bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abdominal surgery induced gastric ileus and activation of M1-like macrophages in the gastric myenteric plexus: prevention by central vagal activation in rats
Authors: Yuan Pu-Qing , Taché Yvette 
Published: July 2017

Inflammation plays a role in abdominal surgery (AS)-induced intestinal ileus that is alleviated by electrical vagal stimulation. Intracisternal injection of RX-77368, the stable thyrotropin-releasing hormone agonist, activates dorsal motor nucleus neurons and gastric vagal efferent discharges. We investigated the gastric inflammation induced by AS and the modulation by intracisternal RX-77368 in rats. RX-77368 (50 ng/rat) or saline was injected followed, 1 h later, by laparotomy and small intestinal/cecal manipulation. The sham group had anesthesia alone. After 6 h, gastric emptying (GE) and the inflammation in gastric corpus were determined. AS inhibited GE by 72% vs. control and doubled the number of M1-like macrophage immunoreactive for major histocompatibility complex class II (MHCII; M1 marker) but not for cluster of differentiation 206 (CD206; M2 marker) (MHCII+/CD206−) while there was no change in M2-like macrophages (MHCII−/CD206+). AS increased mRNA levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) by 1.7- and 1.5-fold, respectively, in the gastric submucosa plus muscle layers and the infiltration of neutrophils labeled by myeloperoxidase by 9.5-fold in the muscularis externa. RX-77368 inhibited AS-related gastric changes while not altering these parameters in the sham group. There was a significant negative correlation between GE and IL-1β ( r = −0.46), TNF-α ( r = −0.44), M1 macrophage ( r = −0.82), and neutrophils ( r = −0.91). The M2-like macrophages and IL-10 expression were unchanged by AS with intracisternal saline or RX-77368. These data indicate that AS activates gastric M1 macrophages and increases proinflammatory cytokines expression, which are prevented by central vagal activation and may contribute to the correlated dampening of postoperative gastric ileus. NEW & NOTEWORTHY MHCII+/CD206− (M1) and MHCII−/CD206+ (M2) constitute two distinct populations of macrophages that are in close apposition to the cholinergic neurons in the rat gastric myenteric plexus (MP). Abdominal surgery (6 h) activates M1 macrophage leading to inflammation in the gastric MP correlated with the delayed gastric emptying, which was abolished by central vagal stimulation via intracisternal injection of RX-77368. Vagal stimulation linked with the cephalic phase may have potential beneficial effects to curtail postoperative gastric ileus.
PD-1+ Polyfunctional T Cells Dominate the Periphery after Tumor-Infiltrating Lymphocyte Therapy for Cancer
Authors: Donia Marco , Kjeldsen Julie Westerlin , Andersen Rikke , Westergaard Marie Christine Wulff , Bianchi Valentina , Legut Mateusz , Attaf Meriem , Szomolay Barbara , Ott Sascha , Dolton Garry , Lyngaa Rikke , Hadrup Sine Reker , Sewell Andrew K. , Svane Inge Marie 
Published: July 2017

Abstract
Purpose: Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TIL) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs 1 month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here, we studied the dynamics of bulk tumor-reactive CD8+ T-cell populations in patients with metastatic melanoma following treatment with TILs.
Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8+ T cells contained in serial blood samples of 16 patients treated with TILs.
Results: Polyfunctional tumor-reactive CD8+ T cells accumulated over time in the peripheral lymphocyte pool. Combinatorial analysis of multiple surface markers (CD57, CD27, CD45RO, PD-1, and LAG-3) showed a unique differentiation pattern of polyfunctional tumor-reactive CD8+ T cells, with highly specific PD-1 upregulation early after infusion. The differentiation and functional status appeared largely stable for up to 1 year after infusion. Despite some degree of clonal diversification occurring in vivo within the bulk tumor-reactive CD8+ T cells, further analyses showed that CD8+ T cells specific for defined tumor antigens had similar differentiation status.
Conclusions: We demonstrated that tumor-reactive CD8+ T-cell subsets that persist after TIL therapy are mostly polyfunctional, display a stable partially differentiated phenotype, and express high levels of PD-1. These partially differentiated PD-1+ polyfunctional TILs have a high capacity for persistence and may be susceptible to PD-L1/PD-L2–mediated inhibition. Clin Cancer Res; 23(19); 5779–88. ©2017 AACR.
Downregulation of Human Endogenous Retrovirus Type K (HERV-K) Viral env RNA in Pancreatic Cancer Cells Decreases Cell Proliferation and Tumor Growth
Authors: Li Ming , Radvanyi Laszlo , Yin Bingnan , Rycaj Kiera , Li Jia , Chivukula Raghavender , Lin Kevin , Lu Yue , Shen JianJun , Chang David Z. , Li Donghui , Johanning Gary L. , Wang-Johanning Feng 
Published: July 2017

Abstract
Purpose: We investigated the role of the human endogenous retrovirus type K (HERV-K) envelope (env) gene in pancreatic cancer.
Experimental Design: shRNA was employed to knockdown (KD) the expression of HERV-K in pancreatic cancer cells.
Results: HERV-K env expression was detected in seven pancreatic cancer cell lines and in 80% of pancreatic cancer patient biopsies, but not in two normal pancreatic cell lines or uninvolved normal tissues. A new HERV-K splice variant was discovered in several pancreatic cancer cell lines. Reverse transcriptase activity and virus-like particles were observed in culture media supernatant obtained from Panc-1 and Panc-2 cells. HERV-K viral RNA levels and anti-HERV-K antibody titers were significantly higher in pancreatic cancer patient sera (N = 106) than in normal donor sera (N = 40). Importantly, the in vitro and in vivo growth rates of three pancreatic cancer cell lines were significantly reduced after HERV-K KD by shRNA targeting HERV-K env, and there was reduced metastasis to lung after treatment. RNA-Seq results revealed changes in gene expression after HERV-K env KD, including RAS and TP53. Furthermore, downregulation of HERV-K Env protein expression by shRNA also resulted in decreased expression of RAS, p-ERK, p-RSK, and p-AKT in several pancreatic cancer cells or tumors.
Conclusions: These results demonstrate that HERV-K influences signal transduction via the RAS–ERK–RSK pathway in pancreatic cancer. Our data highlight the potentially important role of HERV-K in tumorigenesis and progression of pancreatic cancer, and indicate that HERV-K viral proteins may be attractive biomarkers and/or tumor-associated antigens, as well as potentially useful targets for detection, diagnosis, and immunotherapy of pancreatic cancer. Clin Cancer Res; 23(19); 5892–911. ©2017 AACR.
Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer
Authors: Ma Cynthia X. , Bose Ron , Gao Feng , Freedman Rachel A. , Telli Melinda L. , Kimmick Gretchen , Winer Eric , Naughton Michael , Goetz Matthew P. , Russell Christy , Tripathy Debu , Cobleigh Melody , Forero Andres , Pluard Timothy J. , Anders Carey , Niravath Polly Ann , Thomas Shana , Anderson Jill , Bumb Caroline , Banks Kimberly C. , Lanman Richard B. , Bryce Richard , Lalani Alshad S. , Pfeifer John , Hayes Daniel F. , Pegram Mark , Blackwell Kimberly , Bedard Philippe L. , Al-Kateb Hussam , Ellis Matthew J.C. 
Published: July 2017

Abstract
Purpose: Based on promising preclinical data, we conducted a single-arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2mut nonamplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxicity, and circulating tumor DNA (ctDNA) HER2mut detection.
Experimental Design: Tumor tissue positive for HER2mut was required for eligibility. Neratinib was administered 240 mg daily with prophylactic loperamide. ctDNA sequencing was performed retrospectively for 54 patients (14 positive and 40 negative for tumor HER2mut).
Results: Nine of 381 tumors (2.4%) sequenced centrally harbored HER2mut (lobular 7.8% vs. ductal 1.6%; P = 0.026). Thirteen additional HER2mut cases were identified locally. Twenty-one of these 22 HER2mut cases were estrogen receptor positive. Sixteen patients [median age 58 (31–74) years and three (2–10) prior metastatic regimens] received neratinib. The CBR was 31% [90% confidence interval (CI), 13%–55%], including one CR, one PR, and three SD ≥24 weeks. Median PFS was 16 (90% CI, 8–31) weeks. Diarrhea (grade 2, 44%; grade 3, 25%) was the most common adverse event. Baseline ctDNA sequencing identified the same HER2mut in 11 of 14 tumor-positive cases (sensitivity, 79%; 90% CI, 53%–94%) and correctly assigned 32 of 32 informative negative cases (specificity, 100%; 90% CI, 91%–100%). In addition, ctDNA HER2mut variant allele frequency decreased in nine of 11 paired samples at week 4, followed by an increase upon progression.
Conclusions: Neratinib is active in HER2mut, nonamplified MBC. ctDNA sequencing offers a noninvasive strategy to identify patients with HER2mut cancers for clinical trial participation. Clin Cancer Res; 23(19); 5687–95. ©2017 AACR.
Tumor Response Dynamics of Advanced Non–small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome
Authors: Nishino Mizuki , Dahlberg Suzanne E. , Adeni Anika E. , Lydon Christine A. , Hatabu Hiroto , Jänne Pasi A. , Hodi F. Stephen , Awad Mark M. 
Published: July 2017

Abstract
Purpose: We evaluated tumor burden dynamics in patients with advanced non–small cell lung cancer (NSCLC) treated with commercial PD-1 inhibitors to identify imaging markers associated with improved overall survival (OS).
Experimental Design: The study included 160 patients with advanced NSCLC treated with commercial nivolumab or pembrolizumab monotherapy as a part of clinical care. Tumor burden dynamics were studied for the association with OS.
Results: Tumor burden change at best overall response (BOR) ranged from −100% to +278% (median, +3.5%). Response rate (RR) was 18% (29/160). Current and former smokers had a higher RR than never smokers (P = 0.04). Durable disease control for at least 6 months was noted in 26 patients (16%), which included 10 patients with stable disease as BOR. Using a landmark analysis, patients with &lt;20% tumor burden increase from baseline within 8 weeks of therapy had longer OS than patients with ≥20% increase (median OS, 12.4 vs. 4.6 months, P &lt; 0.001). Patients with &lt;20% tumor burden increase throughout therapy had significantly reduced hazards of death (HR, 0.24; Cox P &lt; 0.0001) after adjusting for smoking (HR, 0.86; P = 0.61) and baseline tumor burden (HR, 1.55; P = 0.062), even though some patients met criteria for RECIST progression while on therapy. One patient (0.6%) had atypical response pattern consistent with pseudoprogression.
Conclusions: Objective response or durable disease control was noted in 24% of patients with advanced NSCLC treated with commercial PD-1 inhibitors. A tumor burden increase of &lt;20% from baseline during therapy was associated with longer OS, proposing a practical marker of treatment benefit. Pseudoprogression is rare in NSCLCs treated with PD-1 inhibitors. Clin Cancer Res; 23(19); 5737–44. ©2017 AACR.
The Modernization of the Peasant Economy: In Search of the Socialist Path (小农经济现代化的社会主义道路)
Authors: Wang (王海娟) Haijuan , He (贺雪峰) Xuefeng 
Published: July 2017

Past studies have discussed the “socialist” nature of agricultural development in China in terms of equality in distribution since the introduction of the Household Responsibility System (hrs) and its institutional necessities. This article instead addresses the issue of the modernization of the peasant economy by exploring the various practices in agricultural production that led to a socialist path since 1980. The peasant economy under thehrstakes the form of a dual-layer management, and the collective economy is under the unified management by the collective. The collective economy propels the modernization of the peasant economy by the means of integration of funding, integration of land rights, and land concentration, respectively, in response to the different phases in the development of the forces of production. What is emerging in China is the fourth path to agricultural modernization characteristic of China, after the existing three paths, namely capitalist agriculture of large private farms, socialist agriculture of large collective farms, and the capitalist agriculture of small family farms. This new path, or socialist agriculture of small family farms, is characterized by the enlargement of the management unit on the basis of the collective economy that overcomes the constraints of the peasant economy. However, while institutional possibilities do exist for a socialist path in agricultural development in China, the policies pursued by the Chinese government are turning Chinese agriculture into capitalist agriculture of small family farms.学界从均等分配角度揭示了家庭承包经营制后农业发展的“社会主义”性质及其制度合理性，本文尝试从农业生产角度揭示1980年以来中国社会主义道路实践，探究小农经济现代化问题。家庭承包经营制改革后的小农经济采取双层经营体制，集体经济以集体统一经营的方式存在。在不同生产力阶段，集体经济分别以资金整合、地权整合和土地集中的方式，促进小农经济现代化。从集体经济扩大农业经营单位，克服小农经济局限性的角度，中国在资本主式私人大农场农业、社会主义式集体大农场农业、资本主义式小农家庭农业之外，探索出具有中国特色的第四种农业现代化道路，即社会主义式小农家庭农业。中国农业发展有走向社会主义道路的制度空间，但中国政府的政策选择使得中国农业发展正在走向资本主义式小农家庭农业。(This article is in Chinese.)
Combination of WENO and Explicit Runge–Kutta Methods for Wind Transport in the Meso-NH Model
Authors: Lunet Thibaut , Lac Christine , Auguste Franck , Visentin Florian , Masson Valéry , Escobar Juan 
Published: July 2017

AbstractThis paper investigates the use of the weighted essentially nonoscillatory (WENO) space discretization methods of third and fifth order for momentum transport in the Meso-NH meteorological model, and their association with explicit Runge–Kutta (ERK) methods, with the specific purpose of finding an optimal combination in terms of wall-clock time to solution. A linear stability analysis using von Neumann theory is first conducted that considers six different ERK time integration methods. A new graphical representation of linear stability is proposed, which allows a first discrimination between the ERK methods. The theoretical analysis is then completed by tests on numerical problems of increasing complexity (linear advection of high wind gradient, orographic waves, density current, large eddy simulation of fog, and windstorm simulation), using a fourth-order-centered scheme as a reference basis. The five-stage third-order and fourth-order ERK combinations appear as the time integration methods of choice for coupling with WENO schemes in terms of stability. An explicit time-splitting method added to the ERK temporal scheme for WENO improves the stability properties slightly more. When the spatial discretizations are compared, WENO schemes present the main advantage of maintaining stable, nonoscillatory transitions with sharp discontinuities, but WENO third order is excessively damping, while WENO fifth order provides better accuracy. Finally, WENO fifth order combined with the ERK method makes the whole physics of the model 3 times faster compared to the classical fourth-order centered scheme associated with the leapfrog temporal scheme.
Strategies for Sustainable Crop Production in Semi-Arid Africa
Authors: McCown R.L. , Keating B.A. , Probert M.E. , Jones R.K. 
Published: July 2017

This is a record of the experience of a research team attempting to identify a development path for a farming system in semi-arid Africa. The farming system is the largely-subsistence production of crops and livestock by smallholders in the Machakos and Kitui Districts in Eastern Kenya. The region is known locally as Ukambani- “the place where the Kamba people live”. This region has a long history in which the food demands of rapidly growing populations have periodically outstripped the productive capacity of the land and current technology. Today, the population pressure on land and its rate of growth are among the highest in the world, and emigration is no longer a feasible solution. But numerous other areas of Africa are not far behind in population pressures and a more sustainable agriculture in this region is important not only for Kenya. Almost certainly, the problems of agriculture in Machakos-Kitui today represent a future scenario for much of semi-arid Africa. This article is also concerned with methodology for conducting research on farming systems. While the project was designed according to the concepts of Farming Systems Research (FSR) (Collinson, 1982), the realities of development assistance projects created challenges in implementation. The research also departed from the conventional FSR plan as new possibilities were realized, and with great benefit. The outcome is a well-founded hypothesis: contrary to much contemporary wisdom, a strategy of augmenting traditional soil enrichment practices with modest amounts of fertilizer is economically feasible for many farmers and provides the best prospects for food security and sustainable agriculture in this climatic zone.
Simulation of multiple access protocols for real-time control
Authors: Finn Alan , Decker Randall , McClurg Chris , Harmon Dayle 
Published: July 2017

The simulation activity described in this paper was undertaken for the design of a hierarchical multiple access communication network for a distributed real-time control system. The network consisted of multiple busses hierarchically connected by bridges. High bandwidth control loops were closed over local busses. Lower rate loops and status information were shared between busses. Multiple simulation methodologies were employed to design and valdate the communications protocol for the network. The methodologies included mathematical analysis, functional simulation, and physical simulation. Each method elucidated a separate aspect of the protocol's behavior. The unique contribution of each method yielded a comprehensive understanding of the proposed design and perrnitted model validation by cross-checking the results. The ortginal traffic load for this study included messages with maximurn acceptable delays between 0.001 and 1.0 seconds. The speed of the network was limited to less than 1.0 megabit per second (Mbps) for electrical reasons. The results demonstrated an unacceptable probability of delay for the highest rate messages, even at the muximum bus speed. A separate dedicated link was therefore added to the control system for the highest rate messages.
Different effects of (CIS+TRANS) 1,3-dichloropropene in renal cortical slices derived from male and female rats
Authors: Secondin Livia , Maso Stefano , Trevisan Andrea 
Published: July 2017

1 Nephrotoxic effects of 1,3-dichloropropene (cis and trans isomers mixture) was investigated in vitro by means of renal cortical slice model in male and female rats, including treatment with metabolism modifiers as an inducer of cytochrome P-450 1A class (β-naphtho-flavone), a reduced glutathione depleting (DL-buthio-nine-[S, R]-sulfoximine), an inhibitor of g-glutamyltransferase (AT-125) and inhibitor of cysteine conjugate β-lyase (aminooxiacetic acid). 2 Dose-dependent decrease of p-aminohippurate uptake was observed in male renal cortical slices. Only the high doses (3.0 and 4.0×10-4 M) caused a significant loss of organic anion uptake in females. 3 β-Naphthoflavone and α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125) partially, but significantly, reduced organic anion loss in males. In females, DL-buthionine-[S, R]-sulfoximine significantly increased in females but in males loss of organic anion accumulation caused by 1,3-dichloropropene. Aminooxyacetic acid did not ameliorate 1,3 D effects in vivo and in vitro in male rats. It appeared very toxic for female rats (all rats died) after in vivo injection. 4 Sensitivity to nephrotoxicity induced by 1,3-dichlor-opropene in vitro was about double in male than female rats. Reduced glutathione conjugation appeared involved in nephrotoxicity induced in males but in females, probably by means of a chloropropylcysteinylglycine-conjugate formation; slight toxicity in females is likely related to oxidative metabolism.
Multiple sclerosis progression in a natural history study: Predictive value of cerebrospinal fluid free kappa light chains
Authors: Rudick RA , Medendorp SV , Namey M , Boyle S , Fischer J 
Published: July 2017

Objectives: To determine the relationship between baseline CSF immunologic abnormalities and MS disease progression; To determine progression rates in an untreated, recently-diagnosed MS sample using several validated clinical measures. Background: CSF immune abnormalities are common in MS but have not been linked to disease progression. Design Methods: Thirty-six patients with definite (n=28), probable (n=2), or possible (n=6) MS were studied prospectively. Baseline CSF was analyzed for free kappa and lambda light chains, myelin basic protein, IgG synthesis rate, and IgG index. MS patients were entered into the study within 5 years of symptom onset and examined semiannually for as long as 53.4 months (median length offollow up 38.9 months). MS progression was defined as sustained worsening on the following clinical measurement instruments: the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI), the 9 Hole Peg Test (9HT) and the Box and Blocks test (BBT). Kaplan-Meier estimates of disease progression were calculated and the relationship between baseline CSF values and disease progression was determined using Cox proportional hazards regression models. Results: By 36 months, 33% (95% Cl-10.3, 55.7) of patients had progressed on EDSS and 49.7% (95% Cl=27.7, 71.7) had progressed on at least one of the outcome measures. Patients with CSF free kappa chain levels in the upper quartile had a significantly higher risk of progression on EDSS (Hazard Ratio 3.78; p=0.04) and 9HT (Hazard Ratio 10.77, p=0.04). Conclusions: In this study, CSF free kappa light chains predicted subsequent physical deterioration in prospectively evaluated MS patients. If this is confirmed by larger studies, then CSF free kappa light chains could serve as a target for intervention in therapeutic trials.