bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex vivo‐expanded baboon CD39 + regulatory T cells prevent rejection of porcine islet xenografts in NOD‐SCID IL‐2rγ−/− mice reconstituted with baboon peripheral blood mononuclear cells
Authors: Huang Dandan , Wang Ya , Hawthorne Wayne J. , Hu Min , Hawkes Joanne , Burns Heather , Davies Sussan , Gao Feng , Chew Yi Vee , Yi Shounan , O'Connell Philip J. 
Published: September 2017

AbstractBackgroundA high immunosuppressive burden is required for long‐term islet xenograft survival in non‐human primates even using genetically modified donor pigs.AimsWe aimed to investigate the capacity of baboon regulatory T cells (Treg) to suppress islet xenograft rejection, thereby developing a potential immunoregulatory or tolerance therapy that could be evaluated in NHP models of xenotransplantation.Materials & MethodsBaboon Treg expanded with stimulation by porcine peripheral blood mononuclear cells (PBMC) were characterized by cell phenotyping and suppressive activity assays in vitro. Their function in vivo was evaluated in neonatal porcine islet cell clusters (NICC) transplanted NOD‐SCID IL‐2rγ−/− (NSG) mice receiving baboon PBMC alone or with expanded autologous Treg.ResultsThe majority of expanded Treg coexpressed Foxp3 and CD39 and were highly suppressive of the baboon anti‐pig xenogeneic T cell response in vitro. Reconstitution of mice with baboon PBMC alone resulted in NICC xenograft rejection within 35 days. Cotransfer with baboon PBMC and Treg prolonged islet xenograft survival beyond 100 days, correlating with Treg engraftment, intragraft CD39 and Foxp3 gene expression, and reduced graft infiltrating effector T cells and reduced interferon‐γ production.Discussion & ConclusionOur data supports the capacity of ex vivo expanded CD39+ baboon Treg to suppress islet xenograft rejection in primatized mice, suggesting it has potential as an adjunctive immunotherapy in preclinical NHP models of xenotransplantation.
Full Sequencing and Genomic Analysis of Three
emm
75 Group A
Streptococcus
Strains Recovered in the Course of an Epidemiological Shift in French Brittany
Authors: Rochefort Aude , Boukthir Sarrah , Moullec Séverine , Meygret Alexandra , Adnani Yahia , Lavenier Dominique , Faili Ahmad , Kayal Samer 
Published: September 2017

ABSTRACT

While the incidence and invasiveness of type
emm
75 group A
Streptococcus
(GAS) infections increased in French Brittany during 2013, we sequenced and analyzed the genomes of three independent strains isolated in 2009, 2012, and 2014, respectively. In this short-term evolution, genomic analysis evidenced mainly the integration of new phages encoding virulence factors.
Draft Genome Sequence of Bacillus subtilis AS2, a Heavy Crude Oil-Degrading and Biosurfactant-Producing Bacterium Isolated from a Soil Sample
Authors: Al-Sayegh Abdullah , Al-Wahaibi Yahya , Joshi Sanket , Al-Bahry Saif , Elshafie Abdulkadir , Al-Bemani Ali 
Published: September 2017

ABSTRACT

Here, we report the draft genome sequence of
Bacillus subtilis
AS2 that was isolated from heavy crude oil-contaminated soil samples from sludge pits of an Omani heavy-oil field.
B. subtilis
AS2 was able to biodegrade heavy crude oil and produce biosurfactant. In order to provide a better understanding of the biodegradation mechanism and biosynthesis of metabolites, the
B. subtilis
AS2 genome was sequenced and compared to those of other
B. subtilis
strains.
What does my neighbourhood have to do with my weight? A protocol for systematic review and meta-analysis of the association between neighbourhood socioeconomic status and body weight
Authors: Mohammed Shimels Hussien , Birhanu Mulugeta Molla , Sissay Tesfamichael Awoke , Habtewold Tesfa Dejenie , Tegegn Balewgizie Sileshi , Esmaillzadeh Ahmad 
Published: September 2017

IntroductionIndividuals living in poor neighbourhoods are at a higher risk of overweight/obesity. There is no systematic review and meta-analysis study on the association of neighbourhood socioeconomic status (NSES) with overweight/obesity. We aimed to systematically review and meta-analyse the existing evidence on the association of NSES with overweight/obesity.Methods and analysisCross-sectional, case–control and cohort studies published in English from inception to 15 May 2017 will be systematically searched using the following databases: PubMed, EMBASE, Web of Sciences and Google Scholar. Selection, screening, reviewing and data extraction will be done by two reviewers, independently and in duplicate. The Newcastle–Ottawa Scale (NOS) will be used to assess the quality of evidence. Publication bias will be checked by visual inspection of funnel plots and Egger’s regression test. Heterogeneity will be checked by Higgins’s method (I2statistics). Meta-analysis will be done to estimate the pooled OR. Narrative synthesis will be performed if meta-analysis is not feasible due to high heterogeneity of studies.Ethics and disseminationEthical clearance is not required as we will be using data from published articles. Findings will be communicated through a publication in a peer-reviewed journal and presentations at professional conferences.PROSPERO registration numberCRD42017063889.
Junior doctor psychiatry placements in hospital and community settings: a phenomenological study
Authors: Beattie Sharon , Crampton Paul E S , Schwarzlose Cathleen , Kumar Namita , Cornwall Peter L 
Published: September 2017

ObjectivesThe proportion of junior doctors required to complete psychiatry placements in the UK has increased, due in part to vacant training posts and psychiatry career workforce shortages, as can be seen across the world. The aim of this study was to understand the lived experience of a Foundation Year 1 junior doctor psychiatry placement and to understand how job components influence attitudes.DesignThe study was conducted using a cross-sectional qualitative phenomenological approach.SettingHospital and community psychiatry department settings in the North East of England, UK.ParticipantsIn total, 14 Foundation Year 1 junior doctors were interviewed including seven men and seven women aged between 23 and 34 years. The majority had completed their medical degree in the UK and were White British.ResultsThe lived experience of a junior doctor psychiatry placement was understood by three core themes: exposure to patient recovery, connectedness with others in the healthcare team and subjective interpretations of psychiatry. The experiences were moderated by instances of role definition, reaction to the specialty and the organisational fit of the junior doctor capacity in the specialty.ConclusionsThe study reinforces and adds to the literature by identifying connectedness as being important for both job satisfaction and morale, which is currently damaged within the junior doctor population. The study provides in-depth insights into the lived experience of psychiatry placements and can be taken forward by educationalists to ensure the placements are meaningful experiences for junior doctors by developing role definition, belonging, structure and psychiatric care responsibility.
Effect of a combined education and eHealth programme on the control of oral anticoagulation patients (PORTALS study): a parallel cohort design in Dutch primary care
Authors: Talboom-Kamp Esther P W A , Verdijk Noortje A , Kasteleyn Marise J , Harmans Lara M , Talboom Irvin J S H , Numans Mattijs E , Chavannes Niels H 
Published: September 2017

ObjectivesTo analyse the effect on therapeutic control and self-management skills of the implementation of self-management programmes, including eHealth by e-learning versus group training.SettingPrimary Care Thrombosis Service Center.ParticipantsOf the 247 oral anticoagulation therapy (OAT) patients, 63 started self-management by e-learning, 74 self-management by group training and 110 received usual care.Intervention and methodsParallel cohort design with two randomised self-management groups (e-learning and group training) and a group receiving usual care. The effect of implementation of self-management on time in therapeutic range (TTR) was analysed with multilevel linear regression modelling. Usage of a supporting eHealth platform and the impact on self-efficacy (Generalised Self-Efficacy Scale (GSES)) and education level were analysed with linear regression analysis. After intervention, TTR was measured in three time periods of 6 months.Main outcome measures(1) TTR, severe complications,(2) usage of an eHealth platform,(3) GSES, education level.ResultsAnalysis showed no significant differences in TTR between the three time periods (p=0.520), the three groups (p=0.460) or the groups over time (p=0.263). Comparison of e-learning and group training showed no significant differences in TTR between the time periods (p=0.614), the groups (p=0.460) or the groups over time (p=0.263). No association was found between GSES and TTR (p=0.717) or education level and TTR (p=0.107). No significant difference was found between the self-management groups in usage of the platform (0–6 months p=0.571; 6–12 months p=0.866; 12–18 months p=0.260). The percentage of complications was low in all groups (3.2%; 1.4%; 0%).ConclusionsNo differences were found between OAT patients trained by e-learning or by a group course regarding therapeutic control (TTR) and usage of a supporting eHealth platform. The TTR was similar in self-management and regular care patients. With adequate e-learning or group training, self-management seems safe and reliable for a selected proportion of motivated vitamin K antagonist patients.Trial registration numberNTR3947.
CGRPα within the Trpv1-Cre population contributes to visceral nociception
Authors: Spencer Nick J. , Magnúsdóttir Elín I. , Jakobsson Jon E. T. , Kestell Garreth , Chen Bao Nan , Morris David , Brookes Simon J. , Lagerström Malin C. 
Published: October 2017

The role of calcitonin gene-related peptide (CGRP) in visceral and somatic nociception is incompletely understood. CGRPα is highly expressed in sensory neurons of dorsal root ganglia and particularly in neurons that also express the transient receptor potential cation channel subfamily V member 1 (Trpv1). Therefore, we investigated changes in visceral and somatic nociception following deletion of CGRPα from the Trpv1-Cre population using the Cre/lox system. In control mice, acetic acid injection (0.6%, ip) caused significant immobility (time stationary), an established indicator of visceral pain. In CGRPα-mCherrylx/lx;Trpv1-Cre mice, the duration of immobility was significantly less than controls, and the distance CGRPα-mCherrylx/lx;Trpv1-Cre mice traveled over 20 min following acetic acid was significantly greater than controls. However, following acetic acid injection, there was no difference between genotypes in the writhing reflex, number of abdominal licks, or forepaw wipes of the cheek. CGRPα-mCherrylx/lx;Trpv1-Cre mice developed more pronounced inflammation-induced heat hypersensitivity above baseline values compared with controls. However, analyses of noxious acute heat or cold transmission revealed no difference between genotypes. Also, odor avoidance test, odor preference test, and buried food test for olfaction revealed no differences between genotypes. Our findings suggest that CGRPα-mediated transmission within the Trpv1-Cre population plays a significant role in visceral nociceptive pathways underlying voluntary movement. Monitoring changes in movement over time is a sensitive parameter to identify differences in visceral nociception, compared with writhing reflexes, abdominal licks, or forepaw wipes of the cheek that were unaffected by deletion of CGRPα- from Trpv1-Cre population and likely utilize different mechanisms. NEW & NOTEWORTHY The neuropeptide calcitonin gene-related peptide (CGRP) is highly colocalized with transient receptor potential cation channel subfamily V member 1 (TRPV1)-expressing primary afferent neurons, but the functional role of CGRPα specifically in these neurons is unknown in pain processing from visceral and somatic afferents. We used cre-lox recombination to conditionally delete CGRPα from TRPV1-expressing neurons in mice. We show that CGRPα from within TRPV1-cre population plays an important role in visceral nociception but less so in somatic nociception.
Inorganic nitrate supplementation attenuates peripheral chemoreflex sensitivity but does not improve cardiovagal baroreflex sensitivity in older adults
Authors: Bock Joshua M. , Ueda Kenichi , Schneider Aaron C. , Hughes William E. , Limberg Jacqueline K. , Bryan Nathan S. , Casey Darren P. 
Published: October 2017

Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from −0.14 ± 0.04 to −0.05 ± 0.02 l·min−1·%[Formula: see text]−1, P = 0.01) versus BRP (from −0.10 ± 0.05 to −0.11 ± 0.05 l·min−1·%[Formula: see text]−1, P = 0.80), with no differences in heart rate responsiveness (BRA: from −0.47 ± 0.06 to −0.33 ± 0.04 beats·min−1·%[Formula: see text]−1, BRP: from −0.48 ± 0.07 to −0.42 ± 0.06 beats·min−1·%[Formula: see text]−1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.
Effect of hypocapnia on the sensitivity of hyperthermic hyperventilation and the cerebrovascular response in resting heated humans
Authors: Tsuji Bun , Filingeri Davide , Honda Yasushi , Eguchi Tsubasa , Fujii Naoto , Kondo Narihiko , Nishiyasu Takeshi 
Published: October 2017

Elevating core temperature at rest causes increases in minute ventilation (V̇e), which lead to reductions in both arterial CO2 partial pressure (hypocapnia) and cerebral blood flow. We tested the hypothesis that in resting heated humans this hypocapnia diminishes the ventilatory sensitivity to rising core temperature but does not explain a large portion of the decrease in cerebral blood flow. Fourteen healthy men were passively heated using hot-water immersion (41°C) combined with a water-perfused suit, which caused esophageal temperature (Tes) to reach 39°C. During heating in two separate trials, end-tidal CO2 partial pressure decreased from the level before heating (39.4 ± 2.0 mmHg) to the end of heating (30.5 ± 6.3 mmHg) ( P = 0.005) in the Control trial. This decrease was prevented by breathing CO2-enriched air throughout the heating such that end-tidal CO2 partial pressure did not differ between the beginning (39.8 ± 1.5 mmHg) and end (40.9 ± 2.7 mmHg) of heating ( P = 1.00). The sensitivity to rising Tes (i.e., slope of the Tes − V̇E relation) did not differ between the Control and CO2-breathing trials (37.1 ± 43.1 vs. 16.5 ± 11.1 l·min−1·°C−1, P = 0.31). In both trials, middle cerebral artery blood velocity (MCAV) decreased early during heating (all P < 0.01), despite the absence of hyperventilation-induced hypocapnia. CO2 breathing increased MCAV relative to Control at the end of heating ( P = 0.005) and explained 36.6% of the heat-induced reduction in MCAV. These results indicate that during passive heating at rest ventilatory sensitivity to rising core temperature is not suppressed by hypocapnia and that most of the decrease in cerebral blood flow occurs independently of hypocapnia. NEW & NOTEWORTHY Hyperthermia causes hyperventilation and concomitant hypocapnia and cerebral hypoperfusion. The last may underlie central fatigue. We are the first to demonstrate that hyperthermia-induced hyperventilation is not suppressed by the resultant hypocapnia and that hypocapnia explains only 36% of cerebral hypoperfusion elicited by hyperthermia. These new findings advance our understanding of the mechanisms controlling ventilation and cerebral blood flow during heat stress, which may be useful for developing interventions aimed at preventing central fatigue during hyperthermia.
PI3Kγ Activates Integrin α4 and Promotes Immune Suppressive Myeloid Cell Polarization during Tumor Progression
Authors: Foubert Philippe , Kaneda Megan M. , Varner Judith A. 
Published: September 2017

Abstract
Immunosuppressive myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) accumulate in tumors where they inhibit T cell–mediated antitumor immune responses and promote tumor progression. Myeloid cell PI3Kγ plays a role in regulating tumor immune suppression by promoting integrin α4–dependent MDSC recruitment to tumors and by stimulating the immunosuppressive polarization of MDSCs and TAMs. Here, we show that integrin α4 promotes immunosuppressive polarization of MDSCs and TAMs downstream of PI3Kγ, thereby inhibiting antitumor immunity. Genetic or pharmacological suppression of either PI3Kγ or integrin α4 blocked MDSC recruitment to tumors and also inhibited immune suppressive myeloid cell polarization, thereby reducing expression of IL10 and increasing expression of IL12 and IFNγ within tumors. Inhibition of PI3Kγ or integrin α4 within tumors stimulated dendritic cell and CD8+ T-cell recruitment and maturation, as well as tumor cell cytotoxicity in vivo, thereby inhibiting tumor growth. As blockade of PI3Kγ or integrin α4 prevents accumulation of MDSC and reduces myeloid cell expression of immunosuppressive factors that stimulate tumor immune escape, these results highlight PI3Kγ and integrin α4 as targets for the design of cancer therapeutics. Cancer Immunol Res; 5(11); 957–68. ©2017 AACR.
First-in-human response of BCL-2 inhibitor venetoclax in T-cell prolymphocytic leukemia
Authors: Boidol Bernd , Kornauth Christoph , van der Kouwe Emiel , Prutsch Nicole , Kazianka Lukas , Gültekin Sinan , Hoermann Gregor , Mayerhoefer Marius E. , Hopfinger Georg , Hauswirth Alexander , Panny Michael , Aretin Marie-Bernadette , Hilgarth Bernadette , Sperr Wolfgang R. , Valent Peter , Simonitsch-Klupp Ingrid , Moriggl Richard , Merkel Olaf , Kenner Lukas , Jäger Ulrich , Kubicek Stefan , Staber Philipp B. 
Published: October 2017

Key Points
Strong responses to venetoclax separate T-PLL from other hematologic malignancies in high- throughput drug screening of clinical samples. Two relapsed and refractory T-PLL patients demonstrated clinical response on venetoclax treatment.
Invited commentary on … When unbearable suffering incites psychiatric patients to request euthanasia: A qualitative study
Authors: Pearce Steve 
Published: October 2017

SummaryAlthough the paper in this issue by Verhofstadtet alsheds some light on the features of unbearable suffering stemming from psychiatric disorder leading to a request for euthanasia, this is limited. The bulk of the paper illustrates the particular ethical challenges posed by the policy of making euthanasia available in these circumstances.
Personality disorder services in England: findings from a national survey
Authors: Dale Oliver , Sethi Faisil , Stanton Clive , Evans Sacha , Barnicot Kirsten , Sedgwick Rosemary , Goldsack Steve , Doran Monica , Shoolbred Lucinda , Samele Chiara , Urquia Norman , Haigh Rex , Moran Paul 
Published: October 2017

Aims and methodWe aimed to evaluate the availability and nature of services for people affected by personality disorder in England by conducting a survey of English National Health Service (NHS) mental health trusts and independent organisations.ResultsIn England, 84% of organisations reported having at least one dedicated personality disorder service. This represents a fivefold increase compared with a 2002 survey. However, only 55% of organisations reported that patients had equal access across localities to these dedicated services. Dedicated services commonly had good levels of service use and carer involvement, and engagement in education, research and training. However, a wider multidisciplinary team and a greater number of biopsychosocial interventions were available through generic services.Clinical implicationsThere has been a substantial increase in service provision for people affected by personality disorder, but continued variability in the availability of services is apparent and it remains unclear whether quality of care has improved.
A GAP that Divides
Authors: Basant Angika , Glotzer Michael 
Published: October 2017

Cytokinesis in metazoan cells is mediated by an actomyosin-based contractile ring that assembles in response to activation of the small GTPase RhoA. The guanine nucleotide exchange factor that activates RhoA during cytokinesis, ECT-2, is highly regulated. In most metazoan cells, with the notable exception of the earlyCaenorhabditis elegansembryo, RhoA activation and furrow ingression require the centralspindlin complex. This exception is due to the existence of a parallel pathway for RhoA activation inC. elegans. Centralspindlin contains CYK-4 which contains a predicted Rho family GTPase-activating protein (GAP) domain. The function of this domain has been the subject of considerable debate. Some publications suggest that the GAP domain promotes RhoA activation (for example, Zhang and Glotzer, 2015; Loria, Longhini and Glotzer, 2012), whereas others suggest that it functions to inactivate the GTPase Rac1 (for example, Zhuravlevet al., 2017). Here, we review the mechanisms underlying RhoA activation during cytokinesis, primarily focusing on data inC. elegans.We highlight the importance of considering the parallel pathway for RhoA activation and detailed analyses of cyk-4mutant phenotypes when evaluating the role of the GAP domain of CYK-4.
Newspaper trust and credibility in the age of robot reporters
Authors: Schultz Brad , Sheffer Mary Lou 
Published: October 2017

Abstract
Audience perception of trust and credibility related to computer-generated journalism was investigated through a national survey of news consumers. Results indicated significantly negative attitudes towards news stories produced by computer algorithms rather than human journalists, and that both credibility and trust were key predictive factors in such attitudes. Implications for the newspaper industry were discussed, including a greater need for newspaper transparency and audience education.