bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron-containing micronutrient powders modify the effect of oral antibiotics on the infant gut microbiome and increase post-antibiotic diarrhoea risk: a controlled study in Kenya
Authors: Paganini Daniela , Uyoga Mary A , Kortman Guus A M , Cercamondi Colin I , Winkler Hans C , Boekhorst Jos , Moretti Diego , Lacroix Christophe , Karanja Simon , Zimmermann Michael B 
Published: March 2019

ObjectiveMany African infants receiving iron fortificants also receive antibiotics. Antibiotic efficacy against enteropathogens may be modified by high colonic iron concentrations. In this study, we evaluated the effect of antibiotics on the infant gut microbiome and diarrhoea when given with or without iron-containing micronutrient powders (MNPs).DesignIn a controlled intervention trial, four groups of community-dwelling infants (n=28; aged 8–10 months) received either: (A) antibiotics for 5 days and iron-MNPs for 40 days (Fe+Ab+); (B) antibiotics and no-iron-MNPs (Fe−Ab+); (C) no antibiotics and iron-MNPs (Fe+Ab−); or (D) no antibiotics and no-iron-MNPs (Fe−Ab−). We collected a faecal sample before the first antibiotic dose (D0) and after 5, 10, 20 and 40 days (D5–D40) to assess the gut microbiome composition by 16S profiling, enteropathogens by quantitative PCR, faecal calprotectin and pH and assessed morbidity over the 40-day study period.ResultsIn Fe+Ab+, there was a decrease in Bifidobacterium abundances (p<0.05), but no decrease in Fe−Ab+. In Fe−Ab+, there was a decrease in abundances of pathogenic Escherichia coli (p<0.05), but no decrease in Fe+Ab+. In Fe−Ab+, there was a decrease in pH (p<0.05), but no decrease in Fe+Ab+. Longitudinal prevalence of diarrhoea was higher in Fe+Ab+ (19.6%) compared with Fe−Ab+ (12.4%) (p=0.04) and compared with Fe+Ab− (5.2%) (p=0.00).ConclusionOur findings need confirmation in a larger study but suggest that, in African infants, iron fortification modifies the response to broad-spectrum antibiotics: iron may reduce their efficacy against potential enteropathogens, particularly pathogenic E. coli, and may increase risk for diarrhoea.Trial registration numberNCT02118402; Pre-results.
Examining the acute effects of retrograde versus low mean shear rate on flow-mediated dilation
Authors: Tremblay Joshua C. , Grewal Arman S. , Pyke Kyra E. 
Published: March 2019

Arterial endothelial function is acutely and chronically regulated by blood flow-associated shear stress. An acute intervention employing modest forearm cuff occlusion to simultaneously increase retrograde and decrease mean brachial artery shear rate for 30 min evokes transient impairments in flow-mediated dilation (FMD). However, the independent influence of the low mean versus the retrograde shear stress components is unclear. Healthy young adults [ n = 24 (12 women, 12 men); 22 ± 2 yr, body mass index = 25 ± 2 kg/m2 (mean ± SD)] completed three laboratory visits within 1 wk. Visits consisted of 45 min of supine rest followed by a brachial artery FMD test (duplex ultrasound) before and after a 30-min intervention: control (shear rate unchanged), cuff (mean shear rate decreased, retrograde shear rate increased), or arterial compression (mean shear rate decreased, no increase in retrograde shear rate). The mean shear rate on the compression visit was targeted to match that achieved on the cuff visit. Cuff and compression trials decreased mean shear rate to a similar extent (cuff: 43 ± 22 s−1, compression: 43 ± 21 s−1; P = 0.850) compared with control (65 ± 21 s−1; both P < 0.001), with the retrograde component elevated only in the former (cuff: −83 ± 30 s−1, compression: −7 ± 5 s−1; P < 0.001). FMD decreased by 29 ± 30% ( P < 0.001) after the cuff intervention and 32 ± 24% ( P < 0.001) after the compression trial but was unchanged on the control visit (−0.3 ± 18%; P = 0.754). This was not altered by accounting for the shear rate stimulus. An increased retrograde shear stress does not appear to be obligatory for the transient reduction in FMD achieved after a 30-min exposure to low mean shear stress. These findings provide novel mechanistic insight on the regulation of endothelial function in vivo. NEW & NOTEWORTHY Low mean and retrograde shear stress are considered atherogenic; however, their relative contribution to the acute regulation of endothelial function in humans is unclear. Matched reductions in mean shear stress (30 min), with and without increases in retrograde shear stress, elicited equivalent reductions in flow-mediated dilation in men and women. These findings afford novel insight regarding the shear stress components governing the acute (dys)regulation of conduit artery endothelial function in vivo.
Automated Analysis of Lymphocytic Infiltration, Tumor Budding, and Their Spatial Relationship Improves Prognostic Accuracy in Colorectal Cancer
Authors: Nearchou Ines P. , Lillard Kate , Gavriel Christos G. , Ueno Hideki , Harrison David J. , Caie Peter D. 
Published: March 2019

AbstractBoth immune profiling and tumor budding significantly correlate with colorectal cancer patient outcome but are traditionally reported independently. This study evaluated the association and interaction between lymphocytic infiltration and tumor budding, coregistered on a single slide, in order to determine a more precise prognostic algorithm for patients with stage II colorectal cancer. Multiplexed immunofluorescence and automated image analysis were used for the quantification of CD3+CD8+ T cells, and tumor buds (TBs), across whole slide images of three independent cohorts (training cohort: n = 114, validation cohort 1: n = 56, validation cohort 2: n = 62). Machine learning algorithms were used for feature selection and prognostic risk model development. High numbers of TBs [HR = 5.899; 95% confidence interval (CI) 1.875–18.55], low CD3+ T-cell density (HR = 9.964; 95% CI, 3.156–31.46), and low mean number of CD3+CD8+ T cells within 50 μm of TBs (HR = 8.907; 95% CI, 2.834–28.0) were associated with reduced disease-specific survival. A prognostic signature, derived from integrating TBs, lymphocyte infiltration, and their spatial relationship, reported a more significant cohort stratification (HR = 18.75; 95% CI, 6.46–54.43), than TBs, a lymphocytic infiltration score, or pT stage. This was confirmed in two independent validation cohorts (HR = 12.27; 95% CI, 3.524–42.73; HR = 15.61; 95% CI, 4.692–51.91). The investigation of the spatial relationship between lymphocytes and TBs within the tumor microenvironment improves accuracy of prognosis of patients with stage II colorectal cancer through an automated image analysis and machine learning workflow.
Effects of Maternal Sildenafil Treatment on Vascular Function in Growth-Restricted Fetal Sheep
Authors: Inocencio Ishmael M. , Polglase Graeme R. , Miller Suzanne L. , Sehgal Arvind , Sutherland Amy , Mihelakis Jamie , Li Anqi , Allison Beth J. 
Published: March 2019

Objective—
The objective of this study was to investigate the effect of intravenous maternal sildenafil citrate (SC) administration on vascular function in growth-restricted fetal sheep.

Approach and Results—
Fetal growth restriction (FGR) results in cardiovascular adaptations that redistribute cardiac output to optimize suboptimal intrauterine conditions. These adaptations result in structural and functional cardiovascular changes, which may underlie postnatal neurological and cardiovascular sequelae. Evidence suggests SC, a potent vasodilator, may improve FGR. In contrast, recent clinical evidence suggests potential for adverse fetal consequence. Currently, there is limited data on SC effects in the developing fetus. We hypothesized that SC in utero would improve vascular development and function in an ovine model of FGR. Preterm lambs (0.6 gestation) underwent sterile surgery for single umbilical artery ligation or sham (control, appropriately grown) surgery to replicate FGR. Ewes received continuous intravenous SC (36 mg/24 h) or saline from surgery until 0.83 gestation. Fetuses were delivered and immediately euthanized for collection of femoral and middle cerebral artery vessels. Vessel function was assessed via in vitro wire myography. SC exacerbated growth restriction in growth-restricted fetuses and resulted in endothelial dysfunction in the cerebral and femoral vasculature, irrespective of growth status. Dysfunction in the cerebral circulation is endothelial, whereas smooth muscle in the periphery is the origin of the deficit.

Conclusions—
SC crosses the placenta and alters key fetal vascular development. Extensive studies are required to investigate the effects of SC on fetal development to address safety before additional use of SC as a treatment.
Hypoperfusion Intensity Ratio Is Correlated With Patient Eligibility for Thrombectomy
Authors: Guenego Adrien , Marcellus David G. , Martin Blake W. , Christensen Soren , Albers Gregory W. , Lansberg Maarten G. , Marks Michael P. , Wintermark Max , Heit Jeremy J. 
Published: March 2019

Background and Purpose—
Hypoperfusion intensity ratio (HIR) is associated with collateral status in acute ischemic stroke patients with anterior circulation large vessel occlusion. We assessed whether HIR was correlated to patient eligibility for mechanical thrombectomy (MT).

Methods—
We performed a retrospective cohort study of consecutive acute ischemic stroke patients with a proximal middle cerebral artery or internal carotid artery occlusion who underwent MT triage with computed tomography or magnetic resonance perfusion imaging. Clinical data, ischemic core (mL), HIR (defined as time-to-maximum [TMax] >10 seconds/TMax >6 seconds), mismatch volume between core and penumbra, and MT details were assessed. Primary outcome was favorable HIR collateral score (HIR <0.4) between patients who underwent MT (MT+) and those who did not (MT−) according to American Heart Association guidelines both in the <6 hours and 6 to 24 hours windows. Secondary outcomes were favorable HIR score in MT− subgroups (National Institutes of Health Stroke Scale <6 versus core >70 mL) and core-penumbra mismatch volumes. Patients who did not meet guidelines were not included.

Results—

We included 197 patients (145 MT+ and 52 MT−). MT+ patients had a significantly lower median HIR compared with MT− patients (0.4 [interquartile range, 0.2–0.5] versus 0.6 [interquartile range, 0.5–0.8];
P
<0.001) and a higher mismatch volume (96 versus 27 mL,
P
<0.001). Among MT− patients, 43 had a core >70 mL, and 9 had a National Institutes of Health Stroke Scale <6. MT− patients with National Institutes of Health Stroke Scale <6 had a lower HIR than MT− patients with core >70 mL (0.2 [interquartile range, 0.2–0.3] versus 0.7 [interquartile range, 0.6–0.8],
P
<0.001) but their HIR was not significantly different that MT+ patients.

Conclusions—
Patients who meet American Heart Association guidelines for thrombectomy are more likely to have favorable collaterals (low HIR). HIR may be used as a marker of eligibility for MT triage.
Caregivers’ effects of augmented cognitive-behavioural therapy for post-stroke depressive symptoms in patients: secondary analyses to a randomized controlled trial
Authors: Kootker Joyce A , van Heugten Caroline M , Kral Bart , Rasquin Sascha MC , Geurts Alexander C , Fasotti Luciano 
Published: March 2019

Objective: To investigate the concomitant effects of two patient-directed interventions for post-stroke depressive symptoms on caregivers’ well-being. Design: Secondary analyses of the results of a randomized controlled trial. Subjects: Fifty caregivers of stroke patients receiving outpatient rehabilitation. Interventions: Stroke patients and their caregivers were randomly allocated to either cognitive-behavioural therapy augmented with movement or occupational therapy ( n = 23) or computerized cognitive training ( n = 27) to alleviate depressive symptoms in patients. Main measures: Emotional burden (Involvement Evaluation Questionnaire), practical burden (Caregiver Strain Index), mental health (General Health Questionnaire) and emotional complaints (Hospital Anxiety and Depression Scale). Results: Caregivers of patients who received cognitive-behavioural therapy reported significantly higher mental health levels (mean difference (MD) = 1.78, 95% confidence interval (CI) = 0.43–3.13, P = 0.01) and less worrying about patients’ well-being (MD = 1.9, 95% CI = 0.56–3.24, P < 0.01). In addition, there were positive time effects on the Involvement Evaluation Questionnaire for Brain Injury, particularly the subscales Worrying, Supervision and Tension. Conclusion: The results suggest that augmented cognitive-behavioural therapy aimed at improving patients’ emotional, behavioural and social functioning positively affects some aspects of caregivers’ well-being.
Perinatal Palliative Care: A qualitative study evaluating the perspectives of pregnancy counselors
Authors: Flaig Franziska , Lotz Julia D , Knochel Kathrin , Borasio Gian Domenico , Führer Monika , Hein Kerstin 
Published: March 2019

Background: A prenatal diagnosis of a life-limiting disease raises complex ethical, emotional, and medical issues. Studies suggest that 40%–85% of parents decide to continue the pregnancy if given the option of Perinatal Palliative Care. However, structured Perinatal Palliative Care programs are missing in many European countries. In Germany, parents have the right to free psychosocial support from pregnancy counseling services after the prenatal diagnosis of a life-limiting disease. Aim: We aimed to investigate whether German professional pregnancy counselors perceive the need for structured Perinatal Palliative Care and if so, how it should be conceived. Design: This is a qualitative interview study with purposeful sampling. The interviews were analyzed with the coding method of Saldaña. Setting/participants: A total of 10 professionals from three different pregnancy counseling services participated in the study. Results: The main topics raised by the professionals were as follows: (1) counseling and parental support during the decision-making process; (2) fragmented or missing support infrastructure for parents; and (3) challenges, hesitations, and barriers, particularly from the different stakeholders, regarding a Perinatal Palliative Care framework. They highlighted the importance of the integration of Perinatal Palliative Care in existing structures, a multi-professional approach, continuous coordination of care and education for all healthcare providers involved. Conclusion: A structured Perinatal Palliative Care program is considered as necessary by the pregnancy counselors. Future research should focus on (1) needs reported by concerned parents; (2) attitude and role of all healthcare providers involved; (3) strategies to include stakeholders in the development of Perinatal Palliative Care networks; and (4) outcome parameters for evaluation of Perinatal Palliative Care frameworks.
Vortioxetine for attention deficit hyperactivity disorder in adults: A randomized, double-blind, placebo-controlled, proof-of-concept study
Authors: Biederman Joseph , Lindsten Annika , Sluth Lasse B , Petersen Maria Louise , Ettrup Anders , Eriksen Hanne-Lise F , Fava Maurizio 
Published: March 2019

Background: Stimulants remain the mainstay of treatment for attention-deficit hyperactivity disorder (ADHD) but are often associated with insufficient response or poor tolerability, leading to many patients not wishing to be treated with controlled substances. Aims: This randomized, placebo-controlled, proof-of-concept study (NCT02327013) evaluated the efficacy of a multimodal antidepressant, vortioxetine, in the treatment of ADHD, using a two-stage sequential parallel comparison design. Methods: Patients aged 18–55 years with a diagnosis of ADHD (DSM-5) and a total score ⩾24 on the Adult ADHD Investigator Symptom Rating Scale (AISRS) were randomized in study stage I with a 1:1:3 ratio to six weeks of treatment with vortioxetine 10 or 20 mg/day, or placebo ( n = 227). In study stage II, placebo non-responders (AISRS total score reduction <30% from stage I baseline) were re-randomized with a 1:1:1 ratio to six weeks of vortioxetine 10 or 20 mg/day, or placebo ( n = 59). Results: Across the two study stages combined, ADHD symptoms improved by approximately eight AISRS points in all treatment groups, showing no difference from placebo for either dose of vortioxetine, the study thus failing to meet its primary endpoint. However, both doses of vortioxetine separated from placebo in improving overall patient functioning, as measured by the Sheehan Disability Scale. Conclusion: Studies are warranted to further investigate this suggested benefit of a multimodal antidepressant for patient functioning in ADHD while addressing issues of non-adherence and placebo response. The study confirmed vortioxetine 10 mg and 20 mg as generally well-tolerated.
Are Amniotic Fluid Products Stem Cell Therapies? A Study of Amniotic Fluid Preparations for Mesenchymal Stem Cells With Bone Marrow Comparison
Authors: Panero Alberto J. , Hirahara Alan M. , Andersen Wyatt J. , Rothenberg Joshua , Fierro Fernando 
Published: March 2019

Background: In vivo amniotic fluid is known to contain a population of mesenchymal stem cells (MSCs) and growth factors and has been shown to assist in healing when used as an adjunct in procedures across multiple medical specialties. It is unclear whether amniotic fluid products (AFPs) contain MSCs and, if so, whether the cells remain viable after processing. Purpose: To determine whether MSCs, growth factors, and hyaluronan are present in commercially available AFPs. Study Design: Descriptive laboratory study. Methods: Seven commercial companies that provide amniotic fluid were invited to participate in the study; 3 companies (the manufacturers of PalinGen, FloGraft, and Genesis AFPs) agreed to participate and donated AFPs for analysis. The AFPs were evaluated for the presence of MSCs, various growth factors relevant to orthopaedics (platelet-derived growth factor ββ, vascular endothelial growth factor, interleukin 8, bone morphogenetic protein 2, transforming growth factor β1), and hyaluronan by enzyme-linked immunosorbent assay and culture of fibroblast colony-forming units. These products were compared with unprocessed amniotic fluid and 2 separate samples of MSCs derived from human bone marrow aspirates. All groups used the same culture medium and expansion techniques. Identical testing and analysis procedures were used for all samples. Results: MSCs could not be identified in the commercial AFPs or the unprocessed amniotic fluid. MSCs could be cultured from the bone marrow aspirates. Nucleated cells were found in 2 products (PalinGen and FloGraft), but most of these cells were dead. The few living cells did not exhibit established characteristics of MSCs. Growth factors and hyaluronan were present in all groups at varying levels. Conclusion: The AFPs studied should not be considered “stem cell” therapies, and researchers should use caution when evaluating commercial claims that products contain stem cells. Given their growth factor content, however, AFPs may still represent a promising tool for orthopaedic treatment. Clinical Relevance: Amniotic fluid has been proposed as an allogenic means for introducing MSCs. This study was unable to confirm that commercial AFPs contain MSCs.
Illustrating the Difference Between a Pigovian Tax and Emissions Fee Using Isoquant and Isocost Geometry
Authors: Decker Christopher S. 
Published: March 2019

The study of environmental economics is motivated by the idea that pollution constitutes a negative externality. When production costs do not include the harm to human health and the environment, the market price is too low and output levels are too high, relative to the efficient levels. The initial solution to this problem is usually the “the Pigovian tax” on production. However, all subsequent tax analysis focuses directly on emissions. This tends to leave students wondering (a) why discuss Pigou in the first place and (b) why is it better to focus on pollution emissions rather than production. I provide a graphical analysis, using isoquant and isocost geometry, to illustrate that a direct fee on the externality-generating input is more efficient than a tax on output. This analysis is something teachers might consider utilizing to clarify why there is a transition from output taxation to input taxation. JEL Classifications: A22, A23, Q50
Axonal damage in spinal cord is associated with gray matter atrophy in sensorimotor cortex in experimental autoimmune encephalomyelitis
Authors: Meyer Cassandra E , Gao Josephine L , Cheng James Ying-Jie , Oberoi Mandavi R , Johnsonbaugh Hadley , Lepore Stefano , Kurth Florian , Thurston Mackenzie J , Itoh Noriko , Patel Kevin R , Voskuhl Rhonda R , MacKenzie-Graham Allan 
Published: March 2019

Background: Gray matter (GM) atrophy in brain is one of the best predictors of long-term disability in multiple sclerosis (MS), and recent findings have revealed that localized GM atrophy is associated with clinical disabilities. GM atrophy associated with each disability mapped to a distinct brain region, revealing a disability-specific atlas (DSA) of GM loss. Objective: To uncover the mechanisms underlying the development of localized GM atrophy. Methods: We used voxel-based morphometry (VBM) to evaluate localized GM atrophy and Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging-compatible Tissue-hYdrogel (CLARITY) to evaluate specific pathologies in mice with experimental autoimmune encephalomyelitis (EAE). Results: We observed extensive GM atrophy throughout the cerebral cortex, with additional foci in the thalamus and caudoputamen, in mice with EAE compared to normal controls. Next, we generated pathology-specific atlases (PSAs), voxelwise mappings of the correlation between specific pathologies and localized GM atrophy. Interestingly, axonal damage (end-bulbs and ovoids) in the spinal cord strongly correlated with GM atrophy in the sensorimotor cortex of the brain. Conclusion: The combination of VBM with CLARITY in EAE can localize GM atrophy in brain that is associated with a specific pathology in spinal cord, revealing a PSA of GM loss.
Faulty ‘tools’? Why social work scholarship needs to take a more critical approach to Michel Foucault
Authors: Garrett Paul Michael 
Published: March 2019

Summary Having outlined Foucault’s articulation of power and governmentality, the article critically explores attempts to translate the philosopher’s theorisation into social work. Findings After briefly referring to Jacques Donzelot’s work and that of other writers, it is argued that Foucault’s conceptual ‘tools’ are problematic for those seeking to promote critical approaches within the field of social work. Those influenced by Foucault’s complex contributions may amplify a defective understanding of power which unduly emphasises ‘soft’ power and neglects the continuing significance of hierarchical and coercive power. This is reflected in Foucault’s analysis of the state and, at a micro level, his remarks on sexualised interactions involving adults and children. Efforts to ‘apply’ Foucauldian reasoning within social work may also risk promoting politically passive forms of theory and practice. Applications Contributing to the discipline’s literature on Foucault, the article maintains the social work scholarship has much to gain by engaging with work, but this engagement might aspire to become more critical.