Search

Lijun Du, Lei Zhang, Ling Li, Xin Li, Jiaqin Yan, Xinhua Wang, Xiaorui Fu, Zhenchang Sun, Xudong Zhang, Zhaoming Li, Jingjing Wu, Hui Yu, Yu Chang, Zhiyuan Zhou, Feifei Nan, Xiaolong Wu, Li Tian, Mingzhi Zhang Department of Oncology, Zhengzhou University First Affiliated Hospital, Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Mingzhi ZhangDepartment of Oncology, Zhengzhou University First Affiliated Hospital, Lymphoma Diagnosis and Treatment Center of Henan Province, &Ngr;o. 1 Jianshe East Road, Zhengzhou, Henan, People’s Republic of ChinaTel +86 13838565629Fax +86 37166295563Email mingzhi_zhang1@163.comAbstract: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is a specific subtype of peripheral T cell lymphoma (PTCL) with a poor prognosis. To date, there exist no standard therapeutic regimens for relapsed/refractory (R/R) ENKTL. More potent treatment strategies are urgently needed to improve the survival of these patients with R/R ENKTL. Herein, we present three R/R ENKTL patients who failed prior therapies (L-asparaginase containing chemotherapy, radiotherapy or biological-cell therapy, etc.) benefited from the combination regimen comprised of anti-programmed-death-1 (PD-1) antibody toripalimab, chidamide, etoposide, and thalidomide. They received the treatment regimen continuously until the disease progression occurs. As of data collection, two patients achieved complete remission (CR) after 4, 6 cycles of treatment, respectively, and another patient was evaluated as partial remission (PR) after 2 cycles. Treatment-related adverse events (AEs) mainly presented grade 2∼ 3 leukocytopenia and anemia, which were controllable. It follows that PD-1 antibody, chidamide, etoposide, and thalidomide (PCET) regimen may be a promising choice for patients with R/R ENKTL and warrants further investigation.Keywords: NK/T-cell lymphoma, relapsed/refractory, PD-1, chidamide, targeted treatment

Xinran Ma,* Ling Li,* Lei Zhang, Xiaorui Fu, Xin Li, Xinhua Wang, Jingjing Wu, Zhenchang Sun, Xudong Zhang, Xiaoyan Feng, Yu Chang, Zhiyuan Zhou, Feifei Nan, Jieming Zhang, Zhaoming Li, Mingzhi Zhang Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Lymphoma Diagnosis and Treatment Center of Henan Province, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingzhi ZhangDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Lymphoma Diagnosis and Treatment Centre of Henan Province, Zhengzhou 450002, Henan, People’s Republic of ChinaTel +86-13838565629Email mingzhi_zhang1@163.comPurpose: Treatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor-2 (VEGFR-2) to inhibit tumour angiogenesis. In the present study, we evaluated the efficacy and safety of apatinib for patients with RR DLBCL.Patients and Methods: In this phase II, open-label, single-arm, prospective study, we enrolled patients aged 14– 70 years with treatment failure of at least two chemotherapeutic regimens using Simon’s two-stage design. All patients were administered apatinib at an initial dose of 500 mg on a 4-week cycle at home and visited the outpatient clinic every two cycles to evaluate efficacy and to record adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), and overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.).Results: From January 2017 to February 2019, we screened 35 patients and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses, and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate of 71.9%. The median PFS and OS were 6.9 (95% confidence interval [CI], 5.8– 7.9) and 7.9 months (95% CI, 7.0– 8.7), respectively. The median DoR was 5.0 months (95% CI, 3.5– 6.5) for patients who achieved PR. The most common grade 3– 4 adverse events (AE) were hypertension (12.6%), hand–foot syndrome (9.4%), and leucopenia (6.3%). No apatinib-related deaths were noted.Conclusion: Home administration of apatinib shows promising efficacy and manageable AEs in patients with RR DLBCL.Keywords: apatinib, relapsed or refractory diffuse large B-cell lymphoma, VEGFR-2, efficacy, safety

Longxiang Xie,1 Qiang Wang,1 Fangmei Nan,1 Linna Ge,1 Yifang Dang,1 Xiaoxiao Sun,1 Ning Li,1 Huan Dong,1 Yali Han,1 Guosen Zhang,1 Wan Zhu,2 Xiangqian Guo1 1Bioinformatics Department of Predictive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng 475004, People’s Republic of China; 2Department of Anesthesia, Stanford University, Stanford, CA, USACorrespondence: Xiangqian GuoBioinformatics Department of Predictive Medicine, Institute of Biomedical Informatics, Cell Signal Transduction Laboratory, Bioinformatics Center, Henan Provincial Engineering Center for Tumor Molecular Medicine, School of Software, School of Basic Medical Sciences, Henan University, Kaifeng 475004, People’s Republic of ChinaTel +86-371-23880585Email xqguo@henu.edu.cnAbstract: Gene expression profiling data with long-term clinical follow-up information are great resources to screen, develop, evaluate and validate prognostic biomarkers in translational cancer research. However, an easy-to-use interactive online tool is needed to analyze these profiling and clinical data. In the current work, we developed OSacc (Online consensus Survival analysis of ACC), a web tool that provides rapid and user-friendly survival analysis based on seven independent transcriptomic profiles with long-term clinical follow-up information of 259 ACC patients gathered from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. OSacc allows researchers and clinicians to evaluate the prognostic value of genes of interest by Kaplan–Meier (KM) survival plot with hazard ratio (HR) and log-rank test in ACC. OSacc is freely available athttp://bioinfo.henu.edu.cn/ACC/ACCList.jsp.Keywords: ACC, prognostic marker, over survival, web tool, KM plot

Resumen: Coenurosis es la enfermedad causada por Coenurus cerebralis, forma larvaria de Taenia multiceps. Afecta a rumiantes, equinos, suinos y humanos provocando sintomatología nerviosa. El presente trabajo tuvo como objetivo describir un foco de coenurosis en bovinos en Uruguay, diagnosticado mediante estudios anatomopatológicos y técnicas moleculares (PCR/secuenciación). Se realizó la necropsia de dos vaquillonas Hereford (Caso A y B) de 2-3 años que presentaban desmejoramiento progresivo, ataxia, torneo y desviación de la cabeza. Macroscópicamente, se observó la presencia de una vesícula quística en el hemisferio cerebral izquierdo del caso A, la cual se rompió espontáneamente al extraer el encéfalo del cráneo. En el caso B, se extrajo del hemisferio cerebral derecho una vesícula completa, de color transparente con escólices blanquecinos en su interior. Al examen histopatológico del sistema nervioso central se observó reacción inflamatoria en el tejido adyacente a la ubicación de los quistes constituida por macrófagos, eosinófilos, linfocitos y células gigantes. La vesícula del caso B fue diseccionada y se utilizó un trozo para la extracción de ADN. Mediante PCR se amplificó un fragmento del gen nad1. La secuencia obtenida fue comparada con las secuencias registradas en el GenBank utilizando la herramienta BLAST. El resultado reveló una homología de 99% con T. multiceps. Por lo tanto, este trabajo confirma que la coenurosis bovina se encuentra presente Uruguay. Summary: Coenurosis is a disease caused by Coenurus cerebralis, the larval stage of Taenia multiceps. Ruminants, equids, swine and even humans can be affected developing neurological symptoms. This work reports C. cerebralis infection diagnosed by macroscopic and histologic lesions and molecular tools (PCR/sequencing) in two heifers in Uruguay.Two 2-3 years old Hereford heifers were necropsied (case A and B). Both animals presented progressive deterioration, ataxia, circling and head deviation. Grossly, in case A, a cystic vesicle protruding from the left hemisphere was observed. The vesicle was broken spontaneously while the encephalon was retrieved from the cranial cavity. On case B, the whole cystic vesicle was retrieved from the right hemisphere. Through the translucent wall´svesicle was possible to visualize whitish scolices attached to the inner layer. Histopathology of the central nervous system revealedan inflammatory reaction on the cyst adjacent tissue, characterized by the presence of macrophages, eosinophils, lymphocytes and giant cells. The vesicle of case B was dissected and a small piece was used for DNA extraction. By PCR, a fragment of nad1 gene was amplified and sent for direct sequencing. The obtained sequence was compared with the available sequences registered on GenBank using the BLAST tool. The result revealed a 99% homology with sequences registered as T. multiceps. Therefore, this work confirmed that bovine coenurosis is present in Uruguay.

International audience; Magnetic anomaly analysis is an important method to study the structure of deep crust. With the assumption of random magnetization sources, the structure of a magnetic layer can be inverted via spectral analysis. Curie point depth (CPD), the depth at which rocks lose their ferromagnetic properties, is the bottom of a magnetic layer. In this study, we estimate from the magnetic anomaly data of EMAG2 dataset the CPD and the top of the magnetic layer in North China. With a moving window of 180 km × 180 km, we calculate the average top and centroid depth of the magnetic layer in each window and determine the regional CPD distribution across North China. The CPD of North China varies from 18 to 32 km. In addition, the CPD in the western part of the North China Craton is deeper than that in the eastern part. The shallowest CPD is located near the Bohai Sea. When compared to available heat flow data, the estimated CPD values are consistent with thermal conductivity of 1.8–3.2 Wm−1 K−1 and on heat production value of 0.4–1.3 µWm−3.

While the ecological validity of virtual reality (VR) applications is usually assessed by behavioral data or interrogation, an alternative approach on a neuronal level is offered by brain imaging methods. Because it is yet unclear if 3D space in virtual environments is processed analogically to the real world, we conducted a study investigating virtual spatial processing in the brain using functional magnetic resonance imaging (fMRI). Results show differences in VR spatial brain processing as compared to known brain activations in reality. Identifying differences and commonalities of brain processing in VR reveals limitations and holds important implications for VR therapy and training tools. When VR therapy aims at the rehabilitation of brain function and activity, differences in brain processing have to be taken into account for designing effective VR training tools. Furthermore, for an evaluation of possible restoration effects caused by VR training, it is necessary to integrate information about the brain activation networks elicited by the training. The present study provides an example for demonstrating the benefit of fMRI as an evaluation tool for the mental processes involved in virtual environments.

We seek decision rules for prediction-time cost reduction, where complete data is available for training, but during prediction-time, each feature can only be acquired for an additional cost. We propose a novel random forest algorithm to minimize prediction error for a user-specified {\it average} feature acquisition budget. While random forests yield strong generalization performance, they do not explicitly account for feature costs and furthermore require low correlation among trees, which amplifies costs. Our random forest grows trees with low acquisition cost and high strength based on greedy minimax cost-weighted-impurity splits. Theoretically, we establish near-optimal acquisition cost guarantees for our algorithm. Empirically, on a number of benchmark datasets we demonstrate superior accuracy-cost curves against state-of-the-art prediction-time algorithms.

This study was conducted to investigate the effects of Curcuma zedoaria and Zingiber zerumbet on non-specific immune responses of grouper (Epinephelus coioides). Fish were fed an experimental diet containing 0, 0.5, 1.0, 2.5 g/kg of C. zedoaria and Z. zerumbet mixed diets twice daily for two weeks. Non-specific immune parameters such as respiratory burst activity, reactive oxygen species, phagocytic activities, superoxidase dismutase activity and lysozyme activity were sampled at 0, 1, 2, 4, 7 and 14 days, respectively. Results indicated that in fish fed with C. zedoaria at 0.5 g/kg diet and Z. zerumbet at 1 g/kg and 2.5 g/kg diets the non-specific immune response was affected, especially in cellular defense which had significant effects in the short term. Thus, this study indicated that C. zedoaria and Z. zerumbet supplemented in the diets of orange-spotted grouper acted as immunostimulants and appeared to enhance the non-specific immune responses in this species.

Antiparkinsonian drugs are dopamine agonists and they have been reported to increase striatal acetylcholine (ACh) concentrations. U-91356A is a D2 selective dopamine agonist. Therefore, it was investigated for its effect on rat striatal ACh concentration, and the results were compared with those obtained with pergolide and quinpirole under similar conditions. U-91356A was as potent as pergolide and less potent than quinpirole in increasing striatal ACh in non-reserpinized rats. The intrinsic activity of U-91356A was significantly (P < 0.03) greater than pergolide in non-reserpinized rats. In reserpinized rats, the potency of investigated dopamine agonists was similar for elevating ACh levels, and intrinsic activity of U-91356A (P < 0.01) was higher as compared to that obtained with quinpirole or pergolide. In the unilateral substantia nigra lesioned animals, the intrinsic activity of U-91356A for increasing striatal ACh was significantly (P < 0.01) higher in the denervated, as compared to innervated, striatum. The supersensitive response of quinpirole and pergolide for increasing striatal ACh was also observed on the lesioned as compared to intact side. Haloperidol significantly (P < 0.01) blocked U-91356A-induced elevation in striatal ACh in non-reserpinized rats. Based on these results, U-91356A appears to be a potent agonist of striatal post-synaptic D2 dopamine receptors and is expected to be an effective anti-parkinsonian drug. © 1996 Wiley-Liss, Inc.

International audience; In order to enhance encounters with prey, planktonic predators may display different swimming behavior with respect to food availability and distribution. In this study, we used 3D video techniques to record the swimming behavior of malabar grouper (Epinephelus malabaricus) larvae in both the absence and the presence of prey (Artemia sp. nauplii). Swimming properties were investigated in all of the 3D, the two vertical, and the horizontal projections using scale-dependent (mean speed and Net to Gross Displacement Ratio) and scale-independent (fractal dimension) metrics. When prey was added, larvae swam slower and in a less convoluted way as compared to what was observed in the absence of food. The results obtained with scale-dependant metrics were confirmed by those obtained with scale-independent analyses. Both unveiled the anisotropy of the swimming behavior of grouper larvae that tend to swim toward the vertical axis in order to maximize encounters with prey patches. This study shows that malabar grouper larvae can optimize their search volume by switching their behavior and further draws attention to the need to consider both vertical- and horizontal-projections components while addressing the plankter's swimming trajectories

The prevalence of hyperuricemia is low in Uygurs, who have a high prevalence of cardiovascular risk factors such as hypertension, overweight–obesity, dyslipidemia, hyperglycemia, and insulin resistance (IR). This study sought to investigate the relationships between serum uric acid (UA) and these risk factors in this population. A cross-sectional study was conducted in Uygurs (859 males, 1268 females) aged 20 to 70 years. Demographic data, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and fasting and postprandial blood were obtained, and biological measurements were determined. The mean of BMI, SBP, DBP, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides, fasting blood glucose, fasting insulin, and homeostasis model assessment insulin resistance index (HOMA-IR), and the prevalence of hypertension, IR, hyperglycemia, overweight–obesity, hypercholesteremia, hyper-LDL-c, and hypertriglyceridemia increased with UA but the prevalence of hypo-HDL-c decreased (p < 0.05). Logistic regression analysis showed that the odds ratios for IR, overweight–obesity, hypercholesteremia, hyper-LDL-c, and hypertriglyceridemia against the lowest UA group increased but decreased for hypo-HDL-c (p < 0.05). The UA in the hypo-HDL-c group was lower than that of the controls; the prevalence of hypo-HDL-c in hyperuricemia subjects was lower than in those with normal UA (p < 0.05). But the opposite results were observed between overweight–obesity, hyperglycemia, IR, hypercholesteremia, hypertriglyceridemia, and hyper-LDL-c and correspondence controls, respectively (p < 0.05). In Uygur, elevated UA is associated with overweight–obesity, hypercholesteremia, hyper-LDL-c, hypertriglyceridemia, hyperglycemia, and IR. The HDL-c level significantly increases with UA, whereas the prevalence of hypo-HDL-c decreases. Further studies are needed to clarify why UA is positively correlated to HDL-c.

Combining Virtual Reality (VR) and functional magnetic resonance imaging (fMRI) offers great possibilities to researchers. Brain activation in VR can be studied and more realistic stimuli can be used in fMRI studies. Unfortunately, no standard solution exists for the combination of both methods. As part of an interdisciplinary project addressing the diagnostics and treatment of neglect, we created a neuroscientific VR-fMRI experiment. Our experiences are reported in this paper. The description of problems and our solution are intended as substantial facilitation and help for other researchers interested in creating VR-fMRI experiments.

The research hypothesis of this study states that a systematic and operational method for evaluating rural, cultural, historic landscapes, particularly at the regional level, simply does not exist. The purpose of this study was two-fold: first, to prove, through an informal survey of landscape architecture firms involved in historic preservation and preservation organizations, that the hypothesis was true, and secondly, to develop a method for evaluating a specific kind of rural, cultural, historic landscape -- nineteenth century farms in the Blue Ridge Belt. The overriding objective in developing the method for evaluating nineteenth century Blue Ridge farms was to make the evaluation criteria as operational as possible, and, therefore, create a method which would be accessible to the non-professional. The criteria used to evaluate the farms was based on studies done of farms documented in the archives of the Shenandoah National Park in Luray, Virginia, the Great Smoky Mountains National Park in Gatlinburg, Tennessee, and the Historic Landsmarks Commission in Richmond, Virginia. The method was designed so that every farm evaluated by means of the checksheet can be scored based on the degree to which it represents a typical nineteenth century Blue Ridge farm. M.L. Arch.

We propose to prune a random forest (RF) for resource-constrained prediction. We first construct a RF and then prune it to optimize expected feature cost & accuracy. We pose pruning RFs as a novel 0-1 integer program with linear constraints that encourages feature re-use. We establish total unimodularity of the constraint set to prove that the corresponding LP relaxation solves the original integer program. We then exploit connections to combinatorial optimization and develop an efficient primal-dual algorithm, scalable to large datasets. In contrast to our bottom-up approach, which benefits from good RF initialization, conventional methods are top-down acquiring features based on their utility value and is generally intractable, requiring heuristics. Empirically, our pruning algorithm outperforms existing state-of-the-art resource-constrained algorithms.