proposed method performs the mismatch detection based on the affine transformation relationship between the INS-indicated trajectory and the corresponding matched trajectory. In the distance ratio detection module, we derive the distance ratio constraint between the INS-indicated trajectory and the corresponding matched trajectory. Simulations based on an actual geomagnetic anomaly base map have been performed for the validation of the proposed method.