bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular catalyst systems as key enablers for tailored polyesters and polycarbonate recycling concepts
Authors: Westhues Stefan , Idel Jasmine , Klankermayer Jürgen
Published: August 2018

Molecular catalyst system enables recycling of polymeric consumer products.
Fibroblastic reticular cells initiate immune responses in visceral adipose tissues and secure peritoneal immunity
Authors: Perez-Shibayama Christian , Gil-Cruz Cristina , Cheng Hung-Wei , Onder Lucas , Printz Andrea , Mörbe Urs , Novkovic Mario , Li Conglei , Lopez-Macias Constantino , Buechler Matthew B. , Turley Shannon J. , Mack Matthias , Soneson Charlotte , Robinson Mark D. , Scandella Elke , Gommerman Jennifer , Ludewig Burkhard
Published: August 2018

MYD88 signaling in fibroblastic reticular cells drives the initiation of immune responses in fat-associated lymphoid clusters.
Treatment of Pseudomonas aeruginosa Biofilm Present in Endotracheal Tubes by Poly-
l
-Lysine
Authors: Guillon Antoine , Fouquenet Delphine , Morello Eric , Henry Clémence , Georgeault Sonia , Si-Tahar Mustapha , Hervé Virginie
Published: August 2018

The endotracheal tube (ETT) is an essential interface between the patient and ventilator in mechanically ventilated patients. However, a microbial biofilm is formed gradually on this tube and is associated with the development of ventilator-associated pneumonia.
BmGPAC, an Antigen Capture Assay for Detection of Active Babesia microti Infection
Authors: Thekkiniath Jose , Mootien Sara , Lawres Lauren , Perrin Benjamin A. , Gewirtz Meital , Krause Peter J. , Williams Scott , Doggett J. Stone , Ledizet Michel , Ben Mamoun Choukri
Published: August 2018

Human babesiosis is an emerging zoonotic infectious disease caused by intraerythrocytic protozoan parasites of the genus
Babesia
. Most cases of human babesiosis are caused by
Babesia microti
and often manifest in individuals over the age of 50 years or in patients with a compromised immune system.
Acupuncture with Or without Combined Auricular Acupuncture for Insomnia: A Randomised, Waitlist-Controlled Trial
Authors: Chung Ka-Fai , Yeung Wing-Fai , Yu Branda Yee-Man , Leung Feona Chung-Yin , Zhang Shi-Ping , Zhang Zhang-Jin , Ng Roger Man-Kin , Yiu Gar-Chung
Published: August 2018

Background

Few high-quality, large-scale, controlled trials comparing the effectiveness and safety of acupuncture, auricular acupuncture and combined acupuncture treatment for insomnia are available.

Objective

To carry out a randomised, assessor-blinded, waitlist-controlled trial to test the superiority of combination treatment.

Methods

After in-person and polysomnography screening, 224 subjects (mean age 53.4 years; 75.4% female) with DSM-5 insomnia disorder, who were free from major psychiatric disorders and with sleep-diary-derived sleep efficiency averaged over 1 week of <85%, were randomised to acupuncture alone, acupuncture plus auricular acupuncture (combination treatment), or a waitlist in a 3:3:1 ratio. Standardised acupuncture and combination treatment were provided three times weekly for 3 weeks. The primary outcome was sleep-diary-derived sleep efficiency. Secondary outcomes included wrist actigraphy and self-reported scales on insomnia, anxiety and depression, fatigue, sleepiness and functioning. Assessments were conducted at baseline, 1 week, 4 weeks and 13 weeks after treatment. Participants on the waitlist were re-randomised to receive acupuncture or combination treatment after the second post-baseline assessment.

Results

There was no significant difference between acupuncture and combination treatment in the primary outcome and most secondary outcomes at all time points. However, both treatments were better than waitlist in reducing insomnia, anxiety/depressive symptoms and fatigue, and improving function. Within-group improvements were maintained at 13 weeks after treatment. Of 260 adverse events, 243 were mild (93.5%). Discontinuation due to adverse events was 2.1% and 3.1% for acupuncture and combination treatment, respectively.

Conclusions

Limited by short-term treatment and follow-up, the attempt to augment acupuncture by auricular acupuncture was not supported. Acupuncture and combination treatment were safe and had mild hypnotic effects, which lasted for at least 13 weeks.

Trial Registration Number

NCT01891097; Results.
Criteria led discharge of wheezy children from a short stay assessment unit
Authors: Armstrong Lucinda , Lyttle Mark D
Published: August 2018

Implementation and evaluation of criteria led discharge from a short stay assessment unit for children with wheeze.
Value of hospital resources for effective pressure injury prevention: a cost-effectiveness analysis
Authors: Padula William V , Pronovost Peter J , Makic Mary Beth F , Wald Heidi L , Moran Dane , Mishra Manish K , Meltzer David O
Published: August 2018

Objective

Hospital-acquired pressure injuries are localised skin injuries that cause significant mortality and are costly. Nursing best practices prevent pressure injuries, including time-consuming, complex tasks that lack payment incentives. The Braden Scale is an evidence-based stratification tool nurses use daily to assess pressure-injury risk. Our objective was to analyse the cost-utility of performing repeated risk-assessment for pressure-injury prevention in all patients or high-risk groups.

Design

Cost-utility analysis using Markov modelling from US societal and healthcare sector perspectives within a 1-year time horizon.

Setting

Patient-level longitudinal data on 34 787 encounters from an academic hospital electronic health record (EHR) between 2011 and 2014, including daily Braden scores. Supervised machine learning simulated age-adjusted transition probabilities between risk levels and pressure injuries.

Participants

Hospitalised adults with Braden scores classified into five risk levels: very high risk (6–9), high risk (10–11), moderate risk (12–14), at-risk (15–18), minimal risk (19–23).

Interventions

Standard care, repeated risk assessment in all risk levels or only repeated risk assessment in high-risk strata based on machine-learning simulations.

Main outcome measures

Costs (2016 $US) of pressure-injury treatment and prevention, and quality-adjusted life years (QALYs) related to pressure injuries were weighted by transition probabilities to calculate the incremental cost-effectiveness ratio (ICER) at $100 000/QALY willingness-to-pay. Univariate and probabilistic sensitivity analyses tested model uncertainty.

Results

Simulating prevention for all patients yielded greater QALYs at higher cost from societal and healthcare sector perspectives, equating to ICERs of $2000/QALY and $2142/QALY, respectively. Risk-stratified follow-up in patients with Braden scores <15 dominated standard care. Prevention for all patients was cost-effective in >99% of probabilistic simulations.

Conclusion

Our analysis using EHR data maintains that pressure-injury prevention for all inpatients is cost-effective. Hospitals should invest in nursing compliance with international prevention guidelines.
Assessment of cardiovascular risk and preparticipation screening protocols in masters athletes: the Masters Athlete Screening Study (MASS): a cross-sectional study
Authors: Morrison Barbara N , McKinney James , Isserow Saul , Lithwick Daniel , Taunton Jack , Nazzari Hamed , De Souza Astrid M , Heilbron Brett , Cater Carlee , MacDonald Mackenzie , Hives Benjamin A , Warburton Darren E R
Published: August 2018

Background

Underlying coronary artery disease (CAD) is the primary cause of sudden cardiac death in masters athletes (>35 years). Preparticipation screening may detect cardiovascular disease; however, the optimal screening method is undefined in this population. The Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) and the American Heart Association (AHA) Preparticipation Screening Questionnaire are often currently used; however, a more comprehensive risk assessment may be required. We sought to ascertain the cardiovascular risk and to assess the effectiveness of screening tools in masters athletes.

Methods

This cross-sectional study performed preparticipation screening on masters athletes, which included an ECG, the AHA 14-element recommendations and Framingham Risk Score (FRS). If the preparticipation screening was abnormal, further evaluations were performed. The effectiveness of the screening tools was determined by their positive predictive value (PPV).

Results

798 athletes were included in the preparticipation screening analysis (62.7% male, 54.6±9.5 years, range 35–81). The metabolic equivalent task hours per week was 80.8±44.0, and the average physical activity experience was 35.1±14.8 years. Sixty-four per cent underwent additional evaluations. Cardiovascular disease was detected in 11.4%, with CAD (7.9%) being the most common diagnosis. High FRS (>20%) was seen in 8.5% of the study population. Ten athletes were diagnosed with significant CAD; 90% were asymptomatic. A high FRS was most indicative of underlying CAD (PPV 38.2%).

Conclusion

Masters athletes are not immune to elevated cardiovascular risk and cardiovascular disease. Comprehensive preparticipation screening including an ECG and FRS can detect cardiovascular disease. An exercise stress test should be considered in those with risk factors, regardless of fitness level.
How do trainee doctors introduce themselves to patients?
Authors: Salman Marwa , Tingas Artemis , Yentis Steve M
Published: August 2018

Objectives

To identify how trainee doctors introduce themselves to patients.

Design

Survey.

Setting

Chelsea and Westminster Hospital, London.

Participants

One hundred trainee doctors, of mixed grades and specialties.

Main outcome measures

Introducing oneself by name, using their professional title ‘Dr’, use of the term ‘trainee’.

Results

All 100 participants introduced themselves by name to patients, with 63% using only their first name, 18% using only their last name and 18% using a combination of both. 67% mentioned their specialty and 18% mentioned their training grade. 85% identified themselves as a doctor, but only 22% used their professional title (Dr), and only 6% introduced themselves by name, grade, specialty and title. 80% varied the way they introduced themselves to patients, depending on several factors including the clinical situation and patients’ characteristics/features. 56% said that they had changed the way they introduced themselves over time, and 42% deliberately avoided the term ‘trainee’ during introductions. There was no association between trainees’ age, gender or specialty and their comfort in describing themselves as ‘trainees’, but the more junior trainees were more comfortable using this term than the senior grades (p<0.0001). Overall, 76% disliked the term ‘trainee’, for various reasons.

Conclusion

All doctors in this study introduced themselves by name but the majority did not specify their training grade or trainee status, predominantly because they believed it could trigger anxiety around their competence or undermine confidence in their abilities.
Rheumatoid leptomeningitis presenting with an acute neuropsychiatric disorder
Authors: Lubomski Michal , Sy Joanne , Buckland Michael , Lee Andie S , Richards Bethan , Thompson Elizabeth , Fulham Michael , Breen Nora , Morris Kirsty , Halmagyi G Michael
Published: August 2018

Leptomeningitis is a rare central nervous system manifestation of rheumatoid arthritis, generally in patients with established chronic rheumatoid disease. We report a 41-year-old man without previous rheumatoid arthritis or psychiatric disorder who presented with an acute neuropsychiatric disturbance and polyarthralgia. His MR scan of brain showed asymmetric bifrontal leptomeningitis, confirmed on (18F)-fluoro-D-glucose-positron emission tomography. Other investigations showed highly positive serum and cerebrospinal fluid anti-cyclic citrullinated peptide. A leptomeningeal biopsy showed necrotising leptomeningeal inflammation with ill-defined granulomas and lymphoplasmacytic infiltrate without organisms. Prolonged high-dose corticosteroids and then rituximab resulted in recovery. Chronic leptomeningitis can present with an acute neuropsychiatric disorder. We highlight that early rheumatoid disease can, rarely, cause a chronic leptomeningitis, reversible with immunotherapy.
Acute ibuprofen ingestion does not attenuate fatigue during maximal intermittent knee extensor or all-out cycling exercise
Authors: Morgan Paul T. , Vanhatalo Anni , Bowtell Joanna L. , Jones Andrew M. , Bailey Stephen J.
Published: August 2018

Recent research suggests that acute consumption of pharmacological analgesics can improve exercise performance, but the ergogenic potential of ibuprofen (IBP) administration is poorly understood. This study tested the hypothesis that IBP administration would enhance maximal exercise performance. In one study, 13 physically active males completed 60 × 3-s maximal voluntary contractions (MVCs) of the knee extensors interspersed with 2-s passive recovery periods, on 2 occasions, with the critical torque (CT) estimated as the mean torque over the last 12 contractions (part A). In another study, 16 active males completed two 3-min all-out tests against a fixed resistance on an electronically braked cycle ergometer, with the critical power estimated from the mean power output over the final 30 s of the test (part B). All tests were completed 60 min after ingestion of maltodextrin (placebo, PL) or 400 mg of IBP. Peripheral nerve stimulation was administered at regular intervals and electromyography was measured throughout. For part A, mean torque (IBP: 60% ± 13% of pre-exercise MVC; PL: 58% ± 14% of pre-exercise MVC) and CT (IBP: 41% ± 16% of pre-exercise MVC; PL: 40% ± 15% of pre-exercise MVC) were not different between conditions (P > 0.05). For part B, end-test power output (IBP: 292 ± 28 W; PL: 288 ± 31 W) and work done (IBP: 65.9 ± 5.9 kJ; PL: 65.4 ± 6.4 kJ) during the 3-min all-out cycling tests were not different between conditions (all P > 0.05). For both studies, neuromuscular fatigue declined at a similar rate in both conditions (P > 0.05). In conclusion, acute ingestion of 400 mg of IBP does not improve single-leg or maximal cycling performance in healthy humans.
Genome-wide characterization and expression profiling of diacylglycerol acyltransferase genes from maize
Authors: Yan Bowei , Xu Xiaoxuan , Gu Yingnan , Zhao Ying , Zhao Xunchao , He Lin , Zhao Changjiang , Li Zuotong , Xu Jingyu
Published: August 2018

Diacylglycerol acyltransferase (DGAT) catalyzes the only rate-limiting step in the pathway of plant oil (TAG) biosynthesis and is involved in plant development. In this study, five DGAT family members were identified from maize genome database. Phylogenetic analysis classified the ZmDGATs into type-I, II, and III clusters. Conserved functional domain analysis revealed that the proteins encoded by ZmDGAT1 contained conserved MBOAT domains, while two ZmDGAT2-encoding proteins harbored LPLAT domains. qRT-PCR analysis showed that ZmDGAT genes exhibited very high relative expression in developing seeds, especially at the early stage of seed development. Under various abiotic stress conditions, differential responses of ZmDGAT genes were observed. An overall significant induction of ZmDGAT genes under cold stress in leaves and a quick and strong response to osmotic stresses in roots were highlighted. This study provides useful information for understanding the roles of DGATs in oil accumulation and stress responses in higher plants.
New
40
Ar/
39
Ar dating of the Antrim Plateau Volcanics, Australia: clarifying an age for the eruptive phase of the Kalkarindji continental flood basalt province
Authors: Marshall Peter E. , Halton Alison M. , Kelley Simon P. , Widdowson Mike , Sherlock Sarah C.
Published: August 2018

The Kalkarindji flood basalt province of northern Australia erupted in the mid-Cambrian. Today, the province consists of scattered volcanic and intrusive suites, the largest being the Antrim Plateau Volcanics (APV) in Northern Territory. Accurate dating of the Kalkarindji flood basalt province has proved challenging, with previous studies focused on minor volcanic rocks and intrusive dykes in Northern Territory and Western Australia. These previously published data, corrected to the same decay constants, range from 512.8 to 509.6 ± 2.5 Ma [2σ], placing the Kalkarindji flood basalt province in apparent synchronicity with the Cambrian Stage 4–5 biotic crisis at 510 ± 1 Ma. This study utilizes
40
Ar/
39
Ar dating of basalts from the APV to accurately date the major volcanic eruptions in this province. The results yield an age of 508.0–498.3 ± 5.5 Ma [2σ], indicating that the APV is younger than the intrusive rocks. These dates allude to a relative timing discrepancy, where intrusive activity in the North Australian Craton preceded the eruption of the APV as the last magmatic activity in the region. The determination of these largest eruptions to be later than 510 Ma effectively disassociates the Kalkarindji lavas from being a major cause of the 510 Ma biotic crisis, but cannot definitively discount any deleterious effects on the fragile Cambrian ecosystem.

Supplementary material
:
40
Ar/
39
Ar analysis data tables, XRF geochemical data, alteration study and photomicrographs of all five samples are available at:
https://doi.org/10.6084/m9.figshare.c.4176674
Neural Mechanisms of Motion Processing in the Mammalian Retina
Authors: Wei Wei
Published: August 2018

Visual motion on the retina activates a cohort of retinal ganglion cells (RGCs). This population activity encodes multiple streams of information extracted by parallel retinal circuits. Motion processing in the retina is best studied in the direction-selective circuit. The main focus of this review is the neural basis of direction selectivity, which has been investigated in unprecedented detail using state-of-the-art functional, connectomic, and modeling methods. Mechanisms underlying the encoding of other motion features by broader RGC populations are also discussed. Recent discoveries at both single-cell and population levels highlight the dynamic and stimulus-dependent engagement of multiple mechanisms that collectively implement robust motion detection under diverse visual conditions.
High-fat diet overfeeding promotes nondetrimental liver steatosis in female mice
Authors: Arisqueta Lino , Navarro-Imaz Hiart , Labiano Ibone , Rueda Yuri , Fresnedo Olatz
Published: August 2018

High-fat diet (HFD) feeding or leptin-deficient mice are extensively used as models resembling features of human nonalcoholic fatty liver disease (NAFLD). The concurrence of experimental factors as fat content and source or total caloric intake leads to prominent differences in the development of the hepatic steatosis and related disturbances. In this work, we characterized the hepatic lipid accumulation induced by HFD in wild-type (WT) and ob/ ob mice with the purpose of differentiating adaptations to HFD from those specific of increased overfeeding due to leptin deficiency-associated hyperphagia. Given that most published works have been done in male models, we used female mice with the aim of increasing the body of evidence regarding NAFLD in female subjects. HFD promoted liver lipid accumulation only in the hyperphagic strain. Nevertheless, a decrease of lipid droplet-associated cholesteryl ester (CE) in both WT and obese animals was observed. These changes were accompanied by an improvement in the profile of lipoproteins that transport cholesterol and liver function markers in plasma from ob/ ob mice and a lower hepatic index. Using primary hepatocytes from female mice, overaccumulation of CE induced by 0.4 mM oleic acid reversed in the presence of a specific Takeda G protein-coupled bile acid receptor agonist. Nevertheless, hepatocytes from male mice were not responsive. This study suggests that enterohepatic circulation of bile acids might be one of the factors that can affect sex dimorphism in NAFLD development, which underlines the importance of including female models in the NAFLD research field.

NEW & NOTEWORTHY This work provides new insight into the use of high-fat diet as a model to induce nonalcoholic fatty liver disease in wild-type and ob/ ob female mice. We show that high-fat diet induces steatosis only in ob/ ob mice while, surprisingly, several health indicators improve. Noteworthy, experiments with primary hepatocytes from male and female mice show that they express Takeda G protein-coupled bile acid receptor and that it and bile acid enterohepatic circulation might be accountable for sex dimorphism in nonalcoholic fatty liver disease development.
Ground flaxseed reverses protection of a reduced-fat diet against Citrobacter rodentium-induced colitis
Authors: Määttänen Pekka , Lurz Eberhard , Botts Steven R. , Wu Richard Y. , Yeung C. William , Li Bo , Abiff Sumayyah , Johnson-Henry Kathene C. , Lepp Dion , Power Krista A. , Pierro Agostino , Surette Marc E. , Sherman Philip M.
Published: August 2018

Flaxseed is high in ω-3 polyunsaturated fatty acids, fiber, and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high-fat (HF, ~36%kcal) or reduced-fat (RF, ~12%kcal) diet. After weaning, C57BL/6 mice ( n = 8–15/treatment) were fed ground flaxseed (7 g/100 g diet) with either HF (HF Flx) or RF (RF Flx) diets for 4 wk before infection with C. rodentium or sham gavage. Weight changes, mucosal inflammation, pathogen burden, gut microbiota composition, tissue polyunsaturated fatty acids, and cecal short-chain fatty acids were compared over a 14-day infection period. The RF diet protected against C. rodentium-induced colitis, whereas the RF Flx diet increased pathogen burden, exacerbated gut inflammation, and promoted gut dysbiosis. When compared with the RF diet, both HF and HF Flx diets resulted in more severe pathology in response to C. rodentium infection. Our findings demonstrate that although an RF diet protected against C. rodentium-induced colitis and associated gut dysbiosis in mice, beneficial effects were diminished with ground flaxseed supplementation.

NEW & NOTEWORTHY Our results demonstrate a strong protective effect of a reduced-fat diet against intestinal inflammation, dysbiosis, and pathogen burden during Citrobacter rodentium-induced colitis. However, ground flaxseed supplementation in the setting of a reduced-fat diet exacerbated colitis despite higher levels of intestinal n-3 polyunsaturated fatty acids and cecal short-chain fatty acids.
Leg blood flow and skeletal muscle microvascular perfusion responses to submaximal exercise in peripheral arterial disease
Authors: Meneses Annelise L. , Nam Michael C. Y. , Bailey Tom G. , Magee Rebecca , Golledge Jonathan , Hellsten Ylva , Keske Michelle A. , Greaves Kim , Askew Christopher D.
Published: August 2018

Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. Although leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole leg blood flow and calf muscle microvascular perfusion after cuff occlusion and submaximal leg exercise between patients with PAD ( n = 12, 69 ± 9 yr) and healthy age-matched control participants ( n = 12, 68 ± 7 yr). Microvascular blood flow (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after the following: 1) 5 min of thigh-cuff occlusion, and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400 N) using real-time contrast-enhanced ultrasound. Whole leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Postocclusion whole leg blood flow and calf muscle microvascular perfusion were lower in patients with PAD than control participants, and these parameters were strongly correlated ( r = 0.84, P < 0.01). During submaximal exercise, total whole leg blood flow and vascular conductance were not different between groups. There were also no group differences in postexercise calf muscle microvascular perfusion, although microvascular blood volume was higher in patients with PAD than control participants (12.41 ± 6.98 vs. 6.34 ± 4.98 arbitrary units, P = 0.03). This study demonstrates that the impaired muscle perfusion of patients with PAD during postocclusion hyperemia is strongly correlated with disease severity and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in patients with PAD, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise.

NEW & NOTEWORTHY This study suggests that peripheral arterial disease (PAD) has different effects on the microvascular perfusion responses to cuff occlusion and submaximal leg exercise. Patients with PAD have impaired microvascular perfusion after cuff occlusion, similar to that previously reported after maximal exercise. In response to submaximal exercise, however, the microvascular flow volume response was elevated in patients with PAD compared with control. This finding may reflect a compensatory mechanism to maintain perfusion and oxygen delivery during recovery from exercise.
Cardiac myocyte proliferation and maturation near term is inhibited by early gestation maternal testosterone exposure
Authors: Jonker Sonnet S. , Louey Samantha , Roselli Charles E.
Published: August 2018

Polycystic ovary syndrome is a complex and common disorder in women, and those affected experience an increased burden of cardiovascular disease. It is an intergenerational syndrome, as affected women with high androgen levels during pregnancy “program” fetal development, leading to a similar phenotype in their female offspring. The effect of excess maternal testosterone exposure on fetal cardiomyocyte growth and maturation is unknown. Pregnant ewes received biweekly injections of vehicle (control) or 100 mg testosterone propionate between 30 and 59 days of gestation (early T) or between 60 and 90 days of gestation (late T). Fetuses were delivered at ~135 days of gestation, and their hearts were enzymatically dissociated to measure cardiomyocyte growth (dimensional measurements), maturation (proportion binucleate), and proliferation (nuclear Ki-67 protein). Early T depressed serum insulin-like growth factor 1 and caused intrauterine growth restriction (IUGR; P < 0.0005). Hearts were smaller with early T ( P < 0.001) due to reduced cardiac myocyte maturation ( P < 0.0005) and proliferation ( P = 0.017). Maturation was also lower in male than female fetuses ( P = 0.004) independent of treatment. Late T did not affect cardiac growth. Early excess maternal testosterone exposure depresses circulating insulin-like growth factor 1 near term and causes IUGR in both female and male offspring. These fetuses have small, immature hearts with reduced proliferation, which may reduce cardiac myocyte endowment and predispose to adverse cardiac growth in postnatal life. While excess maternal testosterone exposure leads to polycystic ovary syndrome and cardiovascular disease in female offspring, it may also predispose to complications of IUGR and cardiovascular disease in male offspring.

NEW & NOTEWORTHY Using measurements of cardiac myocyte growth and maturation in an ovine model of polycystic ovary syndrome, this study demonstrates that early gestation excess maternal testosterone exposure reduces near-term cardiomyocyte proliferation and maturation in intrauterine growth-restricted female and male fetuses. The effect of testosterone is restricted to exposure during a specific period early in pregnancy, and the effects appear mediated through reduced insulin-like growth factor 1 signaling. Furthermore, male fetuses, regardless of treatment, had fewer mature cardiomyocytes than female fetuses.
A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
Authors: Enblad Gunilla , Karlsson Hannah , Gammelgård Gustav , Wenthe Jessica , Lövgren Tanja , Amini Rose Marie , Wikstrom Kristina I. , Essand Magnus , Savoldo Barbara , Hallböök Helene , Höglund Martin , Dotti Gianpietro , Brenner Malcolm K. , Hagberg Hans , Loskog Angelica
Published: August 2018

Purpose:

The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19+ B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.

Patients and Methods:

Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.

Results:

Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14+CD33+HLA−DR−) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.

Conclusions:

Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.
Noninvasive Detection of ctDNA Reveals Intratumor Heterogeneity and Is Associated with Tumor Burden in Gastrointestinal Stromal Tumor
Authors: Namløs Heidi M. , Boye Kjetil , Mishkin Skyler J. , Barøy Tale , Lorenz Susanne , Bjerkehagen Bodil , Stratford Eva W. , Munthe Else , Kudlow Brian A. , Myklebost Ola , Meza-Zepeda Leonardo A.
Published: August 2018

Molecular analysis of circulating tumor DNA (ctDNA) has a large potential for clinical application by capturing tumor-specific aberrations through noninvasive sampling. In gastrointestinal stromal tumor (GIST), analysis of KIT and PDGFRA mutations is important for therapeutic decisions, but the invasiveness of traditional biopsies limits the possibilities for repeated sampling. Using targeted next-generation sequencing, we have analyzed circulating cell-free DNA from 50 GIST patients. Tumor-specific mutations were detected in 16 of 44 plasma samples (36%) from treatment-naïve patients and in three of six (50%) patients treated with tyrosine kinase inhibitors. A significant association between detection of ctDNA and the modified National Institutes of Health risk classification was found. All patients with metastatic disease had detectable ctDNA, and tumor burden was the most important detection determinant. Median tumor size was 13.4 cm for patients with detectable mutation in plasma compared with 4.4 cm in patients without detectable mutation (P = 0.006). ctDNA analysis of a patient with disease progression on imatinib revealed that multiple resistance mutations were synchronously present, and detailed analysis of tumor tissue showed that these were spatially distributed in the primary tumor. Plasma samples taken throughout the course of treatment demonstrated that clonal evolution can be monitored over time. In conclusion, we have shown that detection of GIST-specific mutations in plasma is particularly feasible for patients with high tumor burden. In such cases, we have demonstrated that mutational analysis by use of liquid biopsies can capture the molecular heterogeneity of the whole tumor, and may guide treatment decisions during progression. Mol Cancer Ther; 17(11); 2473–80. ©2018 AACR.
Development and Evolution of Cerebral and Cerebellar Cortex
Authors: Van Essen David C. , Donahue Chad J. , Glasser Matthew F.
Published: August 2018

Cerebral cortex and cerebellar cortex both vary enormously across species in their size and complexity of convolutions. We discuss the development and evolution of cortical structures in terms of anatomy and functional organization. We propose that the distinctive shapes of cerebral and cerebellar cortex can be explained by relatively few developmental processes, notably including mechanical tension along axons and dendrites. Regarding functional organization, we show how maps of myelin content in cerebral cortex are evolutionarily conserved across primates but differ in the proportion of cortex devoted to sensory, cognitive, and other functions. We summarize recent progress and challenges in (i) parcellating cerebral cortex into a mosaic of distinct areas, (ii) distinguishing cortical areas that correspond across species from those that are present in one species but not another, and (iii) using this information along with surface-based interspecies registration to gain deeper insights into cortical evolution. We also comment on the methodological challenges imposed by the differences in anatomical and functional organization of cerebellar cortex relative to cerebral cortex.
Case Report: Patient with Hepatitis C, p-ANCA, and Cryoglobulin Antibodies Presenting with Necrotizing Crescentic p-ANCA Glomerulonephritis
Authors: Hanna Ramy M. , So Naomi , Kaldas Marian , Hou Jean , Arman Farid , Sangalang Michelle , Yanny Bishoy , Selamet Umut , Saab Sammy , Nobakht Niloofar , Rastogi Anjay
Published: August 2018

Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in the United States, according to recent Center for Disease Control reports, and can have various renal manifestations. Cryoglobulins, antibodies that precipitate at colder temperatures in vitro, are a relatively common cause of renal disease in HCV infection. The cryoglobulin proteins can form occlusive aggregates in small glomerular capillary lumina or deposit in other areas of the glomerulus, resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The typical biopsy pattern is that of membranoproliferative glomerulonephritis (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti-neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected patients. In many reported cases, ANCA serologic testing may appear positive due to cross-reactivity of the immune assays; however, the biopsy findings do not support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the primary cause of glomerular injury. There are rare reports of microscopic polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies from these HCV-infected patients with concomitant MPA revealed a crescentic GN, associated with normal serum complement levels. We present a case of HCV-associated glomerular disease with the surprising biopsy finding of necrotizing and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in addition to the more typical lesions of MPGN or cryoglobulinemic GN.
Disseminated Strongyloidiasis in Association with Nephrotic Syndrome
Authors: Abdullah Amirahwaty , Winnicka Lydia , Raghu Charumathi , Zeykan Violeta , Singh Jagmeet
Published: August 2018

Strongyloidiasis is a well-known parasitic infection endemic in tropical and subtropical areas of the world. While most infected individuals are asymptomatic, strongyloidiasis-related glomerulopathy has not been well documented. We present a case of disseminated strongyloidiasis in a patient with minimal change nephrotic syndrome treated with high-dose corticosteroids. The remission of nephrotic syndrome after treatment of strongyloidiasis suggests a possible causal relationship between Strongyloides and nephrotic syndrome.
Disassembly of Subplasmalemmal Actin Filaments Induces Cytosolic Ca2+ Increases in Astropecten aranciacus Eggs
Authors: Vasilev Filip , Limatola Nunzia , Park Dae-Ryoung , Kim Uh-Hyun , Santella Luigia , Chun Jong Tai
Published: August 2018

Background/Aims: Eggs of all animal species display intense cytoplasmic Ca2+ increases at fertilization. Previously, we reported that unfertilized eggs of Astropecten aranciacus exposed to an actin drug latrunculin A (LAT-A) exhibit similar Ca2+ waves and cortical flashes after 5-10 min time lag. Here, we have explored the molecular mechanisms underlying this unique phenomenon. Methods: Starfish eggs were pretreated with various agents such as other actin drugs or inhibitors of phospholipase C (PLC), and the changes of the intracellular Ca2+ levels were monitored by use of Calcium Green in the presence or absence of LAT-A. The concomitant changes of the actin cytoskeleton were visualized with fluorescent F-actin probes in confocal microscopy. Results: We have shown that the LAT-A-induced Ca2+ increases are related to the disassembly of actin flaments: i) not only LAT-A but also other agents depolymerizing F-actin (i.e. cytochalasin B and mycalolide B) induced similar Ca2+ increases, albeit with slightly lower efficiency; ii) drugs stabilizing F-actin (i.e. phalloidin and jasplakinolide) either blocked or significantly delayed the LAT-A-induced Ca2+ increases. Further studies utilizing pharmacological inhibitors of PLC (U-73122 and neomycin), dominant negative mutant of PLC-ɣ, specific sequestration of PIP2 (RFP-PH), InsP3 uncaging, and quantitation of endogenous InsP3 all indicated that LAT-A induces Ca2+ increases by stimulating PLC rather than sensitizing InsP3 receptors. In support of the idea, it bears emphasis that LAT-A timely increased intracellular contents of InsP3 with concomitant decrease of PIP2 levels in the plasma membrane. Conclusion: Taken together, our results suggest that suboolemmal actin filaments may serve as a scaffold for cell signaling and modulate the activity of the key enzyme involved in intracellular Ca2+ signaling.
Here and Now: Indigenous Canadian Perspectives and New Media in Works by Ruben Komangapik, Kent Monkman and Adrian Duke
Authors: Myburgh Brittany
Published: August 2018

Examining the use of new media in works by Ruben Komangapik, Kent Monkman and the Wikiup Indigenous Knowledge Network reveals the diverse ways in which technologies are used to disrupt linear time and Western visions of history. New media works challenge those misleading stories that have been told about Canada’s indigenous peoples and assert indigenous presence in both the digital and physical landscape. These artists employ QR codes, video and augmented reality to push artistic boundaries and create representations of the past and present.
Constitutional Patriotism, Moral Sentiment, and International Human Rights
Authors: Krause Sharon R.
Published: August 2018

This essay explores resources for motivating allegiance to international human rights, drawing in particular on the work of Jürgen Habermas and David Hume. It examines the ideal of constitutional patriotism as developed by Habermas and identifies limitations of that ideal in the international context. Hume’s concept of moral sentiment is then examined, specifically its ability to generate an impartial but affectively engaged moral standpoint with the power to motivate action, potentially with a wider reach than that of constitutional patriotism. Finally, the paper shows how a contemporary Hume-inspired form of moral sentiment might interact with and support the deliberative practices through which international human rights are interpreted and applied in practice. It concludes with remarks on the reciprocal relationship between moral sentiment and constitutional patriotism in the realm of human rights.
Rewriting the Legacy of the Turkish Exile of Comparative Literature
Authors: Oruc Firat
Published: August 2018

Numerous critics have revisited the Turkish exile of “the founding fathers” of humanist philology, Erich Auerbach and Leo Spitzer, in the period between the rise of Nazism in Germany and the end of World War II. Yet these recuperative analyses have been centered on the role of the experience of cultural displacement in the intellectual transformation of the émigré scholars. By contrast, this article offers a critical analysis of how the Turkish end of humanism (especially in the case of Auerbach and Spitzer’s students) was entangled with the politics of Kemalist cultural reforms. If comparative literature was “invented” during the Istanbul exile of Spitzer and Auerbach, this article re-writes this invention process by highlighting the semantic and ideological inflections it took in the hands of the Turkish humanists.
Populism in Power: Between Inclusion and Autocracy
Authors: de la Torre Carlos , Peruzzotti Enrique
Published: August 2018

The Latin American historical experience with populist regimes as well as the theoretical reflections produced by Latin Americanists are particularly relevant not just for determining the nature of a very contested political concept but also for understanding the logic of populism in government and the threats it poses to liberal democratic regimes. Populism in government or the attempt at stabilizing a populist regime is no novelty for Latin America, a continent where populism has been a constant presence in politics since the 1930s. Along with their inclusionary impulse, those experiences left a long-lasting troublesome institutional and cultural legacy of political polarization, weak institutions, and recurrent authoritarianism. Populism made a comeback in several countries during the novel democratic period, largely due to the severe crisis that many of the democratic regimes encountered. Inspired by radical democratic ideals, contemporary populism actively engaged in a politics of regime transformation.
The Principal's Duties
Authors: Kirby Byron C.
Published: August 2018

Dividing the principal's activities into organization, social, administrative, and supervisory Mr. Kirby urges that 70 per cent. of the executive's day be given to supervision: He describes a technique for improving instruction.
Tradition Cramps the Curriculum
Authors: Hagie C. E.
Published: August 2018

That we are cramming pupils' minds with consecutive “courses” of uncorrected subject matter, thereby wasting much time and failing to fit children for life, is the contention of this writer.
Character Workshop
Authors: Egan Joseph B.
Published: August 2018

Editor's Note.—“Character Workshop” should be of interest and value to all teachers who are attempting character education. Mr. Egan will develop in this page, from week to week, the underlying philosophy of this phase of educational work, with practical suggestions for immediate use. Schools that have the author's Monthly Service will find in these articles a treatment of correlated matters and, in a sense, an amplification of that service.

You are invited to submit Character Questions to Mr. Egan for consideration in “Character Workshop.”
Books that are Being Talked About
Authors: Belding Mary Allison
Published: August 2018

Each year at this season the Journal of Education offers a selective list of books for non-technical and joyous reading.
The Principal and Supervision
Authors: Kirby Byron C.
Published: August 2018

The efficiency of a school depends mainly upon the principal and his ability to set standards and to secure teamwork.
The Wind that Grew
Authors: Culp V. H.
Published: August 2018

“What this town needs is a new superintendent of schools,” declared the townsfolk. So they got one.
“I Can Read it but Not Talk It”
Authors: Rust Dorothy Ann
Published: August 2018

The writer claims that pupils can and should be taught to SPEAK whatever language they study—even Latin.
Again, those Left-handers
Authors: Clark Robert
Published: August 2018

Lockstep education tried to make everyone righthanded. Today we are awakening to the risks of that attempt.
Thrift Lessons from a Dull Book
Authors: Allen Warner M.
Published: August 2018

A type of institution that teaches better handling of incomes renders truly educational service.
Has Your School a “Toybrary”?
Authors: Rich Frank M.
Published: August 2018

By building up a kit-loan collection you can have materials at hand for for various learning activities.
How about Classes in French?
Authors: Foley Louis
Published: August 2018

The present plight of France itself does not lessen the importance to us of the French language, literature and culture
The Physical Cause of Stammering
Authors: Evans Margaret Towey
Published: August 2018

A Minneapolis speech school proceeds on the theory that tongues as well as feet may have fallen arches.
A Broader Concept of Normalcy
Authors: Garrison Ivan K.
Published: August 2018

As Director of Special Education in the Jacksonville, (Ill.) Public Schools and Editor of Exceptional Children, Ivan Garrison is particularly well qualified to write this article for the JOURNAL OF EDUCATION. He has taught and written extensively on this subject. Fishing, music, and his 9 year old daughter are his chief outside interests.
An Affinity for Learning: Teacher Identity and Powerful Professional Development
Authors: Noonan James
Published: August 2018

Drawing on interviews with a diverse sample of teachers, this study uses the frame of professional identity to interpret the heterogeneity among teachers’ perceptions of professional development. Specifically, it examines how teachers’ “anchoring beliefs” might be reflected in or refracted by their accounts of powerful professional learning. An analysis of three case studies of teacher identity and teacher learning reveals three distinct “learning affinities”: for the what (content), the who (facilitation), and the with whom (community). This learning affinity framework may better model teachers’ experiences of professional development and thus could point the way toward improved research and design.
Mortality, Ethnicity, and Urbanization Among Children Aged 1-4 Years on the US-Mexico Border
Authors: McDonald Jill A. , Brantley Lindsey , Paulozzi Leonard J.
Published: August 2018

Objectives:

Little is known about the mortality of children along the US-Mexico border. The objective of our study was to determine whether mortality rates among Hispanic children along the border (“border Hispanic children”) exceeded mortality rates among non-Hispanic white children along the border.

Methods:

We examined mortality rates from 2001-2015 for children aged 1-4 years in US-Mexico border counties and in the United States overall. We compared mortality rates among Hispanic and non-Hispanic white children by county urbanization level (large central, medium, and small metropolitan; micropolitan nonmetropolitan; and noncore nonmetropolitan).

Results:

During 2001-2015, 1811 children aged 1-4 years died in the border region. The mortality rate per 100 000 children among border Hispanic children (28.3; 95% confidence interval [CI], 26.8-29.9) exceeded the mortality rate of US Hispanic children (24.7; 95% CI, 24.3-25.1) and border non-Hispanic white children (23.2; 95% CI, 20.8-25.6). When stratified by county urbanization level, however, mortality rates of border Hispanic children were not significantly different from mortality rates of US Hispanic or border non-Hispanic white children. Mortality rates in noncore nonmetropolitan counties were twice those in large central metropolitan counties, with injury mortality accounting for most of the excess. Mortality rates increased in nonmetropolitan border counties after 2010.

Conclusions:

Increased risk for injury and disease in noncore nonmetropolitan counties might be related to poverty, reduced access to care, or poorer quality of care. Future research should identify the remediable risk factors in such communities as the next step in preventing deaths among children aged 1-4 years.