bluuebunny/crossref_metadata_2025 huggingface dataset:
State Judgement Model of the Coal and Rock Medium and Its Engineering Application
Authors: Zhu Chuanqi , Wang Lei , Han Xiangang
Published: June 2020

In the loading and failure process of the coal and rock medium, with the increasing of the damaging and failure extent, the medium state gradually changed from the continuous, the quasicontinuous, and the discontinuous to the loose successively. To evaluate the damaging failure extent of the coal and rock mass and distinguish the state of the coal and rock mass medium, first, the medium state index was defined based on the acoustic wave propagation model. Then, based on the coal mass in the working face 8512 in the Chenjiagou Coal Mine in China, the acoustic character and the mechanical character experiments were conducted. Through experiments, the variation law of the ultrasonic wave velocity and the medium state index of the coal mass with the strain under the compressive state were acquired; with the increasing of the strain, the medium state indexes successively experienced the variation process including stabilising around 0, slow increasing, dramatic increasing, and stabilising around 1. Then, based on the variation law of the medium state index, the coal and rock mass medium state judgement model was constructed. This model was applied to judge the coal mass medium state. After it, the mudstones in the roof of the same working face were regarded as the research object, the mudstone medium state was divided into 4 types according to the medium state judgement model, namely, continuous, quasicontinuous, discontinuous, and bulk solid, and the mudstone failure state was basically consistent with the continuous, quasicontinuous, discontinuous, and bulk solid state. The adaptability and rationality of the judgement model was verified. Finally, engineering application of the judgement model was conducted. The distribution law of the top coal with different medium state was acquired. In the top coal that was 186 m away from the working face, it belonged to the continuous medium state. As for the top coal that was 6 m to 186 m far away from the working face, it was under the quasicontinuous medium state. For the top coal that was 3 m to 6 m far away from the working face, it was under the discontinuous medium state. For the top coal that was less than 3 m far away from the working face and behind the working face, it belonged to the bulk solid medium state. The state judgement model can successfully distinguish the medium state of the coal seam and mudstones in the roof in the working face 8512. This provided a new approach to evaluate the damaging failure extent of the coal and rock medium in the Chenjiagou Coal Mine.
Noninvasive Neurally Adjusted Ventilator Assist Ventilation in the Postoperative Period Produces Better Patient-Ventilator Synchrony but Not Comfort
Authors: Harnisch L. O. , Olgemoeller U. , Mann J. , Quintel M. , Moerer O.
Published: June 2020

Background. Noninvasive neurally adjusted ventilatory assist (NAVA) has been shown to improve patient-ventilator interaction in many settings. There is still scarce data with regard to postoperative patients indicated for noninvasive ventilation (NIV) which this study elates. The purpose of this trial was to evaluate postoperative patients for synchrony and comfort in noninvasive pressure support ventilation (NIV-PSV) vs. NIV-NAVA. Methods. Twenty-two subjects received either NIV-NAVA or NIV-PSV in an object-blind, prospective, randomized, crossover fashion (observational trial). We evaluated blood gases and ventilator tracings throughout as well as comfort of ventilation at the end of each ventilation phase. Results. There was an effective reduction in ventilator delays (p<0.001) and negative pressure duration in NIV-NAVA as compared to NIV-PSV (p<0.001). Although we used optimized settings in NIV-PSV, explaining the overall low incidence of asynchrony, NIV-NAVA led to reductions in the NeuroSync-index (p<0.001) and all types of asynchrony except for double triggering that was significantly more frequent in NIV-NAVA vs. NIV-PSV (p=0.02); ineffective efforts were reduced to zero by use of NIV-NAVA. In our population of previously lung-healthy subjects, we did not find differences in blood gases and patient comfort between the two modes. Conclusion. In the postoperative setting, NIV-NAVA is well suitable for use and effective in reducing asynchronies as well as a surrogate for work of breathing. Although increased synchrony was not transferred into an increased comfort, there was an advantage with regard to patient-ventilator interaction. The trial was registered at the German clinical Trials Register (DRKS no.: DRKS00005408).
Deviatoric Stress Evolution Laws and Control in Surrounding Rock of Soft Coal and Soft Roof Roadway under Intense Mining Conditions
Authors: Chen Dongdong , Ji Chunwei , Xie Shengrong , Wang En , He Fulian , Cheng Qiong , Zhang Qing
Published: June 2020

Aiming at the problem of large deformation and instability failure and its control of soft coal and soft roof roadway under intense mining, laboratory experiments, theoretical calculations, Flac3D numerical simulation, borehole peeping, and pressure observation were used to study the deflection characteristics of the deviatoric stress of the gas tailgate and the distribution and failure characteristics of the plastic zone in the mining face considering the strain softening characteristics of the roof and coal of roadway, and then the truss anchor cable‐control technology is proposed. The results show the following: (1) The intense mining influence on the working face will deflect the peak deviatoric stress zone (PDSZ) of the surrounding rock of the gas tailgate. The influence distance of PDSZ is about 20 m in advance and 60 m in lag; the PDSZ at the gob side of the roadway is located in the range of 3–5.5 m from the surface of the coal pillar, while the coal wall side is mainly located in the range of 3–4.5 m at the shoulder corner and bottom corner of the solid coal. (2) The intense mining in the working face caused the nonuniform expansion of the surrounding rock plastic area of the gas tailgate. The two shoulder angles of the roadway and the bottom of the coal pillar have the largest damage range, and the maximum damage location is the side angle of the coal pillar (5 m). Angle and bottom angle of coal pillar are the key points of support control. (3) The plastic failure line of the surrounding rock of the gas tailgate is always between the inner and outer contours of the PDSZ, and the rock mass in the PDSZ is in a stable and unstable transition state, so the range of anchor cable support should be cross plastic failure line. (4) The theoretical calculations and numerical simulation results agree well with the drilling peep results. Based on the deflection law of the PDSZ and the expansion characteristics of the plastic zone, a truss anchor cable supporting system with integrated locking and large‐scale support function is proposed to jointly control the roof and the two sides, which effectively solves the problem of weak surrounding rock roadway under severe mining deformation control problems realizing safety and efficient production in coal mines under intense mining.
Research on Fault Feature Extraction Method Based on FDM-RobustICA and MOMEDA
Authors: Yang Jingzong , Li Xuefeng , Wu Limei
Published: June 2020

Aiming at the difficulty of extracting rolling bearing fault features under strong background noise conditions, a method based on the Fourier decomposition method (FDM), robust independent component analysis (RobustICA), and multipoint optimal minimum entropy deconvolution adjusted (MOMEDA) is proposed. Firstly, the FDM method is introduced to decompose the single-channel bearing fault signal into several Fourier intrinsic band functions (FIBF). Secondly, by setting the cross-correlation coefficient and kurtosis as a new selection criterion, it can effectively construct the virtual noise channel and the observation signal channel, which makes RobustICA complete the separation of the useful signal and noise well. Finally, MOMEDA is introduced to enhance the periodic impact components in the denoised signal, and then the filtered signal is analyzed by the Hilbert envelope spectrum to extract the fault characteristic frequency. Through the experimental analysis of the simulated signals and the actual bearing fault signals, the results show that the proposed method not only has the ability to suppress noise and accurately extract fault feature information but also has better performance than the traditional method of local mean decomposition (LMD) and intrinsic time-scale decomposition (ITD), highlighting its practicality in the fault diagnosis of rotating machinery.
Research on SKINNY Optimal Differential Trail Search
Authors: Liu Shaoqiang , Peng Chaiyang , Li Chunjiang
Published: June 2020

SKINNY is a tweakable lightweight block cipher algorithm. In order to test its security, this paper performs optimal differential trail search analysis on all SKINNY-64 versions under single-key setting based on the MILP (Mixed Integer Linear Programming) algorithm. Firstly, SKINNY round function is abstracted equivalently by precise constraints, and the objective function is set as the minimum number of active S-box number to optimize SKINNY-64 MILP model. Experiments show the differential trail searched by this method is not necessarily optimal. In order to directly search for the optimal differential trail, the S-box differential probability coding information is added to the optimized SKINNY-64 MILP model, the S-box differential characteristic is reconstructed, and the objective function is set to the minimum value of the probability coding information, which improves the SKINNY-64 MILP model. The results of experimental show that the improved MILP model can directly search for the optimal differential trail, and the complexity is slightly increased, but the search efficiency is significantly improved. Under single-key setting, this method has obvious advantage in searching the optimal differential trails of SKINNY-64 with low round number.
An Immunohistochemical Study of the Increase in Antioxidant Capacity of Corneal Epithelial Cells by Molecular Hydrogen, Leading to the Suppression of Alkali-Induced Oxidative Stress
Authors: Cejka Cestmir , Kossl Jan , Holan Vladimir , Zhang John H. , Cejkova Jitka
Published: June 2020

Corneal alkali burns are potentially blinding injuries. Alkali induces oxidative stress in corneas followed by excessive corneal inflammation, neovascularization, and untransparent scar formation. Molecular hydrogen (H2), a potent reactive oxygen species (ROS) scavenger, suppresses oxidative stress and enables corneal healing when applied on the corneal surface. The purpose of this study was to examine whether the H2 pretreatment of healthy corneas evokes a protective effect against corneal alkali-induced oxidative stress. Rabbit eyes were pretreated with a H2 solution or buffer solution, by drops onto the ocular surface, and the corneas were then burned with 0.25 M NaOH. The results obtained with immunohistochemistry and pachymetry showed that in the corneas of H2-pretreated eyes, slight oxidative stress appeared followed by an increased expression of antioxidant enzymes. When these corneas were postburned with alkali, the alkali-induced oxidative stress was suppressed. This was in contrast to postburned buffer-pretreated corneas, where the oxidative stress was strong. These corneas healed with scar formation and neovascularization, whereas corneas of H2-pretreated eyes healed with restoration of transparency in the majority of cases. Corneal neovascularization was strongly suppressed. Our results suggest that the corneal alkali-induced oxidative stress was reduced via the increased antioxidant capacity of corneal cells against reactive oxygen species (ROS). It is further suggested that the ability of H2 to induce the increase in antioxidant cell capacity is important for eye protection against various diseases or external influences associated with ROS production.
Burning Rate Enhancement Analysis of End-Burning Solid Propellant Grains Based on X-Ray Real-Time Radiography
Authors: Xianggeng Wei , Tao Bo , Pengbo Wang , Xinjian Ma , Yongchun Lou , Jian Chen
Published: June 2020

Unexpected pressure rise may occur in the end-burning grain solid rocket motor. It is generally believed that this phenomenon is caused by the nonparallel layer combustion of the burning surface, resulting in the increase of burning rate along the inhibitor. In order to explain the cause of this phenomenon, the experimental investigation on four different end configurations were carried out. Based on the X-ray real-time radiography (RTR) technique, a new method for determining the dynamic burning rate of propellant and obtaining the real-time end-burning profile was developed. From the real-time images of the burning surface, it is found that there was a phenomenon of nonuniform burning surface displacement in the end-burning grain solid rocket motor. Through image processing, the real-time burning rate of grain center line and the real-time cone angle are obtained. Based on the analysis of the real-time burning rate at different positions of the end surface, the end face cone burning process in the motor working process is obtained. The closer to the shell, the higher the burning rate of the propellant. Considering the actual structure of this end-burning grain motor, it is speculated that the main cause of the cone burning of the grain may be due to the heat conduction of the metal wall. By adjusting the initial shape of the grain end surface, the operating pressure of the combustion chamber can be basically unchanged, so as to meet the mission requirements. The results show that the method can measure the burning rate of solid propellant in real time and provide support for the study of nonuniform combustion of solid propellant.
Dynamic Splitting Experimental Study on Sandstone at Actual High Temperatures under Different Loading Rates
Authors: Ping Qi , Wu Mingjing , Yuan Pu , Su Haipeng , Zhang Huan
Published: June 2020

The tensile failure of rocks is a common failure mode in rock engineering. Many studies have been conducted on the tensile strength and failure mode of rocks after high-temperature treatment under dynamic loading. However, research on the effects of high temperature on the dynamic splitting tensile characteristics of sandstone at actual high temperatures is lacking. To investigate the dynamic tensile characteristics of rocks at actual high temperatures, split Hopkinson pressure bar (SHPB) test apparatus and high-temperature environment box were used to perform dynamic splitting tensile tests under six striker velocities for sandstone specimens at 25°C–800°C. The dynamic splitting tensile strength, radial strain, average strain rate, and failure mode of sandstone under different test conditions were investigated. Test results revealed that the brittleness of sandstone specimens is enhanced at 200°C and 400°C, but slight ductility is observed at 600°C and 800°C. The strain rate effect of dynamic tensile strength is closely related to temperature. When the striker velocity exceeds 2.3 m/s, the dynamic radial strain first decreases and then increases with rising temperature. A quadratic polynomial relationship between the dynamic radial strain and temperature was observed. The temperature effect on the average strain rate is strong at low striker velocity and weak at high striker velocity. In the dynamic splitting tensile tests, high-temperature sandstone specimens are split into two semicylinders along the radial loading direction.
Postpartum Pulmonary Hypertension Masquerading as Submassive Pulmonary Embolism: A Case Report and a Literature Review
Authors: Mubasher Mahmood , Hanafi Amir , Syed Tausif , Zinal Abir , Abubeker Ibrahim Y. , Mohamed Mouhand F. H. , Rao Mohan , Hoefen Ryan , Danjuma Mohammed
Published: June 2020

Postpartum pulmonary hypertension (PPPHT) is an extremely rare disorder, with few reported cases. Late diagnosis and treatment are associated with significant morbidity and mortality. We present an 18-year-old female patient who presented four-week postpartum with a typical submissive pulmonary embolism picture subsequently diagnosed as postpartum pulmonary hypertension. The patient had an excellent response to treatment, with a dramatic improvement in her functional status. The authors aim to urge physicians to keep this rare disorder in mind as timely and accurate diagnosis is crucial for management—additionally, the importance of counseling patients about the imminent risks associated with planned future pregnancies.
A Modified Range Consensus Algorithm Based on GA for Receiver Autonomous Integrity Monitoring
Authors: Zhao Jing , Xu Chengdong , Jian Yimei , Zhang Pengfei
Published: June 2020

With the considerable increase of visible satellites for positioning, the fault detection and identification performance of Range Consensus (RANCO) algorithm for Receiver Autonomous Integrity Monitoring (RAIM) will significantly be improved. However, the calculation amount of RANCO algorithm will exponentially increase for the sharp addition of visible satellite subsets. This paper proposes a modified RANCO algorithm based on genetic algorithm (GA-RANCO) for RAIM to inhibit the exponentially expanded calculation amount. To reduce the calculation amount in searching the optimal minimal necessary subset (MNS), the preselection step is developed to speed up the convergence process of GA-RANCO. It is executed to exclude the chromosome-represented MNS for which the count of faulty satellites will exceed the upper limit of independent simultaneous satellite faults to be monitored. Mathematical simulations are introduced to determine the GA parameters, and simulation experiments under different schemes are designed to evaluate the performance of GA-RANCO algorithm. Results illustrate that the time consumption under a large number of visible satellites of GA-RANCO is much lower than that of RANCO and the faulty detection and identification performance of GA-RANCO is the same as that of RANCO.
Analysis of Cyclic Response of Bucket Foundations Based on Simplified Kinematic Hardening Model
Authors: Fan Qing-lai , Xiao Guo-feng , Chen Xiao-di
Published: June 2020

The response of bucket foundations for offshore wind turbines subjected to cyclic loading in saturated clay is explored through three‐dimensional finite element numerical analyses. In the analyses, nonlinear cyclic hysteretic behavior of clay under undrained condition is modeled through a simple kinematic hardening constitutive model embedded in ABAQUS. The finite element model is validated against published in situ tests of bucket foundations under quasistatic cyclic loading in Bothkennar clay. The computed results agreed generally with those from in situ tests. The behavior of bucket foundations with different aspect ratios under displacement‐controlled cyclic loading mode is investigated. Then, the evolution of foundation displacement with increasing number of cycles is studied subjected to wind and wave combined loading. The results show that, for the cycles of low‐amplitude rotation, dimensionless moment‐rotation curve is approximately elastic; however, the curve engenders obvious hysteresis loop, whose shape is influenced by soil‐sidewall interface condition, during high‐amplitude cycles. Under thousands of loading cycles, for bucket foundations of low aspect ratio, the oscillatory displacement component is smaller; however, the residual component will accumulate gradually until the serviceability rotation is exceeded. For foundations of high aspect ratio, the oscillatory component is relatively larger, but the accumulation rate of residual displacement decreases gradually.
Clinical Evaluation of the Safety and Effectiveness of Heptonica: A Ghanaian Hepatorestorative Polyherbal Product
Authors: Agyemang A. O. , Mensah M. L. K. , Yamile R. C. , Ocloo A. , Appiah A. A. , Mensah A. Y. , Thomford K. P.
Published: June 2020

The incidence of liver diseases is increasing globally, and many patients in developing countries are resorting to the use of herbal products as treatment. This study was aimed at establishing the safety and effectiveness outcomes for patients with deranged liver panel treated with a Ghanaian finished polyherbal product. The product Heptonica is prepared by CPMR from three medicinal plants: Bidens pilosa, Citrus aurantifolia, and Trema orientalis. Fifty (50) participants with clinical and biochemical signs of liver impairment were purposively recruited and treated for a period of 28 days. Participants received Heptonica at a dose of 30 mL 8 hourly after meals for the treatment period. Clinical and biochemical evaluation (liver panel test, renal function test, haematology, and urinalysis) of subjects for the safety and effectiveness of the product was undertaken at days 0 (baseline), 14, and 28. Compared to the baseline values, Heptonica did not have any untoward effect on renal function, haematological parameters, and urine parameters of subjects. Clinical and liver panel results of the participants also improved compared to the baseline: serum aspartate transaminase (AST) (p < 0.0001), alanine transaminase (ALT) (p < 0.0001), gamma‐glutamyltransferase (GGT) (p‐ 0.0013), total bilirubin (p‐0.0136), direct bilirubin (p < 0.0001), total proteins (p‐0.0409), and alkaline phosphates (p‐ 0.0284). Level of albumin showed no significant difference within the study period. The outcome of this study indicates Heptonica has hepatorestorative action with no observable toxicity and can be used with confidence as indicated as a liver tonic.
Effect of Wenshen-Yanggan Decoction on Movement Disorder and Substantia Nigra Dopaminergic Neurons in Mice with Chronic Parkinson’s Disease
Authors: Tang Lili , Chen Chang , Xia Baomei , Wu Wei , Wei Ruide , Zhu Guoxue , Tang Juanjuan , Zhou Xin , Liang Yan , Zhang Zhen-Nian , Lu Yan , Yang Ye , Zhao Yang
Published: June 2020

This study aimed to explore the protective effects of Wenshen-Yanggan decoction on dopaminergic (DA) neuron injury in a rotenone‐induced mouse model with chronic Parkinson’s disease (PD) and explore its mechanism of action. Ultraperformance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) was used to measure the content of six main components in the Wenshen-Yanggan decoction. The chronic PD mouse model was established by treating 10‐month‐old healthy wild C57BL/6 male mice with rotenone 30 mg/kg/day for 28 days in succession. The pole test and rotarod test were applied to detect the rescue effect of Wenshen-Yanggan decoction in high, medium, and low dosages, respectively, on PD‐like behaviors in mice with chronic PD. The protective effect of Wenshen-Yanggan decoction on the mesencephalic nigrostriatal DA neuron injury was determined employing tyrosine hydroxylase (TH) immunofluorescence staining. Enzyme‐linked immunosorbent assay (ELISA) was adopted to measure the inflammatory cytokines in serum, including TNF‐α (tumor necrosis factor‐alpha), IFN‐γ (interferon gamma), NF‐κB (nuclear factor kappa‐B), and IL‐1β (interleukin‐1 beta). Western blotting was performed to quantify the expression of phosphorylated c‐Jun N‐terminal kinase (p‐JNK), cleaved caspase‐3, B‐cell lymphoma‐2 (Bcl‐2), and NF‐κB in the brain. Our results showed that the Wenshen-Yanggan decoction in high, medium, and low dosages reduced the turning time of mice (P < 0.01, P < 0.01,  and P < 0.05). The high and medium dosages shortened the total climbing time of PD mice in the pole test (P < 0.01 and P < 0.05). Meanwhile, the high, medium, and low dosages increased the rod‐standing time of PD mice in the rotarod test (P < 0.01, P < 0.05,  and P < 0.05). Besides, the decoction reversed the decrease in TH‐positive neurons induced by rotenone, upregulated TH protein expression, and downregulated the α‐syn expression in the PD model. Moreover, the decoction in high dosage significantly inhibited the expression of p‐JNK, cleaved caspase‐3, and NF‐κB in the midbrain of PD mice (P < 0.05, P < 0.05,  and P < 0.01), upregulated the expression of Bcl‐2 (P < 0.05), and decreased the content of TNF‐α, IFN‐γ, NF‐κB, and IL‐1β in the serum (P < 0.001, P < 0.001, P < 0.001,  and P < 0.001). Taken together, the Wenshen-Yanggan decoction could protect mice from rotenone‐induced chronic PD, which might be related to the reduction of the DA neuron apoptosis via suppressing the inflammatory reaction and the neuronal apoptosis pathway.
Novel Therapeutic Interventions Early in the Disease Trajectory: Drug Development Beyond the Refractory Setting
Authors: Hafez Navid , Rugo Hope S. , Tempero Margaret A. , Fox Elizabeth , Reaman Gregory H. , Lyerly Herbert Kim , Walker Desiree , LoRusso Patricia M.
Published: June 2020

The 2019 Accelerating Anticancer Agent Development Workshop assembled a panel of experts for an in-depth discussion session to present “novel therapeutic interventions early in the disease trajectory.” The panel reviewed the limitations of evaluating investigational cancer therapeutics solely in advanced metastatic and relapsed/refractory disease settings, and recommended strategies for drug evaluation earlier in the disease course, including in the first line in combination with standard chemotherapy, and in the maintenance and neoadjuvant disease settings. Advantages of earlier drug evaluation were discussed, including expanding the population of evaluable patients, earlier response assessment via surrogate endpoints, earlier clinical benefit in the disease course, tailoring of therapies based on response, and furthering our understanding of biomarker-driven therapies.
Key Regulatory miRNAs and their Interplay with Mechanosensing and Mechanotransduction Signaling Pathways in Breast Cancer Progression
Authors: Najminejad Hamid , Farhadihosseinabadi Behrouz , Dabaghian Mehran , Dezhkam Asiyeh , Rigi Yousofabadi Esmat , Najminejad Reza , Abdollahpour-Alitappeh Meghdad , Karimi Mohammad Hossein , Bagheri Nader , Mahi-Birjand Motahareh , Ghasemi Nasrin , Mazaheri Mahta , Kalantar Seyed Mehdi , Seifalian Alexander , Sheikhha Mohammad Hasan
Published: June 2020

According to the WHO, breast cancer is the most common cancer in women worldwide. Identification of underlying mechanisms in breast cancer progression is the main concerns of researches. The mechanical forces within the tumor microenvironment, in addition to biochemical stimuli such as different growth factors and cytokines, activate signaling cascades, resulting in various changes in cancer cell physiology. Cancer cell proliferation, invasiveness, migration, and, even, resistance to cancer therapeutic agents are changed due to activation of mechanotransduction signaling. The mechanotransduction signaling is frequently dysregulated in breast cancer, indicating its important role in cancer cell features. So far, a variety of experimental investigations have been conducted to determine the main regulators of the mechanotransduction signaling. Currently, the role of miRNAs has been well-defined in the cancer process through advances in molecular-based approaches. miRNAs are small groups of RNAs (∼22 nucleotides) that contribute to various biological events in cells. The central role of miRNAs in the regulation of various mediators involved in the mechanotransduction signaling has been well clarified over the last decade. Unbalanced expression of miRNAs is associated with different pathologic conditions. Overexpression and downregulation of certain miRNAs were found to be along with dysregulation of mechanotransduction signaling effectors. This study aimed to critically review the role of miRNAs in the regulation of mediators involved in the mechanosensing pathways and clarify how the cross-talk between miRNAs and their targets affect the cell behavior and physiology of breast cancer cells.
Association between Ankle Brachial Index, Brachial-Ankle Pulse Wave Velocity, and Mild Cognitive Impairment in Patients with Acute Lacunar Infarction
Authors: Huang Junling , Tang Jian , Zhang Yueling , Zhang Jian , Tan Zhong , Shi Shengliang
Published: June 2020

Background: The link between arterial stiffness and mild cognitive impairment (MCI) is receiving increasing attention, and the goal of this study was to explore the relationship among the ankle brachial index (ABI), brachial-ankle pulse wave velocity (Ba-PWV), and MCI in patients with acute lacunar infarction (ALI). Methods: A total of 103 hospitalized patients with ALI were divided into a non-MCI group (n = 41) and an MCI group (n = 62) according to their Montreal Cognitive Assessment (MoCA) scores. A binary logistic regression model was used to assess the association among ABI, Ba-PWV, and MCI after adjusting for confounding factors. Spearman correlation was utilized to analyse the correlations between ABI, Ba-PWV, and MoCA total scores and sub-scores in ALI patients. Results: Participants with cognitive impairment had significantly higher Ba-PWV and lower ABI than those with normal cognition. Correlation analysis suggested that Ba-PWV (r = −0.854, p < 0.05) and ABI (r = 0.734, p < 0.05) were correlated with MoCA total scores; of all MoCA sub-scores, visuospatial/executive function was the most strongly correlated with the vascular variables. In the binary logistic regression analysis, Ba-PWV (odds ratio [OR] = 4.507, 95% confidence interval [CI] = 2.152–9.441) and ABI (OR = 1.124, 95% CI = 1.015–1.254) were significantly associated with MCI, even after adjusting for lipoprotein (a) and systolic and diastolic blood pressure. Conclusion: The present study suggested that a higher Ba-PWV and a lower ABI were independent risk factors for MCI in patients with ALI.
A Metabolomics Study of Hypoxia Ischemia during Mouse Brain Development Using Hyperpolarized 13C
Authors: Mikrogeorgiou Alkisti , Chen Yiran , Lee Byong Sop , Bok Robert , Sheldon R. Ann , Barkovich A. James , Xu Duan , Ferriero Donna M.
Published: June 2020

Background: Hyperpolarized 13C spectroscopic magnetic resonance spectroscopy (MRS) is an advanced imaging tool that may provide important real-time information about brain metabolism. Methods: Mice underwent unilateral hypoxia-ischemia (HI) on postnatal day (P)10. Injured and sham mice were scanned at P10, P17, and P31. We used hyperpolarized 13C MRS to investigate the metabolic exchange of pyruvate to lactate in real time during brain development following HI. 13C-1-labeled pyruvate was hyperpolarized and injected into the tail vein through a tail-vein catheter. Chemical-shift imaging was performed to acquire spectral-spatial information of the metabolites in the brain. A voxel placed on each of the injured and contralateral hemispheres was chosen for comparison. The difference in pyruvate delivery and lactate to pyruvate ratio was calculated for each of the voxels at each time point. The normalized lactate level of the injured hemisphere was also calculated for each mouse at each of the scanning time points. Results: There was a significant reduction in pyruvate delivery and a higher lactate to pyruvate ratio in the ipsilateral (HI) hemisphere at P10. The differences decreased at P17 and disappeared at P31. The normalized lactate level in the injured hemisphere increased from P10 to P31 in both sham and HI mice without brain injury. Conclusion: We describe a method for detecting and monitoring the evolution of HI injury during brain maturation which could prove to be an excellent biomarker of injury.
Negative-Pressure Ureteroscopic Holmium-YAG Laser Lithotripsy for Ureteral Stones
Authors: Wu Zhong-Hua , Liu Tong-Zu , Wang Xing-Huan , Wang Yong-Zhi , Zheng Hang , Zhang Yin-Gao , Zhang Xin-Hua
Published: June 2020

Objectives: The aim of this study was to describe a novel negative-pressure laser lithotripsy device to overcome the deficiencies of the conventional procedure. Patients and Methods: Between August 2018 and March 2019, 78 patients with a single ureteral stone underwent retrograde ureteroscopy with a Wolf 8F/9.8F rigid ureteroscope and a 200-μm holmium-YAG laser. The mean stone size was 11.8 mm, measured for the maximum length. The negative-pressure laser lithotripsy device consists of an F5 ureter catheter and a T joint. The closed tip of an F5 ureter catheter is cut off, and it is then inserted within one opening of the T joint. The 200-μm laser fiber is introduced into the ureteral catheter through the other opening of the T joint. The third opening of the T joint is connected to the negative-pressure pipe. The valve end of the Foley catheter is used for sealing the cap. Continuous suction and active irrigation throughout the lithotripsy could maintain adequate visibility. Results: All ureteroscopic procedures were successful. The negative-pressure device showed good stone retention capabilities, with no observed stone migration. We did not observe any major complications. The stone-free rate was 97.44% (76/78), demonstrated on plain radiography of the kidney-ureter-bladder on the first postoperative day. The stone-free rate after 1 month was 100%. Conclusions: The negative-pressure ureteroscopic lithotripsy is easy and safe management for the ureteral stones. It might reduce the risk of stone fragment retropulsion, improve surgical vision, shorten the operative time, and decrease the renal pelvic pressure.
Emerging Treatment Options in Inflammatory Bowel Disease: Janus Kinases, Stem Cells, and More
Authors: Misselwitz Benjamin , Juillerat Pascal , Sulz Michael Christian , Siegmund Britta , Brand Stephan ,   on behalf of Swiss IBDnet, an official working group of the Swiss Society of Gastroenterology
Published: June 2020

Background: Treatment of inflammatory bowel diseases (IBD) has tremendously improved during the last 20 years; however, a substantial fraction of patients does not respond to available therapies or lose response, and new strategies are needed. Summary: Two pharmacological principles have been successfully used for IBD treatment: inhibition of cellular signaling and interference with leukocyte trafficking. Besides tumor necrosis factor, interleukin (IL)-23 is a promising drug target, and antibodies for the combined inhibition of IL-23 and IL-12 (ustekinumab and briakinumab) or selective IL-23 inhibition (brazikumab, risankizumab, and mirikizumab) seem to be effective in Crohn’s disease (CD) with emerging evidence also for ulcerative colitis (UC). Janus kinase (JAK) mediates intracellular signaling of a large number of cytokines. Tofacitinib is the first JAK inhibitor approved for UC, and the JAK inhibitors filgotinib and upadacitinib showed potential in CD. Leukocyte trafficking can be inhibited by interference with lymphocyte integrin-α4β7 or endothelial MadCAM-1. The α4β7 integrin inhibitor vedolizumab is an established treatment in IBD, and long-term data of pivotal studies are now available. Additional molecules with therapeutic potential are α4β7-specific abrilumab, β7-specific etrolizumab, and the α4-specific small molecule AJM300. PF-00547659, an antibody against endothelial MadCAM-1, also showed therapeutic potential in UC. Modulation of sphingosine-1-phosphate receptor (S1PR) activity is necessary for the egress of lymphocytes into the circulation, and S1PR modulation results in lymphocyte trapping in lymphatic organs. Ozanimod, an S1PR1 and S1PR5 inhibitor, has been successfully tested in initial studies in UC. Mesenchymal stem cell therapy has been approved for the treatment of complex, active CD fistula, and mesenchymal stem cell therapy might be a paradigm shift for this condition. Autologous stem cell transplantation (ASCT) has been successfully used in CD case series; however, in a randomized trial, a highly stringent endpoint was not met. However, considering positive effects in secondary endpoints, ASCT might be a future treatment of last resort in severe, refractory CD cases, provided that safer protocols can be provided. Key messages: New IBD treatments are successful for a significant fraction of patients. However, new strategies for patient selection, treatment combinations, and/or additional therapies must be developed to serve the need of all IBD patients.
CASC9 Facilitates Cell Proliferation in Bladder Cancer by Regulating CBX2 Expression
Authors: Huo Wenqian , Tan Dan , Chen Qingbiao
Published: June 2020

Background: As the seventh most common urologic carcinoma worldwide, approximately 430,000 patients are diagnosed with bladder cancer (BC) every year. Increasing evidence indicates that long noncoding RNAs (lncRNAs) play crucial roles in the progression of BC. Objectives: This study is aimed to explore the function and mechanism of CASC9 in BC. Methods: Bioinformatics analysis and experiments including RT-qPCR, luciferase reporter, Cell Counting Kit-8 assay, Western blot, RNA immunoprecipitation assay, and TUNEL staining were applied to explore the function and mechanism of CASC9 in BC tissues and cell lines. Results: Our study demonstrated that CASC9 was upregulated in BC tissues and cell lines. Moreover, we found that CASC9 knockdown notably decreased proliferation while increased apoptotic rate in BC cells. Mechanistically, bioinformatics prediction and following experiments indicated that CASC9 worked as a competing endogenous RNA (ceRNA) of CBX2 through sponging miR-497-5p. Meanwhile, we recognized that CASC9 and miR-497-5p negatively regulated each other in a mutual way. Furthermore, we found that miR-497-5p shared binding site with CBX2. In addition, miR-497-5p could negatively regulated CBX2, while CASC9 could positively regulated CBX2. Rescue assays reveled that CBX2 overexpression could reversed the reduction of cell proliferation or the enhancement of cell apoptosis induced by CASC9 suppression. Conclusions: Our study manifests the first evidence that CASC9 serves as an oncogene in BC and accelerates cell proliferation by modulating miR-497-5p/CBX2 axis. The present study may provide a cogitable target for BC therapy.
Durvalumab-Induced Diffuse Alveolar Hemorrhage: An Autopsy Case Report
Authors: Kanaoka Kensuke , Ikebe Saori , Ihara Shouichi , Tsuji Hiromi , Yasuoka Hironao , Minami Seigo
Published: June 2020

Durvalumab, a programmed cell death ligand 1 inhibitor, induces various immune-related adverse events (irAEs), including lung injury. However, diffuse alveolar hemorrhage (DAH) is a rare type of lung injury due to immune checkpoint inhibitors. A 76-year-old man with c-stage IIIA squamous cell carcinoma of the lung received maintenance durvalumab therapy after chemoradiotherapy. He developed dyspnea and malaise after 11 cycles of durvalumab. Chest computed tomography showed rapidly spreading bilateral ground-glass opacity in the lungs. We diagnosed DAH by hemosiderin-laden macrophages in bloody bronchoalveolar lavage fluid. Despite mechanical ventilation, steroids, and cyclophosphamide, he died of respiratory failure. The autopsy revealed that fresh and old bleeding areas coexisted, and neither pulmonary vasculitis nor diffuse alveolar damage was detected microscopically. Furthermore, CD3+ and CD8+ lymphocytes were observed in the lung interstitium, whereas CD20+ and CD4+ lymphocytes were scarcely detected. We report the first case of durvalumab-induced DAH. We should be alert to irAEs with DAH as a potential differential diagnosis of lung injury during durvalumab treatment.
Adult Attention-Deficit/Hyperactivity Disorder and Quality of Life in High-Dose Benzodiazepine and Related Z-Drug Users
Authors: Lugoboni Fabio , Bertoldi Anna , Casari Rebecca , Mantovani Elisa , Morbioli Laura , Tamburin Stefano
Published: June 2020

Background: Problematic high-dose benzodiazepine (BZD) and related Z-drug use for a long period is a substance use disorder previously found to be associated with adult attention-deficit/hyperactivity disorder (ADHD) and worse quality of life (QoL). Whether adult ADHD impacts QoL in high-dose BZD/Z-drug users has not been explored. Aim: The aim of the study was to explore the impact of adult ADHD on QoL in high-dose BZD and related Z-drug users. Methods: We recruited 393 patients (205 men and 188 women) consecutively admitted to the Department of Medicine, Addiction Medicine Unit, Verona University Hospital, Italy, from July 2016 to July 2019 for detoxification from high-dose BZD or Z-drug dependence. Demographic and clinical variables and QoL measures were recorded. The World Health Organization ADHD Self-Report Scale version 1.1 Symptom Checklist Part A was used to detect adult ADHD. Results: In our sample, 39.4% of patients were positive to adult ADHD testing (ADHD+), with some clinical features differing in comparison to patients negative to ADHD testing (ADHD−). QoL was worse in high-dose BZD/Z-drug users than the general population. The ADHD+ group showed significantly worse QoL measures than the ADHD− group. Multivariate analysis, including potential covariates showed adult ADHD and age to have the most robust and consistent positive effect for age (i.e., higher QoL) and negative effect for ADHD (i.e., lower QoL) on QoL measures. Conclusions: Adult ADHD is associated with worse QoL measures in high-dose BZD/Z-drug users. Future studies should explore whether appropriate BZD/Z-drug detoxification might improve QoL measures and whether the most appropriate detoxification protocol differs in ADHD+ versus ADHD− populations.
Epstein-Barr Virus-Associated Encephalopathy Presenting with Nonconvulsive Status Epilepticus in an Immunosuppressive State
Authors: Ohya Yuichiro , Nakamura Kuniyuki , Wakisaka Yoshinobu , Sato Hiroaki , Wakisaka Kayo , Kumamoto Masaya , Muraya Yohei , Kuroda Junya , Nakane Hiroshi , Yoshimoto Goichi , Kitazono Takanari , Ago Tetsuro
Published: June 2020

Epstein-Barr virus (EBV) infection is occasionally accompanied by central nervous system (CNS) complications, particularly in immunosuppressed patients. However, the symptoms and clinical features of EBV infection in the CNS are rather heterogeneous and remain unknown. We herein describe the first reported adult case manifesting nonconvulsive status epilepticus (NCSE), possibly associated with reactivation of EBV in an immunosuppressive state. A 63-year-old man with a history of acute myeloid leukemia and taking immunosuppressants was admitted due to progressively impaired consciousness without any focal neurological signs, including paralysis or convulsions. Arterial spin labeling magnetic resonance imaging (ASL-MRI) and brain perfusion single-photon emission computed tomography showed hyperperfusion in the right temporal region, despite no morphological abnormalities in other MRI sequences. White blood cell counts, EBV viral load, and virus-capsid antigen IgG in cerebrospinal fluid were elevated. We diagnosed him with EBV-associated encephalopathy presenting with NCSE. Administration of levetiracetam, an antiepileptic, improved the consciousness and the abnormal hyperperfusion. This case suggests a new concept of EBV-associated encephalopathy leading to epilepsy, particularly in immunosuppressed patients.
Unilateral Optic Neuritis in Children: Experience of a Tertiary Centre
Authors: Duarte Armindo Rui , Pinto Joana , Pereira Cristina , Vasconcelos Mónica , Palavra Filipe
Published: June 2020

Introduction: Optic neuritis (ON) is an inflammation of the optic nerve that can be associated with a multitude of different systemic conditions and primary CNS disorders. In children, only around 25% of unilateral ON cases are considered idiopathic. Despite being considered a clinical diagnosis per se, neuroimaging plays a crucial role in the diagnostic pathway for these patients. Methods: Demographic, clinical, and imaging data of all patients presenting with unilateral ON at a tertiary paediatric centre over 40 months (January 1, 2016, to April 30, 2019) were retrospectively analyzed. Results: A total of 10 patients filled the inclusion criteria. The average age of presentation was 14.1 years. Patients in this series had ON associated with multiple sclerosis (n = 2), anti-MOG demyelinating disorders (n = 2), and neuromyelitis optica with anti-AQP4 antibodies (n = 1). ON was determined to be secondary to Toxocara canis infection in 1 case and a side effect of anti-TNFα therapy (adalimumab) in another. MR imaging showed T2 hyperintensity and/or gadolinium enhancement of one of the optic nerves in all but 3 patients, and coincidently these were the cases with monophasic idiopathic ON (average follow-up period of 2 years). Additional brain MR findings directly contributed to the final diagnosis in half of the cases. Conclusions: These cases are demonstrative of the wide range of possible causes of unilateral ON in the paediatric population. The absence of typical ON features in MR imaging was strongly suggestive of idiopathic ON in this cohort (p < 0.01).
Sustained Complete Remission with Incomplete Hematologic Recovery (CRi) in a Patient with Relapsed AML and Concurrent BCR-ABL1 and CBFB Rearrangement Treated with a Combination of Venetoclax and 5-Azacytidine
Authors: Levato Luciano , Gianfelici Valentina , Caglioti Francesca , Russo Antonio , Giugliano Emilia , Mannella Ada , Molica Stefano
Published: June 2020

The co-occurrence of BCR-ABL1 fusion and core-binding factor (CBF) rearrangements is uncommonly reported in AML. Although CBF rearrangements carry a favorable prognosis, the coexistence of BCR-ABL1 is associated with aggressive disease suggesting a potential advantage of high-intensity chemotherapy in association with tyrosine kinase inhibitors. Herein, we describe a refractory AML patient harboring BCR-ABL1 fusion and CBFB rearrangement that was successfully treated with a combination of venetoclax and hypomethylating agent.
Clinical Characteristics of Metastatic Prostate Cancer Patients Infected with COVID-19 in South Italy
Authors: Di Lorenzo Giuseppe , Buonerba Luciana , Ingenito Concetta , Crocetto Felice , Buonerba Carlo , Libroia Annamaria , Sciarra Antonella , Ragone Gianluca , Sanseverino Roberto , Iaccarino Simona , Napodano Giorgio , Imbimbo Ciro , Leo Emilio , Kozlakidis Zisis , De Placido Sabino
Published: June 2020

Background: To date, the clinical characteristics of coronavirus disease 19 (COVID-19)-infected urologic cancer patients are unknown. Methods: We have analyzed all patients with prostate cancer undergoing hormonal or chemotherapy treatment and receiving telephone and in person pre-triage between March 1 and 27, 2020, at the Tortora Hospital, Pagani, Italy. Results: Among 72 patients, 48 and 24 were hormone-sensitive (HS) and castration-resistant prostate cancer (CRPC), respectively; 0 HS and 2 (8.3%) CRPC (p < 0.05) were positive for COVID-19. Both patients were receiving LHRH agonist therapy, and 1 patient was receiving enzalutamide. Urgent intensive care unit admission was required due to clinical worsening. Blood tests showed severe lymphopenia, anemia, and an increase in platelets. Retroviral therapy, antibiotics, heparin, and chloroquine were prescribed at the beginning. One patient also received tocilizumab as a salvage treatment. After 3 weeks of hospitalization, the patients were discharged from the hospital. Both patients suffered from an aggressive COVID-19 course due to concomitant comorbidities. Conclusions: Investigating whether hormonal therapy, especially in advanced disease, acts as a protective factor or a risk factor during COVID-19 could be useful.