bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of the Renal NaCl Cotransporter and Its Role in Potassium Homeostasis
Authors: Hoorn Ewout J. , Gritter Martin , Cuevas Catherina A. , Fenton Robert A.
Published: August 2020

Daily dietary potassium (K+) intake may be as large as the extracellular K+pool. To avoid acute hyperkalemia, rapid removal of K+from the extracellular space is essential. This is achieved by translocating K+into cells and increasing urinary K+excretion. Emerging data now indicate that the renal thiazide-sensitive NaCl cotransporter (NCC) is critically involved in this homeostatic kaliuretic response. This suggests that the early distal convoluted tubule (DCT) is a K+sensor that can modify sodium (Na+) delivery to downstream segments to promote or limit K+secretion. K+sensing is mediated by the basolateral K+channels Kir4.1/5.1, a capacity that the DCT likely shares with other nephron segments. Thus, next to K+-induced aldosterone secretion, K+sensing by renal epithelial cells represents a second feedback mechanism to control K+balance. NCC’s role in K+homeostasis has both physiological and pathophysiological implications. During hypovolemia, NCC activation by the renin-angiotensin system stimulates Na+reabsorption while preventing K+secretion. Conversely, NCC inactivation by high dietary K+intake maximizes kaliuresis and limits Na+retention, despite high aldosterone levels. NCC activation by a low-K+diet contributes to salt-sensitive hypertension. K+-induced natriuresis through NCC offers a novel explanation for the antihypertensive effects of a high-K+diet. A possible role for K+in chronic kidney disease is also emerging, as epidemiological data reveal associations between higher urinary K+excretion and improved renal outcomes. This comprehensive review will embed these novel insights on NCC regulation into existing concepts of K+homeostasis in health and disease.
Network Pharmacology‐Based Approach to Revealing Biological Mechanisms of Qingkailing Injection against IschemicStroke: Focusing on Blood‐Brain Barrier
Authors: Zhang Shuang , Wang Xueqian , Cheng Fafeng , Ma Chongyang , Fan Shuning , Xu Wenxiu , Jin Na , Liu Shuling , Lv Kai , Wang Qingguo
Published: August 2020

Ischemic stroke is the most common type of cerebrovascular accident worldwide. It causes long‐term disability and death. Qingkailing (QKL) injection is a traditional Chinese patent medicine which has been clinically applied in the treatment of ischemic stroke for nearly thirty years. In the present study, network pharmacology combined with experimentation was used to elucidate the mechanisms of QKL. ADME screening and target prediction identified 62 active compounds and 275 targets for QKL. Topological screening of the protein‐protein interaction (PPI) network was used to build a core PPI network consisting of 408 nodes and 17,830 edges. KEGG enrichment indicated that the main signaling pathway implicated in ischemic stroke involved hypoxia‐inducible factor‐1 (HIF‐1). Experimentation showed that QKL alleviated neurological deficits, brain infraction, blood‐brain barrier (BBB) leakage, and tight junction degeneration in a mouse ischemic stroke model. Two‐photon laser scanning microscopy was used to evaluate BBB permeability and cerebral microvessel structure in living mice. HIF‐1α, matrix metalloproteinase‐9 (MMP‐9), and tight junction proteins such as occludin, zonula occludins‐1 (ZO‐1), claudin‐5, and VE‐Cadherin were measured by western blotting. QKL upregulated ZO‐1 and downregulated HIF‐1α and MMP‐9. QKL has a multiapproach, multitarget, and synergistic effect against ischemic stroke.
A Rational Model for Agroecology as a Science
Authors: Gómez-Echeverri Luis Fernando , Ríos-Osorio Leonardo Alberto , Eschenhagen-Durán María Luisa
Published: August 2020

Agroecology was born as a competing theory to sciences derived from the Green Revolution like conventional agronomy or modernized animal husbandry. In recent years, several theoretical models or approaches have been developed in order to explain this science. However, any of them can explain its change or difference with its rival theories in a rational manner that allows assessment of its success. As a result, the aim of this study was to propose a rational model of scientific change based on main and auxiliary hypotheses. We found that seven basic principles have been formulated throughout theoretical books and papers as well as several auxiliary hypotheses that can be derived from them. These principles are as follows: (1) characteristic systemic principle of agroecology, (2) principle of biomimicry, (3) principle of biodiversity, (4) principle of specificity of agroecosystems, (5) principle of governance, (6) principle of socioecological resilience, and (7) principle of vulnerability. Also, three principles for food systems approach were retrieved. This model shows agroecology more like an organic theory that moves in different scales than a set of rival theories competing for success. However, a proper articulation and discussion of these basic principles is yet to be done.
The Immersed Boundary-Lattice Boltzmann Method Parallel Model for Fluid-Structure Interaction on Heterogeneous Platforms
Authors: Liu Zhixiang , Liu Huichao , Huang Dongmei , Zhou Liping
Published: August 2020

Immersed boundary-lattice Boltzmann method (IB-LBM) has become a popular method for studying fluid-structure interaction (FSI) problems. However, the performance issues of the IB-LBM have to be considered when simulating the practical problems. The Graphics Processing Units (GPUs) from NVIDIA offer a possible solution for the parallel computing, while the CPU is a multicore processor that can also improve the parallel performance. This paper proposes a parallel algorithm for IB-LBM on a CPU-GPU heterogeneous platform, in which the CPU not only controls the launch of the kernel function but also performs calculations. According to the relatively local calculation characteristics of IB-LBM and the features of the heterogeneous platform, the flow field is divided into two parts: GPU computing domain and CPU computing domain. CUDA and OpenMP are used for parallel computing on the two computing domains, respectively. Since the calculation time is less than the data transmission time, a buffer is set at the junction of two computational domains. The size of the buffer determines the number of the evolution of the flow field before the data exchange. Therefore, the number of communications can be reduced by increasing buffer size. The performance of the method was investigated and analyzed using the traditional metric MFLUPS. The new algorithm is applied to the computational simulation of red blood cells (RBCs) in Poiseuille flow and through a microchannel.
MicroRNA-155 Participates in the Expression of LSD1 and Proinflammatory Cytokines in Rheumatoid Synovial Cells
Authors: Yu Ziliang , Liu Hao , Fan Jianbo , Chen Feihu , Liu Wei
Published: August 2020

MicroRNA-155 (miRNA-155) is abundant in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Lysine-specific demethylase 1 (LSD1) has been found that it can ameliorate the severity of RA. Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 are key proinflammatory cytokines implicated in the pathogenesis of RA. In our study, we investigated whether miRNA-155 participates in the expression of LSD1 and proinflammatory cytokines in rheumatoid synovial cells. First of all, flow cytometry and cell counting kit-8 analysis were employed to explore the apoptosis and proliferation of FLS, respectively. Subsequently, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to probe into the level of miRNA-155 in FLS when stimulated by miRNA-155 molecules. Moreover, RT-qPCR was used to explore the relative LSD1 miRNA expression in FLS when stimulated by miRNA-155 molecules, and Western blot and immunofluorescence assay were applied to probe into the expression level of LSD1. Finally, enzyme-linked immunosorbent assay was employed to analyze the secreting level of proinflammatory cytokines in FLS when stimulated by miRNA-155 molecules. RA-FLS showed a higher apoptosis rate than normal FLS. The cell proliferation of both HFLS and MH7A cells was promoted by miRNA-155 upregulation. Meanwhile, the expression of LSD1 and proinflammatory cytokines in the FLS of RA was also changed by miRNA-155 regulation. In conclusion, miRNA-155 participates in the expression of LSD1 and proinflammatory cytokines in rheumatoid synovial cells. These findings imply a potential function and interaction of miRNA-155 and LSD1.
Multirobot Collaborative Navigation Algorithms Based on Odometer/Vision Information Fusion
Authors: Liu Guohua , Guan Juan , Liu Haiying , Wang Chenlin
Published: August 2020

Collaborative navigation is the key technology for multimobile robot system. In order to improve the performance of collaborative navigation system, the collaborative navigation algorithms based on odometer/vision multisource information fusion are presented in this paper. Firstly, the multisource information fusion collaborative navigation system model is established, including mobile robot model, odometry measurement model, lidar relative measurement model, UWB relative measurement model, and the SLAM model based on lidar measurement. Secondly, the frameworks of centralized and decentralized collaborative navigation based on odometer/vision fusion are given, and the SLAM algorithms based on vision are presented. Then, the centralized and decentralized odometer/vision collaborative navigation algorithms are derived, including the time update, single node measurement update, relative measurement update between nodes, and covariance cross filtering algorithm. Finally, different simulation experiments are designed to verify the effectiveness of the algorithms. Two kinds of multirobot collaborative navigation experimental scenes, which are relative measurement aided odometer and odometer/SLAM fusion, are designed, respectively. The advantages and disadvantages of centralized versus decentralized collaborative navigation algorithms in different experimental scenes are analyzed.
Damage Evaluation of the Paving around Manholes under Vehicle Dynamic Load
Authors: Hu Wenjun , Zhao Quanman , Liu Yao , Li Zhigang , Kong Xianghui
Published: August 2020

It is very important for pavement engineers to know which factors are the main reasons for the damage of the paving around manholes. Based on the investigation on the damage of paving around manholes, a vibration model with multidegree of freedom for the vehicle‐manhole cover was established and analyzed. After that, the Matlab software was used to obtain the variation law of impact load over time, and the 95% fourth power of the aggregate force was used as the index to evaluate the pavement damage. Finally, many influencing factors on pavement damage were analyzed by the method of grey correlation entropy. The results indicated that the impact load reached the maximum for the first time when the vehicle reached the top of the manhole cover, which was 1.29 times that of the static load, and the pavement damage coefficient was 2.12 times that of the static load. The influencing factors had different degrees of influence on the pavement damage; from large to small, they were change of road longitudinal slope > driving speed > damping of tire > stiffness of tire > height difference from the pavement damage > height difference from the manhole settlement > stiffness of the manhole cover.
A Hierarchical Static-Dynamic Encoder-Decoder Structure for 3D Human Motion Prediction with Residual CNNs
Authors: Tang Jin , Liu Jin , Yin JianQin
Published: August 2020

Human motion prediction aims at predicting the future poses according to the motion dynamics given by the sequence of history poses. We present a new hierarchical static-dynamic encoder-decoder structure to predict the human motion with residual CNNs. Specifically, to better mine the law of the motion, a new residual CNN-based structure, v-CMU, is proposed to encode not only the static information but also the dynamic information. Based on v-CMU, a hierarchical structure is proposed to model different correlations between the different given poses and the predicted pose. Moreover, a new loss function combining the static and dynamic information is introduced in the decoder to guide the prediction of the future poses. Our framework features two-folds: (1) more effective dynamics mined due to the fusion of information of the poses and the dynamic information between poses and the hierarchical structure; (2) better decoding or prediction performance, thanks to the mid-level supervision introduced by the new loss function considering both the static and dynamic losses. Extensive experiments show that our algorithm can achieve state-of-the-art performance on the challenging G3D and FNTU datasets. The code is available at https://github.com/liujin0/SDnet.
Complexity Analysis of a Four-Dimensional Energy-Economy-Environment Dynamic System
Authors: Jin Shuai , Zhao Liuwei
Published: August 2020

A novel four-dimensional energy, economic, and environmental (3E) under energy reduction constraints chaotic system is proposed. The acquisition of environmental quality data is the key to this paper. During the course of the study, we used Bayesian estimation algorithm to calibrate the environmental quality. Based on the official data, the Levenberg–Marquardt backpropagation neural network method was optimized by genetic algorithm to effectively identify the parameters in the 3E system. The research results show that although increasing energy reduction inputs can improve environmental quality, the effect on energy intensity and overall stability of the system is not obvious. When polluting input in the ecological environment system affects its maximum capacity, the environmental system collapses (i.e., the ecological system can no longer purify the environment through the self-circulation process and will eventually die out). Therefore, it is necessary to correctly grasp the ecological environment protection and the relationship between economic developments and explore synergies to promote ecological priorities and green development new ideas.
A New Therapy for Vitiligo Using Fire Needles: A Systematic Review of Evidence from 3618 Subjects
Authors: Luo Ying , Qian Wei , Dai Ting , Ru Yi , Sun Xiaoying , Kuai Le , Liu Liu , Xing Meng , Zheng Qi , Zhang Ying , Chen Xi , Zhao Huaibo , Li Bin , Li Xin
Published: August 2020

Introduction. Fire needle therapy has been reported as an effective treatment for vitiligo. However, current clinical evidence has not been systematically evaluated. The aim of this study was to determine whether fire needle therapy is effective and safe for treating vitiligo. Methods. Seven databases were searched until October 2019 for randomized controlled trials on fire needle therapy, with and without conventional treatments, versus any type of conventional therapy for treating vitiligo. The RevMan 5.3.5 software was used to perform meta‐analysis of the included studies. Results. Forty‐seven trials comprising 3618 patients were included. Fire needle combined with conventional vitiligo treatments had a higher efficacy (risk ratio (RR): 1.55, 95% confidence interval (CI): 1.46–1.65, P < 0.00001 and RR: 1.41, 95% CI: 1.24–1.61, P < 0.00001, respectively) and a greater effect on restoring the color of the area of the skin lesion (mean difference (MD): 3.40, 95% CI: 2.11–4.69, P < 0.00001), increasing the pigment point of vitiligo (MD: 0.83, 95% CI: 0.54–1.13, P < 0.00001) and improving the cytokine level (MD: 8.10, 95% CI: 6.94–9.27, P < 0.00001) and effectual time (MD: −4.76, 95% CI: −7.33 to −2.19, P = 0.0003) than traditional methods. Limb lesions (RR: 1.60, 95% CI: 1.31–1.95, P < 0.00001) were more effectively treated when the treatments included fire needles, whereas the therapeutic effect of fire needles on either the head and neck (RR: 1.13, 95% CI: 0.78–1.64, P = 0.52) or torso lesions (RR: 1.22, 95% CI: 0.82–1.81, P = 0.33) was not significantly different compared to that without fire needles. No statistically significant differences in adverse effects (RR: 1.15, 95% CI: 0.89–1.49, P = 0.28) and recurrence rates (RR: 0.90, 95% CI: 0.17–4.92, P = 0.91) during the follow‐up period were observed between treatment with and without fire needles. Conclusions. Fire needle therapy combined with other conventional treatments is useful in treating vitiligo. Further studies with larger sample sizes should be performed to make a conclusive judgment. This trial is registered with CRD42018094918.
Differential Expression and PAH Degradation: What Burkholderia vietnamiensis G4 Can Tell Us?
Authors: Cauduro Guilherme Pinto , Leal Ana Lusia , Lopes Tiago Falcón , Marmitt Marcela , Valiati Victor Hugo
Published: August 2020

Petroleum is the major energy matrix in the world whose refining generates chemical byproducts that may damage the environment. Among such waste, polycyclic aromatic hydrocarbons (PAH) are considered persistent pollutants. Sixteen of these are considered priority for remediation, and among them is benzo(a)pyrene. Amid remediation techniques, bioremediation stands out. The genus Burkholderia is amongst the microorganisms known for being capable of degrading persistent compounds; its strains are used as models to study such ability. High-throughput sequencing allows researchers to reach a wider knowledge about biodegradation by bacteria. Using transcripts and mRNA analysis, the genomic regions involved in this aptitude can be detected. To unravel these processes, we used the model B. vietnamiensis strain G4 in two experimental groups: one was exposed to benzo(a)pyrene and the other one (control) was not. Six transcriptomes were generated from each group aiming to compare gene expression and infer which genes are involved in degradation pathways. One hundred fifty-six genes were differentially expressed in the benzo(a)pyrene exposed group, from which 33% are involved in catalytic activity. Among these, the most significant genomic regions were phenylacetic acid degradation protein paaN, involved in the degradation of organic compounds to obtain energy; oxidoreductase FAD-binding subunit, related to the regulation of electrons within groups of dioxygenase enzymes with potential to cleave benzene rings; and dehydrogenase, described as accountable for phenol degradation. These data provide the basis for understanding the bioremediation of benzo(a)pyrene and the possible applications of this strain in polluted environments.
Soy-Maize Crop Rotations in Sub-Saharan Africa: A Literature Review
Authors: Acevedo-Siaca Liana , Goldsmith Peter D.
Published: August 2020

Empirical evidence shows complementarity between maize and soybean as a sustained agricultural system across North and South America as well as Eastern Europe. The potential application to sub-Saharan Africa motivates this literature review. Maize is one of the most important crops on the African subcontinent, accounting for over half of daily caloric intake in some regions. However, continuous cropping of maize has led to extensive degradation of soil and decrease in crop productivity and endangers household food and nutritional security. The cultivation of soybean holds great promise in improving agricultural systems in sub-Saharan Africa. Introducing soy into rotation with maize is a method to diversify diets, better nutritional status, reduce abiotic and biotic stresses, and improve soil fertility, while enhancing crop productivity and generating more income for farmers. However, limited access to extension services and other sources of technical support constrains adoption of the more complex rotation cropping system involving a new crop, soybean. Rotating soybean with maize too challenges farmers as there is not a specific prescription that can guide farmers operating across Africa’s diverse agroecological environments. Finally, soybean is an input-intensive crop requiring significant investment at planting, which may not allow small holders with limited resources and no access to credit.
Subacute Hepatotoxicity of Extracts ofSenna occidentalisSeeds in Swiss Albino Mice
Authors: Gebrezgi Egziharia Mokonen , Hiben Mebrahtom Gebrelibanos , Kidanu Kidanemariam Gaim , Tsegay Amanuel Tesfay
Published: August 2020

Senna occidentalisis potentially toxic to humans and animals. Its seeds are crop contaminant weeds in some localities where liver disease is prevalent. This study assessed the subacute hepatotoxicity ofS. occidentalisseeds in mice model. Three groups of female Swiss Albino mice (25–28 g, aged 8–10 weeks) received distilled water (control), 400, and 1000 mg/kg extract ofS. occidentalisseed, respectively. At the end of the study, body weight and liver organ weight were recorded, and tissue and blood samples were collected and analyzed. The results indicated that the extract treated groups, at both doses, showed significant (p≤0.001) decrease in mean body weight gain in the fourth week of the experiment. Besides, the extract treated groups showed significant (p≤0.001) elevation of liver enzyme markers: alanine aminotransferase and aspartate aminotransferase. Also, histopathological examinations of liver tissue showed moderate microvesicular steatosis of hepatocytes and mild inflammation in the 400 mg/kg treated group as well as marked micro- and macrovesicular steatosis, focal area necrosis, and periportal inflammation with mononuclear cell infiltration in the 1000 mg/kg treated group. Thus, these findings show thatS. occidentalisseeds exhibit hepatotoxicity in mice, characterized by changes in liver tissue architecture and liver enzyme levels.
Pleiotropic Mechanisms Drive Endocrine Resistance in the Three-Dimensional Bone Microenvironment
Authors: Dhimolea Eugen , de Matos Simoes Ricardo , Kansara Dhvanir , Weng Xiang , Sharma Shruti , Awate Pallavi , Liu Zhiyi , Gao Dong , Mitsiades Nicholas , Schwab Joseph H. , Chen Yu , Jeselsohn Rinath , Culhane Aedín C. , Brown Myles , Georgakoudi Irene , Mitsiades Constantine S.
Published: August 2020

Although hormonal therapy (HT) inhibits the growth of hormone receptor–positive (HR+) breast and prostate cancers, HT resistance frequently develops within the complex metastatic microenvironment of the host organ (often the bone), a setting poorly recapitulated in 2D culture systems. To address this limitation, we cultured HR+ breast cancer and prostate cancer spheroids and patient-derived organoids in 3D extracellular matrices (ECM) alone or together with bone marrow stromal cells (BMSC). In 3D monocultures, antiestrogens and antiandrogens induced anoikis by abrogating anchorage-independent growth of HR+ cancer cells but exhibited only modest effects against tumor cells residing in the ECM niche. In contrast, BMSC induced hormone-independent growth of breast cancer and prostate cancer spheroids and restored lumen filling in the presence of HR-targeting agents. Molecular and functional characterization of BMSC-induced hormone independence and HT resistance in anchorage-independent cells revealed distinct context-dependent mechanisms. Cocultures of ZR75-1 and LNCaP with BMSCs exhibited paracrine IL6-induced HT resistance via attenuation of HR protein expression, which was reversed by inhibition of IL6 or JAK signaling. Paracrine IL6/JAK/STAT3-mediated HT resistance was confirmed in patient-derived organoids cocultured with BMSCs. Distinctly, MCF7 and T47D spheroids retained ER protein expression in cocultures but acquired redundant compensatory signals enabling anchorage independence via ERK and PI3K bypass cascades activated in a non–IL6-dependent manner. Collectively, these data characterize the pleiotropic hormone-independent mechanisms underlying acquisition and restoration of anchorage-independent growth in HR+ tumors. Combined analysis of tumor and microenvironmental biomarkers in metastatic biopsies of HT-resistant patients can help refine treatment approaches.

Significance:

This study uncovers a previously underappreciated dependency of tumor cells on HR signaling for anchorage-independent growth and highlights how the metastatic microenvironment restores this malignant property of cancer cells during hormone therapy.
Circulating Tumor DNA Genomics Reveal Potential Mechanisms of Resistance to BRAF-Targeted Therapies in Patients withBRAF-Mutant Metastatic Non–Small Cell Lung Cancer
Authors: Ortiz-Cuaran Sandra , Mezquita Laura , Swalduz Aurélie , Aldea Mihalea , Mazieres Julien , Leonce Camille , Jovelet Cecile , Pradines Anne , Avrillon Virginie , Chumbi Flores Washington R. , Lacroix Ludovic , Loriot Yohann , Westeel Virginie , Ngo-Camus Maud , Tissot Claire , Raynaud Christine , Gervais Radj , Brain Etienne , Monnet Isabelle , Giroux Leprieur Etienne , Caramella Caroline , Mahier-Aït Oukhatar Celine , Hoog-Labouret Natalie , de Kievit Frank , Howarth Karen , Morris Clive , Green Emma , Friboulet Luc , Chabaud Sylvie , Guichou Jean-François , Perol Maurice , Besse Benjamin , Blay Jean-Yves , Saintigny Pierre , Planchard David
Published: August 2020

Purpose:

The limited knowledge on the molecular profile of patients with BRAF-mutant non–small cell lung cancer (NSCLC) who progress under BRAF-targeted therapies (BRAF-TT) has hampered the development of subsequent therapeutic strategies for these patients. Here, we evaluated the clinical utility of circulating tumor DNA (ctDNA)-targeted sequencing to identify canonical BRAF mutations and genomic alterations potentially related to resistance to BRAF-TT, in a large cohort of patients with BRAF-mutant NSCLC.

Experimental Design:

This was a prospective study of 78 patients with advanced BRAF-mutant NSCLC, enrolled in 27 centers across France. Blood samples (n = 208) were collected from BRAF-TT–naïve patients (n = 47), patients nonprogressive under treatment (n = 115), or patients at disease progression (PD) to BRAF-TT (24/46 on BRAF monotherapy and 22/46 on BRAF/MEK combination therapy). ctDNA sequencing was performed using InVisionFirst-Lung. In silico structural modeling was used to predict the potential functional effect of the alterations found in ctDNA.

Results:

BRAFV600E ctDNA was detected in 74% of BRAF-TT–naïve patients, where alterations in genes related with the MAPK and PI3K pathways, signal transducers, and protein kinases were identified in 29% of the samples. ctDNA positivity at the first radiographic evaluation under treatment, as well as BRAF-mutant ctDNA positivity at PD were associated with poor survival. Potential drivers of resistance to either BRAF-TT monotherapy or BRAF/MEK combination were identified in 46% of patients and these included activating mutations in effectors of the MAPK and PI3K pathways, as well as alterations in U2AF1, IDH1, and CTNNB1.

Conclusions:

ctDNA sequencing is clinically relevant for the detection of BRAF-activating mutations and the identification of alterations potentially related to resistance to BRAF-TT in BRAF-mutant NSCLC.
The Long and Winding Road for Breast Cancer Biomarkers to Reach Clinical Utility
Authors: Hunter Natasha B. , Kilgore Mark R. , Davidson Nancy E.
Published: August 2020

Tumor data from the ABCSG 5 trial of chemotherapy versus endocrine therapy for premenopausal ER+ breast cancer supports molecular subtyping by Ki-67 IHC as a prognostic marker. But while this tissue was handled uniformly, Ki-67 testing overall is unstandardized, complicating clinical utility. Increasing potential biomarkers herald more challenges in biomarker validation.

See related article by Bago-Horvath et al., p. 5682
Low Geriatric Nutritional Risk Index as a Poor Prognostic Marker for Second-Line Pembrolizumab Treatment in Patients with Metastatic Urothelial Carcinoma: A Retrospective Multicenter Analysis
Authors: Etani Toshiki , Naiki Taku , Sugiyama Yosuke , Nagai Takashi , Iida Keitaro , Noda Yusuke , Shimizu Nobuhiko , Tasaki Yoshihiko , Mimura Yoshihisa , Okada Tomoki , Banno Rika , Kubota Hiroki , Hamamoto Shuzo , Ando Ryosuke , Kawai Noriyasu , Yasui Takahiro
Published: August 2020

Background: We evaluated the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in second-line pembrolizumab (PEM) therapy for patients with metastatic urothelial carcinoma (mUC). Patients and Methods: From January 2018 to October 2019, 52 mUC patients, treated previously with platinum-based chemotherapy, underwent second-line PEM therapy. Peripheral blood parameters were measured at the start of treatment: serum neutrophil-to-lymphocyte ratio (NLR), serum albumin, serum C-reactive protein (CRP), and body height and weight. PEM was intravenously administered (200 mg every 3 weeks). The patients were organized into two groups based on their GNRI (<92 [low GNRI] and ≥92 [high GNRI]), and the data were retrospectively analyzed. Adverse events (AEs) were evaluated and imaging studies assessed for all patients. Analyses of survival and recurrence were performed using Kaplan-Meier curves. Potential prognostic factors affecting cancer-specific survival (CSS) were assessed by univariate and multivariate Cox regression analyses. Results: patients’ baseline characteristics, except for their BMI and objective response rate, did not significantly differ between the two groups. The median total number of cycles of PEM therapy was significantly higher for the high-GNRI group (n [range]: 6 [2–20] vs. 3 [1–6]). The median CSS with second-line PEM therapy was 3.6 months (95% confidence interval [CI]: 2.5–6.1) and 11.8 months (95% CI: 6.2–NA) in the low-GNRI and the high-GNRI group (p < 0.01), respectively. Significant differences in CSS between the low- and high-CRP or -NRL groups were not found. Multivariate Cox proportional-hazards regression analysis revealed that a poor Eastern Cooperative Oncology Group performance status, visceral metastasis, and a low GNRI were significant prognostic factors for short CSS (95% CI: 1.62–6.10, HR: 3.14; 95% CI: 1.13–8.11, HR: 3.03; 95% CI: 1.32–8.02, HR: 3.25, respectively). Of the AEs, fatigue showed a significantly higher incidence in the low-GNRI group. Conclusions: For mUC patients receiving second-line PEM therapy, the GNRI is a useful predictive biomarker for survival outcome.
Heart Rate–Induced Myocardial Ca
2+
Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Silverman Daniel N. , Rambod Mehdi , Lustgarten Daniel L. , Lobel Robert , LeWinter Martin M. , Meyer Markus
Published: August 2020

Background

Increases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca
2+
overload caused by increased myocardial Na
+
levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension.

Methods and Results

In 22 fully sedated and instrumented patients (12 controls and 10 patients with HFpEF) in sinus rhythm with a preserved ejection fraction (≥50%) we assessed left‐sided filling pressures and volumes in sinus rhythm and with atrial pacing (95 beats per minute and 125 beats per minute) before atrial fibrillation ablation. Coronary sinus blood samples and flow measurements were also obtained. Seven women and 15 men were studied (aged 59±10 years, ejection fraction 61%±4%). Patients with HFpEF had a history of hypertension, dyspnea on exertion, concentric LV remodeling and a dilated left atrium, whereas controls did not. Pacing at 125 beats per minute lowered the mean LV end‐diastolic pressure in both groups (controls −4.3±4.1 mm Hg versus patients with HFpEF −8.5±6.0 mm Hg,
P
=0.08). Pacing also reduced LV end‐diastolic volumes. The volume loss was about twice as much in the HFpEF group (controls −15%±14% versus patients with HFpEF −32%±11%,
P
=0.009). Coronary venous [Ca
2+
] increased after pacing at 125 beats per minute in patients with HFpEF but not in controls. [Na
+
] did not change.

Conclusions

Higher resting heart rates are associated with lower filling pressures in patients with and without HFpEF. Incomplete relaxation and LV filling at high heart rates lead to a reduction in LV volumes that is more pronounced in patients with HFpEF and may be associated with myocardial Ca
2+
retention.
Right Patient, Right Place, Right Time
Authors: Gough Benjamin L. , Painter Matthew D. , Hoffman Autumn L. , Caplan Richard J. , Peters Cynthia A. , Cipolle Mark D.
Published: August 2020

Introduction

This study sought to compare outcomes of trauma patients taken directly from the field to a Level I trauma center (direct) versus patients that were first brought to a Level III trauma center prior to being transferred to a Level I (transfer) within our inclusive Delaware trauma system.

Methods

A retrospective review of the Level I center’s trauma registry was performed using data from 2013 to 2017 for patients brought to a single Level I trauma center from 2 surrounding counties. The direct cohort consisted of 362 patients, while the transfer cohort contained 204 patients. Linear regression analysis was performed to investigate hospital length of stay (LOS), while logistic regression was used for mortality, complications, and craniotomy. Covariates included age, gender, county, and injury severity score (ISS). Propensity score weighting was also performed between the direct and transfer cohorts.

Results

When adjusting for age, gender, ISS, and county, transferred patients demonstrated worse outcomes compared with direct patients in both the regression and propensity score analyses. Transferred patients were at increased risk of mortality (odds ratio [OR] 2.17, CI 1.10-4.37, P = .027) and craniotomy (OR 3.92, CI 1.87-8.72, P < .001). Age was predictive of mortality ( P < .001). ISS was predictive of increased risk of mortality ( P < .001), increased LOS ( P < .001), and craniotomy ( P < .001). Older age, Sussex County, and higher ISS were predictive of patients being transferred ( P < .001).

Discussion

Delays in the presentation to our Level I trauma center resulted in worse outcomes. Patients that meet criteria should be considered for transport directly to the highest level trauma center in the system to avoid delays in care.
Transitioning Collaborative Cross-Sector Business Models for Sustainability Innovation: Multilevel Tension Management as a Dynamic Capability
Authors: Rey-Garcia Marta , Mato-Santiso Vanessa , Felgueiras Ana
Published: August 2020

Collaborative cross-sector business models for sustainability innovation (CCSBMSI) in response to grand challenges are rich foci for tensions. This is the case of CCSBMSI targeting independent living through Information and Communication Technology–enabled care. This research aims at identifying the relevant tensions, understanding their interactions, and assessing how they can be effectively managed so that CCSBMSI become more valuable for partners and transformative for society. A conceptual framework that understands the management of interrelated institutional and interorganizational tensions as a dynamic capability is substantiated through in-depth, qualitative analysis of the long-term dynamics of a four-sector CCSBMSI in telecare—including government, businesses, nonprofits, and informal actors. Its effects on the transition of business models in terms of value creation, delivery, and capture; on relevant stakeholders—particularly nonprofits and beneficiaries; and on the development of the sustainability innovation are discussed. The conceptualization, tension categories, and management capabilities of CCSBMSI are amplified.
Using Bayesian Updating to Improve Decisions under Uncertainty
Authors: McCann Brian T.
Published: August 2020

Decision making requires managers to constantly estimate the probability of uncertain outcomes and update those estimates in light of new information. This article provides guidance to managers on how they can improve that process by more explicitly adopting a Bayesian approach. Clear understanding and application of the Bayesian approach leads to more accurate probability estimates, resulting in better informed decisions. More importantly, adopting a Bayesian approach, even informally, promises to improve the quality of managerial thinking, analysis, and decisions in a variety of additional ways.
The cost of illiteracy: A causal inference study on how illiteracy affects physical and mental health
Authors: Zhang Qiyang
Published: August 2020

Objective:

The aim of this study was to investigate the impact of illiteracy on physical health and mental health.

Design:

Matching methods (nearest neighbour matching, Mahalanobis metric matching, and propensity score matching).

Setting:

Elderly people at least 65 years old in 22 provinces of China.

Methods:

The analysis used data from Chinese Longitudinal Healthy Longevity Survey (CLHLS). The independent variable was a dummy variable, which was coded as 1 for illiterate or semiliterate, and 0 for literate. Dependent variables were indicators of physical and mental health derived from the survey results. Matching methodologies controlled for confounding variables including age, sex, living sites, access to tap water and financial support.

Results:

Illiteracy was found to have a significant impact on physical health, exercise habits, anxiety, loneliness and happiness. On average, illiteracy decreased physical health by 19.9%, decreased exercise habits by 7%, increased anxiety by 11.56%, increased loneliness by 17.6% and decreased happiness by 11.3%.

Conclusion:

Findings confirm the past literature in which illiteracy has been found to be adversely associated with physical and mental health. The analysis uniquely found that illiteracy had a higher cost on mental health as compared to physical health for elderly people in China.
A Measure of Service Quality in the Grocery Stores
Authors: Kumar Abhishek , Chaudhuri Sumana , Satpathy Ipseeta , Patnaik B. C. M
Published: August 2020

The main purpose of this study is to increase the understanding of the perceived service quality of the customer within grocery retailing from an Indian perspective. In this dissertation, data were collected from 403 customers who buy grocery from Big Bazaar and Reliance Fresh during February–July 2017 from Bhubaneswar and Cuttack. A quantitative approach using Statistical Package for the Social Science (SPSS) version 20 is used, which caters to the exploratory nature of the work. Statistical techniques such as exploratory factor analysis, multiple regression, t-test and ANOVA have been used to test the hypotheses and answer the research questions. It can be inferred from this study that consumer behaviour is dependent on the demographic factors. Differences were also found with regard to the impact of service quality on the satisfaction and the loyalty of the customers. This research adds to the study on service quality in the grocery business of the global market by enriching the content of service quality dimensions applicable to the Indian grocery sector. Six key dimensions in the grocery sector have been identified. This will deepen the understanding of the explored factors of service quality, which can then be applied to the grocery stores.
COVID-19 India: An insight into the impact of lockdown and community behavioural response
Authors: Sharma Sahiba , Paul Anubrata
Published: August 2020

The emerging and re-emerging infectious diseases pose a threat to the global economy. The tendency to confront these pandemics is still questionable. In January 2020, the first case of coronavirus (COVID-19) in India was identified in Kerala. Later, the Indian government announced lockdown as a remedial action against COVID-19. The present work aims to elucidate the community behavioural response towards COVID-19 lockdown in India and presents comprehensive observations. Protection motivational theory has been used to build a conceptual framework. It was observed that community behavioural response includes maladaptive, adaptive and prosocial behaviours. In addition, we conclude that the effective strategy against the prevention, spread and control of pandemics and strategic management is still lacking. Hence, we propose a framework based on the learnings from COVID-19 to tackle future pandemics.
Investigation of various techniques for controlled void formation in fiberglass/epoxy composites
Authors: Klosterman Donald , Browning Charles , Hakim Issa , Lach Kyle
Published: August 2020

The effect of porosity in composite materials has been studied for years due to its deleterious effects on mechanical properties, especially matrix dominated properties. Currently there is an increasing use of composites in infrastructure worldwide, for example bridge components, residential and building structures, marine structures such as piers and docks, and large industrial chemical tanks. Most of these applications use fiberglass composites. Unfortunately, most of the published literature has focused on carbon fiber composites, in which fiber diameter and gas-fiber interactions are different than fiberglass composites. Therefore, the present study was undertaken to revisit the effect of porosity but specifically in fiberglass composites. The goal of this experimental study was to implement and evaluate various methods for creating porosity in fiberglass composites in a controlled manner in terms of obtaining repeatable void content, morphology, and location within the laminate. The various methods included using different amounts of autoclave pressure, adding a small amount of water between prepreg layers, and using dry fabric layers to starve the laminate of resin. Ultrasonic C-scan nondestructive evaluation was used to assess the quality of the cured panels, as well as optical and electron microscopy and void content measurements via resin burn-out. The cured panels were mechanically tested using the short beam shear (SBS) method. The results showed that the water spray method proved to be the best in terms of producing noticeably different levels of porosity, although the panels required drying to remove residual water after cure. The voids from all three techniques were either oval or elongated in-plane between the plies, but they were not uniformly distributed in-plane. The use of C-scan proved to be helpful for characterizing overall uniformity of each panel, although the results could not be used to directly compare void content between panels. The use of SBS testing was successful for evaluating void dominated properties in panels with high void content, although it was not very sensitive to coupons with lower void contents. Several interesting observations are offered in this manuscript of the fracture surface details and their relation to the SBS load deflection curves. Overall, it was found that the failure mechanisms were mixed mode and the voids did not serve as failure initiation sites. However, the voids participated mainly in the horizontal propagation of cracks between layers, presumably making it easier when they were intersected by a crack and reducing SBS strength.
A comparison on microstructure and mechanical properties of electric discharge metal matrix nickel and silica composite coating on duplex stainless steel
Authors: Arun Ilangovan , Yuvaraj C , Madhu A , Ramesh T
Published: August 2020

Electric Discharge Alloying/Coating a thermal process of elemental deposition together with pyrolysis carbon enhance various properties. Nickel and silica both provide excellent property, but the solidification rate differs the material microstructural properties (amorphous) that improves its properties under diverse working conditions. In present study analysis of properties such as surface roughness, Microstructure, layer thickness, elemental composition, porosity, decarburizing depth is detailed through metallurgical characterizations and mechanical testing are compared to nickel and silica. Nickel holds a hardness value of 1272 HV and across 968 HV with minimal in carter, pokes, splatters having uniform boundaries that improves friction co-efficient, limiting wear resistant, phase transformation, oxidation, and graphite flakes confirm self-lubrication properties at room temperature under higher loading condition. Silica having 1284 HV on the surface and across it reaches to 980 HV due to dispersed elements and its phase transformation of silica to silica carbide directs secondary arching improves bonding by restrictive carbon deposition promotes passage to speak. This limits the porosity, coating layer thickness and increases metal matrix composition in decarburizing layer holds stability towards coating. Nickel affords surface properties limiting matrix composite, oxidation, and grain growth where else silica provides exceptional in metallurgical mixed composition improves the mechanical behaviour of coating.
Do Sociotropic Concerns Mask Prejudice? Experimental Evidence on the Sources of Public Opposition to Immigration
Authors: Solodoch Omer
Published: August 2020

Does opposition to immigration mostly stem from prejudice or from sociotropic concerns about broad economic and cultural implications on the nation as a whole? Previous work on immigration preferences cannot answer this question because the two explanations are observationally equivalent when focusing on the attitudes of natives. I analyze a unique survey experiment that asks both natives and immigrants of various origins to evaluate different profiles of visa applicants to the Netherlands. The experiment also assigns an “ingroup treatment”—applications by individuals of the same ethnocultural background as the respondent. Using this rich data, I show that sociotropic concerns are the major source of immigration preferences, while ethnic biases play a moderate role. Remarkably, the ingroup treatment has limited effects on admission. However, bias against specific immigrant groups is detected in preferences of immigrant respondents and of those who sympathize with the far-right Freedom Party.
Impact of Race/Ethnicity, Veteran Status, and Place of Birth on Attitudes Towards Welfare Recipients: An Experimental Approach
Authors: ElBassiouny Amanda , Khan Sabith
Published: August 2020

The current study explored the differences in the public’s attitudes and emotions towards welfare recipients based on their race/ethnicity, birthplace, and veteran status. Participants read a mock news story created for the current study about a woman labeled as a “welfare queen” who was receiving assistance, but persuaded the reader to be sympathetic to her case. The mock news story varied based on the race/ethnicity, veteran status, and birthplace of the welfare recipient. Participants assessed the welfare recipient on various evaluative measures. A 4 (race/ethnicity: White/Black/Hispanic/Asian) × 2 (veteran status: veteran/not veteran) × 2 (country of origin: born in the US/not born in the US) between-subjects ANOVA was performed on the attitude and personality evaluations of the welfare recipient. The general pattern of results showed that welfare recipients were evaluated more positively when they were veterans, born in the United States, or were White or Asian. Conversely, the public evaluated the welfare recipient more negatively or held more aversive emotions towards them when they were Hispanic, Black, not born in the United States, or not a veteran. This research adds to the psychological literature and nonprofit sector by testing the persistence of stereotypes on the perception of individual welfare recipients.