bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic T cell subsets in allergic and chronic inflammatory bowel disorders
Authors: Zundler Sebastian , Neurath Markus F. 
Published: June 2017

SummaryHomeostasis in the gastrointestinal tract relies on a sensitive equilibrium between permissive and protective functions. This is closely reflected in the regulation of the intestinal immune system and especially T cells in the gut. This balance, however, is susceptible to disturbances as demonstrated by pathological conditions like food allergy, celiac disease, or inflammatory bowel disease. In these allergic and chronic inflammatory bowel disorders, luminal antigens get access to the lamina propria where they trigger a dysregulated immune response with crucial involvement of different T cell subsets. We will begin this review with some comprehensive remarks on current concepts on the pathogenesis of these diseases before taking a closer look at the life cycle of intestinal T cells consisting of priming, homing, differentiation and proliferation and apoptosis respectively. Subsequently we will discuss the specific implication of distinct T cell subsets in allergic and chronic inflammatory conditions of the gastrointestinal tract in detail and comment on current and future approaches to targeted therapy in this context.
The effects of group memberships of victims and perpetrators in humanly caused disasters on charitable donations to victims
Authors: James Trevor Keith , Zagefka Hanna 
Published: June 2017

AbstractThe effects of group memberships of disaster victims and perpetrators on charitable donations were measured. In Study 1 (N = 92), victim group membership was experimentally varied to demonstrate an ingroup bias. In Study 2 (N = 84), a similar bias was demonstrated by varying perpetrator group membership. In Study 3 (N = 182), both victim and perpetrator group memberships were assessed. Perpetrator group membership interacted with victim group membership. Moreover, donations were highest when both victims and perpetrators shared a group membership. These effects were mediated by empathy with the victims, and perceived responsibility of the donor to intervene and aid the victim. Findings show that a salient perpetrator group can be harnessed to encourage helping of disaster victims.
Mechanisms of PTHrP‐induced inhibition of smooth muscle contractility in the guinea pig gastric antrum
Authors: Ohguchi H. , Mitsui R. , Imaeda K. , Joh T. , Hashitani H. 
Published: June 2017

AbstractBackgroundParathyroid hormone‐related protein (PTHrP) that causes hypercalcemia of malignancy appears to function as an endogenous smooth muscle relaxant. For example, PTHrP released upon bladder wall distension relaxes detrusor smooth muscle to accommodate urine. Here, we explored mechanisms underlying PTHrP‐induced suppression of the smooth muscle contractility in the gastric antrum that also undergoes a passive distension.MethodsEffects of PTHrP on phasic contractions and electrical slow waves in the antral smooth muscle of the guinea pig stomach were studied using isometric tension and intracellular microelectrode recordings, respectively. Fluorescent immunohistochemistry was also carried out to identify the distribution of PTH/PTHrP receptors.Key ResultsParathyroid hormone‐related protein (1‐100 nM) reduced the amplitude of phasic contractions and the basal tension. Nω‐nitro‐l‐arginine (L‐NA, 100 μM), a nitric oxide (NO) synthase inhibitor, or 1H‐[1,2,4]oxadiazolo‐[4, 3‐a]quinoxalin‐1‐one (ODQ, 10 µM), a guanylate cyclase inhibitor, diminished the PTHrP (10 nM)‐induced reduction in the amplitude of phasic contractions. SQ22536 (300 μM), an adenylate cyclase inhibitor, attenuated the PTHrP‐induced reduction in basal tension. The combination of ODQ (10 μM) and SQ22536 (300 μM) inhibited the PTHrP‐induced reductions in both phasic contractions and basal tension. PTHrP (100 nM) had no inhibitory effect on the electrical slow waves in the antral smooth muscle. PTH/PTHrP receptors were expressed in cell bodies of PGP9.5‐positive neurons in the myenteric plexus.Conclusions & InferencesParathyroid hormone‐related protein exerts its inhibitory actions on the antral smooth muscle via both nitric oxide‐cyclic guanosine monophosphate (NO‐cGMP) and cyclic adenosine monophosphate (AMP) pathways. Thus, PTHrP may act as an endogenous relaxant of the gastric antrum employing the two complementary signaling pathways to ensure the adaptive relaxation of stomach.
Yellow sigatoka epidemics caused by a panmictic population of Mycosphaerella musicola in Brazil
Authors: Gomes L. I. S. , Douhan G. W. , Lehner M. S. , Bibiano L. B. J. , Mizubuti E. S. G. 
Published: June 2017

The genetic structure of Mycosphaerella musicola has never been investigated in Brazil to address epidemiologically related questions associated with yellow sigatoka. A total of 223 single‐conidium isolates from four regions (North, South, Zona da Mata and Triângulo Mineiro) of Minas Gerais State, Brazil, were used to assess the population genetic structure of M. musicola. Isolates were characterized regarding the frequency of the MAT1‐1‐1 or MAT1‐2‐1 idiomorphs and polymorphism at nine microsatellite loci. The mating‐type ratio in three of the four subpopulations was c. 1:1. A total of 87 alleles and 216 multilocus genotypes were identified. The overall population was in linkage equilibrium. Most (93.9%) genetic variation was detected within the subpopulations and there was weak differentiation between them. In total, eight genetic groups were detected and isolates of seven groups were present in all regions. The population of M. musicola in Minas Gerais seems to have high evolutionary potential: it is panmictic and both sexual reproduction and gene flow affect genetic variability. Strategies to avoid fungicide resistance should be enforced and breeding programmes need to consider quantitative resistance in the banana cultivars.
Ultra-low-dose intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case series
Authors: Hillier Roxane J , Connor Alan J , Shafiq Ayad E 
Published: June 2017

BackgroundIntravitreal bevacizumab (IVB) has emerged as an effective treatment modality for the management of retinopathy of prematurity (ROP) where the disease is severe and posterior. Despite evidence of systemic vascular endothelial growth factor suppression and concerns about how this might affect the developing neonate, the optimal dose is unknown to date. We report our experience of using ultra-low-dose (0.16 mg) IVB, one-quarter of the ‘standard’ dose that has widely been reported in the treatment of ROP.MethodsA retrospective observational case series of consecutive infants who underwent ultra-low-dose IVB injection for the management of ROP at a regional neonatal intensive care unit in the North East of England, between November 2013 and August 2016.Results29 eyes of 15 infants underwent IVB injection. We defined ‘treatment success’ as complete regression of retinopathy and vascularisation into (or laser ablation of) zone 3. Primary success (in response to IVB 0.16 mg alone) was observed in 23/29 eyes (79.3%). Secondary success (where additional treatment was required) was observed in 27/29 eyes (93.1%). One infant died of respiratory disease during follow-up. Retreatment occurred in 6/29 eyes (20.6%). Retreatments occurred at a mean of 9.8 weeks after initial IVB (range 6–15) and at a mean of 44 weeks postmenstrual age (range 40–50).Conclusion0.16 mg IVB is effective in the treatment of severe and posterior ROP, with no adverse ocular outcomes occurring in our series.
Thinker, Soldier, Scribe: cross-sectional study of researchers' roles and author order in theAnnals of Internal Medicine
Authors: Perneger Thomas V , Poncet Antoine , Carpentier Marc , Agoritsas Thomas , Combescure Christophe , Gayet-Ageron Angèle 
Published: June 2017

ObjectiveHow researchers’ contributions relate to author order on the byline remains unclear. We sought to identify researchers’ contributions associated with author order, and to explore the existence of author profiles.DesignObservational study.SettingPublished record.Participants1139 authors of 119 research articles published in 2015 in theAnnals of Internal Medicine.Primary outcomesPresence or absence of 10 contributions, reported by each author, published in the journal.ResultsOn average, first authors reported 7.1 contributions, second authors 5.2, middle authors 4.0, penultimate authors 4.5 and last authors 6.4 (p<0.001). The first author made the greatest contributions to drafting the article, designing the study, analysing and interpreting the data, and providing study materials or patients. The second author contributed to data analysis as well and to drafting the article. The last author was most involved in obtaining the funding, critically revising the article, designing the study and providing support. Factor analysis yielded three author profiles—Thinker(study design, revision of article, obtaining funding),Soldier(providing material or patients, providing administrative and logistical support, collecting data) andScribe(analysis and interpretation of data, drafting the article, statistical expertise). These profiles do not strictly correspond to byline position.ConclusionsFirst, second and last authors of research articles made distinct contributions to published research. Three authorship profiles can be used to summarise author contributions. These findings shed light on the organisation of clinical research teams and may help researchers discuss, plan and report authorship in a more transparent way.
Out-of-hospital cardiac arrests in the older population in Ireland
Authors: Tanner Richard , Masterson Siobhan , Jensen Mette , Wright Peter , Hennelly David , O’Reilly Martin , Murphy Andrew W , Bury Gerard , O’Donnell Cathal , Deasy Conor 
Published: June 2017

IntroductionAge influences survival from an out-of-hospital cardiac arrest (OHCA) but it is unclear to what extent. Improved understanding of the impact of increasing age may be helpful in improving decision making on who should receive attempted resuscitation to optimise outcomes and minimise inappropriate end-of-life management. Our aim is to describe the demographics, characteristics and outcomes following resuscitation attempts in OHCA patients aged 70 years and older in Ireland.MethodsData were extracted from the national OHCA Register. Patient and event characteristics were compared across three age categories (70-79; 80-89; ≥90 years). Multivariable logistic regression was used to determine the predictors of the primary outcome (survival to hospital discharge).ResultsA total of 2281 patients aged 70 years and older were attended by emergency medical services and had resuscitation attempted between 2012 and 2014. Overall survival to hospital discharge was 2.9%. For those aged 70–79 years, 80–89 years, 90 years and older survival to hospital discharge in each age group was 4.0%, 1.8% and 1.4%, respectively. Older age (adjusted OR (AOR) 0.95 95% CI 0.90 to 0.99) and having an arrest in the subjects own home (AOR 0.14 95% CI 0.07 to 0.28) were independent predictor associated with reduced odds of survival to hospital discharge. An initial shockable rhythm (AOR 17.9. 95% CI 8.19 to 39.2) and having a bystander witnessed OHCA (AOR 3.98. 95% CI 1.38 to 11.50) were independent predictors associated with increased odds of survival to hospital discharge.ConclusionIn those aged 70 years and older, the rate of survival to hospital discharge declined with increasing age group. Younger age, an initial shockable rhythm and witnessed arrest were independent predictors of survival to hospital discharge.
Dynamics ofHelicobacter pyloriinfection as a determinant of progression of gastric precancerous lesions: 16-year follow-up of an eradication trial
Authors: Mera Robertino M , Bravo Luis E , Camargo M Constanza , Bravo Juan C , Delgado Alberto G , Romero-Gallo Judith , Yepez Maria C , Realpe José L , Schneider Barbara G , Morgan Douglas R , Peek Richard M , Correa Pelayo , Wilson Keith T , Piazuelo M Blanca 
Published: June 2017

ObjectiveTo evaluate the long-term effect of cumulative time exposed toHelicobacter pyloriinfection on the progression of gastric lesions.Design795 adults with precancerous gastric lesions were randomised to receive anti-H. pyloritreatment at baseline. Gastric biopsies were obtained at baseline and at 3, 6, 12 and 16 years. A total of 456 individuals attended the 16-year visit. Cumulative time ofH. pyloriexposure was calculated as the number of years infected during follow-up. Multivariable logistic regression models were used to estimate the risk of progression to a more advanced diagnosis (versus no change/regression) as well as gastric cancer risk by intestinal metaplasia (IM) subtype. For a more detailed analysis of progression, we also used a histopathology score assessing both severity and extension of the gastric lesions (range 1–6). The score difference between baseline and 16 years was modelled by generalised linear models.ResultsIndividuals who were continuously infected withH. pylorifor 16 years had a higher probability of progression to a more advanced diagnosis than those who cleared the infection and remained negative after baseline (p=0.001). Incomplete-type IM was associated with higher risk of progression to cancer than complete-type (OR, 11.3; 95% CI 1.4 to 91.4). The average histopathology score increased by 0.20 units/year (95% CI 0.12 to 0.28) among individuals continuously infected withH. pylori. The effect of cumulative time of infection on progression in the histopathology score was significantly higher for individuals with atrophy (without IM) than for individuals with IM (p<0.001).ConclusionsLong-term exposure toH. pyloriinfection was associated with progression of precancerous lesions. Individuals infected withH. pyloriwith these lesions may benefit from eradication, particularly those with atrophic gastritis without IM. Incomplete-type IM may be a useful marker for the identification of individuals at higher risk for cancer.
Selling a gun to a stranger without a background check: acceptable behaviour?
Authors: Hemenway David , Azrael Deborah , Miller Matthew 
Published: June 2017

ObjectiveOne way that guns get into the wrong hands is via gun sales without a background check. While the large majority of Americans support laws requiring universal background checks, no prior study has assessed whether Americans think it is acceptable behaviour to sell a gun to a stranger without a background check, whether or not there is a law against it.MethodsWe sponsored a nationally representative survey of over 3900 American adults, oversampling gun owners, using an online panel provided by the survey firm Growth for Knowledge.ResultsOver 72% of American adults agree or strongly agree with the statement that ‘whether it is legal or not, it is NOT acceptable to sell a gun to a stranger without a background check’ and 11% disagree or strongly disagree. Subgroups less likely to agree are young adults, men, conservatives, those with less than a high school education and gun owners.ConclusionReducing the number of guns sold without a background check could help reduce the flow of guns to felons. Changes in normative attitudes and behaviours, as well as changes in law, could help accomplish this goal. Most Americans, including gun owners, believe selling a gun to a stranger without a background check is not acceptable behaviour.
Response preparation and execution during intentional bimanual pattern switching
Authors: Maslovat Dana , Carter Michael J. , Carlsen Anthony N. 
Published: June 2017

During continuous bimanual coordination, in-phase (IP; 0° relative phase) and anti-phase (AP; 180° relative phase) patterns can be stably performed without practice. Paradigms in which participants are required to intentionally switch between these coordination patterns have been used to investigate the interaction between the performer’s intentions and intrinsic dynamics of the body’s preferred patterns. The current study examined the processes associated with switching preparation and execution through the use of a startling acoustic stimulus (SAS) as the switch stimulus. A SAS is known to involuntarily trigger preprogrammed responses at a shortened latency and, thus, can be used to probe advance preparation. Participants performed cyclical IP and AP bimanual elbow extension-flexion movements in which they were required to switch patterns in response to an auditory switch cue, which was either nonstartling (80 dB) or a SAS (120 dB). Results indicated that reaction time to the switch stimulus (i.e., switch onset) was significantly reduced on startle trials, indicative of advance preparation of the switch response. Similarly, switching time was reduced on startle trials, which was attributed to increased neural activation caused by the SAS. Switching time was also shorter for AP to IP trials, but only when the switching stimulus occurred at either the midpoint or reversal locations within the movement cycle, suggesting that the switch location may affect the intrinsic dynamics of the system. NEW & NOTEWORTHY The current study provides novel information regarding preparation and execution of intentional switching between in-phase and anti-phase bimanual coordination patterns. Using a startling acoustic stimulus, we provide strong evidence that the switching response is prepared before the switch stimulus, and switch execution is accelerated by the startling stimulus. In addition, the time required to switch between patterns and relative limb contribution is dependent upon where in the movement cycle the switch stimulus occurred.
Discrimination of curvature from motion during smooth pursuit eye movements and fixation
Authors: Ross Nicholas M. , Goettker Alexander , Schütz Alexander C. , Braun Doris I. , Gegenfurtner Karl R. 
Published: June 2017

Smooth pursuit and motion perception have mainly been investigated with stimuli moving along linear trajectories. Here we studied the quality of pursuit movements to curved motion trajectories in human observers and examined whether the pursuit responses would be sensitive enough to discriminate various degrees of curvature. In a two-interval forced-choice task subjects pursued a Gaussian blob moving along a curved trajectory and then indicated in which interval the curve was flatter. We also measured discrimination thresholds for the same curvatures during fixation. Motion curvature had some specific effects on smooth pursuit properties: trajectories with larger amounts of curvature elicited lower open-loop acceleration, lower pursuit gain, and larger catch-up saccades compared with less curved trajectories. Initially, target motion curvatures were underestimated; however, ∼300 ms after pursuit onset pursuit responses closely matched the actual curved trajectory. We calculated perceptual thresholds for curvature discrimination, which were on the order of 1.5 degrees of visual angle (°) for a 7.9° curvature standard. Oculometric sensitivity to curvature discrimination based on the whole pursuit trajectory was quite similar to perceptual performance. Oculometric thresholds based on smaller time windows were higher. Thus smooth pursuit can quite accurately follow moving targets with curved trajectories, but temporal integration over longer periods is necessary to reach perceptual thresholds for curvature discrimination. NEW & NOTEWORTHY Even though motion trajectories in the real world are frequently curved, most studies of smooth pursuit and motion perception have investigated linear motion. We show that pursuit initially underestimates the curvature of target motion and is able to reproduce the target curvature ∼300 ms after pursuit onset. Temporal integration of target motion over longer periods is necessary for pursuit to reach the level of precision found in perceptual discrimination of curvature.
PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer
Authors: Hsu Jessie Hao-Ru , Hubbell-Engler Benjamin , Adelmant Guillaume , Huang Jialiang , Joyce Cailin E. , Vazquez Francisca , Weir Barbara A. , Montgomery Philip , Tsherniak Aviad , Giacomelli Andrew O. , Perry Jennifer A. , Trowbridge Jennifer , Fujiwara Yuko , Cowley Glenn S. , Xie Huafeng , Kim Woojin , Novina Carl D. , Hahn William C. , Marto Jarrod A. , Orkin Stuart H. 
Published: June 2017

Abstract
Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo. Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. Cancer Res; 77(17); 4613–25. ©2017 AACR.
First-in-Human Study of AMG 820, a Monoclonal Anti-Colony-Stimulating Factor 1 Receptor Antibody, in Patients with Advanced Solid Tumors
Authors: Papadopoulos Kyriakos P. , Gluck Larry , Martin Lainie P. , Olszanski Anthony J. , Tolcher Anthony W. , Ngarmchamnanrith Gataree , Rasmussen Erik , Amore Benny M. , Nagorsen Dirk , Hill John S. , Stephenson Joe 
Published: June 2017

Abstract
Purpose: Binding of colony-stimulating factor 1 (CSF1) ligand to the CSF1 receptor (CSF1R) regulates survival of tumor-associated macrophages, which generally promote an immunosuppressive tumor microenvironment. AMG 820 is an investigational, fully human CSF1R antibody that inhibits binding of the ligands CSF1 and IL34 and subsequent ligand-mediated receptor activation. This first-in-human phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AMG 820.
Experimental Design: Adult patients with relapsed or refractory advanced solid tumors received intravenous AMG 820 0.5 mg/kg once weekly or 1.5 to 20 mg/kg every 2 weeks until disease progression, adverse event (AE), or consent withdrawal.
Results: Twenty-five patients received ≥1 dose of AMG 820. AMG 820 was tolerated up to 20 mg/kg; the MTD was not reached. One dose-limiting toxicity was observed (20 mg/kg; nonreversible grade 3 deafness). Most patients (76%) had treatment-related AEs; the most common were periorbital edema (44%), increased aspartate aminotransferase (AST; 28%), fatigue (24%), nausea (16%), increased blood alkaline phosphatase (12%), and blurred vision (12%). No patients had serious or fatal treatment-related AEs; 28% had grade ≥3 treatment-related AEs. Grade 3 AST elevations resolved when treatment was withheld. AMG 820 showed linear pharmacokinetics, with minimal accumulation (&lt;2-fold) after repeated dosing. Pharmacodynamic increases in serum CSF1 concentrations and reduced numbers of skin macrophages were observed. Best response was stable disease in 8 patients (32%).
Conclusions: AMG 820 was tolerated with manageable toxicities up to 20 mg/kg every 2 weeks. Pharmacodynamic response was demonstrated, and limited antitumor activity was observed. Clin Cancer Res; 23(19); 5703–10. ©2017 AACR.