bluuebunny/crossref_metadata_2025_split huggingface dataset:
The promise of immunotherapy in genitourinary malignancies
Authors: Zhang Tian , Armstrong Andrew J , George Daniel J , Huang Jiaoti 
Published: December 2018

Abstract
A broad understanding of the tumor immune landscape has led to a revolution of immune checkpoint inhibitors in the treatment of multiple cancer types. In genitourinary malignancies, immune checkpoint inhibitors have improved outcomes for patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma; however, these treatments have not yet proven broadly beneficial for patients with metastatic prostate cancer. Numerous prospective trials are ongoing to further improve outcomes with immunotherapy combinations and for biomarker development to predict benefit from immune checkpoint inhibition. This perspective article highlights our current immunotherapy approaches in each of the genitourinary malignancies and the ongoing clinical trials that may inform our future treatments in renal, urothelial, and prostate cancers.
RADIATION DOSES TO ANAESTHETISTS DURING PROSTATIC ARTERY EMBOLIZATION INTERVENTIONAL PROCEDURES
Authors: Garzón W J , Khoury H J 
Published: December 2018

Abstract
The objective of this study was to assess the radiation doses received by anaesthetists from prostatic artery embolization (PAE) procedures. Ten PAE procedures conducted in a reference hospital in the city of Recife, Brazil were investigated. Occupational dosimetry was performed using thermoluminescent dosemeters which were located next to the eyes, close to the thyroid (over the shielding), on the thorax (under the apron), on the wrist and on the feet of the physician’s body. The results showed that the anaesthetist’s feet received the highest doses followed by the eyes and the hands. In some complex PAE procedures the doses received by anaesthetists on the lens of the eyes and the effective dose were higher than those received by the main operator due to the anaesthetist’s close position to the patient’s table and the use of oblique projections. The personal dose equivalent Hp(3) per procedure for the anaesthetist’s right eyebrow ranged from 20.2 μSv to 568.3 μSv. This result shows that anaesthetists assisting PAE procedures can exceeds the annual eye lens dose limit of 20 mSv recommended by the ICRP with only one procedure per week if radiation protection measures are not implemented during procedures.
The cultural foundations of economic categories: finance and class in the marginalist revolution
Authors: Kaldor Yair 
Published: December 2018

AbstractEconomic categories are part of the everyday concepts people use to apprehend social reality. While scholars recognize their importance for social and economic processes, it is not clear how these categories develop when reality itself changes. I address this issue with a framework that incorporates a cultural emphasis on meaning-making with a macro-structural analysis of the conditions in which they take place. I apply this framework to the marginalist revolution of the late 19th century, which marks the birth of neoclassical economics and focus on the new understanding of ‘value’ that emerged during this period. I trace it to the rise of finance and the problem of price fluctuations, and show how its class standpoint helps explain the different outcomes of the marginalist revolution in England, Austria and France. The analysis provides insights into the power of economic ideas and the cultural dimension of structural changes.
Effects of extended-release eprinomectin on productivity measures in cow–calf systems and subsequent feedlot performance and carcass characteristics of calves
Authors: Andresen Claire E , Loy Dan D , Brick Troy A , Schulz Lee L , Gunn Patrick J 
Published: December 2018

AbstractThe objective of this study was to estimate the impact of a single injection of extended-release eprinomectin on economically relevant production variables in beef cows and calves as well as subsequent feedlot health, performance, and carcass traits of calves compared with a traditional, short duration anthelmintic. Animals from 13 cooperator herds across seven states were stratified within herd and assigned to one of two treatments; injectable doramectin (DOR; Dectomax; n = 828) or injectable eprinomection (EPR; Longrange; n = 832). Fecal samples were randomly collected from a subset of cows at both treatment and the end of grazing to evaluate fecal egg count (FEC). Continuous and categorical data were analyzed using the MIXED and GLIMMIX procedures of SAS, respectively. Cow treatment body weight (BW) and final BW were not different (P ≥ 0.40) between treatments. There were no differences (P ≥ 0.12) between treatments in cow ADG, change in BW, or body condition scores during the grazing season. While FEC at treatment did not differ (P = 0.18), cows treated with EPR had lower final FEC at the end of the grazing season (P = 0.02) and a greater reduction of FEC over the grazing season (P = 0.01). Calf treatment BW, weaning BW, and ADG did not differ between treatments (P ≥ 0.34). Incidence of pinkeye tended to be less (P = 0.06) for cows treated with EPR but was not different for calves (P = 0.43). Conception to AI, overall pregnancy rates, and calving interval were not different between treatments (P ≥ 0.45). A subset of calves from each herd was sent to Tri-County Steer Carcass Futurity (TCSCF) feedlot for the finishing phase. Calf BW did not differ at initiation of feeding (P = 0.20). While EPR calves tended to be heavier at reimplantation (P = 0.07), final BW and overall ADG were not different between treatments (P ≥ 0.13). Health records indicated lower morbidity for EPR calves (P = 0.05). Carcass performance including HCW, dressing percent, backfat, KPH, REA, YG, were not different between treatment groups (P ≥ 0.12). However, EPR calves had a greater marbling score, greater average quality grade (P &lt; 0.01), and higher proportion of calves that graded average choice or greater (P = 0.03). Results of this study indicate no difference in cow or preweaning calf performance, however, carcass quality in the feedlot phase was improved. Thus, economic analysis indicates opportunities for return on investment if animals treated with EPR have improved health status and/or carcass quality during the feeding phase.
The impact of farrowing room noise on sows’ reactivity to piglets
Authors: Chapel Nichole M , Radcliffe J Scott , Stewart Kara R , Lucas Jeffrey R , Lay Donald C 
Published: December 2018

AbstractDespite much interest in sow welfare, the impact of the acoustic environment on sow reactivity to her piglets is rarely considered. The objective of this study was to understand the impact of noise produced by mechanical ventilation and other sows on a sow’s reactivity to her piglets. Sows were farrowed in one of three environments: 1) with eight other sows exposed to constant fan noise (GROUP-FAN; n = 10), 2) alone with fan noise present (ISO-FAN; n = 10), and 3) alone without fans running (ISO-QUIET; n = 10). Sows were subjected for 5 min to a piglet removal event (REMOVAL) by an unknown handler twice, at 24 and 48 h postfarrowing. During a REMOVAL, sows were observed via video recording for changes in posture, eating and drinking behavior, and head orientation. Audio was recorded to quantify vocalizations by the sow. Once piglets were returned, sows underwent further behavior observations for 10 min (RETURN), resulting in approximately 15 min of total video observation. Sows were classified as young (second and third parity) and old (fifth parity and older). The YOUNG sows tended to be more Alert (looking toward the handler or their piglets) during REMOVE than OLD sows (P = 0.07; 2.01 and 1.33, respectively). The ISO-FAN sows vocalized the loudest during REMOVAL (P &lt; 0.001) with ISO-QUIET sows performing the quietest vocalizations (GROUP-FAN: 72.22 ± 1.06 dB; ISO-FAN: 73.61 ± 1.07 dB; ISO-QUIET: 67.41 ± 0.99 dB). During RETURN, YOUNG sows spent more time sitting than OLD sows (P &lt; 0.01; 7.48 ± 1.6% and 0.91 ± 1.8%, respectively). The ISO-QUIET sows tended to have more posture changes during the RETURN with ISO-FAN having the least changes (P = 0.06; GROUP-FAN: 1.23 ± 0.4; ISO-FAN: 0.44 ± 0.3; ISO-QUIET: 1.61 ± 0.4). Finally, sows decreased the amount of time Alert in the second RETURN (P = 0.03; first: 3.9 ± 0.6%; second: 2.5 ± 0.6%). Overall, sows acclimated to the removal and return events with decreased vocalizations and decreased Alert behaviors in the second REMOVAL and RETURN. Additionally, YOUNG sows performed more active behaviors than OLD sows, indicating that sows may become less interested in or cannot hear their piglets as they age. Finally, there is some indication that ventilation presence has an effect on sow–piglet communication with ISO-FAN sows having the loudest vocalizations when compared with sows without ventilation noise, indicating that ventilation noise may be a possible competitor with a sow’s ability to communicate with her piglets.
Methylene Blue Administration During and After Life-Threatening Intoxication by Hydrogen Sulfide: Efficacy Studies in Adult Sheep and Mechanisms of Action
Authors: Haouzi Philippe , Tubbs Nicole , Cheung Joseph , Judenherc-Haouzi Annick 
Published: December 2018

AbstractExposure to toxic levels of hydrogen sulfide (H2S) produces an acute cardiac depression that can be rapidly fatal. We sought to characterize the time course of the cardiac effects produced by the toxicity of H2S in sheep, a human sized mammal, and to describe the in vivo and in vitro antidotal properties of methylene blue (MB), which has shown efficacy in sulfide intoxicated rats. Infusing NaHS (720 mg) in anesthetized adult sheep produced a rapid dilation of the left ventricular with a decrease in contractility, which was lethal within about 10 min by pulseless electrical activity. MB (7 mg/kg), administered during sulfide exposure, maintained cardiac contractility and allowed all of the treated animals to recover. At a dose of 350 mg NaHS, we were able to produce an intoxication, which led to a persistent decrease in ventricular function for at least 1 h in nontreated animals. Administration of MB, 3 or 30 min after the end of exposure, whereas all free H2S had already vanished, restored cardiac contractility and the pyruvate/lactate (P/L) ratio. We found that MB exerts its antidotal effects through at least 4 different mechanisms: (1) a direct oxidation of free sulfide; (2) an increase in the pool of “trapped” H2S in red cells; (3) a restoration of the mitochondrial substrate-level phosphorylation; and (4) a rescue of the mitochondrial electron chain. In conclusion, H2S intoxication produces acute and long persisting alteration in cardiac function in large mammals even after all free H2S has vanished. MB exerts its antidotal effects against life-threatening sulfide intoxication via multifarious properties, some of them unrelated to any direct interaction with free H2S.
Rehabilitation treatment of spastic cerebral palsy with radial extracorporeal shock wave therapy and rehabilitation therapy
Authors: Lin Yongjie , Wang Guowei , Wang Bingchen 
Published: December 2018

Abstract
This aims to investigate the effect of combined use of radial extracorporeal shock wave therapy (rESWT) and conventional rehabilitation therapy on postoperative rehabilitation of children with spastic cerebral palsy.
Children with spastic cerebral palsy 6 weeks after multistage surgery were randomly divided into treatment group (received rESWT and conventional rehabilitation therapy) and control group (received conventional rehabilitation only). Before treatment, 2 weeks and 1 month after treatment, the Gross Motor Function Measure (GMFM), modified Ashworth Scale (MAS) of the hamstrings and triceps, plantar area and plantar pressure were examined for efficacy assessment.
A total of 82 children with spastic cerebral palsy were recruited, including 43 children in treatment group and 39 children in control group. There was no significant difference in the age, MAS score, and GMFM score between the 2 groups before treatment. There were statistically significant differences between the 2 groups at 2 weeks and 4 weeks after treatment, including the MAS score, GMFM score, plantar area and plantar pressure (P < .05). Within groups, there were also significant differences at different times (P < .05).
The rESWT combined with rehabilitation can quickly and effectively relieve paralysis of lower extremities, reduce the tension of hamstrings and calf muscles, relieve muscle spasm, and rapidly improve limb function in children with spastic cerebral palsy.
Formation of desiccation crack patterns in electric fields: a review
Authors: Tarafdar Sujata , Dutta Tapati 
Published: December 2018

Desiccation crack formation is an important and interesting part of the broad area of fracture mechanics. Generation of cracks due to drying depends on ambient conditions, which may include externally applied fields. In this review, we discuss the effect of both direct and alternating electrical fields on desiccation crack formation. After a brief introduction to materials which crack on drying, e.g. colloids, clay and ceramics we discuss how they respond to an electric field. Following that, we present an account of experiments and modelling studies performed on granular pastes or clays drying while exposed to an electric field. Specific patterns formed under different geometries, strengths and frequencies of the electric field are described and explained. The review includes work on cracks formed in clay droplets, where a memory effect has been observed and analysed using a generalized calculus formalism.
This article is part of the theme issue ‘Statistical physics of fracture and earthquakes’.
Constitutive and stimulated macropinocytosis in macrophages: roles in immunity and in the pathogenesis of atherosclerosis
Authors: Doodnauth Sasha A. , Grinstein Sergio , Maxson Michelle E. 
Published: December 2018

Macrophages respond to several stimuli by forming florid membrane ruffles that lead to fluid uptake by macropinocytosis. This type of induced macropinocytosis, executed by a variety of non-malignant and malignant cells, is initiated by transmembrane receptors and is involved in nutrient acquisition and mTOR signalling. However, macrophages also perform a unique type of constitutive ruffling and macropinocytosis that is dependent on the presence of extracellular calcium. Calcium-sensing receptors are responsible for this activity. This distinct form of macropinocytosis enables macrophages to continuously sample their microenvironment for antigenic molecules and for pathogen- and danger-associated molecular patterns, as part of their immune surveillance functions. Interestingly, even within the monocyte lineage, there are differences in macropinocytic ability that reflect the polarized functional roles of distinct macrophage subsets. This review discusses the shared and distinct features of both induced and constitutive macropinocytosis displayed by the macrophage lineage and their roles in physiology, immunity and pathophysiology. In particular, we analyse the role of macropinocytosis in the uptake of modified low-density lipoprotein (LDL) and its contribution to foam cell and atherosclerotic plaque formation. We propose a combined role of scavenger receptors and constitutive macropinocytosis in oxidized LDL uptake, a process we have termed ‘receptor-assisted macropinocytosis'.This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Function of small GTPases inDictyosteliummacropinocytosis
Authors: Williams Thomas D. , Paschke Peggy I. , Kay Robert R. 
Published: December 2018

Macropinocytosis—the large-scale, non-specific uptake of fluid by cells—is used byDictyostelium discoideumamoebae to obtain nutrients. These cells form circular ruffles around regions of membrane defined by a patch of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the activated forms of the small G-proteins Ras and Rac. When this ruffle closes, a vesicle of the medium is delivered to the cell interior for further processing. It is accepted that PIP3 is required for efficient macropinocytosis. Here, we assess the roles of Ras and Rac inDictyosteliummacropinocytosis. Gain-of-function experiments show that macropinocytosis is stimulated by persistent Ras activation and genetic analysis suggests that RasG and RasS are the key Ras proteins involved. Among the activating guanine exchange factors (GEFs), GefF is implicated in macropinocytosis by an insertional mutant. The individual roles of Rho family proteins are little understood but activation of at least some may be independent of PIP3.This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Rab8a localisation and activation by Toll-like receptors on macrophage macropinosomes
Authors: Wall Adam A. , Condon Nicholas D. , Luo Lin , Stow Jennifer L. 
Published: December 2018

Macropinocytosis is a prevalent and essential pathway in macrophages where it contributes to anti-microbial responses and innate immune cell functions. Cell surface ruffles give rise to phagosomes and to macropinosomes as multi-functional compartments that contribute to environmental sampling, pathogen entry, plasma membrane turnover and receptor signalling. Rapid, high resolution, lattice light sheet imaging demonstrates the dynamic nature of macrophage ruffling. Pathogen-mediated activation of surface and endosomal Toll-like receptors (TLRs) in macrophages upregulates macropinocytosis. Here, using multiple forms of imaging and microscopy, we track membrane-associated, fluorescently-tagged Rab8a expressed in live macrophages, using a variety of cell markers to demonstrate Rab8a localization and its enrichment on early macropinosomes. Production of a novel biosensor and its use for quantitative FRET analysis in live cells, pinpoints macropinosomes as the site for TLR-induced activation of Rab8a. We have previously shown that TLR signalling, cytokine outputs and macrophage programming are regulated by the GTPase Rab8a with PI3 Kγ as its effector. Finally, we highlight another effector, the phosphatase OCRL, which is located on macropinosomes and interacts with Rab8a, suggesting that Rab8a may operate on multiple levels to modulate phosphoinositides in macropinosomes. These findings extend our understanding of macropinosomes as regulatory compartments for innate immune function in macrophages.This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
The pervasiveness of macropinocytosis in oncological malignancies
Authors: Commisso Cosimo 
Published: December 2018

In tumour cells, macropinocytosis functions as an amino acid supply route and supports cancer cell survival and proliferation. Initially demonstrated in oncogenicKRAS-driven models of pancreatic cancer, macropinocytosis triggers the internalization of extracellular proteins via discrete endocytic vesicles called macropinosomes. The incoming protein cargo is targeted for lysosome-dependent degradation, causing the intracellular release of amino acids. These protein-derived amino acids support metabolic fitness by contributing to the intracellular amino acid pools, as well as to the biosynthesis of central carbon metabolites. In this way, macropinocytosis represents a novel amino acid supply route that tumour cells use to survive the nutrient-poor conditions of the tumour microenvironment. Macropinocytosis has also emerged as an entry mechanism for a variety of nanomedicines, suggesting that macropinocytosis regulation in the tumour setting can be harnessed for the delivery of anti-cancer therapeutics. A slew of recent studies point to the possibility that macropinocytosis is a pervasive feature of many different tumour types. In this review, we focus on the role of this important uptake mechanism in a variety of cancers and highlight the main molecular drivers of macropinocytosis in these malignancies.This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Using macropinocytosis for intracellular delivery of therapeutic nucleic acids to tumour cells
Authors: Desai Arpan S. , Hunter Morag R. , Kapustin Alexander N. 
Published: December 2018

Nucleic acids are a rapidly emerging therapeutic modality with the potential to become the third major drug modality alongside antibodies and small molecules. Owing to the unfavourable physico-chemical characteristics of nucleic acids, such as large size and negative charge, intracellular delivery remains a fundamental challenge to realizing this potential. Delivery technologies such as lipids, polymers and peptides have been used to facilitate delivery, with many of the most successful technologies using macropinocytosis to gain cellular entry; mostly by default rather than design. Fundamental knowledge of macropinocytosis is rapidly growing, presenting opportunities to better tailor design strategies to target this pathway. Furthermore, certain types of tumour cells have been observed to have high levels of macropinocytic activity and traffic cargo to favourable destinations within the cell for endosomal release, providing unique opportunities to further use this entry route for drug delivery. In this article, we review the delivery systems reported to be taken up by macropinocytosis and what is known about the mechanisms for regulating macropinocytosis in tumour cells. From this analysis, we identify new opportunities for exploiting this pathway for the intracellular delivery of nucleic acids to tumour cells.
This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Metabolic functions of macropinocytosis
Authors: Palm Wilhelm 
Published: December 2018

Macropinocytosis is an evolutionarily conserved form of endocytosis that mediates non-selective uptake of extracellular fluid and the solutes contained therein. In mammalian cells, macropinocytosis is initiated by growth factor-mediated activation of the Ras and PI3-kinase signalling pathways. In malignant cells, oncogenic activation of growth factor signalling sustains macropinocytosis cell autonomously. Recent studies of cancer metabolism, discussed here, have begun to define a role for macropinocytosis as a nutrient uptake route. Macropinocytic cancer cells ingest macromolecules in bulk and break them down in the lysosome to support metabolism and macromolecular synthesis. Thereby, macropinocytosis allows cells to tap into the copious nutrient stores of extracellular macromolecules when canonical nutrients are scarce. These findings demonstrate that macropinocytosis promotes metabolic flexibility and resilience, which enables cancer cells to survive and grow in nutrient-poor environments. Implications for physiological roles of growth factor-stimulated macropinocytosis in cell metabolism and its relationship with other nutrient uptake pathways are considered.
This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.