bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) Working Group
Authors: Jung‐König Mona , Füllenbach Christoph , Murphy Michael F. , Manzini Paola , Laspina Stefan , Pendry Kate , Mühling Jörg , Wikman Agneta , Humbrecht Catherine , Rigal Jean‐Christophe , Lasocki Sigismond , Folléa Gilles , Seifried Erhard , Müller Markus M. , Geisen Christof , Aranko Kari , Zacharowski Kai , Meybohm Patrick ,   the PaBloE (Patient Blood Management in Europe) working group
Published: December 2019

Background and objectivesPreoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce.Materials and methodsTo gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016.ResultsOrganization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron.ConclusionImplementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia.
Predictors of comorbidities and mortality in cats with pelvic fractures
Authors: Hammer Meike , Gutbrod Andreas , Sigrist Nadja E. , Jacot Valentine , Del Chicca Francesca , Evans Richard , Pozzi Antonio 
Published: December 2019

AbstractObjectiveTo characterize and evaluate risk factors for comorbidities and death of cats with pelvic fractures.Study designRetrospective case study.AnimalsCats (n = 280).MethodsMedical records were reviewed for cats in which pelvic fractures had been diagnosed (January 2003 to November 2016). Retrieved data included signalment, mechanism of injury, clinical findings, diagnostic imaging investigations, type and number of concurrent injuries based on anatomical location, type of therapy, and survival. Pelvic fractures were classified according to location and severity. Descriptive statistics were performed, and logistic regression models were constructed to examine associations between risk factors and outcome.ResultsCases consisted of 280 cats with no (9%), unilateral (43%), and bilateral (48%) involvement of the weight‐bearing axis. Sacral fractures were found in 12% of cats. Surgical treatment and mortality rates increased progressively with the severity of the pelvic fractures (P < .001). Mean number of concurrent body regions injured was 2.4 ± 1.2 and was associated with mortality (P < .01). Twenty percent of cats did not survive to discharge. Cats with neurologic injuries were more likely not to survive (P = .02).ConclusionConcurrent injuries to at least one body region, especially the abdomen and thorax, were observed in cats sustaining pelvic fractures. Mortality was associated with increased severity of the fractures, neurologic injuries, and increased number of concurrent injuries.Clinical significanceConcurrent injuries are common in cats with pelvic fractures, and comorbidities may be associated with mortality.
The weirding of English, trans‐scripting, and humour in digital communication
Authors: Spilioti Tereza 
Published: December 2019

AbstractThis article examines local appropriations of English‐related forms in digital communication, especially (re)appropriations that play with and modify significantly what we conventionally recognize as English (‘weird English’; Ch'ien, 2005). It investigates a case of trans‐scripting where English‐related forms are respelled with Greek characters in a series of memes and YouTube comments shared among primarily Greek‐speaking Internet users. Drawing on the notions of indexicality and enregisterment, it analyses the global and/or local orientations of such humorous acts of respelling, their indexical values in online participatory formats and their potential to function as register alerts that point to particular voices and ideological positions.
A novel method using ambient glutamate for the electrophysiological quantification of extrasynaptic NMDA receptor function in acute brain slices
Authors: Moldavski Alexander , Behr Joachim , Bading Hilmar , Bengtson C. Peter 
Published: December 2019

Key points
We present a novel protocol to quantify extrasynaptic NMDA receptor function utilizing the semi‐selective activation of extrasynaptic receptors by ambient extracellular glutamate in acute brain slices from adult rats.
We use whole cell patch clamp to measure the effect of the NMDA receptor antagonist MK‐801 on both synaptic and brief, local agonist application‐evoked responses.
The level of ambient glutamate was estimated from tonic NMDA receptor activity to be ∼77 nM and an equivalent concentration of NMDA was used to estimate the degree of extrasynaptic blockade (>82%) by our MK‐801 protocol.
The extrasynaptic component of the total NMDA receptor pool can be mathematically derived from these data and was estimated to be 29–39% in the stratum radiatum of the CA1 region of the rat hippocampus.
This technique could be used to quantify extrasynaptic NMDA receptor function in rodent models of diseases where extrasynaptic NMDA receptors are implicated in neuron death.
AbstractSynaptic NMDA receptors (NMDARs) play a central role in pro‐survival signalling and synaptic plasticity in the majority of excitatory synapses in the central nervous system whereas extrasynaptic NMDARs (ES‐NMDARs) activate pro‐death pathways and have been implicated in many neurodegenerative diseases. ES‐NMDARs have been characterized in acute brain slice preparations using the largely irreversible, activity‐dependent NMDAR antagonist MK‐801 to block synaptic NMDARs. This approach is limited by the concomitant MK‐801 blockade of ES‐NMDARs activated by ambient extracellular glutamate, which is largely absent from the synaptic cleft due to the high density of nearby glutamate transporters. In acute hippocampal slices from rats aged 35–42 postnatal days, we estimated ambient glutamate to be 72–83 nM resulting in a block of more than 82% of ES‐NMDARs during a 5 min MK‐801 application. This paper describes a novel electrophysiological and mathematical method to quantify the proportion of NMDARs located at extrasynaptic locations in a confined region of an acute brain slice preparation using MK‐801 to preferentially block ES‐NMDARs. The protocol uses whole cell patch clamp measurement of NMDAR responses to synaptic stimulation and brief local pressure application of NMDA before and after MK‐801 application. After mathematically correcting for the relative block of both synaptic and extrasynaptic receptors, ES‐NMDARs were estimated to comprise 29–39% of the total NMDAR pool in the apical dendrites of hippocampal CA1 pyramidal neurons. This new method may prove useful for accurate quantification of NMDAR distributions in neurodegenerative diseases that are associated with increased toxic ES‐NMDAR signalling.
A porcine model for studying the cardiovascular consequences of high‐thoracic spinal cord injury
Authors: West Christopher R. , Poormasjedi‐Meibod Malihe‐Sadat , Manouchehri Neda , Williams Alexandra M. , Erskine Erin L. , Webster Megan , Fisk Shera , Morrison Charlotte , Short Katelyn , So Kitty , Cheung Amanda , Streijger Femke , Kwon Brian K. 
Published: December 2019

Key points
We have developed a novel porcine model of high‐thoracic midline contusion spinal cord injury (SCI) at the T2 spinal level.
We describe this model and the ensuing cardiovascular and neurohormonal responses, and demonstrate the model is efficacious for studying clinically relevant cardiovascular dysfunction post‐SCI.
We demonstrate that the high‐thoracic SCI model, but not a low‐thoracic SCI model, induces persistent hypotension along with a gradual reduction in plasma noradrenaline and increases in plasma aldosterone and angiotensin II.
We additionally conducted a proof‐of‐concept long‐term (12 weeks) survival study in animals with T2 contusion SCI demonstrating the potential utility of this model for not only acute experimentation but also long‐term drug studies prior to translation to the clinic.
AbstractCardiovascular disease is a leading cause of morbidity and mortality in the spinal cord injury (SCI) population, especially in those with high‐thoracic or cervical SCI. With this in mind, we aimed to develop a large animal (porcine) model of high‐thoracic (T2 level) contusion SCI and compare the haemodynamic and neurohormonal responses of this injury against a low‐thoracic (T10 level) model. Ten Yorkshire pigs were randomly subjected to 20 cm weight drop contusion SCI at either the T2 or the T10 spinal level. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were continuously monitored until 4 h post‐SCI. Plasma noradrenaline (NA), aldosterone and angiotensin II (ANGII) were measured pre‐SCI and at 30, 60, 120 and 240 min post‐SCI. Additionally, two Yucatan pigs were subjected to T2‐SCI and survived up to 12 weeks post‐injury to demonstrate the efficacy of this model for long‐term survival studies. Immediately after T2‐SCI, SBP, MAP and HR increased (P < 0.0001). Between decompression (5 min post‐SCI) and 30 min post‐decompression in T2‐SCI, SBP and MAP were lower than pre‐SCI (P < 0.038). At 3 and 4 h after T2‐SCI, SBP remained lower than pre‐SCI (P = 0.048). After T10‐SCI, haemodynamic indices remained largely unaffected. Plasma NA was lower in T2‐ vs. T10‐SCI post‐SCI, whilst aldosterone and ANGII were higher. Both chronically injured pigs demonstrated a vast reduction in SBP at 12 weeks post‐SCI. Our model of T2‐SCI causes a rapid and sustained alteration in neurohormonal control and cardiovascular function, which does not occur in the T10 model.
Influence of dog‐appeasing pheromone on canine maternal behaviour during the peripartum and neonatal periods
Authors: Santos Natalia R , Beck Alexandra , Blondel Thomas , Maenhoudt Cindy , Fontbonne Alain 
Published: December 2019

BackgroundParturition and the initial postpartum period are important moments in the reproductive cycle of dogs.MethodsA study assessed the effect of ADAPTIL, a dog‐appeasing pheromone, on maternal behaviour during peripartum. Bitches were continuously exposed to ADAPTIL (n=20) or placebo (n=21) in double‐blinded conditions from an average of about seven days before parturition up to 21 days postpartum. Differences in maternal behaviour in relation to the treatment were evaluated by the observation of specific activities through video recordings, such as the time spent by the bitch in close contact with the puppies, oronasal interaction and nursing duration and position. Videos were recorded at four time points (W0: within the first 48 hours of whelping; W1: one week after parturition; W2: two weeks after parturition; and W3: three weeks after parturition). In addition, the perception of breeders in relation to the quality of maternal care, puppies’ wellbeing and overall relationship between the bitches and the puppies was evaluated using Visual Analogue Scale at the same time points. Moreover, the daily activity of the bitches was measured by using an electronic device (FitBark dog activity trackers, Kansas City, Missouri).ResultsFor all observed maternal behaviours, there was a steady decrease in levels as the puppies developed, independently of treatment. However, bitches exposed to ADAPTIL tended to nurse significantly more in lying position, while those exposed to the placebo nursed more in a seated position, especially at W1 (P=0.06) and W3 (P=0.005). According to the breeders, the attention scores of bitches towards puppies were significantly higher in ADAPTIL than in the placebo group at each time point (P=0.01). Moreover, a difference according to parity was observed (P=0.004), with greater attention score displayed by primiparous bitches exposed to ADAPTIL compared with placebo on W0 (P=0.02), W1 and W3 (P<0.001). The global mother–puppies relationship was also perceived as significantly better (P=0.0002) by breeders of bitches exposed to ADAPTIL, with significant differences at W2 (P=0.01) and W3 (P=0.001). The bitches’ daily activity increased starting two days before the whelp, peaked during parturition and then gradually declined up until four days postpartum. There was a trend towards a difference in the activity level according to the treatment during the full study period (P=0.09) and at two days before parturition (P=0.07). Bitches exposed to ADAPTIL were more active compared with placebo in relation to the FitBark data.ConclusionThe use of ADAPTIL in maternity modulated maternal behaviours. Concerning the caregiver's view, bitches under the influence of ADAPTIL had greater and extended attention towards the puppies and they were eager to stay with the puppies for a longer time.
PIN1 Inhibition Sensitizes Chemotherapy in Gastric Cancer Cells by Targeting Stem Cell–like Traits and Multiple Biomarkers
Authors: Zhang Zhen-Zhen , Yu Wei-Xing , Zheng Min , Liao Xin-Hua , Wang Ji-Chuang , Yang Da-Yun , Lu Wen-Xian , Wang Long , Zhang Sheng , Liu He-Kun , Zhou Xiao Zhen , Lu Kun Ping 
Published: December 2019

Abstract
Gastric cancer is the third leading cause of cancer-related death worldwide. Diffuse type gastric cancer has the worst prognosis due to notorious resistance to chemotherapy and enrichment of cancer stem-like cells (CSC) associated with the epithelial-to-mesenchymal transition (EMT). The unique proline isomerase PIN1 is a common regulator of oncogenic signaling networks and is important for gastric cancer development. However, little is known about its roles in CSCs and drug resistance in gastric cancer. In this article, we demonstrate that PIN1 overexpression is closely correlated with advanced tumor stages, poor chemo-response and shorter recurrence-free survival in diffuse type gastric cancer in human patients. Furthermore, shRNA-mediated genetic or all-trans retinoic acid–mediated pharmaceutical inhibition of PIN1 in multiple human gastric cancer cells potently suppresses the EMT, cell migration and invasion, and lung metastasis. Moreover, PIN1 genetic or pharmaceutical inhibition potently eliminates gastric CSCs and suppresses their self-renewal and tumorigenicity in vitro and in vivo. Consistent with these phenotypes, are that PIN1 biochemically targets multiple signaling molecules and biomarkers in EMT and CSCs and that genetic and pharmaceutical PIN1 inhibition functionally and drastically enhances the sensitivity of gastric cancer to multiple chemotherapy drugs in vitro and in vivo. These results demonstrate that PIN1 inhibition sensitizes chemotherapy in gastric cancer cells by targeting CSCs, and suggest that PIN1 inhibitors may be used to overcome drug resistance in gastric cancer.
Targeting Phosphorylation of Y-Box–Binding Protein YBX1 by TAS0612 and Everolimus in Overcoming Antiestrogen Resistance
Authors: Shibata Tomohiro , Watari Kosuke , Kawahara Akihiko , Sudo Tomoya , Hattori Satoshi , Murakami Yuichi , Izumi Hiroto , Itou Junji , Toi Masakazu , Akiba Jun , Akagi Yoshito , Tanaka Maki , Kuwano Michihiko , Ono Mayumi 
Published: December 2019

Abstract
Nuclear expression of Y-box–binding protein (YBX1) is closely correlated with clinical poor outcomes and drug resistance in breast cancer. Nuclear translocation of YBX1 is facilitated by YBX1 phosphorylation at serine 102 by AKT, p70S6K, and p90RSK, and the phosphorylated YBX1 (pYBX1) promotes expression of genes related to drug resistance and cell growth. A forthcoming problem to be addressed is whether targeting the phosphorylation of YBX1 overcomes antiestrogen resistance by progressive breast cancer. Here, we found that increased expression of pYBX1 was accompanied by acquired resistance to antiestrogens, fulvestrant and tamoxifen. Forced expression of YBX1/S102E, a constitutive phosphorylated form, resulted in acquired resistance to fulvestrant. Inversely, YBX1 silencing specifically overcame antiestrogen resistance. Furthermore, treatment with everolimus, an mTORC1 inhibitor, or TAS0612, a novel multikinase inhibitor of AKT, p70S6K, and p90RSK, suppressed YBX1 phosphorylation and overcame antiestrogen resistance in vitro and in vivo. IHC analysis revealed that expression of pYBX1 and YBX1 was augmented in patients who experienced recurrence during treatment with adjuvant endocrine therapies. Furthermore, pYBX1 was highly expressed in patients with triple-negative breast cancer compared with other subtypes. TAS0612 also demonstrated antitumor effect against triple-negative breast cancer in vivo. Taken together, our findings suggest that pYBX1 represents a potential therapeutic target for treatment of antiestrogen-resistant and progressive breast cancer.
Genomic and Expression Analyses Define MUC17 and PCNX1 as Predictors of Chemotherapy Response in Breast Cancer
Authors: Al Amri Waleed S. , Allinson Lisa M. , Baxter Diana E. , Bell Sandra M. , Hanby Andrew M. , Jones Stacey J. , Shaaban Abeer M. , Stead Lucy F. , Verghese Eldo T. , Hughes Thomas A. 
Published: December 2019

Abstract
Poor-prognosis breast cancers are treated with cytotoxic chemotherapy, but often without any guidance from therapy predictive markers because universally accepted markers are not currently available. Treatment failure, in the form of recurrences, is relatively common. We aimed to identify chemotherapy predictive markers and resistance pathways in breast cancer. Our hypothesis was that tumor cells remaining after neoadjuvant chemotherapy (NAC) contain somatic variants causing therapy resistance, while variants present pre-NAC but lost post-NAC cause sensitivity. Whole-exome sequencing was performed on matched pre- and post-NAC cancer cells, which were isolated by laser microdissection, from 6 cancer cases, and somatic variants selected for or against by NAC were identified. Somatic variant diversity was significantly reduced after therapy (P &lt; 0.05). MUC17 variants were identified in 3 tumors and were selected against by NAC in each case, while PCNX1 variants were identified in 2 tumors and were selected for in both cases, implicating the function of these genes in defining chemoresponse. In vitro knockdown of MUC17 or PCNX1 was associated with significantly increased or decreased chemotherapy sensitivity, respectively (P &lt; 0.05), further supporting their roles in chemotherapy response. Expression was tested for predictive value in two independent cohorts of chemotherapy-treated breast cancers (n = 53, n = 303). Kaplan–Meier analyses revealed that low MUC17 expression was significantly associated with longer survival after chemotherapy, whereas low PCNX1 was significantly associated with reduced survival. We concluded that therapy-driven selection of somatic variants allows identification of chemotherapy response genes. With respect to MUC17 and PCNX1, therapy-driven selection acting on somatic variants, in vitro knockdown data concerning drug sensitivity, and survival analysis of expression levels in patient cohorts all define the genes as mediators of and predictive markers for chemotherapy response in breast cancer.
Development of AO-176, a Next-Generation Humanized Anti-CD47 Antibody with Novel Anticancer Properties and Negligible Red Blood Cell Binding
Authors: Puro Robyn J. , Bouchlaka Myriam N. , Hiebsch Ronald R. , Capoccia Benjamin J. , Donio Michael J. , Manning Pamela T. , Frazier William A. , Karr Robert W. , Pereira Daniel S. 
Published: December 2019

AbstractInhibitors of adaptive immune checkpoints have shown promise as cancer treatments. CD47 is an innate immune checkpoint receptor broadly expressed on normal tissues and overexpressed on many tumors. Binding of tumor CD47 to signal regulatory protein alpha (SIRPα) on macrophages and dendritic cells triggers a “don't eat me” signal that inhibits phagocytosis enabling escape of innate immune surveillance. Blocking CD47/SIRPα interaction promotes phagocytosis reducing tumor burden in numerous xenograft and syngeneic animal models. We have developed a next-generation humanized anti-CD47 antibody, AO-176, that not only blocks the CD47/SIRPα interaction to induce tumor cell phagocytosis, but also induces tumor cytotoxicity in hematologic and solid human tumor cell lines, but not normal noncancerous cells, by a cell autonomous mechanism (not ADCC). AO-176 also binds preferentially to tumor versus many normal cell types. In particular, AO-176 binds negligibly to RBCs in contrast to tumor cells, even at high concentrations up to 200 μg/mL and does not agglutinate RBCs up to 1 mg/mL in vitro. These properties are expected not only to decrease the antigen sink, but also to minimize on-target clinical adverse effects observed following treatment with other reported RBC-binding anti-CD47 antibodies. When tested in cynomolgus monkeys, AO-176 was well tolerated with no adverse effects. Finally, we show that AO-176 demonstrates dose-dependent antitumor activity in tumor xenograft models. Taken together, the unique properties and antitumor activity of our next-generation anti-CD47 antibody, AO-176, distinguishes it from other CD47/SIRPα axis targeting agents in clinical development.