bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracorporeal Membrane Oxygenation in Cardiogenic Shock due to Acute Myocardial Infarction: A Systematic Review
Authors: Zavalichi Marius Andrei , Nistor Ionut , Nedelcu Alina-Elena , Zavalichi Simona Daniela , Georgescu Cătălina Marina Arsenescu , Stătescu Cristian , Covic Adrian
Published: April 2020

Background. Cardiogenic shock is associated with high mortality, despite new strategies for reperfusion therapy. Short‐term circulatory support devices may provide adequate support for appropriate myocardial and organ perfusion. Objectives. This review is aimed at evaluating the impact on survival when using venoarterial extracorporeal membrane oxygenation (V‐A ECMO) in patients with cardiogenic shock due to acute myocardial infarction (AMI). Methods. We performed a systematic review that included studies using V‐A ECMO in patients with cardiogenic shock. Time on ECMO, side effects, and the number of deceased patients, transplanted or upgraded to durable assist devices were analysed. Literature search was done using PubMed/MEDLINE (inception (1969) to January 10, 2019), ProQuest (inception (January 14, 1988) to January 10, 2019), and clinicaltrials.gov (inception (September 12, 2005) to January 10, 2019), by 2 authors. This protocol is registered with PROSPERO (no. CRD42019123982). Results. We included 9 studies with a total of 1,998 adult patients receiving V‐A ECMO for AMI‐induced cardiogenic shock. Survival rate varied from 30.0% to 79.2% at discharge and from 23.2% to 36.1% at 12 months. Time on ECMO varied between 1.96 and 6.0 days. Reported serious adverse events were gastrointestinal bleeding (3.6%) and peripheral complications (8.5%). Conclusion. The use of V‐A ECMO among patients with AMI‐induced cardiogenic shock may provide survival benefits. However, V‐A ECMO treatment effects are inconclusive because of limitations in cohort design and reporting.
The Course of Circulating Small Extracellular Vesicles in Patients Undergoing Surgical Aortic Valve Replacement
Authors: Weber Andreas , Liu Shining Sophie , Cardone Letizia , Rellecke Philipp , Sixt Stephan Urs , Lichtenberg Artur , Akhyari Payam
Published: April 2020

In the last years, increasing efforts have been devoted to investigating the role of small extracellular vesicles (sEVs) in cardiovascular diseases. These nano‐sized particles (30‐150 nm), secreted by different cell types, contain signalling molecules that enable participation in intercellular communication processes. In this study, we examined the course of circulating sEVs in patients undergoing surgical aortic valve replacement (SAVR) and correlated them with echocardiographic and standard blood parameters. Peripheral blood samples were collected from 135 patients undergoing SAVR preoperatively and at three follow‐up points. Circulating sEVs were precipitated using Exoquick™ exosome isolation reagent and analyzed by nanoparticle tracking analysis (NTA). Our findings indicate that no more than 7 days after SAVR, there was a marked increase of circulating sEVs before returning to initial values after 3 months. Further, shear stress is not a trigger for the formation and release of circulating sEVs. Moreover, we pointed out a correlation between circulating sEVs and erythrocytes as well as LDH and creatinine levels in peripheral blood. Finally, all patients with a moderate prosthesis‐patient mismatch as well as with an impaired left ventricular mass regression had lower levels of circulating sEVs 3 months after SAVR compared to their respective status before surgery. We conclude that in patients with aortic valve stenosis (AVS), sEVs may play an important part in mediating cell‐cell communication and SAVR may have a crucial and lasting impact on their circulating levels. Besides, lower levels of sEVs portend to be associated with inferior recovery after major surgical interventions. The additional use of circulating sEVs beyond echocardiographic and laboratory parameters could have a prognostic value to estimate adverse outcomes in patients undergoing SAVR.
Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of Cytochromecand Cardiolipin
Authors: Díaz-Quintana Antonio , Pérez-Mejías Gonzalo , Guerra-Castellano Alejandra , De la Rosa Miguel A. , Díaz-Moreno Irene
Published: April 2020

Cardiolipin oxidation and degradation by different factors under severe cell stress serve as a trigger for genetically encoded cell death programs. In this context, the interplay between cardiolipin and another mitochondrial factor—cytochromec—is a key process in the early stages of apoptosis, and it is a matter of intense research. Cytochromecinteracts with lipid membranes by electrostatic interactions, hydrogen bonds, and hydrophobic effects. Experimental conditions (including pH, lipid composition, and post-translational modifications) determine which specific amino acid residues are involved in the interaction and influence the heme iron coordination state. In fact, up to four binding sites (A, C, N, and L), driven by different interactions, have been reported. Nevertheless, key aspects of the mechanism for cardiolipin oxidation by the hemeprotein are well established. First, cytochromecacts as a pseudoperoxidase, a process orchestrated by tyrosine residues which are crucial for peroxygenase activity and sensitivity towards oxidation caused by protein self-degradation. Second, flexibility of two weakest folding units of the hemeprotein correlates with its peroxidase activity and the stability of the iron coordination sphere. Third, the diversity of the mode of interaction parallels a broad diversity in the specific reaction pathway. Thus, current knowledge has already enabled the design of novel drugs designed to successfully inhibit cardiolipin oxidation.
Real-Time Low-Cost Speed Monitoring and Control of Three-Phase Induction Motor via a Voltage/Frequency Control Approach
Authors: Hmidet Ali , Boubaker Olfa
Published: April 2020

In this paper, a new design of a real-time low-cost speed monitoring and closed-loop control of the three-phase induction motor (IM) is proposed. The proposed solution is based on a voltage/frequency (V/F) control approach and a PI antiwindup regulator. It uses the Waijung Blockset which considerably alleviates the heaviness and the difficulty of the microcontroller’s programming task incessantly crucial for the implementation and the management of such complex applications. Indeed, it automatically generates C codes for many types of microcontrollers like the STM32F4 family, also used in this application. Furthermore, it offers a cost-effective design reducing the system components and increasing its efficiency. To prove the efficiency of the suggested design, not only simulation results are carried out for a wide range of variations in load and reference speed but also experimental assessment. The real-time closed-loop control performances are proved using the aMG SQLite Data Server via the UART port board, whereas Waijung WebPage Designer (W2D) is used for the web monitoring task. Experimental results prove the accuracy and robustness of the proposed solution.
Energy Dissipation Characteristic of Red Sandstone in the Dynamic Brazilian Disc Test with SHPB Setup
Authors: Gong Fengqiang , Hu Jian
Published: April 2020

In order to quantitatively investigate the energy dissipation characteristic during the dynamic tension failure of rock materials, the dynamic Brazilian disc tests on red sandstone were conducted using the split Hopkinson pressure bar (SHPB) setup. The states of the specimens after different incident energies can be divided into three forms (i.e., the unruptured state, the ruptured state, and the broken state), and the failure processes of the specimens were recorded by using a high‐speed camera. The results show that the ruptured state of the specimen corresponds to the critical failure strain. Taking the critical incident energy as a turning point, two positive linear fitting relations between the dissipated energy and incident energy before and after the point are obtained, and the dynamic linear dissipation law is found. When the incident energy is less than the critical energy, specimens were unruptured after impact. When the incident energy is greater than the critical energy, specimens will be broken after impact. According to the obtained linear energy dissipation law, the dynamic tensile energy dissipation coefficient (DTEDC) was introduced for quantitatively describing the dynamic energy dissipation capacity of rock materials in the dynamic Brazilian disc test. When the specimen is in the unruptured state, the ideal DTEDC is a constant value. When the specimen is in a broken state, the DTEDC increases with the increase of incident energy.
Tissue Distribution of Hirsutine and Hirsuteine in Mice by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry
Authors: Zhou Quan , Ma Jianshe , Chen Limei
Published: April 2020

Hirsutine and hirsuteine were two alkaloid monomers extracted from the traditional Chinese medicine Uncaria rhynchophylla, which have pharmacological effects such as antihypertension, anti-infection, and heart protection. An ultrahigh-performance liquid chromatography-mass spectrometry was established for the determination of hirsutine and hirsuteine in tissues (liver, kidney, heart, spleen, brain, and lung), and their absorption, distribution, and metabolism were studied for providing information on its pharmacological mechanism. UPLC BEH C18 column (2.1  mm × 100  mm, 1.7 μm) was used for chromatographic separation. The mobile phase was acetonitrile-0.1% formic acid, with a gradient elution, and the total run time was 4 min. Electrospray was used in the positive ion mode, and the multiple reaction monitoring (MRM) mode was for quantification. The acetonitrile precipitation method was used to remove protein-treated mouse plasma and tissue homogenate samples. In the concentration range of 2–5000 ng/g, hirsutine and hirsuteine in tissues showed good linearity (r > 0.995), and the lower limit of quantification was 2 ng/g. In the plasma and liver tissues, the interday and intraday precision of hirsutine and hirsuteine was less than 15%, the accuracy was between 90.9% and 110.1%, and the average recovery was better than 73.0%. The matrix effect was between 86.2% and 104.7%. The results showed that the precision, accuracy, recovery, and matrix effects meet the requirements for the study on the distribution of hirsutine and hirsuteine. After intraperitoneal administration of 10 mg/kg hirsutine and hirsuteine in mice, the distribution levels were highest in liver and kidney tissues, followed by the spleen and lung. Hirsutine and hirsuteine were low in brain tissue, but had obvious distribution, suggesting that they may pass through the blood-brain barrier.
Application of Fly Ash and Slag Generated by Incineration of Municipal Solid Waste in Concrete
Authors: Zeng Cong , Lyu Yan , Wang Dehong , Ju Yanzhong , Shang Xiaoyu , Li Luoke
Published: April 2020

As landfill space for the disposal of products of municipal solid waste incineration (MSWI) such as fly ash and slag becomes increasingly scarce, a reduction of disposed material is urgently required. The method of using incineration products in concrete production is explored in this paper through a feasibility study of utilizing fly ash and slag to replace cement and coarse aggregate in appropriate proportions. Results show that C30 concrete optimum replacement rates of fly ash and slag are 30% and 20%, which can meet the minimum strength requirement. The leaching concentrations of Cu, Zn, Pb, Cr, and Cd in MSWI concrete samples are determined to be less than the identification value of solid waste leaching toxicity. Based on scanning electron microscopy (SEM) and X‐ray diffraction (XRD) analyses, MSWI fly ash has certain dispersion. The particle size of MSWI fly ash is determined to be close to that of the coal fly ash, and the surface morphology is irregular. The main components include SiO2, CaCO3, and Ca2SiO4, and they are similar to those present in the coal fly ash. The slag structure is loose as well as irregular, and its main component is SiO2. The SiO2 and Al2O3 in fly ash and slag participate in the hydration reaction of cement and can increase concrete strength. It is thus confirmed that fly ash and slag generated by waste incineration can be used to replace cement and coarse aggregate in appropriate proportions, and it is an effective method to solve the problem of scarcity of solid waste landfill space.
Extension of Research on Security as a Service for VMs in IaaS Platform
Authors: Yin Xueyuan , Chen Xingshu , Chen Lin , Li Hui
Published: April 2020

To satisfy security concerns including infrastructure as a service (IaaS) security framework, security service access, network anomaly detection, and virtual machine (VM) monitoring, a layered security framework is built which composes of a physical layer, a virtualization layer, and a security management layer. Then, two security service access methods are realized for various security tools from the perspective of whether security tools generate communication traffic. One without generating traffic employs the VM traffic redirection technology and the other leveraged the mechanism of multitasking process access. Moreover, a stacked LSTM-based network anomaly detection agentless method is proposed, which has advantages of a higher ratio of precision and recall. Finally, a Hypervisor-based agentless monitoring method for VMs based on dynamic code injection is proposed, which has benefits of high security of the external monitoring method and good context analysis of the internal monitoring mechanism. The experimental results demonstrate the effectiveness of the proposed protection framework and the corresponding security mechanisms, respectively.
Improved Approaches to Minimize the Makespan on Single-Machine Scheduling with Periodic Preventive Maintenance Activities
Authors: Zhou Hongming , Tsai Ya-Chih , Wu Ful-Chiang , Huang Shenquan , Chou Fuh-Der
Published: April 2020

This paper addresses a single-machine scheduling problem with periodic preventive maintenance activities that are predeterministic so that the machine is not available all the time, and jobs have to be processed between two consecutive maintenance periods. We propose a mixed integer programming (MIP) model and two heuristics to minimize the makespan. With more constraints in our model, the model is more efficient than the recent model of Perez-Gonzalez and Framinan , and our model could solve problems with up to fifty jobs. Two heuristic algorithms, namely, H (MW) and H (LB∗), are also proposed, in which two bin-packing policies of the minimum waste and minimum lower bound are used, respectively. Furthermore, we also proposed an improvement procedure. The results showed that the heuristic H (MW) outperformed other heuristics of the paper, indicating that the bin-packing policy of the minimum waste is more effective than well-known ones such as full batch and best fit. Additionally, all the heuristic algorithms addressed in this paper combined with the improvement procedure could achieve a similar and high quality of solutions with a very tiny increase in computational expense.
Prediction of the Network Pharmacology‐Based Mechanism for Attenuation of Atherosclerosis in Apolipoprotein E Knockout Mice by Panax notoginseng Saponins
Authors: Long Linzi , Yu Zikai , Qu Hua , Wang Ning , Guo Ming , Zhou Xuezhong , Fu Changgeng , Gao Zhuye
Published: April 2020

This study investigated whether Panax notoginseng saponins (PNS) reduced atherosclerotic lesion formation in apolipoprotein E knockout (ApoE‐KO) mice and illustrated the potential mechanism for a network pharmacology approach. Pharmacodynamics studies on ApoE‐KO mice with atherosclerosis (AS) showed that PNS generated an obvious anti‐AS action. Then, we explored the possible mechanisms underlying its anti‐AS effect using the network pharmacology approach. The main chemical components and their targets of PNS were collected from TCMSP public database and SymMap. The STRING v11.0 was used to establish the protein‐protein interactions of PNS. Furthermore, the Gene Ontology (GO) function and KEGG pathways were analyzed using STRING to investigate the possible mechanisms involved in the anti‐AS effect of PNS. The predicted results showed that 27 potential targets regulated by DSLHG were related to AS, including ACTA2, AKT1, BCL2, and BDNF. Mechanistically, the anti‐AS effect of PNS was exerted by interfering with multiple signaling pathways, such as AGE‐RAGE signaling pathway, fluid shear stress and atherosclerosis, and TNF signaling pathway. Network analysis showed that PNS could generate the anti‐AS action by affecting multiple targets and multiple pathways and provides a novel basis to clarify the mechanisms of anti‐AS of PNS.
Two New Conjugate Gradient Methods for Unconstrained Optimization
Authors: Liu Meixing , Ma Guodong , Yin Jianghua
Published: April 2020

The conjugate gradient method is very effective in solving large-scale unconstrained optimal problems. In this paper, on the basis of the conjugate parameter of the conjugate descent (CD) method and the second inequality in the strong Wolfe line search, two new conjugate parameters are devised. Using the strong Wolfe line search to obtain the step lengths, two modified conjugate gradient methods are proposed for general unconstrained optimization. Under the standard assumptions, the two presented methods are proved to be sufficient descent and globally convergent. Finally, preliminary numerical results are reported to show that the proposed methods are promising.
Microtubule Engagement with Taxane Is Altered in Taxane-Resistant Gastric Cancer
Authors: Galletti Giuseppe , Zhang Chao , Gjyrezi Ada , Cleveland Kyle , Zhang Jiaren , Powell Sarah , Thakkar Prashant V. , Betel Doron , Shah Manish A. , Giannakakou Paraskevi
Published: April 2020

Purpose:

Although taxane-based therapy is standard treatment for advanced gastric cancer, a majority of patients exhibit intrinsic resistance to taxanes. Here, we aim to identify the molecular basis of taxane resistance in gastric cancer.

Experimental Design:

We performed a post hoc analysis of the TAX-325 clinical trial and molecular interrogation of gastric cancer cell lines to assess the benefit of docetaxel in diffuse (DIF-GC) versus intestinal (INT-GC) gastric cancer. We assessed drug-induced microtubule stabilization in gastric cancer cells and in biopsies of patients with gastric cancer treated with taxanes. We performed transcriptome analysis in taxane-treated gastric cancer cells and patients to identify molecular drivers of taxane resistance.

Results:

Patients with DIF-GC did not derive a clinical benefit from taxane treatment suggesting intrinsic taxane resistance. DIF-GC cell lines displayed intrinsic resistance specific to taxanes because of impaired drug-induced microtubule stabilization, in the absence of tubulin mutations or decreased drug accumulation. Using taxane-treated gastric cancer patient biopsies, we demonstrated that absence of drug–target engagement was correlated with clinical taxane resistance. Taxane-sensitive cell lines displayed faster microtubule dynamics at baseline, implicating proteins that regulate cytoskeletal dynamics in intrinsic taxane resistance. Differential gene expression analysis of untreated and docetaxel-treated gastric cancer lines and patient samples identified kinesins to be associated with taxane sensitivity in vitro and in patient samples.

Conclusions:

Our data reveal that taxane resistance is more prevalent in patients with DIF-GC, support assessment of drug–target engagement as an early read-out of taxane clinical efficacy, and encourage the investigation of kinesins and other microtubule-associated proteins as potentially targetable mediators of taxane resistance in gastric cancer.
Safety, Efficacy, and Biomarker Analysis of Toripalimab in Previously Treated Advanced Melanoma: Results of the POLARIS-01 Multicenter Phase II Trial
Authors: Tang Bixia , Chi Zhihong , Chen Yingbo , Liu Xiufeng , Wu Di , Chen Jing , Song Xin , Wang Weifeng , Dong Lihou , Song Haifeng , Wu Hai , Feng Hui , Yao Sheng , Qin Shuikui , Zhang Xiaoshi , Guo Jun
Published: April 2020

Purpose:

In contrast to the predominant chronic UV exposure–induced cutaneous melanoma in Caucasians, acral and mucosal comprise the majority of melanomas in Asia and respond less effectively to established treatments. The clinical application of PD-1 blockade is yet to be explored in metastatic melanoma in China.

Patients and Methods:

This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese patients with melanoma who had failed in systemic treatments. Toripalimab was given at 3 mg/kg i.v. once every 2 weeks until disease progression or unacceptable toxicity. The primary objective was safety and objective response rate.

Results:

128 Patients with melanoma were enrolled, including 50 acral and 22 mucosal. As of August 15, 2019, 23 months after the last enrollment, 116 (90.6%) experienced treatment-related adverse events. ≥Grade 3 TRAEs occurred in 25 (19.5%) patients. Among 127 patients assessed, 1 complete response, 21 partial response, and 51 stable disease were observed for objective response rate of 17.3% and disease control rate of 57.5%. Median duration of response was not reached. Median progression-free survival was 3.6 months [95% confidence interval (CI) 2.7–5.3] and median overall survival was 22.2 months (95% CI, 15.3–NE). Patients with positive PD-L1 staining in tumor biopsies had significant better ORR (38.5% vs. 11.9%, P = 0.0065), PFS (7.7 months vs. 2.7 months, P = 0.013), and OS (not reached vs. 14.4 months, P = 0.0005) than PD-L1–negative patients.

Conclusions:

This is the largest prospective anti-PD-1 clinical study in advanced melanoma with predominantly acral and mucosal subtypes. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma refractory to standard therapy.

See related commentary by Shoushtari et al., p. 4171
AMPK Activation by Metformin Promotes Survival of Dormant ER+ Breast Cancer Cells
Authors: Hampsch Riley A. , Wells Jason D. , Traphagen Nicole A. , McCleery Charlotte F. , Fields Jennifer L. , Shee Kevin , Dillon Lloye M. , Pooler Darcy B. , Lewis Lionel D. , Demidenko Eugene , Huang Yina H. , Marotti Jonathan D. , Goen Abigail E. , Kinlaw William B. , Miller Todd W.
Published: April 2020

Purpose:

Despite adjuvant endocrine therapy for patients with estrogen receptor alpha (ER)-positive breast cancer, dormant residual disease can persist for years and eventually cause tumor recurrence. We sought to deduce mechanisms underlying the persistence of dormant cancer cells to identify therapeutic strategies.

Experimental Design:

Mimicking the aromatase inhibitor–induced depletion of estrogen levels used to treat patients, we developed preclinical models of dormancy in ER+ breast cancer induced by estrogen withdrawal in mice. We analyzed tumor xenografts and cultured cancer cells for molecular and cellular responses to estrogen withdrawal and drug treatments. Publicly available clinical breast tumor gene expression datasets were analyzed for responses to neoadjuvant endocrine therapy.

Results:

Dormant breast cancer cells exhibited upregulated 5′ adenosine monophosphate-activated protein kinase (AMPK) levels and activity, and upregulated fatty acid oxidation. While the antidiabetes AMPK-activating drug metformin slowed the estrogen-driven growth of cells and tumors, metformin promoted the persistence of estrogen-deprived cells and tumors through increased mitochondrial respiration driven by fatty acid oxidation. Pharmacologic or genetic inhibition of AMPK or fatty acid oxidation promoted clearance of dormant residual disease, while dietary fat increased tumor cell survival.

Conclusions:

AMPK has context-dependent effects in cancer, cautioning against the widespread use of an AMPK activator across disease settings. The development of therapeutics targeting fat metabolism is warranted in ER+ breast cancer.
Event-Related Potential Evidence of Enhanced Visual Processing in Auditory-Associated Cortex in Adults with Hearing Loss
Authors: Liang Maojin , Liu Jiahao , Cai Yuexin , Zhao Fei , Chen Suijun , Chen Lin , Chen Yuebo , Zheng Yiqing
Published: April 2020

Objective: The present study investigated the characteristics of visual processing in the auditory-associated cortex in adults with hearing loss using event-related potentials. Methods: Ten subjects with bilateral postlingual hearing loss were recruited. Ten age- and sex-matched normal-hearing subjects were included as controls. Visual (“sound” and “non-sound” photos)-evoked potentials were performed. The P170 response in the occipital area as well as N1 and N2 responses in FC3 and FC4 were analyzed. Results: Adults with hearing loss had higher P170 amplitudes, significantly higher N2 amplitudes, and shorter N2 latency in response to “sound” and “non-sound” photo stimuli at both FC3 and FC4, with the exception of the N2 amplitude which responded to “sound” photo stimuli at FC3. Further topographic mapping analysis revealed that patients had a large difference in response to “sound” and “non-sound” photos in the right frontotemporal area, starting from approximately 200 to 400 ms. Localization of source showed the difference to be located in the middle frontal gyrus region (BA10) at around 266 ms. Conclusions: The significantly stronger responses to visual stimuli indicate enhanced visual processing in the auditory-associated cortex in adults with hearing loss, which may be attributed to cortical visual reorganization involving the right frontotemporal cortex.
Stereotactic Body Radiotherapy Combined with Transcatheter Arterial Chemoembolization versus Stereotactic Body Radiotherapy Alone as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review
Authors: Zhao Jiani , Zeng Lianli , Wu Qian , Wang Li , Lei Jun , Luo Hongliang , Yi Fengming , Wei Yiping , Yu Jiao , Zhang Wenxiong
Published: April 2020

Background: The superiority of stereotactic body radiotherapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) compared to SBRT alone as the first-line therapy for unresectable hepatocellular carcinoma (HCC) remains unclear. We conducted this meta-analysis to compare the efficiency and safety of SBRT combined with TACE (ST group) and SBRT alone (SA group). Methods: We searched PubMed, Ovid Medline, Web of Science, Scopus, The Cochrane Library, ScienceDirect, EMBASE, Google Scholar, and CNKI (China National Knowledge Infrastructure) for related studies. We analyzed overall survival (OS), local control survival (LCS), progression-free survival (PFS), the response rate and adverse effects (AEs) between the 2 groups. Results: Ten articles were included, with a total of 980 patients. The results showed that the ST (SBRT + TACE) group had a longer OS (95% CIs 0.60–0.85, p = 0.0002), a higher 5-year OS rate (95% CI 1.01–2.04, p = 0.04), a higher rate of complete response (95% CI 1.08–1.90, p = 0.01), and a higher disease control rate (95% CI 1.02–1.16, p = 0.02) than the SA (SBRT alone) group. No significant difference was found in LCS, PFS and total AEs of all grades and grades 3–5 AEs between the 2 groups. In the subgroup analysis, the patients with HCC + PVTT or treated with SBRT followed by TACE in the ST group had the same OS as those in the SA group, and the patients in the ST group had a higher incidence rate of leukopenia and fever than those in the SA group. Conclusion: SBRT + TACE appears to be more effective than SBRT alone in treating unresectable HCC. However, its higher incidence rate of leukopenia and fever need to be monitored.
Pronounced Impairment of Activities of Daily Living in Posterior Cortical Atrophy
Authors: Ahmed Samrah , Culley Siobhan , Blanco-Duque Cristina , Hodges John R. , Butler Christopher , Mioshi Eneida
Published: April 2020

Introduction: The impact of several dementia syndromes on activities of daily living (ADLs) has been well documented, but no study has yet investigated functional ability in posterior cortical atrophy (PCA). The primarily visual nature of deficits in this condition is likely to have a pronounced impact on ADLs. Objective: The aim of this study was to profile functional change in PCA and identify predictors of change. Method: Twenty-nine PCA patients and 25 patients with typical Alzheimer’s disease (AD) and their caregivers were included in this cross-sectional study. ADLs were assessed using the Disability Assessment for Dementia (DAD), administered to caregivers, assessing basic ADLs (e.g., eating, dressing) and instrumental ADLs (e.g., managing finances, meal preparation). The predictive utility of cognitive domains (Addenbrooke’s Cognitive Examination), behavioural impairment (Cambridge Behavioural Inventory-Revised) and demographic variables on ADL ability was also examined. Results: PCA patients showed significantly reduced total ADL scores compared to AD patients (medium effect size, d = –0.7; p < 0.05), with significantly more impairment on basic ADLs (large effect size, d = –0.8; p < 0.05) but similar impairment on instrumental ADLs (medium effect size, d = –0.5; p > 0.05). A model combining patient mood, disinhibition, apathy, symptom duration, and memory and attention/orientation scores explained the variance of scores in functional decline (61.2%), but the key factor predicting ADL scores was attention/orientation (p = 0.048). Conclusion: This study shows the profound impact of PCA on ADLs and factors underpinning patients’ disability. Attention/orientation deficits were found to correlate and contribute to variance in ADL scores. Future work to develop tailored interventions to manage ADL impairment in PCA should take these findings into account.
Characteristics of Perfusion Computed Tomography Imaging in Patients with Seizures Mimicking Acute Stroke
Authors: Khoo Ching Soong , Kim Si Eun , Lee Byung In , Shin Kyong Jin , Ha Sam Yeol , Park JinSe , Park Kang Min , Bae Soo-young , Lee Dongah , Kim Byung Joon , Bae Min-jeong , Kim Sung Eun
Published: April 2020

Introduction: Seizures as acute stroke mimics are a diagnostic challenge. Objective: The aim of the study was to characterize the perfusion patterns on perfusion computed tomography (PCT) in patients with seizures masquerading as acute stroke. Methods: We conducted a study on patients with acute seizures as stroke mimics. The inclusion criteria for this study were patients (1) initially presenting with stroke-like symptoms but finally diagnosed to have seizures and (2) with PCT performed within 72 h of seizures. The PCT of seizure patients (n = 27) was compared with that of revascularized stroke patients (n = 20) as the control group. Results: Among the 27 patients with seizures as stroke mimics, 70.4% (n = 19) showed characteristic PCT findings compared with the revascularized stroke patients, which were as follows: (1) multi-territorial cortical hyperperfusion {(73.7% [14/19] vs. 0% [0/20], p = 0.002), sensitivity of 73.7%, negative predictive value (NPV) of 80%}, (2) involvement of the ipsilateral thalamus {(57.9% [11/19] vs. 0% [0/20], p = 0.007), sensitivity of 57.9%, NPV of 71.4%}, and (3) reduced perfusion time {(84.2% [16/19] vs. 0% [0/20], p = 0.001), sensitivity of 84.2%, NPV of 87%}. These 3 findings had 100% specificity and positive predictive value in predicting patients with acute seizures in comparison with reperfused stroke patients. Older age was strongly associated with abnormal perfusion changes (p = 0.038), with a mean age of 66.8 ± 14.5 years versus 49.2 ± 27.4 years (in seizure patients with normal perfusion scan). Conclusions: PCT is a reliable tool to differentiate acute seizures from acute stroke in the emergency setting.
Cecal Volvulus: A Rare Cause of Intestinal Obstruction
Authors: Solis Rojas Carolina , Vidrio Duarte Ramon , García Vivanco Diego Martín , Montalvo-Javé Eduardo E.
Published: April 2020

Cecal volvulus is a rare cause of intestinal obstruction, with multifactorial etiologies. This is a case report describing a 52-year-old female with a cecal volvulus diagnosis made during the laparotomy procedure, which was treated with a right hemicolectomy with a side-to-side ileotransverse anastomosis. The aim of this report is to emphasize the importance of a diagnosis and appropriate treatment in this rare pathology in abdominal procedures. In this particular case, the patient benefited from an early surgical intervention without further complications, as well as an adequate postoperative evolution; it is important to acknowledge and consider this pathology during differential diagnosis, and not delay the treatment in patients with cecal volvulus. A critical review of the literature is included and discussed.
Possible “Premotor” Multiple System Atrophy-Cerebellar Form
Authors: Sakakibara Ryuji , Panicker Jalesh N. , Aiba Yosuke , Tateno Fuyuki , Ogata Tsuyoshi , Yano Masashi , Suzuki Hiroyoshi , Sugisaki Yuuka , Shimizu Ayami , Takahashi Osamu , Simeoni Sara
Published: April 2020

We report the case of a 52-year-old Japanese man who, while he had no cerebellar ataxia or parkinsonism, was revealed to have silent cerebellar hypoperfusion/mild cerebellar atrophy and sacral autonomic disorder. His sacral autonomic disorder was urinary retention without marked prostate hyperplasia. Urodynamics-sphincter electromyography revealed detrusor hyperactivity with impaired contraction and neurogenic changes of the sphincter motor unit potentials. Although he did not have a motor disorder, these features suggested possible multiple system atrophy-cerebellar (MSA-C) form. The present case report suggests that neuroimaging helps in diagnosing “premotor” MSA-C form in situ.
Impact of the Tumor Microenvironment on the Gene Expression Profile in Papillary Thyroid Cancer
Authors: Oczko-Wojciechowska Malgorzata , Pfeifer Aleksandra , Jarzab Michal , Swierniak Michał , Rusinek Dagmara , Tyszkiewicz Tomasz , Kowalska Malgorzata , Chmielik Ewa , Zembala-Nozynska Ewa , Czarniecka Agnieszka , Jarzab Barbara , Krajewska Jolanta
Published: April 2020

Transcriptome of papillary thyroid cancer (PTC) is well characterized and correlates with some prognostic and genotypic factors, but data addressing the interaction between PTC and tumor microenvironment (TME) are scarce. Therefore, in the present study, we aimed to assess the impact of TME on gene expression profile in PTC. We evaluated the gene expression profile in PTC and normal thyroid cells isolated by laser capture microdissection and in whole tissue slides corresponding to the entire tumor. We included 26 microdissected samples for gene expression analysis (HG-U133 PLUS 2.0, Affymetrix, currently Thermo Fisher Scientific USA): 15 PTC samples, 11 samples of normal thyrocytes, and 30 whole slides (15 PTC and 15 normal thyroid). Transcripts were divided into three groups: differentially expressed both in microdissected and whole slides, transcripts differently expressed in microdissected samples and not changed in whole slides, and transcripts differentially expressed in whole slides and not changed in microdissected samples. Eleven genes were selected for validation in an independent set of samples; among them, four genes differentiated only microdissected PTC and normal cells. Two genes (PTCSC and CTGF) were confirmed. One gene (FOS) was not confirmed by the validation, whereas EGR1 was also significant in whole slide analysis. The other seven genes (TFF3, FN1, MPPED2, MET, KCNJ2, TACSTD2, and GALE) showed differentiated expression in microdissected thyrocytes and in whole tumor slides. Most of identified genes were related to the tumor-microenvironment interaction and confirmed the crosstalk between TME and cancer cells.
Predictors of Hypophosphatemia and Outcomes during Continuous Renal Replacement Therapy
Authors: Hendrix Rachel Jenkins , Hastings M. Colleen , Samarin Michael , Hudson Joanna Q.
Published: April 2020

Introduction: Hypophosphatemia occurs in up to 80% of patients undergoing continuous renal replacement therapy (CRRT) and has been associated with poor outcomes. Whether preemptive phosphate supplementation is warranted in select patients has not been adequately explored. This single-center, retrospective cohort study evaluates predictors of hypophosphatemia and characterizes treatment approaches in adult patients undergoing at least 12 h of CRRT. Methods: Patients were divided into 2 groups based on the presence or absence of hypophosphatemia as defined by serum phosphorus <2.5 mg/dL. Select laboratory values at baseline and during CRRT, medications and nutritional sources affecting phosphorus, and CRRT parameters were compared. Patient outcomes including resolution of acute kidney injury (AKI), freedom from renal replacement therapy at hospital discharge, duration of intensive care unit (ICU) and hospital stay, duration of mechanical ventilation, and ICU mortality were evaluated. Results: Seventy-two patients were included. The group was 43% female and 51% African American. CRRT was ordered for AKI in 83% and for end-stage renal disease in 15%. Hypophosphatemia occurred in 45 patients (63%). Mean time to development of hypophosphatemia was 34 ± 22 h. Patients who developed hypophosphatemia received a longer duration of CRRT (p = 0.001), were more likely to have a diet ordered (p = 0.005), less likely to have received calcium infusions (p = 0.045), and had lower phosphorus (p = 0.017) and potassium levels (p = 0.038) and higher calcium levels at baseline (p = 0.048). Development of hypophosphatemia was associated with an increased duration of ICU stay (p = 0.014) but not with the other patient outcomes evaluated. Twenty-seven of the 45 patients (60%) who developed hypophosphatemia received phosphorus supplementation with near equal use of intravenous, oral, and combination routes. Only 17 patients (38%) achieved resolution of hypophosphatemia while on CRRT. Conclusion: Hypophosphatemia is common, difficult to correct, and contributes to longer ICU stays in patients requiring CRRT. A preemptive approach to address hypophosphatemia including aggressive supplementation strategies to correct phosphorus is warranted in patients requiring CRRT.
Acute Kidney Injury Associated with Minimal Change Nephrotic Syndrome in an Elderly Patient Successfully Treated with both Fluid Management and Specific Therapy Based on Kidney Biopsy Findings
Authors: Oyama Yuko , Iwafuchi Yoichi , Morioka Tetsuo , Narita Ichiei
Published: April 2020

Oliguric acute kidney injury (AKI) with minimal change nephrotic syndrome (MCNS) has long been recognized. Several mechanisms such as hypovolemia due to hypoalbuminemia and the nephrosarca hypothesis have been proposed. However, the precise mechanism by which MCNS causes AKI has not been fully elucidated. Herein, we describe an elderly patient with AKI caused by MCNS who fully recovered after aggressive volume withdrawal by hemodialysis and administration of a glucocorticoid. A 75-year-old woman presented with diarrhea and oliguria, and laboratory examination revealed nephrotic syndrome (NS) and severe azotemia. Fluid administration had no effect on renal dysfunction, and hemodialysis was initiated. Her renal function improved upon aggressive fluid removal through hemodialysis. Renal pathological findings revealed minimal change disease with faint mesangial deposits of IgA. After administration of methylprednisolone pulse therapy followed by oral prednisolone, she achieved complete remission from NS. The clinical course of this case supports the nephrosarca hypothesis regarding the mechanism of AKI caused by MCNS. Furthermore, appropriate fluid management and kidney biopsy are also important in elderly patients with AKI caused by NS.
Bone Marrow Endothelial Cells Regulate Myelopoiesis in Diabetes Mellitus
Authors: Hoyer Friedrich Felix , Zhang Xinyi , Coppin Emilie , Vasamsetti Sathish Babu , Modugu Ganesh , Schloss Maximilian J. , Rohde David , McAlpine Cameron S. , Iwamoto Yoshiko , Libby Peter , Naxerova Kamila , Swirski Filip K. , Dutta Partha , Nahrendorf Matthias
Published: April 2020

Background:

Diabetes mellitus is a prevalent public health problem that affects about one-third of the US population and leads to serious vascular complications with increased risk for coronary artery disease. How bone marrow hematopoiesis contributes to diabetes mellitus complications is incompletely understood. We investigated the role of bone marrow endothelial cells in diabetic regulation of inflammatory myeloid cell production.

Methods:

In 3 types of mouse diabetes mellitus, including streptozotocin, high-fat diet, and genetic induction using leptin-receptor-deficient db/db mice, we assayed leukocytes, hematopoietic stem and progenitor cells (HSPC). In addition, we investigated bone marrow endothelial cells with flow cytometry and expression profiling.

Results:

In diabetes mellitus, we observed enhanced proliferation of HSPC leading to augmented circulating myeloid cell numbers. Analysis of bone marrow niche cells revealed that endothelial cells in diabetic mice expressed less
Cxcl12
, a retention factor promoting HSPC quiescence. Transcriptome-wide analysis of bone marrow endothelial cells demonstrated enrichment of genes involved in epithelial growth factor receptor (Egfr) signaling in mice with diet-induced diabetes mellitus. To explore whether endothelial Egfr plays a functional role in myelopoiesis, we generated mice with endothelial-specific deletion of Egfr (
Cdh5

Cre

Egfr

fl/fl

). We found enhanced HSPC proliferation and increased myeloid cell production in
Cdh5

Cre

Egfr

fl/fl

mice compared with wild-type mice with diabetes mellitus. Disrupted Egfr signaling in endothelial cells decreased their expression of the HSPC retention factor angiopoietin-1. We tested the functional relevance of these findings for wound healing and atherosclerosis, both implicated in complications of diabetes mellitus. Inflammatory myeloid cells accumulated more in skin wounds of diabetic
Cdh5

Cre

Egfr

fl/fl

mice, significantly delaying wound closure. Atherosclerosis was accelerated in
Cdh5

Cre

Egfr

fl/fl

mice, leading to larger and more inflamed atherosclerotic lesions in the aorta.

Conclusions:

In diabetes mellitus, bone marrow endothelial cells participate in the dysregulation of bone marrow hematopoiesis. Diabetes mellitus reduces endothelial production of Cxcl12, a quiescence-promoting niche factor that reduces stem cell proliferation. We describe a previously unknown counterregulatory pathway, in which protective endothelial Egfr signaling curbs HSPC proliferation and myeloid cell production.
Distinct Characteristics of VEGF‐D and VEGF‐C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease
Authors: Wada Hiromichi , Suzuki Masahiro , Matsuda Morihiro , Ajiro Yoichi , Shinozaki Tsuyoshi , Sakagami Satoru , Yonezawa Kazuya , Shimizu Masatoshi , Funada Junichi , Takenaka Takashi , Morita Yukiko , Nakamura Toshihiro , Fujimoto Kazuteru , Matsubara Hiromi , Kato Toru , Unoki Takashi , Takagi Daisuke , Wada Kyohma , Wada Miyaka , Iguchi Moritake , Masunaga Nobutoyo , Ishii Mitsuru , Yamakage Hajime , Kusakabe Toru , Yasoda Akihiro , Shimatsu Akira , Kotani Kazuhiko , Satoh‐Asahara Noriko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji ,   ANOX Study Investigators
Published: April 2020

Background

VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients.

Methods and Results

We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old.

Conclusions

In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.
Speaking in the Brain: The Interaction between Words and Syntax in Sentence Production
Authors: Takashima Atsuko , Konopka Agnieszka , Meyer Antje , Hagoort Peter , Weber Kirsten
Published: April 2020

This neuroimaging study investigated the neural infrastructure of sentence-level language production. We compared brain activation patterns, as measured with BOLD-fMRI, during production of sentences that differed in verb argument structures (intransitives, transitives, ditransitives) and the lexical status of the verb (known verbs or pseudoverbs). The experiment consisted of 30 mini-blocks of six sentences each. Each mini-block started with an example for the type of sentence to be produced in that block. On each trial in the mini-blocks, participants were first given the (pseudo-)verb followed by three geometric shapes to serve as verb arguments in the sentences. Production of sentences with known verbs yielded greater activation compared to sentences with pseudoverbs in the core language network of the left inferior frontal gyrus, the left posterior middle temporal gyrus, and a more posterior middle temporal region extending into the angular gyrus, analogous to effects observed in language comprehension. Increasing the number of verb arguments led to greater activation in an overlapping left posterior middle temporal gyrus/angular gyrus area, particularly for known verbs, as well as in the bilateral precuneus. Thus, producing sentences with more complex structures using existing verbs leads to increased activation in the language network, suggesting some reliance on memory retrieval of stored lexical–syntactic information during sentence production. This study thus provides evidence from sentence-level language production in line with functional models of the language network that have so far been mainly based on single-word production, comprehension, and language processing in aphasia.