bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulator use does not prevent first loss of response to anti‐tumour necrosis factor alpha therapy in inflammatory bowel disease: long‐term outcomes in a real‐world cohort
Authors: Varma Poornima , Rajadurai Anton S. , Holt Darcy Q. , Devonshire David A. , Desmond Chris P. , Swan Michael P. , Nathan Debra , Shelton Edward T. , Prideaux Lani , Sorrell Catherine , Rusli Ferry , Crantock Luke R. F. , Dev Anouk , Ratnam Dilip T. , Pianko Stephen , Moore Gregory T. 
Published: November 2018

AbstractBackgroundRecent prospective studies suggest combination therapy with immunomodulators improves efficacy, but long‐term data is limited.AimTo assess whether anti‐tumour necrosis factor alpha (anti‐TNF) monotherapy was associated with earlier loss of response (LOR) than combination therapy in a real‐world cohort with long‐term follow up.MethodsA retrospective audit was conducted of inflammatory bowel disease patients receiving anti‐TNF therapy in a tertiary centre and specialist private practices. All patients with accurate data for anti‐TNF commencement and adequate correspondence to determine end‐points were included. Outcomes measured included time to first LOR, causes and biochemical parameters.ResultsTwo hundred and twenty‐four patients were identified; 139 (62.1%) on combination therapy and 85 (37.9%) on monotherapy. Forty‐five percent of patients had LOR during follow up until a maximum of 8.5 years; 59.4% on combination therapy and 40.6% on monotherapy (P = 0.533). The median time to LOR was not different between groups; 1069 days for combination therapy and 1489 days for monotherapy (P = 0.533). There was no difference in time to LOR between patients treated with different combination regimens or different anti‐TNF agents.ConclusionIn this large cohort of patients in a real‐world setting, patients treated with anti‐TNF monotherapy had similar rates of LOR as patients on anti‐TNF combination therapy, at both short‐ and long‐term follow up.
Updates management in mobile applications: iTunes versus Google Play
Authors: Comino Stefano , Manenti Fabio M. , Mariuzzo Franco 
Published: November 2018

AbstractThis paper focuses on a specific strategy that developers of mobile applications may use to stimulate demand: The release of updates. We develop a theoretical analysis that shows that developers have incentives to release updates when experiencing a drop in performance. The predictions of the model are then tested using an unbalanced panel of top 1,000 apps in iTunes and Google Play for five European countries. We estimate that while in iTunes the release of an update stimulates a 26% increase in download growth, in Google Play updates play a less significant role. This difference is partly due to systematic differences in apps and in developers operating in the two stores (“selection effect”), and partly to a lack of quality control on apps and updates in Google Play (“quality check effect”). These findings highlight the crucial importance of an appropriate management of updates as well as the relevance of institutional characteristics of the app stores.
Species‐specific inhibition of capripoxvirus replication by host antiviral protein kinase R
Authors: Zhao Zhixun , Zhu Xueliang , Wu Na , Qin Xiaodong , Huang Caiyun , Wu Guohua , Zhang Qiang , Zhang Zhidong 
Published: November 2018

AbstractThe role of interferon (IFN)‐induced protein kinase R (PKR) in capripoxvirus (CaPV)‐infected cells remains unknown. In this study, we show that CaPV infection triggered PKR and eukaryotic translation initiation factor 2 alpha (eIF2α) protein phosphorylation in a dose‐dependent manner, and that this leads to decreased CaPV replication. Overexpression of PKR compromised viral gene expression and inhibited sheeppox virus (SPPV) replication. Downregulation of PKR with siRNAs significantly decreased eIF2α phosphorylation and reduced the mRNA level of IFN‐β, which increased virus replication. In luciferase assays, species‐different CaPVs K3L proteins inhibited sheep PKR (sPKR): goatpox virus K3L strongly inhibited sPKR and goat PKR (gPKR), but SPPV K3L only partially inhibited gPKR. These results are the first to show that SPPV infection induces phosphorylation of eIF2α through PKR activation, which then results in restriction of CaPV replication. Furthermore, our data show that CaPV K3L inhibits PKR in a species‐specific manner. The results presented are consistent with the hypothesis that different levels of PKR inhibition by K3L orthologs from various viruses could potentially contribute to the host range function of K3L.
Effects of phytochemicals on thyroid function and their possible role in thyroid disease
Authors: Pistollato Francesca , Masias Manuel , Agudo Pablo , Giampieri Francesca , Battino Maurizio 
Published: November 2018

AbstractAbout 1 of 10 women, particularly those older than 60 years of age, shows some degree of thyroid hormone deficiency. Thyroid diseases are generally characterized by perturbations of thyroid signaling homeostasis. The most common examples of thyroid diseases include hypothyroidism, hyperthyroidism, and several types of thyroid cancers. Phytochemicals have been shown to have either beneficial or detrimental effects on thyroid function. Some flavonoids have been reported to affect the expression and the activity of several thyroid‐related enzymes and proteins, and for this reason some concerns have been raised about the possible thyroid‐disruptive properties of foods enriched in these substances. On the other hand, the beneficial effects of some plant‐derived compounds, such as myricetin, quercetin, apigenin, rutin, genistein, and curcumin, and their possible role as adjuvants for the treatment of thyroid cancers have been described. Here, the role of phytochemicals in thyroid signaling modulation and their possible beneficial or detrimental effects on thyroid disease risk are discussed.
Gastric cancer in children and adolescents in Japan
Authors: Okuda Masumi , Nomura Keiko , Kato Mototsugu , Lin Yingsong , Mabe Katsuhiro , Miyamoto Ryosuke , Okumura Akihisa , Kikuchi Shogo 
Published: November 2018

AbstractBackgroundVery limited data are available on childhood gastric cancer. Using a retrospective survey and literature review, we assessed the clinical features of gastric cancer in children and adolescents.MethodsWe collected information on childhood gastric cancer from pediatricians of 518 hospitals that issue the title of “certified board pediatrician” approved by Japan Pediatric Society, using a questionnaire on background, diagnosis year, onset symptoms, tumor location, histology, nodular gastritis, Helicobacter pylori testing, treatment, and prognosis. Studies were collected using PubMed and the NPO Japan Medical Abstracts Society database. Data for childhood gastric cancer were abstracted from the Japanese Vital Statistics database.ResultsOf the 518 hospitals, 349 returned the questionnaire, which identified four patients. Literature review identified 77 cases of gastric cancer, and we analyzed data for 80 children <16 years old. Most patients were >10 years old, and there were no sex differences. Onset symptoms ranged from abdominal pain to non‐localized. Sixteen of 44 children had a family history of cancer; 10 had a family history of gastric cancer. Histologically, approximately 80% had undifferentiated‐type carcinoma. Prognosis was extremely poor, and two of three tested children were positive for H. pylori infection. Childhood gastric cancer death has been declining.ConclusionsChildhood gastric cancer is rare in Japan, and information on H. pylori in childhood gastric cancer patients is limited. Declining childhood gastric cancer rates may reflect the decreasing prevalence of infection but further study is necessary to clarify the relationship between H. pylori and gastric cancer.
Higher intraoperative plasma transfusion volumes are associated with inferior perioperative outcomes
Authors: Warner Matthew A. , Frank Ryan D. , Weister Timothy J. , Smith Mark M. , Stubbs James R. , Kor Daryl J. 
Published: November 2018

BACKGROUNDIntraoperative plasma transfusion is common, yet little is known regarding its effects on perioperative coagulation tests or clinical outcomes.STUDY DESIGN AND METHODSThis is a retrospective cohort study of adults receiving intraoperative plasma transfusion at a single center from 2011 to 2015. Relationships between plasma transfusion volume, changes in coagulation test values, and clinical outcomes, including a primary outcome of early postoperative red blood cell (RBC) transfusion, were assessed with multivariable regression analyses. Secondary outcomes included hospital mortality, intensive care unit (ICU)‐ and hospital‐free days, intraoperative RBC transfusions, and estimated blood loss.RESULTSA total of 3393 unique patients were included, with median (IQR) transfusion of 2 (2‐4) units. In multivariable analyses, higher plasma volumes were associated with worse outcomes, with each 1 mL/kg increase associated with increased odds for postoperative (1.02 [1.01‐1.03], p < 0.001) and intraoperative RBCs (1.17 [1.16‐1.19], p < 0.001) and fewer ICU‐ and hospital‐free days (mean difference [95% CI], –0.08 [−0.12 to −0.05], p < 0.001; and −0.09 [−0.13 to −0.06], p < 0.001, respectively). Greater decreases in international normalized ratio (INR) following plasma transfusion were associated with decreased odds of postoperative RBCs (0.35 [0.25‐0.47], p < 0.001), decreased mortality (0.50 [0.31‐0.83], p = 0.007), and increased mean ICU‐ (1.31 [0.41‐2.21], p = 0.004) and hospital‐free days (1.15 [0.19‐2.10], p = 0.018).CONCLUSIONIn patients receiving intraoperative plasma transfusion, higher transfusion volumes were associated with inferior clinical outcomes; however, greater improvements in INR were associated with improved outcomes. Future prospective studies are necessary to better define these relationships and to explore plasma transfusion triggers beyond the limitations of INR.
The burden of invasive infections in neutropenic patients: incidence, outcomes, and use of granulocyte transfusions
Authors: Netelenbos Tanja , Massey Edwin , de Wreede Liesbeth C. , Harding Kay , Hamblin Angela , Sekhar Mallika , Li Anna , Ypma Paula F. , Ball Lynn , Zwaginga Jaap Jan , Stanworth Simon J. 
Published: November 2018

BACKGROUNDPatients with prolonged neutropenia caused by chemotherapy or underlying marrow disorders are at risk of invasive bacterial and fungal infections. New treatment options alongside targeted antimicrobial therapy that might improve outcomes include granulocyte transfusions (GTX). To inform the research agenda, a prospective observational cohort study was performed in the Netherlands and United Kingdom. The aim was to describe the incidence, characteristics, and outcomes of patients developing invasive infections and assess patients fulfilling criteria for GTX.STUDY DESIGN AND METHODSAll patients receiving myeloablative chemotherapy and anticipated to develop 7 or more days of neutropenia (<0.5 × 109/L) were eligible and followed for the development of invasive infections according to a defined algorithm and mortality up to 100 days. Secondary outcomes were types of infection and eligibility for GTX.RESULTSA total of 471 patients enrolled at six hematology‐oncology departments were followed for 569 neutropenic episodes. Overall, 32.5% of patients developed invasive infections during their first episode. Significant baseline risk factors for developing infections were high comorbidity scores (WHO performance status ≥ 2, hazard ratio [HR], 2.6 [1.7‐3.9]; and hematopoietic cell transplantation‐comorbidity index score ≥ 2 HR 1.3 [0.9‐1.8]). Infections were bacterial (59.4%) and fungal (22.3%). Despite 34 patients (6.3% of all episodes) appearing to meet criteria to receive GTX, only nine patients received granulocytes. The HR for death was 5.8 (2.5‐13.0) for patients with invasive infections.CONCLUSIONThis study documents that invasive infections are associated with significant mortality. There is a need for new strategies to prevent and treat infections, which may include better understanding of use GTX.
Do bilateral investment treaties attract foreign direct investment? The role of international dispute settlement provisions
Authors: Frenkel Michael , Walter Benedikt 
Published: November 2018

AbstractThis paper studies the effects of the strength of bilateral investment treaties (BITs) on foreign direct investment (FDI) activity. We develop an index for the strength of international dispute settlement provisions included in BITs in order to examine the role the content of BITs plays in attracting FDI. To this end, we make use of data from UNCTAD's International Investment Agreement Mapping Project and measure the provision strength of 2,571 BITs. Using panel data of bilateral and total FDI inflows and inward FDI stocks, we study the effect of BITs on FDI. Our main finding indicates that stronger international dispute settlement provisions in BITs are indeed associated with positive effects on FDI activity.
Protein kinase Cδ constrains the S‐pathway to phrenic motor facilitation elicited by spinal 5‐HT7 receptors or severe acute intermittent hypoxia
Authors: Perim Raphael R. , Fields Daryl P. , Mitchell Gordon S. 
Published: November 2018

Key points
Concurrent 5‐HT2A (Q pathway) and 5‐HT7 (S pathway) serotonin receptor activation cancels phrenic motor facilitation due to mutual cross‐talk inhibition.
Spinal protein kinase Cδ (PKCδ) or protein kinase A inhibition restores phrenic motor facilitation with concurrent Q and S pathway activation, demonstrating a key role for these kinases in cross‐talk inhibition.
Spinal PKCδ inhibition enhances adenosine‐dependent severe acute intermittent hypoxia‐induced phrenic long‐term facilitation (S pathway), consistent with relief of cross‐talk inhibition.
AbstractIntermittent spinal serotonin receptor activation elicits long‐lasting phrenic motor facilitation (pMF), a form of respiratory motor plasticity. When activated alone, spinal Gq protein‐coupled serotonin 2A receptors (5‐HT2A) initiate pMF by a mechanism that requires ERK‐MAP kinase signalling and new BDNF protein synthesis (Q pathway). Spinal Gs protein‐coupled serotonin 7 (5‐HT7) and adenosine 2A (A2A) receptor activation also elicits pMF, but via distinct mechanisms (S pathway) that require Akt signalling and new TrkB protein synthesis. Although studies have shown inhibitory cross‐talk interactions between these competing pathways, the underlying cellular mechanisms are unknown. We propose the following hypotheses: (1) concurrent 5‐HT2A and 5‐HT7 activation undermines pMF; (2) protein kinase A (PKA) and (3) NADPH oxidase mediate inhibitory interactions between Q (5‐HT2A) and S (5‐HT7) pathways. Selective 5‐HT2A (DOI hydrochloride) and 5HT7 (AS‐19) agonists were administered intrathecally at C4 (three injections, 5‐min intervals) in anaesthetized, vagotomized and ventilated male rats. With either spinal 5‐HT2A or 5‐HT7 activation alone, phrenic amplitude progressively increased (pMF). In contrast, concurrent 5‐HT2A and 5‐HT7 activation failed to elicit pMF. The 5‐HT2A‐induced Q pathway was restored by inhibiting PKA activity (Rp‐8‐Br‐cAMPS). NADPH oxidase inhibition did not prevent cross‐talk inhibition. Therefore, we investigated alternative mechanisms to explain Q to S pathway inhibition. Spinal protein kinase C (PKC) inhibition with Gö6983 or PKCδ peptide inhibitor restored the 5‐HT7‐induced S pathway to pMF, revealing PKCδ as the relevant isoform. Spinal PKCδ inhibition enhanced the S pathway‐dependent form of pMF elicited by severe acute intermittent hypoxia. We suggest that powerful constraints between 5‐HT2A and 5‐HT7 or A2A receptor‐induced pMF are mediated by PKCδ and PKA, respectively.
Learning and the Rhizome: Reconceptualisation in the Qualitative Research Process
Authors: Rodrigues de Amorim Antonio Carlos , Scott David 
Published: November 2018

This article explores the concept of learning as a space of exchange and connection between signs, events and bodies, inspired by Gilles Deleuze’s philosophy of difference. This qualitative methodology is based on the rhizome, with, amongst others, its characteristics or principles of heterogeneity, multiplicity and a-signification. It allows a productive conversation with studies of learning environments and sense productions through images and sounds from cinema media, such as the swimmer and swimming. The focus of this article is on learning, its environment and its role in the relationship between mind and world, pointing to an alternative to the representational perspective.
Outer retinal layer thickness in patients with glaucoma with horizontal hemifield visual field defects
Authors: Vianna Jayme R , Butty Ziad , Torres Lucas A , Sharpe Glen P , Hutchison Donna M , Shuba Lesya M , Nicolela Marcelo T , Chauhan Balwantray C 
Published: November 2018

Background/AimsTo determine the effect of glaucoma on outer retinal layer thickness in eyes with horizontal hemifield visual field (VF) defects.MethodsWe conducted a cross-sectional study in glaucomatous eyes with repeatable (in three or examinations) horizontal hemifield VF (programme 24–2) defect defined as: all five nasal VF locations immediately either above or below the horizontal midline abnormal in the pattern deviation plot with p<0.5%; no mirror-image adjacent 5 VF locations abnormal in the pattern deviation plot and no non-edge VF locations in the non-affected hemifield abnormal in the pattern deviation plot with p<1%. We used optical coherence tomography to measure thickness of each retinal layer in the temporal macula (12° horizontally and 24° vertically) and computed the absolute (µm) and relative (%) intraindividual asymmetry between the perimetrically normal and abnormal hemimacula.ResultsWe included 10 eyes of 8 patients with median age of 67 years and median VF mean deviation of −8.85 dB. The nerve fibre, ganglion cell and inner plexiform layers were significantly thinner in the perimetrically abnormal hemimacula (median asymmetry of –6.4, –11.5 and −3.8 µm, (corresponding to –27.7, –40.5 and −15.7 %), respectively, all p≤0.01). The inner nuclear layer was slightly thicker in the perimetrically abnormal hemimacula (median asymmetry of 1.3 µm (5.0 %), p=0.01). The outer plexiform, outer nuclear and photoreceptor layers asymmetry values were negligible.ConclusionOur study showed no evidence that glaucoma has an effect on the outer retinal layer thickness. In contrast, a large impact was observed in inner layer thickness.
Anticoagulant therapies for acute venous thromboembolism among a cohort of patients discharged from Canadian urban and rural hospitals
Authors: Bungard Tammy J , Ritchie Bruce , Bolt Jennifer , Semchuk William M 
Published: November 2018

ObjectiveTo determine anticoagulant therapy at hospital discharge for patients with acute venous thromboembolism (VTE) and secondarily, to describe factors affecting choice of therapy.DesignA retrospective chart review.SettingCanadian hospitals in Edmonton, Alberta (n=4), Regina, Saskatchewan (n=2) and rural Alberta (n=3) from April 2014 to March 2015.ParticipantsAll patients discharged with an acute VTE were screened. Those with atypical clots, another indication for anticoagulation, pregnancy/breast feeding or lifespan <3 months were excluded.Primary and secondary outcomesPrimarily, we identified the proportion of patients discharged from hospital with acute VTE that were prescribed either traditional therapy (parenteral anticoagulant±warfarin) or a direct oral anticoagulant (DOAC). Secondarily, management based on setting, therapy choice based on deep vein thrombosis (DVT) versus pulmonary embolism (PE), clot burden and renal function was compared. DOAC dosing was assessed (when prescribed), length of hospital stay based on therapy was compared and planned follow-up in the community was described.ResultsAmong the 695 patients included, most were discharged following a diagnosis of PE (82.9%) on traditional therapy (parenteral anticoagulant±warfarin) (70.2%) with follow-up by either a family doctor (51.5%) or specialist/clinic (46.9%) postdischarge. Regional variation was most evident between urban and rural sites. Of those prescribed a DOAC (28.3%), the majority were dosed appropriately (85.8%). DOAC use did not differ between those with DVT and PE, was proportionately higher for less severe clots and declined with worsening renal function. Patients prescribed DOACs versus traditional therapy had a shorter length of stay (4 vs 7 days, respectively).ConclusionsUptake of DOAC therapy for acute VTE was modest and may have been influenced by the timing of the audit in relation to the approval of these agents for this indication. Future audits should occur to assess temporal changes and ongoing appropriateness of care delivery.
How do healthcare professionals working in accountable care organisations understand patient activation and engagement? Qualitative interviews across two time points
Authors: Mishra Manish K , Saunders Catherine H , Rodriguez Hector P , Shortell Stephen M , Fisher Elliott , Elwyn Glyn 
Published: November 2018

ObjectiveIf patient engagement is the new ‘blockbuster drug’ why are we not seeing spectacular effects? Studies have shown that activated patients have improved health outcomes, and patient engagement has become an integral component of value-based payment and delivery models, including accountable care organisations (ACO). Yet the extent to which clinicians and managers at ACOs understand and reliably execute patient engagement in clinical encounters remains unknown. We assessed the use and understanding of patient engagement approaches among frontline clinicians and managers at ACO-affiliated practices.DesignQualitative study; 103 in-depth, semi-structured interviews.ParticipantsSixty clinicians and eight managers were interviewed at two established ACOs.ApproachWe interviewed healthcare professionals about their awareness, attitudes, understanding and experiences of implementing three key approaches to patient engagement and activation: 1) goal-setting, 2) motivational interviewing and 3) shared decision making. Of the 60 clinicians, 33 were interviewed twice leading to 93 clinician interviews. Of the 8 managers, 2 were interviewed twice leading to 10 manager interviews. We used a thematic analysis approach to the data.Key resultsInterviewees recognised the term ‘patient activation and engagement’ and had favourable attitudes about the utility of the associated skills. However, in-depth probing revealed that although interviewees reported that they used these patient activation and engagement approaches, they have limited understanding of these approaches.ConclusionsWithout understanding the concept of patient activation and the associated approaches of shared decision making and motivational interviewing, effective implementation in routine care seems like a distant goal. Clinical teams in the ACO model would benefit from specificity defining key terms pertaining to the principles of patient activation and engagement. Measuring the degree of understanding with reward that are better-aligned for behaviour change will minimise the notion that these techniques are already being used and help fulfil the potential of patient-centred care.