bluuebunny/crossref_metadata_2025 huggingface dataset:
Human coronaviruses 229E and OC43 replicate and induce distinct antiviral responses in differentiated primary human bronchial epithelial cells
Authors: Loo Su-Ling , Wark Peter A. B. , Esneau Camille , Nichol Kristy S. , Hsu Alan C-Y. , Bartlett Nathan W.
Published: September 2020

The recurrent emergence of novel, pathogenic coronaviruses (CoVs) severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; 2002), Middle East respiratory syndrome (MERS)-CoV (2012), and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of antiviral therapies. To address this, we developed an in vitro infection model for two human coronaviruses; alphacoronavirus 229E-CoV (229E) and betacoronavirus OC43-CoV (OC43) in differentiated primary human bronchial epithelial cells (pBECs). Primary BECs from healthy subjects were grown at air-liquid interface (ALI) and infected with 229E or OC43, and replication kinetics and time-course expression of innate immune mediators were assessed. OC43 and 229E-CoVs replicated in differentiated pBECs but displayed distinct replication kinetics: 229E replicated rapidly with viral load peaking at 24 h postinfection, while OC43 replication was slower peaking at 96 h after infection. This was associated with diverse antiviral response profiles defined by increased expression of type I/III interferons and interferon-stimulated genes (ISGs) by 229E compared with no innate immune activation with OC43 infection. Understanding the host-virus interaction for previously established coronaviruses will give insight into pathogenic mechanisms underpinning SARS-CoV-2-induced respiratory disease and other future coronaviruses that may arise from zoonotic sources.
Amplitude modulation transfer functions reveal opposing populations within both the inferior colliculus and medial geniculate body
Authors: Kim Duck O. , Carney Laurel , Kuwada Shigeyuki
Published: September 2020

Opposing populations of neurons have been identified in the mammalian auditory midbrain and thalamus. In response to amplitude-modulated sounds, responses of one population (band-enhanced) increased whereas responses of another (band-suppressed) decreased relative to their responses to an unmodulated sound. These opposing auditory populations are analogous to the ON and OFF populations of the visual system and may improve transfer of information carried by the temporal envelopes of complex sounds such as speech.
Symmetric interlimb transfer of newly acquired skilled movements
Authors: Yadav Goldy , Mutha Pratik K.
Published: September 2020

How newly acquired motor skills generalize across effectors is not well understood. Here, we show that newly learned skilled actions transfer symmetrically across the arms and that task-level variability influences learning rate but not transfer magnitude or direction. Interestingly, strategies developed during learning with one arm transfer to the untrained arm. This likely reflects the outcome of learning driven by cognitive mechanisms during the initial stages of motor skill acquisition.
New Results on Synchronization of Fractional-Order Memristor‐Based Neural Networks via State Feedback Control
Authors: Li Xiaofan , Ge Yuan , Liu Hongjian , Li Huiyuan , Fang Jian-an
Published: September 2020

This paper addresses the synchronization issue for the drive-response fractional-order memristor‐based neural networks (FOMNNs) via state feedback control. To achieve the synchronization for considered drive-response FOMNNs, two feedback controllers are introduced. Then, by adopting nonsmooth analysis, fractional Lyapunov’s direct method, Young inequality, and fractional-order differential inclusions, several algebraic sufficient criteria are obtained for guaranteeing the synchronization of the drive-response FOMNNs. Lastly, for illustrating the effectiveness of the obtained theoretical results, an example is given.
Study of the Complexity Game of Supply Chain Green Innovation Introduction under EPR Policy and Government Subsidies
Authors: Zhan Xueli , Tian Yi , Liu Chengjin , Hou Aili , Ma Junhai
Published: September 2020

Nowadays, with global scientific and technological levels rapidly improving, innovation has been a great need for enterprises to solve the dilemma. Combined with EPR (Extended Producer Responsibility) and the topic of remanufacturer, adopting green innovation has been an effective way when green supply chain management is applied. In this paper, we focus on the activity of green innovation and build a model where the manufacturer will invest in green innovation to improve the product availability rate of recycled products and save the cost in the process of remanufacturing. Besides, we take three stages in a cycle into consideration, that is, production/sale, recycling used production, and remanufacture/sale, and meanwhile, the government gives a subsidy to enterprises to encourage the activity of recycling. In the process of model solving, we take a dynamic decision-making way into consideration. We find that the decision adjustment speed of players has a significant effect on the stability, and in a long dynamic repeated game process, with the speed of decision adjustment increasing, the system enters into chaos at the end of the process. It is interesting that when the speed of decision adjustment exceeds the critical point of the bifurcation diagram, the profit of the manufacturer decreases and then enters a chaotic state. Besides, with the level of subsidies increasing, the area of stable region decreases gradually. Certain investment has a positive effect on product selling and recycling as well as the profit, and the government subsidy undoubtedly raises the profit of manufacturers and encourages the activity of recycling. In the end, we make chaos control by adjusting the decision method.
Named Entity Recognition in Chinese Medical Literature Using Pretraining Models
Authors: Wang Yu , Sun Yining , Ma Zuchang , Gao Lisheng , Xu Yang
Published: September 2020

The medical literature contains valuable knowledge, such as the clinical symptoms, diagnosis, and treatments of a particular disease. Named Entity Recognition (NER) is the initial step in extracting this knowledge from unstructured text and presenting it as a Knowledge Graph (KG). However, the previous approaches of NER have often suffered from small-scale human-labelled training data. Furthermore, extracting knowledge from Chinese medical literature is a more complex task because there is no segmentation between Chinese characters. Recently, the pretraining models, which obtain representations with the prior semantic knowledge on large-scale unlabelled corpora, have achieved state-of-the-art results for a wide variety of Natural Language Processing (NLP) tasks. However, the capabilities of pretraining models have not been fully exploited, and applications of other pretraining models except BERT in specific domains, such as NER in Chinese medical literature, are also of interest. In this paper, we enhance the performance of NER in Chinese medical literature using pretraining models. First, we propose a method of data augmentation by replacing the words in the training set with synonyms through the Mask Language Model (MLM), which is a pretraining task. Then, we consider NER as the downstream task of the pretraining model and transfer the prior semantic knowledge obtained during pretraining to it. Finally, we conduct experiments to compare the performances of six pretraining models (BERT, BERT-WWM, BERT-WWM-EXT, ERNIE, ERNIE-tiny, and RoBERTa) in recognizing named entities from Chinese medical literature. The effects of feature extraction and fine-tuning, as well as different downstream model structures, are also explored. Experimental results demonstrate that the method of data augmentation we proposed can obtain meaningful improvements in the performance of recognition. Besides, RoBERTa-CRF achieves the highest F1-score compared with the previous methods and other pretraining models.
Occurrence and Exposure Assessment of Aflatoxin B1 in Omena (Rastrineobola argentea) from Kenya
Authors: Marijani Esther , Charo-Karisa Harrison , Kigadye Emmanuel , Okoth Sheila
Published: September 2020

Omena (Rastrineobola argentea) is the most consumed fish species in Kenya. In this study, we assessed the occurrence of aflatoxin B1 (AFB1) in Omena and the potential health risk of AFB1 to Kenyan consumers of this fish. A total of 74 samples comprising Omena intended for human consumption and fish feed production were analyzed in this study. Aflatoxin levels in Omena were determined using the enzyme-linked immunosorbent assay (ELISA). Omena intended for fish feed production was most contaminated with a mean concentration of 46.93 μg·kg−1 (2.24–115.23 μg·kg−1) compared with Omena intended for human consumption (mean = 19.42 μg·kg−1, range = 2.01–49.30 μg·kg−1). Thirty-five positive samples (83.3%) exceeded the maximum level permitted (5 μg·kg−1) by the East Africa Community standard for food used for human consumption. The exposure dose of AFB1 from consuming Omena was estimated to be 1.34 ng·kg−1 BW day−1, and margin of exposure (MoE) value for AFB1 was found to be 126.3, which indicates health risk to Omena consumers. The results suggest that the current situation of aflatoxin contamination in Omena has an adverse effect on the health of the consumers as well as the animals. Therefore, more surveys are needed to understand the scope and extent of aflatoxin contamination in Omena.
Stress-Induced Cardiomyopathy Secondary to COVID-19
Authors: Bapat Aneesh , Maan Abhishek , Heist E. Kevin
Published: September 2020

A 67-year-old female with prior medical history of HTN and asthma presented with acute-onset dyspnea and nausea for 4 days prior to admission. Upon initial encounter in the emergency room, she was found to have findings of abnormal pulmonary infiltrates and consequent workup revealed COVID-19. During further hospital course, the patient developed abnormal EKG and echocardiographic findings consistent with stress-induced cardiomyopathy.
Dual Role of MSC-Derived Exosomes in Tumor Development
Authors: Zhao Rou , Chen Xinke , Song Hui , Bie Qingli , Zhang Bin
Published: September 2020

Mesenchymal stem cells (MSCs) are a class of adult stem cells derived from the mesoderm. They can self-renew, have multidirectional differentiation potential, and can differentiate into a variety of mesenchymal tissues. MSCs can produce a large number of exosomes, which can mediate information exchange and transmission between cells in the tumor microenvironment under conditions of rest or stress. Recent studies have reported conflicting findings regarding the effect of MSC-derived exosomes on tumors. Some studies have suggested that MSC-derived exosomes can promote tumor growth and metastasis, but others have reported that they can inhibit tumor cell growth. Here, we investigate the two sides of the debate regarding the effect of MSC-derived exosomes on tumors and analyze the reasons for the divergent findings.
True‐Triaxial Drained Test of Tengger Desert Sand
Authors: Li Xuefeng , Ma Zhigang , Lu Wennan , Wang Yandong
Published: September 2020

For the lack of accurate test results in design and maintenance of desert‐crossing highways in the Tengger Desert of western China, the GDS true‐triaxial system was used to conduct the drained test on dense sand. Under the condition of different intermediate principal stress ratio b‐value, the results showed that the stress‐strain relationships in three orthogonal directions had significant differences, presenting significant anisotropy. The peak of the generalized shear stress increased with the increase of b‐value. Except under the condition of b = 0, the specimen contracted firstly and then dilated, while the others dilated. The results of the different confining pressures showed that the stress‐strain relationships appeared as a hardening type at low confining pressures, and as the confining pressure increased, the stress‐strain relationships exhibit hardening, peaking, softening, and stable deformation characteristics. At low confining pressure, the contractive behaviors were not obvious, mainly as dilatancy, and as the confining pressure increased, the dilatancy increased gradually. The specimen transformed contract to dilatancy, and when the confining pressure reached 800 kPa, the specimen exhibited contractive behavior. The test results will provide data for subgrade design and construction in desert area.
Combined Transplantation of Mesenchymal Stem Cells and Endothelial Colony-Forming Cells Accelerates Refractory Diabetic Foot Ulcer Healing
Authors: Zhao Liling , Guo Zi , Chen Ke , Yang Wenjun , Wan Xinxing , Zeng Pingyu , He Honghui , Luo Yufang , Xiao Qian , Mo Zhaohui
Published: September 2020

Background. This study is aimed at investigating the effect of combined transplantation of umbilical cord mesenchymal stem cells (UCMSCs) and umbilical cord blood-derived endothelial colony-forming cells (ECFCs) on diabetic foot ulcer healing and at providing a novel therapy for chronic diabetic foot ulcer. Methods. We reported the treatment of refractory diabetic foot ulcers in twelve patients. Among them, five patients had two or more wounds; thus, one wound in the same patient was treated with cell injection, and other wounds were regarded as self-controls. The remaining seven patients had only one wound; therefore, the difference between the area of wound before and after treatment was estimated. The UCMSCs and ECFCs were injected into the wound along with topically applied hyaluronic acid (HA). Results. In this report, we compared the healing rate of multiple separate wounds in the same foot of the same patient: one treated with cell injection combined with topically applied HA-based hydrogel and was later covered by the hydrocolloid dressings, while the self-control wounds were only treated with conventional therapy and covered by the hydrocolloid dressings. The wound underwent cell injection showed accelerated healing in comparison to control wound within the first week after treatment. In other diabetic patients with only one refractory wound, the healing rate after cell transplantation was significantly faster than that before injection. Two large wounds healed without needing skin grafts after combination therapy of cell injection and HA. After four weeks of combination treatment, wound closure was reached in six patients, and the wounds of the other six patients were significantly reduced in size. Conclusions. Our study suggests that the combination of UCMSCs, ECFCs, and HA can safely synergize the accelerated healing of refractory diabetic foot ulcers.
A Fusion Recognition Method Based on Multifeature Hidden Markov Model for Dynamic Hand Gesture
Authors: Chen Guoliang , Ge Kaikai
Published: September 2020

In this paper, a fusion method based on multiple features and hidden Markov model (HMM) is proposed for recognizing dynamic hand gestures corresponding to an operator’s instructions in robot teleoperation. In the first place, a valid dynamic hand gesture from continuously obtained data according to the velocity of the moving hand needs to be separated. Secondly, a feature set is introduced for dynamic hand gesture expression, which includes four sorts of features: palm posture, bending angle, the opening angle of the fingers, and gesture trajectory. Finally, HMM classifiers based on these features are built, and a weighted calculation model fusing the probabilities of four sorts of features is presented. The proposed method is evaluated by recognizing dynamic hand gestures acquired by leap motion (LM), and it reaches recognition rates of about 90.63% for LM-Gesture3D dataset created by the paper and 93.3% for Letter-gesture dataset, respectively.
Deformation Rules for Surrounding Rock in Directional Weakening of End Roofs of Thin Bedrocks and Ultrathick Seams
Authors: Liu Fei , Ma Zhanguo , Han Yongsheng , Huang Zhimin
Published: September 2020

With the deployment of China’s energy strategy in the western regions, complex geological mining conditions such as thin bedrock and ultrathick seams in western China have caused a series of problems such as serious deformation of the surrounding rock at the ends of the working face and the increase in the lead abutment pressure of the roadways; the research on end roof deformation in the resource exploitation in western China has become one of the great demands of the industry. Based on the failure characteristics of rock mass, relying on the actual mining geological conditions of a coal mine in Inner Mongolia, the failure characteristics of the overlying rock strata under the influence of mining were simulated and analyzed using similar material simulation experiment, which intuitively reproduced the failure and deformation processes of the immediate roof, main roof, and key strata and revealed the mechanical mechanism of the directional weakening of the end roof. It is of great significance for the stability control of the surrounding rock at the end of the fully mechanized caving face in the thin bedrocks and ultrathick seams, reducing the abutment pressure of gate roadway and controlling the spontaneous combustion of residual coal in the goaf.
Blood Oxidative Stress Marker Aberrations in Patients with Huntington’s Disease: A Meta-Analysis Study
Authors: Tang Quan , Liu Hua , Shi Xiao-Jie , Cheng Yong
Published: September 2020

Huntington’s disease (HD) is a hereditary autosomal dominant neurodegenerative disease. Although studies have shown that blood oxidative stress markers are dysregulated in HD patients, clinical data on the blood oxidative stress markers of HD patients is inconsistent. To better understand the pathogenesis of HD, we performed a systematic review and meta-analysis of blood oxidative stress markers in HD patients and healthy control (HC) subjects. A database search from PubMed and Web of Science identified 12 studies with 375 HD patients and 447 HC subjects in this meta-analysis. A random-effects meta-analysis showed that blood lipid peroxidation products (Hedges’ g=0.883, 95%CI=0.637 to 1.130, p<0.001), 8-hydroxyguanosine (Hedges’ g=1.727, 95%CI=0.489 to 2.965, p=0.006) levels, and the activity of glutathione peroxidase (Hedges’ g=2.026, 95%CI=0.570 to 3.482, p=0.006) were significantly increased in HD patients compared to controls. In contrast, reduced glutathione levels were lower in HD patients than in controls (Hedges’ g=−0.611, 95%CI=−1.016 to−0.207, p=0.003). However, blood superoxide dismutase, cholesterol, high-density lipoproteins, low-density lipoproteins, and triglycerides did not show significant differences between cases and controls. Taken together, this study clarified the associations between blood oxidative stress markers and HD, supporting the clinical evidence that HD is accompanied by increased oxidative stress.
Role of Endoplasmic Reticulum Stress in Atherosclerosis and Its Potential as a Therapeutic Target
Authors: Yang Shengjie , Wu Min , Li Xiaoya , Zhao Ran , Zhao Yixi , Liu Longtao , Wang Songzi
Published: September 2020

Endoplasmic reticulum (ER) stress is closely associated with atherosclerosis and related cardiovascular diseases (CVDs). It occurs due to various pathological factors that interfere with ER homeostasis, resulting in the accumulation of unfolded or misfolded proteins in the ER lumen, thereby causing ER dysfunction. Here, we discuss the role of ER stress in different types of cells in atherosclerotic lesions. This discussion includes the activation of apoptotic and inflammatory pathways induced by prolonged ER stress, especially in advanced lesional macrophages and endothelial cells (ECs), as well as common atherosclerosis-related ER stressors in different lesional cells, which all contribute to the clinical progression of atherosclerosis. In view of the important role of ER stress and the unfolded protein response (UPR) signaling pathways in atherosclerosis and CVDs, targeting these processes to reduce ER stress may be a novel therapeutic strategy.
EZH2 Regulates Pancreatic Cancer Subtype Identity and Tumor Progression via Transcriptional Repression of GATA6
Authors: Patil Shilpa , Steuber Benjamin , Kopp Waltraut , Kari Vijayalakshmi , Urbach Laura , Wang Xin , Küffer Stefan , Bohnenberger Hanibal , Spyropoulou Dimitra , Zhang Zhe , Versemann Lennart , Bösherz Mark Sebastian , Brunner Marius , Gaedcke Jochen , Ströbel Philipp , Zhang Jin-San , Neesse Albrecht , Ellenrieder Volker , Singh Shiv K. , Johnsen Steven A. , Hessmann Elisabeth
Published: September 2020

Recent studies have thoroughly described genome-wide expression patterns defining molecular subtypes of pancreatic ductal adenocarcinoma (PDAC), with different prognostic and predictive implications. Although the reversible nature of key regulatory transcription circuits defining the two extreme PDAC subtype lineages “classical” and “basal-like” suggests that subtype states are not permanently encoded but underlie a certain degree of plasticity, pharmacologically actionable drivers of PDAC subtype identity remain elusive. Here, we characterized the mechanistic and functional implications of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in controlling PDAC plasticity, dedifferentiation, and molecular subtype identity. Utilization of transgenic PDAC models and human PDAC samples linked EZH2 activity to PDAC dedifferentiation and tumor progression. Combined RNA- and chromatin immunoprecipitation sequencing studies identified EZH2 as a pivotal suppressor of differentiation programs in PDAC and revealed EZH2-dependent transcriptional repression of the classical subtype defining transcription factor Gata6 as a mechanistic basis for EZH2-dependent PDAC progression. Importantly, genetic or pharmacologic depletion of EZH2 sufficiently increased GATA6 expression, thus inducing a gene signature shift in favor of a less aggressive and more therapy-susceptible, classical PDAC subtype state. Consistently, abrogation of GATA6 expression in EZH2-deficient PDAC cells counteracted the acquisition of classical gene signatures and rescued their invasive capacities, suggesting that GATA6 derepression is critical to overcome PDAC progression in the context of EZH2 inhibition. Together, our findings link the EZH2-GATA6 axis to PDAC subtype identity and uncover EZH2 inhibition as an appealing strategy to induce subtype-switching in favor of a less aggressive PDAC phenotype.

Significance:

This study highlights the role of EZH2 in PDAC progression and molecular subtype identity and suggests EZH2 inhibition as a strategy to recalibrate GATA6 expression in favor of a less aggressive disease.
Sebaceous Carcinoma Epidemiology and Genetics: Emerging Concepts and Clinical Implications for Screening, Prevention, and Treatment
Authors: Sargen Michael R. , Starrett Gabriel J. , Engels Eric A. , Cahoon Elizabeth K. , Tucker Margaret A. , Goldstein Alisa M.
Published: September 2020

Sebaceous carcinoma is an aggressive skin cancer with a 5-year overall survival rate of 78% for localized/regional disease and 50% for metastatic disease. The incidence of this cancer has been increasing in the United States for several decades, but the underlying reasons for this increase are unclear. In this article, we review the epidemiology and genetics of sebaceous carcinoma, including recent population data and tumor genomic analyses that provide new insights into underlying tumor biology. We further discuss emerging evidence of a possible viral etiology for this cancer. Finally, we review the clinical implications of recent advances in sebaceous carcinoma research for screening, prevention, and treatment.
Analysis of Click and Swept-Tone Auditory Brainstem Response Results for Moderate and Severe Sensorineural Hearing Loss
Authors: Tan Jingqian , Luo Jia , Wang Xin , Jiang Yanbing , Zeng Xiangli , Chen Shixiong , Li Peng
Published: September 2020

Introduction: Auditory brainstem response (ABR) is one of the commonly used methods in clinical settings to evaluate the hearing sensitivity and auditory function. The current ABR measurement usually adopts click sound as the stimuli. However, there may be partial ABR amplitude attenuation due to the delay characteristics of the cochlear traveling wave along the basilar membrane. To solve that problem, a swept-tone method was proposed, in which the show-up time of different frequency components was adjusted to compensate the delay characteristics of the cochlear basilar membrane; therefore, different ABR subcomponents of different frequencies were synchronized. Methods: The normal hearing group, moderate sensorineural hearing loss group, and severe sensorineural hearing loss group underwent click ABR and swept-tone ABR with different stimulus intensities. The latencies and amplitudes of waves I, III, and V in 2 detections were recorded. Results: It was found that the latency of each of the recorded I, III, and V waves detected by swept-tone ABR was shorter than that by click ABR in both the control group and experimental groups. In addition, the amplitude of each of the recorded I, III, and V waves, except V waves under 60 dB nHL in the moderate sensorineural hearing loss group, detected by swept-tone ABR was larger than that by click ABR. The results also showed that the swept-tone ABR could measure the visible V waves at lower stimulus levels in the severe sensorineural hearing loss group. Conclusion: Swept-tone improves the ABR waveforms and helps to obtain more accurate threshold to some extent. Therefore, the proposed swept-tone ABR may provide a new solution for better morphology of ABR waveform, which can help to make more accurate diagnosis about the hearing functionality in the clinic.
Living-Related Kidney Transplantation in a Patient with Juvenile Nephronophthisis
Authors: Vnučák Matej , Graňák Karol , Skálová Petra , Laca Ľudovít , Mokáň Marián , Dedinská Ivana
Published: September 2020

Nephronophthisis (NPHP) is an autosomal recessive disease manifesting as tubulointerstitial nephritis uniformly progressing to ESRD in approximately 5–10% patients in childhood. Living donor transplantation is the most beneficial mean of renal replacement therapy compared to other methods. However, living kidney donation is contraindicated in potential donor with diseases of autosomal dominant mode of inheritance potentially leading to kidney failure in future. On the other hand, autosomal recessive genetic kidney diseases, such as NPHP, are not usually contraindication to living kidney donation. Herein, we are reporting related living kidney transplantation with a family history of NPHP form 46-year-old mother (heterozygote) to 17-year-old daughter with (autosomal recessive homozygote) with focus on donor follow-up after nephrectomy.
Sex Differences in the Swordtail Xiphophorus hellerii Revealed by a New Method to Investigate Volumetric Data
Authors: Hofmann Michael H.
Published: September 2020

Comparing the relative volumes of body parts is a useful tool in morphology, but it is not trivial to do this in animals that differ in overall size. To account for scaling differences, a “reference size” has to be determined and the original absolute volumes have to be “corrected for” by this scaling reference. However, the outcome of a statistical analysis is greatly affected by this “reference size,” and it is practically impossible to determine the “overall size” of a structure independent of the changes in the relative size of the parts of it. Here, a new method is introduced to compare the relative volumes of parts that does not need a scaling reference. The method transforms the absolute part volumes into a ratio matrix (volume ratio transformation, VRT). The VRT is free of any scaling factors and can be used to compare groups of animals. This paper also reviews various other errors made frequently when comparing brain morphology between animals. Finally, the VRT is applied to investigate sex differences in the swordtail fish (Xiphophorus hellerii), which show profound differences in the size of the valvula cerebelli.
Clinical Significance of Conversion Surgery for Gastric Cancer with Peritoneal Dissemination: A Retrospective Study
Authors: Arigami Takaaki , Matsushita Daisuke , Okubo Keishi , Sasaki Ken , Noda Masahiro , Kita Yoshiaki , Mori Shinichiro , Kurahara Hiroshi , Yanagita Shigehiro , Uenosono Yoshikazu , Ishigami Sumiya , Ohtsuka Takao , Natsugoe Shoji
Published: September 2020

Objective: Although chemotherapy has been clinically recommended as the initial treatment for patients with peritoneal dissemination of gastric cancer, poor prognosis has been noted among the same patients. However, the prognostic significance of conversion surgery after chemotherapy remains unclear. The present study therefore aimed to assess the clinical impact of conversion surgery among patients with peritoneal dissemination of gastric cancer. Methods: A total of 93 patients with peritoneal dissemination of gastric cancer undergoing chemotherapy between February 2002 and October 2019 were retrospectively enrolled and subsequently divided into progressive disease (PD) and non-PD groups based on tumor response to chemotherapy. Results: Among the included patients, 17 developed distant metastases at another site besides peritoneal dissemination. Based on tumor response, 24 and 69 patients were determined to have PD and non-PD, respectively, with the former having significantly poorer prognosis than the latter (p < 0.0001). A total of 19 patients underwent conversion surgery after chemotherapy, with the presence or absence of conversion surgery being significantly correlated with age, first-line chemotherapy regimen, and tumor response (p = 0.0134, p = 0.0337, and p = 0.0024, respectively). Patients in the non-PD group who underwent conversion surgery or chemotherapy alone had 3-year overall survival rates of 55.6 and 6.6%, respectively. Multivariate analysis identified conversion surgery alone as an independent prognostic factor in the non-PD group (p < 0.0001). Conclusion: Our retrospective study demonstrated that conversion surgery for gastric cancer with peritoneal dissemination might improve the prognosis of responders who developed no peritoneal dissemination after chemotherapy.
Stereotactic Gamma Knife Radiosurgery for Extracranial Arteriovenous Malformations
Authors: Dedeciusova Michaela , Tuleasca Constantin , Hajdu Steven David , Schiappacasse Luis , Patin David , Levivier Marc
Published: September 2020

Introduction: Head and neck extracranial arteriovenous malformations (AVMs) are rare pathological conditions which pose diagnostic and reconstruction challenges. Stereotactic radiosurgery (SRS) is nowadays an established treatment method for brain AVMs, with high obliteration and low complication rates. Here we describe the first report of head extracranial AVMs successfully treated by Gamma Knife (GK) as a retrospective historical cohort. Methods: Over a 9-year period, 2 cases of extracranial AVMs were treated by GK Perfexion (Elekta Instruments AB, Stockholm, Sweden) at a single institution. A stereotactic frame and multimodal imaging, including digital subtraction angiography (DSA), were used. The prescribed dose was 24 Gy at the 50% isodose line. Results: The first case was of a patient with pulsating tinnitus and left superficial parotido-condylian AVM. Embolization achieved partial obliteration. Tinnitus disappeared during the following 6 months after GK. The second case was a patient with repetitive gingival hemorrhages and right superior maxillary AVM, fed by the right internal maxillary and facial arteries. Embolization achieved partial obliteration with recurrence of symptoms. GK was further performed. DSA confirmed complete obliteration in both patients. Conclusions: Single-fraction GK radiosurgery appears to be safe and effective for extracranial AVMs. We recommend prescribing doses that are comparable to the ones used for brain AVMs (i.e., 24 Gy). A stereotactic frame is an important tool to ensure higher accuracy in the context of these particular locations. However, in selected cases, a mask could be applied either for single fraction purposes (if in a non-mobile location) or for hypofractionation, in case of larger volumes. These findings should be validated in larger cohorts, inclusively in terms of dose prescription.
Tubular Biomarkers and Chronic Kidney Disease Progression in SPRINT Participants
Authors: Jotwani Vasantha , Garimella Pranav S. , Katz Ronit , Malhotra Rakesh , Bates Jeffrey , Cheung Alfred K. , Chonchol Michel , Drawz Paul E. , Freedman Barry I. , Haley William E. , Killeen Anthony A. , Punzi Henry , Sarnak Mark J. , Segal Mark S. , Shlipak Michael G. , Ix Joachim H. ,   for the SPRINT Research Group
Published: September 2020

Background: Kidney tubular atrophy on biopsy is a strong predictor of chronic kidney disease (CKD) progression, but tubular health is poorly quantified by traditional measures including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of impaired tubule function would be associated with faster eGFR declines in persons with CKD. Methods: We measured baseline urine concentrations of uromodulin, β2-microglobulin (β2m), and α1-microglobulin (α1m) among 2,428 participants of the Systolic Blood Pressure Intervention Trial with an eGFR <60 mL/min/1.73 m2. We used linear mixed models to evaluate biomarker associations with annualized relative change in eGFR, stratified by randomization arm. Results: At baseline, the mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. In the standard blood pressure treatment arm, each 2-fold higher urinary uromodulin was associated with slower % annual eGFR decline (0.34 [95% CI: 0.08, 0.60]), whereas higher urinary β2m was associated with faster % annual eGFR decline (−0.10 [95% CI: −0.18, −0.02]) in multivariable-adjusted models including baseline eGFR and albuminuria. Associations were weaker and did not reach statistical significance in the intensive blood pressure treatment arm for either uromodulin (0.11 [−0.13, 0.35], p value for interaction by treatment arm = 0.045) or β2m (−0.01 [−0.08, 0.08], p value for interaction = 0.001). Urinary α1m was not independently associated with eGFR decline in the standard (0.01 [−0.22, 0.23]) or intensive (0.03 [−0.20, 0.25]) arm. Conclusions: Among trial participants with hypertension and CKD, baseline measures of tubular function were associated with subsequent declines in kidney function, although these associations were diminished by intensive blood pressure control.
Comparison of High-Resolution Manometry in Patients Complaining of Dysphagia among Patients with or without Diabetes Mellitus
Authors: Muroi Koichi , Miyahara Ryoji , Funasaka Kohei , Furukawa Kazuhiro , Sawada Tsunaki , Maeda Keiko , Yamamura Takeshi , Ishikawa Takuya , Ohno Eizaburo , Nakamura Masanao , Kawashima Hiroki , Onoue Takeshi , Arima Hiroshi , Hirooka Yoshiki , Fujishiro Mitsuhiro
Published: September 2020

Introduction: Dysphagia is a common symptom that occurs in patients with diabetes mellitus (DM). There have been few prospective observational studies on esophageal motility disorders in DM using high-resolution manometry (HRM). This study aimed to clarify the characteristics of esophageal motility disorders using HRM in patients with dysphagia and compare them between DM and non-DM patients. Methods: Patients with dysphagia were prospectively recruited between October 2018 and July 2019. Patients (n = 89) underwent esophagogastroduodenoscopy and HRM and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Manometry parameters and motility disorder classifications were compared between DM and non-DM patients. We also investigated the differences in clinical backgrounds and questionnaire scores among DM patients with normal and abnormal manometry results. Results: A higher prevalence of esophageal motility disorder was observed in DM patients (60%, 21/35) compared to non-DM patients (29.6%, 16/54) (p = 0.001). The prevalence of minor disorders such as ineffective esophageal motor disorder and fragmented peristalsis was significantly higher (45 vs. 11%), and the distal contractile integral, integrated relaxation pressure, and contractile front velocity values were lower in the DM group. Among DM patients, those with abnormal esophageal motility had a significantly higher prevalence of neuropathy, retinopathy, and nephropathy, as well as higher reflux or constipation scores on the GSRS, than those with normal results. Conclusions: Among patients with dysphagia, the frequency of minor esophageal motility disorders was higher in DM patients than in non-DM patients. Abnormal esophageal motility related to poor esophageal clearance was associated with higher prevalence of diabetic complications.
Real-World Clinical Experience with SGLT2 Inhibitors: Use of Special Screening Tool for Type 2 Diabetes Patients to Avoid Serious Adverse Events: A Single-Centre Prospective Study
Authors: Unadkat Vishwa B. , Sharma Sandeep , Omar Ruchi
Published: September 2020

Background: Promising results of clinical trials involving SGLT2 inhibitors urge every clinician managing diabetes to use them. However, upcoming real-world data still show increased incidence of adverse events, but efficacy is comparable to clinical trials. Objectives: Genitourinary infection is the most commonly reported adverse effect with SGLT2 inhibitors. We evaluated effectiveness of patient screening protocol and advice of hygiene and hydration to avoid adverse effects of SGLT2 inhibitors in real-world setting. Method: This was a prospective observational longitudinal study which included consecutive subjects with uncontrolled T2DM recommended with SGLT2i after a simple screening protocol from December 2017 to November 2018. The adverse effects and metabolic parameters were evaluated at 1st, 3rd, 6th, and 12th months for each patient. Results: Of 413 patients recommended for SGLT2 inhibitors, 335 patients started the medication. At baseline, average age, glycosylated haemoglobin (HbA1c), and weight were 53 years, 9.5%, and 82 kg, respectively. Data of 332, 299, 270, and 231 patients were available at the 1st, 3rd, 6th, and 12th months for safety follow-up, respectively. Genitourinary tract infection was the most common adverse effect (8%) followed by ketosis (4%). Two patients needed to stop the drug permanently due to recurrent transient ischaemic attack and emphysematous pyelonephritis. Significant reduction in mean weight and HbA1c was observed at 6 months (n = 270): 2.9 kg and 1.1%, respectively, and at 12 months (n = 231): 3.8 kg and 1.6%, respectively. Conclusion: Simple screening protocol for patients considered for SGLT2i significantly reduced incidence of genitourinary adverse events.
Association of Single-Nucleotide Polymorphisms in ABCC5 Gene with Primary Angle Closure Glaucoma and the Ocular Biometric Parameters in a Northern Chinese Population
Authors: Wang Shaolin , Zhuang Wenjuan , Zhang Wen , Xu Manyun , Li Wenjing , Piao Shunyu , Xue Zhongqi , Cai Bo , Ha Shaoping
Published: September 2020

Background: The rs1401999 gene in ABCC5 gene was the first locus confirmed by a genome-wide association study (GWAS) to be associated with both anterior chamber depth (ACD) and primary angle closure glaucoma (PACG); however, this locus was of obvious heterogeneity among different populations in the GWAS, and the conclusion has not been further verified by other studies. Therefore, this study was carried out to investigate whether the single-nucleotide polymorphisms (SNPs) in ABCC5 gene are associated with PACG and the ocular biometric parameters ACD and axial length (AL) in samples from northern China. Methods: Case-control association study included 500 PACG patients and 720 unrelated controls from northern China, and genotyping was performed for ten SNPs in ABCC5 gene using an improved multiplex ligation detection reaction technique. The association between these SNPs and risk of PACG was estimated by PLINK using a logistic regression model, while the association between genotypes and ocular biometric parameters was performed by SPSS using generalized estimation equation. Results: An SNP rs4148568 (p = 0.046) and a haplotype TCGGAG (p = 0.0364) in ABCC5 were associated with PACG, and rs4148568 was nominally associated with AL (β = 0.092, p = 0.08). Conclusions: The SNP rs4148568 and a haplotype TCGGAG in ABCC5 contribute to PACG in northern Chinese people. In addition, rs4148568 might be associated with the AL, the variant allele of which may have effect of making the AL longer. Further studies are needed to elucidate the exact mechanism of ABCC5 in the progress of PACG.
Impact of Left Ventricular Function and Heart Failure Symptoms on Outcomes Post Ablation of Atrial Fibrillation in Heart Failure
Authors: Sohns Christian , Zintl Konstantin , Zhao Yan , Dagher Lilas , Andresen Dietrich , Siebels Jürgen , Wegscheider Karl , Sehner Susanne , Boersma Lucas , Merkely Béla , Pokushalov Evgeny , Sanders Prashanthan , Schunkert Heribert , Bänsch Dietmar , Mahnkopf Christian , Brachmann Johannes , Marrouche Nassir F.
Published: September 2020

Background:

Recent data demonstrate promising effects on left ventricular dysfunction and left ventricular ejection fraction (LVEF) improvement following ablation for atrial fibrillation (AF) in patients with heart failure. We sought to study the relationship between LVEF, New York Heart Association class on presentation, and the end points of mortality and heart failure admissions in the CASTLE-AF study (Catheter Ablation for Atrial Fibrillation With Heart Failure) population. Furthermore, predictors for LVEF improvement were examined.

Methods:

The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function and New York Heart Association class were assessed at baseline (after randomization) and at each follow-up visit.

Results:

In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to >35% at the end of the study (odds ratio, 2.17;
P
<0.001). Compared with the pharmacological therapy arm, both ablation patient groups with severe (<20%) or moderate/severe (≥20% and <35%) baseline LVEF had a significantly lower number of composite end points (hazard ratio [HR], 0.60;
P
=0.006), all-cause mortality (HR, 0.54;
P
=0.019), and cardiovascular hospitalizations (HR, 0.66;
P
=0.017). In the ablation group, New York Heart Association I/II patients at the time of treatment had the strongest improvement in clinical outcomes (primary end point: HR, 0.43;
P
<0.001; mortality: HR, 0.30;
P
=0.001).

Conclusions:

Compared with pharmacological treatment, AF ablation was associated with a significant improvement in LVEF, independent from the severity of left ventricular dysfunction. AF ablation should be performed at early stages of the patient’s heart failure symptoms.
Invasive Hemodynamic Assessment and Classification of In-Hospital Mortality Risk Among Patients With Cardiogenic Shock
Authors: Thayer Katherine L. , Zweck Elric , Ayouty Mohyee , Garan A. Reshad , Hernandez-Montfort Jaime , Mahr Claudius , Morine Kevin J. , Newman Sarah , Jorde Lena , Haywood Jillian L. , Harwani Neil M. , Esposito Michele L. , Davila Carlos D. , Wencker Detlef , Sinha Shashank S. , Vorovich Esther , Abraham Jacob , O’Neill William , Udelson James , Burkhoff Daniel , Kapur Navin K.
Published: September 2020

Background:

Risk stratifying patients with cardiogenic shock (CS) is a major unmet need. The recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) stages as an approach to identify patients at risk for in-hospital mortality remains under investigation. We studied the utility of the SCAI stages and further explored the impact of hemodynamic congestion on clinical outcomes.

Methods:

The CS Working Group registry includes patients with CS from 8 medical centers enrolled between 2016 and 2019. Patients were classified by the maximum SCAI stage (B–E) reached during their hospital stay according to drug and device utilization. In-hospital mortality was evaluated for association with SCAI stages and hemodynamic congestion.

Results:

Of the 1414 patients with CS, the majority were due to decompensated heart failure (50%) or myocardial infarction (MI; 35%). In-hospital mortality was 31% for the total cohort, but higher among patients with MI (41% versus 26%, MI versus heart failure,
P
<0.0001). Risk for in-hospital mortality was associated with increasing SCAI stage (odds ratio [95% CI], 3.25 [2.63–4.02]) in both MI and heart failure cohorts. Hemodynamic data was available in 1116 (79%) patients. Elevated biventricular filling pressures were common among patients with CS, and right atrial pressure was associated with increased mortality and higher SCAI Stage.

Conclusions:

Our findings support an association between the proposed SCAI staging system and in-hospital mortality among patient with heart failure and MI. We further identify that venous congestion is common and identifies patients with CS at high risk for in-hospital mortality. These findings provide may inform future management protocols and clinical studies.
Complementary Diagnostic and Prognostic Contributions of Cardiac Computed Tomography for Infective Endocarditis Surgery
Authors: Wang Tom Kai Ming , Bin Saeedan Mnahi , Chan Nicholas , Obuchowski Nancy A. , Shrestha Nabin , Xu Bo , Unai Shinya , Cremer Paul , Grimm Richard A. , Griffin Brian P. , Flamm Scott D. , Pettersson Gosta B. , Popovic Zoran B. , Bolen Michael A.
Published: September 2020

Background:

Cardiac computed tomography (CT) is emerging as an adjunctive modality to echocardiography in the evaluation of infective endocarditis (IE) and surgical planning. CT studies in IE have, however, focused on its diagnostic rather than prognostic utility, the latter of which is important in high-risk diseases like IE. We evaluated the associations between cardiac CT and transesophageal echocardiography (TEE) findings and adverse outcomes after IE surgery.

Methods:

Of 833 consecutive patients with surgically proven IE during May 1, 2014 to May 1, 2019, at Cleveland Clinic, 155 underwent both preoperative ECG-gated contrast-enhanced CT and TEE. Multivariable analyses were performed to identify CT and TEE biomarkers that predict adverse outcomes after IE surgery, adjusting for EuroSCORE II (European System for Cardiac operative Risk Evaluation II).

Results:

CT and TEE were positive for IE in 123 (75.0%) and 124 (75.6%) of patients, respectively. Thirty-day mortality occurred in 3 (1.9%) patients and composite mortality or morbidities in 72 (46.5%). Pseudoaneurysm or abscess detected on TEE was the only imaging biomarker to show independent association with composite mortality or morbidities in-hospital, with odds ratio (95% CI) of 3.66 (1.76–7.59),
P
=0.001. There were 17 late deaths, and both pseudoaneurysm or abscess detected on CT and fistula detected on CT were the only independent predictors of total mortality during follow-up, with hazards ratios (95% CI) of 3.82 (1.25–11.7),
P
<0.001 and 9.84 (1.89–51.0),
P
=0.007, respectively.

Conclusions:

We identified cardiac CT and TEE features that predicted separate adverse outcomes after IE surgery. Imaging biomarkers can play important roles incremental to conventional clinical factors for risk stratification in patients undergoing IE surgery.