bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: An analysis of the National Cancer Database
Authors: Yusuf Mehran B , Gaskins Jeremy , Wall Weston , Tennant Paul , Bumpous Jeffrey , Dunlap Neal
Published: May 2020

Background

Immunosuppressed (IS) patients with Merkel cell carcinoma (MCC) have worse outcomes compared to immunocompetent (IC) patients, and it is unclear if adjuvant radiotherapy (RT) is beneficial for these patients. We sought to determine the effect of immune status on adjuvant RT efficacy regarding overall survival (OS) for patients with localized MCC.

Methods

This was an observational study of National Cancer Database (NCDB) identifying patients with stage I/II or III MCC with known immune status diagnosed from 2010 to 2014. The median follow‐up time was 29 months. OS was described using Kaplan–Meier methods and compared for subgroups by immune status and adjuvant RT using log‐rank tests, multivariable Cox regression and interaction effect testing.

Results

A total of 2049 IC and 255 IS patients were included. Adjuvant RT was associated with decreased hazard of death for stage I/II MCC (HR 0.65, CI 0.54–0.78) adjusting for factors including immune status. Interaction effect testing did not demonstrate a significant difference in the effect of adjuvant RT on OS between IC and IS status in either stage I/II or III MCC (both P values > 0.05).

Conclusions

In this observational study, adjuvant RT was associated with decreased hazard of death for patients with stage I/II MCC regardless of immune status. Adjuvant RT should be considered for both IS and IC patients with localized MCC.
LncRNA HOTAIR enhances breast cancer radioresistance through facilitating HSPA1A expression via sequestering miR‐449b‐5p
Authors: Zhang Shuqin , Wang Bin , Xiao Huiwen , Dong Jiali , Li Yuan , Zhu Changchun , Jin Yuxiao , Li Hang , Cui Ming , Fan Saijun
Published: May 2020

Background

Breast cancer (BRCA) is the leading cause of cancer‐related death in women worldwide. Pre‐ and postoperative radiotherapy play a pivotal role in BRCA treatment but its efficacy remains limited and plagued by the emergence of radiation resistance, which aggravates patient prognosis. The long noncoding RNA (lncRNA)‐implicated mechanisms underlying radiation resistance are rarely reported. The aim of this study was to determine whether lncRNA HOX transcript antisense RNA (HOTAIR) modulated the radiosensitivity of breast cancer through HSPA1A.

Methods

A Gammacell 40 Exactor was used for irradiation treatment. Bioinformatic tools and luciferase reporter assay were adopted to explore gene expression profile and demonstrate the interactions between lncRNA, miRNA and target mRNA 3′‐untranslated region (3′‐UTR). The expression levels of certain genes were determined by real‐time PCR and western‐blot analyses. in vitro and in vivo functional assays were conducted by cell viability and tumorigenicity assays.

Results

The levels of oncogenic lncRNA HOTAIR were positively correlated with the malignancy of BRCA but reversely correlated with the radiosensitivity of breast cancer cells. Moreover, the expression levels of HOTAIR were positively associated with those of heat shock protein family A (Hsp70) member 1A (HSPA1A) in clinical BRCA tissues and HOTAIR upregulated HSPA1A at the mRNA and protein levels in irradiated BRCA cells. Mechanistically, miR‐449b‐5p restrained HSPA1A expression through targeting the 3′‐UTR of HSPA1A mRNA, whereas HOTAIR acted as a competing sponge to sequester miR‐449b‐5p and thereby relieved the miR‐449b‐5p‐mediated HSPA1A repression. Functionally, HOTAIR conferred decreased radiosensitivity on BRCA cells, while miR‐449b‐5p overexpression or HSPA1A knockdown abrogated the HOTAIR‐enhanced BRCA growth under the irradiation exposure both in vitro and in vivo.

Conclusions

LncRNA HOTAIR facilitates the expression of HSPA1A by sequestering miR‐449b‐5p post‐transcriptionally and thereby endows BRCA with radiation resistance.

Key points

Therapeutically, HOTAIR and HSPA1A may be employed as potential targets for BRCA radiotherapy. Our findings shed new light into the mechanism by which lncRNAs modulate the radiosensitivity of tumors.
Progressive dyspnea and diffuse ground‐glass opacities after treatment for lymphoma with rituximab‐containing chemotherapy: A case report
Authors: Sun Yuxin , Shao Chi , Xu Kai , Li Ji , Zhang Ying , Liu Peng , Huang Hui , Feng Ruie
Published: May 2020

A 49‐year‐old man presented to our outpatient clinic complaining of nonproductive cough and exertional dyspnea for two months. He had been diagnosed with large B cell non‐Hodgkin's lymphoma seven months previously, and the tumor had almost disappeared after four cycles of rituximab‐containing chemotherapy. He then developed a severe dry cough, progressive dyspnea and hypoxia two weeks after the fifth cycle. Bilateral diffuse ground‐glass opacities were visible on chest X‐ray. Although the patient's symptoms were ameliorated temporarily after two weeks of methylprednisolone administration and multiple antibiotics, exertional dyspnea had progressed slowly starting one month after discontinuation of the corticosteroid. A repeat chest computed tomography (CT) scan showed diffuse ground‐glass opacities, bronchoalveolar lavage fluid tests for pathogens were negative and the pathological manifestation of the transbronchial lung biopsy showed nonspecific interstitial pneumonia. Rituximab‐induced interstitial lung disease was diagnosed after multidisciplinary discussion. Prednisone was again prescribed and his symptoms and the pulmonary opacities gradually disappeared. Although various pulmonary infections are the most common respiratory complications in patients with non‐Hodgkin's lymphoma undergoing rituximab‐containing chemotherapy, noninfectious diffuse lung disease, eg, drug‐associated interstitial lung disease might be considered as a differential diagnosis of patients treated with rituximab, especially if a patient is nearing the time of administration of a fourth cycle of rituximab.
Life‐threatening pneumonitis after first‐line treatment with osimertinib for primary T790M mutated non‐small cell lung cancer
Authors: Häntschel Maik , Niebling Johannes , Häring Almut , Häring Max‐Felix , Groß Thorben , Horger Marius , Riessen Reimer , Haap Michael , Lewis Richard A , Böckeler Michael , Hetzel Jürgen
Published: May 2020

Epithelial growth factor receptor (EGFR) directed tyrosine kinase inhibitor (TKI) treatment is the standard approach in patients with advanced, EGFR‐mutated non‐small cell lung cancer (NSCLC). Although benefit/risk ratio is favorable for these TKI and side effects are manageable in the vast majority of patients, severe and even life‐threatening side effects have been reported. TKI‐induced interstitial lung disease (ILD) has been reported for single cases in modest severity, predominantly in EGFR‐TKI pretreated patients. Here, we report a case of successful stabilization of a life‐threatening ILD in a de novo T790M mutated NSCLC during first‐line treatment with osimertinib. As osimertinib will be used more often in many EGFR‐positive NSCLC patients in the future, this potentially life‐threatening side effect should receive special attention, especially in first‐line treatment.
Stuck in the Tearoom: Facial Reconstruction and Postapartheid Headache
Authors: Schramm Katharina
Published: May 2020

This article examines a project of facial reconstruction of human remains from an archaeological excavation that took place in 1994 in the inner city of Cape Town, South Africa. The initiators of the project envisioned it as an opportunity to translate the power of scientific knowledge to a lay audience, conveying a postapartheid, postracial vision of unity in diversity. However, this translation failed, and the faces got stuck in limbo. I demonstrate how the logic of face resisted a linear translation whereby past could be juxtaposed with present, death with “bringing back to life,” or slavery, colonialism, and apartheid with a new nonracial democracy. Instead, all these different temporalities were collapsed in the practice of face‐making and the politics surrounding it. I argue that it is important to pay attention to such failed translation as an avenue to understanding race as an ongoing and troubling matter of concern. [facial reconstruction, race trouble, Indigenous human remains, postapartheid South Africa]
A Colonial‐Scientific Interface: The Construction, Viewing, and Circulation of Faces via a 1906 German Racial Atlas
Authors: Mak Geertje
Published: May 2020

Atlases of anthropometric portraits—a scientific genre that emerged during the last quarter of the nineteenth century in the context of classical physical anthropology—invite readers to compare different races from all over the world. Concentrating on Bernard Hagen's Atlas of Heads and Faces of Asian and Melanesian People (1906), this article describes the apparatus that enabled such a way of viewing. A microanalysis of Hagen's facial atlas reveals the circumstances under which the portraits were produced, the reading strategies the atlas stimulates, as well as the reification of data through their circulation. It shows how precisely a facial atlas could function as an imperceptible interface between harsh colonial practices and German public support for colonizing “missions,” between individual subjectivity and racialized category, and between everyday colonial recognition and scientific analysis of “races.” Obscuring the apparatus facilitating such a vision naturalizes the position of a viewer surveying, analyzing, and comparing people of different geographic backgrounds as races. [colonial history, photography, face, racial science, Dutch East Indies]
Pain is frequent in children with cerebral palsy and negatively affects physical activity and participation
Authors: Østergaard Cecilie Schmidt , Pedersen Nanna Sofie Astrup , Thomasen Anne , Mechlenburg Inger , Nordbye‐Nielsen Kirsten
Published: May 2020

Aim

The aim was to identify the prevalence of long‐lasting pain among children with cerebral palsy (CP) and to investigate the association between pain and participation in physical leisure activities.

Methods

This is a cross‐sectional study based on data from the National Danish Clinical Quality Database of children with CP. The study population consisted of 960 children aged 2‐11 years across all Gross Motor Function Classification System (GMFCS) levels. Data were collected at children’s regular clinical visits in 2016 or 2017. Information about pain and participation in physical leisure activities were obtained. The association was estimated as odds ratios (OR) and 95% confidence intervals (95% CI) by logistic regression adjusted for age and sex.

Results

We included data from 817 children (59% boys) median age 6 years, 52% classified as GMFCS level I. A total of 36% reported pain, and the most frequent pain locations were hips, feet and knees. Children reporting pain had lower odds for participation in physical leisure activities (OR 0.71, 95% CI 0.53‐0.96).

Conclusion

A large proportion of children with CP reported pain. There is an indication that long‐lasting pain influences participation in physical leisure activities. Pain‐relieving interventions are important to decrease pain‐related suffering and facilitate participation.
The signaling effect of ambidexterity of social enterprises on acquiring financial resources in South Korea
Authors: Lim Chang Gue , Lee Sang‐Youn , Seo Jinseon
Published: May 2020

Financial resources are critical for any young social enterprise. This study investigates the impact of social and economic signals on those social enterprises receiving loans from a social finance institution. Analysis of a sample of 109 social enterprises in South Korea showed that social entrepreneurship and management capabilities at the CEO level, and the corporate pursuit of social values and validity of business plans at the firm level, have a positive impact on getting loans approved by a social finance institution. We also found that those social enterprises that perform well on both social and economic dimensions, namely ambidextrous enterprises, are at a disadvantage when it comes to securing loan approval. Such a trade‐off is counterintuitive, making the financial resource strategies and consequent signals of social enterprises more complicated than previously assumed.
Nonalcoholic fatty liver disease progression rates to cirrhosis and progression of cirrhosis to decompensation and mortality: a real world analysis of Medicare data
Authors: Loomba Rohit , Wong Robert , Fraysse Jeremy , Shreay Sanatan , Li Suying , Harrison Stephen , Gordon Stuart C.
Published: May 2020

Background

Risk factors and timing associated with disease progression and mortality in nonalcoholic fatty liver disease (NAFLD) are poorly understood.

Aims

To evaluate the impact of disease severity, demographics and comorbidities on risk of mortality and time to progression in a large, real‐world cohort of diagnosed NAFLD patients.

Methods

Claims data from a 20% Medicare representative sample between 2007 and 2015 were analysed retrospectively. Adults were categorised into disease severity groups: NAFLD/nonalcoholic steatohepatitis (NASH) alone, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma. Cumulative incidence of mortality and disease progression were calculated for each group and multivariate analyses performed adjusting for demographics, comorbidities and disease severity.

Results

A total of 10 826 456, patients were assessed and the prevalence of NAFLD was 5.7% (N = 621 253). Among patients with NAFLD, 71.1% had NAFLD/NASH alone and 28.9% had NAFLD cirrhosis. Overall, 85.5% of patients had hypertension, 84.1% dyslipidemia, 68.7% had cardiovascular disease and 55.5% diabetes. The cumulative risk of progression of NAFLD to cirrhosis, and compensated cirrhosis to decompensated cirrhosis was 39% and 45%, respectively, over 8 years of follow‐up. The independent predictors of progression included cardiovascular disease, renal impairment, dyslipidemia and diabetes. The cumulative risk of mortality for NAFLD, NAFLD cirrhosis, decompensated cirrhosis and hepatocellular carcinoma was 12.6%, 31.1%, 51.4% and 76.2%, respectively.

Conclusions

The present report (a) demonstrates that NAFLD is grossly underdiagnosed in real‐world clinical settings and (b) provides new evidence on the progression rates of NAFLD and risk factors of mortality across the spectrum of severity of NAFLD and cirrhosis.
Letter: intestinal inflammation, COVID‐19 and gastrointestinal ACE2—exploring RAS inhibitors
Authors: Garg Mayur , Royce Simon G. , Lubel John S.
Published: May 2020

LINKED CONTENT

This article is linked to Taxonera et al papers. To view these articles, visit
https://doi.org/10.1111/apt.15804 and https://doi.org/10.1111/apt.15893.
Scientifically based combination therapies with immuno‐oncology checkpoint inhibitors
Authors: Chew Hui Yi , Dolcetti Riccardo , Simpson Fiona
Published: May 2020

The discovery of immune checkpoints and their role in modulating immune response have revolutionised cancer treatment in recent years. The immune checkpoints, cytotoxic T‐lymphocyte‐associated protein 4, programmed cell death protein 1 and its ligand, programmed cell death‐ligand 1, have been extensively studied. Currently 7 monoclonal antibodies targeting these immune checkpoints are approved for treatment of various cancers. Inhibiting immune checkpoints has shown some success in clinic, however, a proportion of patients do not benefit from this treatment. Several other inhibitory molecules, in addition to lymphocyte‐associated protein 4 and programmed cell death protein 1, are known to be involved in regulating immune response. To further improve patient outcomes, studies have examined targeting these inhibitory molecules through combination therapies. This review discusses the current landscape of combination therapies of checkpoint inhibitors.
Reporting rates of adverse reactions to specialty care medicines exhibit a direct positive correlation with patient exposure: A lack of evidence for the Weber effect
Authors: Modgill Vikas , Dormegny Léa , Lewis David J.
Published: May 2020

Aims

The classical Weber effect describes an increase in adverse reaction (AR) reports after medicinal product authorisation, with a peak in AR reporting at the end of the second year followed by a decline, despite increasing patient exposure. The present study aimed to evaluate the validity of the Weber effect in the context of authorised medicines in a specialty care setting.

Methods

Using 6‐monthly sales data as a proxy for exposure, the exposure–adjusted reporting rates for AR reports for 10 selected specialty care medicines were plotted against time. These data were also evaluated based on the source of report (solicited or unsolicited) and the nature of the AR contained within the reports (listed or unlisted). Unsolicited reports were analysed against sales volumes. Goodness of fit (R2) was calculated and the trend representing the highest R2 was selected.

Results

Study data comprised a total of 1 222 852 AR reports for 10 specialty care medicines. Amongst all of the products evaluated, none of the associated data represented reporting patterns entirely consistent with the classical Weber effect (see Figure 1). The results, however, showed a systemic direct correlation between AR reporting and sales volumes, especially throughout the first 5 years post‐authorisation.

Conclusion

The study not only presents evidence of the absence of the Weber effect with specialty care medicines but also provides a substantial evidence of linear AR reporting correlating with sales volumes, especially during the first 5 years after marketing.
Practical guidance for the management of adults with immune thrombocytopenia during the COVID‐19 pandemic
Authors: Pavord Sue , Thachil Jecko , Hunt Beverley J. , Murphy Mike , Lowe Gillian , Laffan Mike , Makris Mike , Newland Adrian C. , Provan Drew , Grainger John D. , Hill Quentin A.
Published: May 2020

This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID‐19 pandemic. The intention is to support clinicians and, although recommendations have been provided, it is not a formal guideline. Nor is there sufficient evidence base to conclude that alternative approaches to treatment are incorrect. Instead, it is a consensus written by clinicians with an interest in ITP or coagulation disorders and reviewed by members of the UK ITP forum.
Accelerating Liquid Simulation With an Improved Data‐Driven Method
Authors: Gao Yang , Zhang Quancheng , Li Shuai , Hao Aimin , Qin Hong
Published: May 2020

In physics‐based liquid simulation for graphics applications, pressure projection consumes a significant amount of computational time and is frequently the bottleneck of the computational efficiency. How to rapidly apply the pressure projection and at the same time how to accurately capture the liquid geometry are always among the most popular topics in the current research trend in liquid simulations. In this paper, we incorporate an artificial neural network into the simulation pipeline for handling the tricky projection step for liquid animation. Compared with the previous neural‐network‐based works for gas flows, this paper advocates new advances in the composition of representative features as well as the loss functions in order to facilitate fluid simulation with free‐surface boundary. Specifically, we choose both the velocity and the level‐set function as the additional representation of the fluid states, which allows not only the motion but also the boundary position to be considered in the neural network solver. Meanwhile, we use the divergence error in the loss function to further emulate the lifelike behaviours of liquid. With these arrangements, our method could greatly accelerate the pressure projection step in liquid simulation, while maintaining fairly convincing visual results. Additionally, our neutral network performs well when being applied to new scene synthesis even with varied boundaries or scales.
The effect of glucagon‐like peptide‐1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials
Authors: Leiter Lawrence A. , Bain Stephen C. , Bhatt Deepak L. , Buse John B. , Mazer C. David , Pratley Richard E. , Rasmussen Søren , Ripa Maria Sejersten , Vrazic Hrvoje , Verma Subodh
Published: May 2020

It is unknown if the cardioprotective and renal effects of glucagon‐like peptide‐1 receptor agonists are consistent across blood pressure (BP) categories in patients with type 2 diabetes and at high risk of cardiovascular events. Using data from the LEADER (9340 patients) and SUSTAIN 6 (3297 patients) trials, we evaluated post hoc the cardiorenal effect of liraglutide and semaglutide on major adverse cardiovascular events (MACE) and nephropathy by baseline BP categories using a Cox proportional hazards model (treatment and subgroup as factors; adjusted for cardiorenal risk factors). Data from the two trials were analysed separately. In the LEADER and SUSTAIN 6 trials, the prevalence of stage 1 hypertension was 30% and 31%, respectively, and of stage 2 hypertension 41% and 43%, respectively. There was no statistical heterogeneity across the BP categories for the effects of liraglutide (P = .06 for MACE; P = .14 for nephropathy) or semaglutide (P = .40 for MACE; P = .27 for nephropathy) versus placebo. This implies that liraglutide and semaglutide may be beneficial for patients with type 2 diabetes, irrespective of their baseline BP.
Hypocalcaemia predicts 12‐month re‐hospitalization in heart failure
Authors: Liu Feng , Zhang Han , Li Yanming , Lu Xueli
Published: May 2020

Background

Potential pathophysiology of heart failure with preserved ejection fraction (HFpEF) has not been fully explored. The aim of the study was to reveal the association of serum calcium concentration at baseline with 12‐month clinical outcome in the disease.

Materials and methods

A total of 350 patients with newly diagnosed HFpEF were included in this prospective observational study. There were no malignant tumour, kidney disease, thyroid disease, calcium and vitamin D supplements in the patients. All of them received 12‐month follow‐up, and endpoints were cardiac re‐hospitalization and death. Baseline serum calcium concentration was measured using AIA2000ST enzyme immunoassay analyser. Cardiopulmonary exercise, six‐minute walk distance test, EQ5D questionnaire and cardiac ultrasound were performed to evaluate exercise capacity, quality of life and left ventricle function.

Results

Multivariate COX regression analysis revealed that baseline hypocalcaemia was associated with the increased risk of cardiac re‐hospitalization and death during the follow‐up period (HR: 2.10, 95% CI: 1.69‐2.61; HR: 8.26, 95% CI: 2.88‐23.70). Furthermore, baseline hypocalcaemia was related to the deterioration of 6‐minute walk distance, quality of life score (EQ‐5D), right quadriceps strength, left atrium volume index and left ventricular ejection fraction during the follow‐up period (HR: 1.65, 95% CI: 1.21‐2.26; HR: 1.55, 95% CI: 1.12‐2.11; HR: 2.56, 95% CI: 1.68‐3.89; HR: 1.44, 95% CI: 1.03‐1.98; HR: 1.36, 95% CI: 1.02‐1.80).

Conclusion

Baseline hypocalcaemia predicted 12‐month cardiac re‐hospitalization and death in HFpEF patients without calcium and vitamin D supplements partly through left ventricle and skeletal muscle function pathways.
Evaluating Content‐Related Validity Evidence Using a Text‐Based Machine Learning Procedure
Authors: Anderson Daniel , Rowley Brock , Stegenga Sondra , Irvin P. Shawn , Rosenberg Joshua M.
Published: May 2020

Validity evidence based on test content is critical to meaningful interpretation of test scores. Within high‐stakes testing and accountability frameworks, content‐related validity evidence is typically gathered via alignment studies, with panels of experts providing qualitative judgments on the degree to which test items align with the representative content standards. Various summary statistics are then calculated (e.g., categorical concurrence, balance of representation) to aid in decision‐making. In this paper, we propose an alternative approach for gathering content‐related validity evidence that capitalizes on the overlap in vocabulary used in test items and the corresponding content standards, which we define as textual congruence. We use a text‐based, machine learning model, specifically topic modeling, to identify clusters of related content within the standards. This model then serves as the basis from which items are evaluated. We illustrate our method by building a model from the Next Generation Science Standards, with textual congruence evaluated against items within the Oregon statewide alternate assessment. We discuss the utility of this approach as a source of triangulating and diagnostic information and show how visualizations can be used to evaluate the overall coverage of the content standards across the test items.
Cognitive disturbances in the cuprizone model of multiple sclerosis
Authors: Kopanitsa Maksym V. , Lehtimäki Kimmo K. , Forsman Markku , Suhonen Ari , Koponen Juho , Piiponniemi Tuukka O. , Kärkkäinen Anna‐Mari , Pavlidi Pavlina , Shatillo Artem , Sweeney Patrick J. , Merenlender‐Wagner Avia , Kaye Joel , Orbach Aric , Nurmi Antti
Published: May 2020

Cognitive problems frequently accompany neurological manifestations of multiple sclerosis (MS). However, during screening of preclinical candidates, assessments of behaviour in mouse models of MS typically focus on locomotor activity. In the present study, we analysed cognitive behaviour of 9 to 10‐week‐old female C57Bl/6J mice orally administered with the toxin cuprizone that induces demyelination, a characteristic feature of MS. Animals received 400 mg/kg cuprizone daily for 2 or 4 weeks, and their performance was compared with that of vehicle‐treated mice. Cuprizone‐treated animals showed multiple deficits in short touchscreen‐based operant tasks: they responded more slowly to visual stimuli, rewards and made more errors in a simple rule‐learning task. In contextual/cued fear conditioning experiments, cuprizone‐treated mice showed significantly lower levels of contextual freezing than vehicle‐treated mice. Diffusion tensor imaging showed treatment‐dependent changes in fractional anisotropy as well as in axial and mean diffusivities in different white matter areas. Lower values of fractional anisotropy and axial diffusivity in cuprizone‐treated mice indicated developing demyelination and/or axonal damage. Several diffusion tensor imaging measurements correlated with learning parameters. Our results show that translational touchscreen operant tests and fear conditioning paradigms can reliably detect cognitive consequences of cuprizone treatment. The suggested experimental approach enables screening novel MS drug candidates in longitudinal experiments for their ability to improve pathological changes in brain structure and reverse cognitive deficits.
Associations of childcare type, age at start, and intensity with body mass index trajectories from 10 to 42 years of age in the 1970 British Cohort Study
Authors: Costa Silvia , Bann David , Benjamin‐Neelon Sara E. , Adams Jean , Johnson William
Published: May 2020

Background

Attending childcare is related to greater childhood obesity risk, but there are few long‐term follow‐up studies. We aimed to examine the associations of childcare type, age at start, and intensity with body mass index body mass index (BMI) trajectories from ages 10 to 42 years.

Methods

The sample comprised 8234 individuals in the 1970 British Cohort Study, who had data on childcare attendance (no, yes), type (formal, informal), age at start (4‐5, 3‐3.99, 0‐2.99 years old), and intensity (1, 2, 3, 4‐5 days/week) reported at age 5 years and 32 563 BMI observations. Multilevel linear spline models were used to estimate the association of each exposure with the sample‐average BMI trajectory, with covariate adjustment. A combined age at start and intensity exposure was also examined.

Results

Attending vs not attending and the type of childcare (none vs formal/informal) were not strongly related to BMI trajectories. Among participants who attended childcare 1 to 2 days a week, those who started when 3 to 3.99 years old had a 0.197 (−0.004, 0.399) kg/m2 higher BMI at age 10 years than those who started when 4 to 5 years old, and those who started when 0 to 2.99 years old had a 0.289 (0.049, 0.529) kg/m2 higher BMI. A similar dose‐response pattern for intensity was observed when holding age at start constant. By age 42 years, individuals who started childcare at age 0 to 2.99 years and attended 3 to 5 days/week had a 1.356 kg/m2 (0.637, 2.075) higher BMI than individuals who started at age 4 to 5 years and attended 1 to 2 days/week.

Conclusions

Children who start childcare earlier and/or attend more frequently may have greater long‐term obesity risk.
Phase equilibria in the Fe‐V‐O system near “FeO”‐V2O3 isopleth
Authors: Xie Wei , Xing Xianran , Cao Zhanmin
Published: May 2020

Phase equilibria in the “FeO”‐V2O3 system from 1273 to 1808 K and in the range of oxygen partial pressure from 10−15 to 10−4 atm are investigated. High‐temperature quenching, XRD, SEM‐EDS, and DSC are used to determine the phase relations. Stable regions of (FeO)s.s., (V2O3)s.s., and spinel phases are considerably effected by the oxygen partial pressure, and structural models are proposed as (Fe2+, Fe3+, V2+)1‐xO, (V2+, V3+, V4+, Fe3+)2O3+x, and (Fe2+, Fe3+, V3+)(Fe2+, Fe3+, V3+, Va)2O4. Continuous solid solution FeV2O4‐Fe3O4 is formed. The nonstoichiometry of FeV2O4 is attributed to the appearance of vanadium vacancies for electroneutrality due to the oxidation of Fe2+. The standard Gibbs energy of formation for FeV2O4 and component activities in FeV2O4‐Fe3O4 solid solution at 1623 and 1773 K are derived based on the equilibrium oxygen partial pressure. The cation distribution in FeV2O4 at different temperatures is obtained according to site preference energy.
Calcitonin gene‐related peptide inhibits angiotensin II‐induced NADPH oxidase‐dependent ROS via the Src/STAT3 signalling pathway
Authors: Luo Hong‐min , Wu Xia , Xian Xian , Wang Lu‐yao , Zhu Liang‐yu , Sun Hong‐yu , Yang Lei , Liu Wen‐xuan
Published: May 2020

We had previously demonstrated that the calcitonin gene‐related peptide (CGRP) suppresses the oxidative stress and vascular smooth muscle cell (VSMC) proliferation induced by vascular injury. A recent study also indicated that CGRP protects against the onset and development of angiotensin II (Ang II)‐induced hypertension, vascular hypertrophy and oxidative stress. However, the mechanism behind the effects of CGRP on Ang II‐induced oxidative stress is unclear. CGRP significantly suppressed the level of reactive oxygen species (ROS) generated by NADPH oxidase in Ang II‐induced VSMCs. The Ang II‐stimulated activation of both Src and the downstream transcription factor, STAT3, was abrogated by CGRP. However, the antioxidative effect of CGRP was lost following the expression of constitutively activated Src or STAT3. Pre‐treatment with H‐89 or CGRP8–37 also blocked the CGRP inhibitory effects against Ang II‐induced oxidative stress. Additionally, both in vitro and in vivo analyses show that CGRP treatment inhibited Ang II‐induced VSMC proliferation and hypertrophy, accompanied by a reduction in ROS generation. Collectively, these results demonstrate that CGRP exhibits its antioxidative effect by blocking the Src/STAT3 signalling pathway that is associated with Ang II‐induced VSMC hypertrophy and hyperplasia.
Validation process of a high‐resolution database in a paediatric intensive care unit—Describing the perpetual patient's validation
Authors: Mathieu Audrey , Sauthier Michael , Jouvet Philippe , Emeriaud Guillaume , Brossier David
Published: May 2020

Rationale

High data quality is essential to ensure the validity of clinical and research inferences based on it. However, these data quality assessments are often missing even though these data are used in daily practice and research.

Aims and objectives

Our objective was to evaluate the data quality of our high‐resolution electronic database (HRDB) implemented in our paediatric intensive care unit (PICU).

Methods

We conducted a prospective validation study of a HRDB in a 32‐bed paediatric medical, surgical, and cardiac PICU in a tertiary care freestanding maternal‐child health centre in Canada. All patients admitted to the PICU with at least one vital sign monitored using a cardiorespiratory monitor connected to the central monitoring station.

Results

Between June 2017 and August 2018, data from 295 patient days were recorded from medical devices and 4645 data points were video recorded and compared to the corresponding data collected in the HRDB. Statistical analysis showed an excellent overall correlation (R2 = 1), accuracy (100%), agreement (bias = 0, limits of agreement = 0), completeness (2% missing data), and reliability (ICC = 1) between recorded and collected data within clinically significant pre‐defined limits of agreement. Divergent points could all be explained.

Conclusions

This prospective validation of a representative sample showed an excellent overall data quality.
Erythrosine B (Red Dye No. 3): A potential photosensitizer for the photodynamic inactivation of foodborne pathogens in tomato juice
Authors: Cho Ga‐Lam , Ha Jae‐Won
Published: May 2020

The objectives of this study were to evaluate the efficacy of erythrosine B (ERY, Red No. 3)‐mediated photodynamic therapy (PDT) for inactivating Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes in tomato juice. The inoculated tomato juice was subjected to xenon light (E − L+), ERY (E + L−), or xenon light and ERY combination (E + L+) treatments. Treatment with E + L+ for 15 min decreased the cell counts of E. coli O157:H7, S. Typhimurium, and L. monocytogenes by 6.77, 2.74, and 6.43 log CFU/mL, respectively, without generating sublethally injured cells. The cell count reductions of E. coli O157:H7 and L. monocytogenes in the E + L+ treatment group were higher than the sum of cell count reductions in the E − L+ and E + L− treatment groups, which indicated the synergistic activity of the treatment combination. The T3d and T5d values calculated by the Weibull model indicated that S. Typhimurium exhibited higher resistance to the E + L+ treatment than the other two pathogens. Compared with control group, the E + L+ treatment group exhibited higher lycopene content and a* (red) value, whereas the pH value and sensory attributes were not significantly (p > .05) altered. These results suggest that ERY‐mediated PDT can be potentially applied to control foodborne pathogens in tomato juice products without negatively affecting the product quality.
Transforming Undergraduate Student Perceptions of Dementia through Music and Filmmaking
Authors: Gubner Jennie , Smith Alexander K. , Allison Theresa A.
Published: May 2020

BACKGROUND

With nearly 6 million people with dementia (PWD) in the United States, there is a critical need to build an interprofessional dementia workforce. Among the novel approaches to expanding a new workforce, music and the arts show promise for engaging students and trainees. To understand how and why the arts affect attitudes about and engagement with PWD, we examined a service‐learning general education undergraduate course centering on music, filmmaking, and dementia.

METHODS

The undergraduate course curriculum brought students to meet with PWD in dementia care settings, build personalized music playlists, coproduce short films about PWD, and write reflective essays. Two researchers independently completed inductive thematic analysis of the films, essays, and course evaluations. Differences were reconciled by consensus.

RESULTS

A total of 52 students from three classes completed the course; 24 (46%) were majoring in health sciences. Three key themes emerged: (1) Music helps students connect with people living with dementia in meaningful ways; (2) filmmaking offers students the opportunity to share unique, person‐centered stories about dementia and music that empower the voices of PWD; and (3) reflective writing enables students to process new experiences and lessons learned. Unexpectedly, 29 students (56%) reported continued engagement with PWD in their careers, families, and communities after course completion.

CONCLUSION

This study identifies reproducible ways in which undergraduate arts courses thematically focused on dementia not only transform student perceptions about dementia but change the ways in which those students choose to engage with PWD following course completion. Arts and music departments may represent an untapped resource for building a geriatrics workforce. J Am Geriatr Soc 68:1083–1089, 2020
Choosing Inpatient vs Home Treatment: Why Patients Accept or Decline Hospital at Home
Authors: Saenger Pamela , Federman Alex D. , DeCherrie Linda V. , Lubetsky Sara , Catalan Elisse , Leff Bruce , Siu Albert L.
Published: May 2020

BACKGROUND/OBJECTIVES

Hospital at home (HaH) provides interdisciplinary acute care in the home as a substitute for inpatient hospitalization. Studies have demonstrated that HaH care is associated with better quality care, fewer complications, and better patient and caregiver experience. Still, some patients decline HaH. The objective of the study was to characterize patients who accept vs decline HaH care and describe reasons for their decisions in the context of a Center for Medicare and Medicaid Innovation demonstration of HaH.

DESIGN/SETTING/PARTICIPANTS

A total of 442 patients with Medicare or other eligible insurance, 18 years or older, who met study eligibility criteria were offered HaH at Mount Sinai Hospitals in New York, NY, between September 1, 2014, and August 31, 2017.

MEASUREMENTS

Reasons for accepting or declining HaH were recorded. Age, sex, insurance type, and admission diagnoses of HaH acceptors and refusers were compared in univariate analyses.

RESULTS

Of the 442 patients offered HaH, 66.7% accepted. Main reasons for enrolling in HaH included being more comfortable at home (78.2%) and being near family (40.7%). Specific reasons given for refusing HaH included preferring in‐hospital care (15.0%) and concern that HaH would not meet care needs (12.9%).

CONCLUSION

Two‐thirds of patients offered HaH care opted to receive it. The reasons for declining HaH provided by those who chose not to participate should be considered for quality improvement, and reasons for acceptance may be helpful in marketing and other efforts to promote HaH participation. J Am Geriatr Soc 68:1579‐1583, 2020.
Why Dementia‐Specific Advance Directives Are a Misguided Idea
Authors: Sulmasy Daniel P.
Published: May 2020

This is a response to the article by Susan Merel
Tumour biomarkers: association with heart failure outcomes
Authors: Shi C. , van der Wal H. H. , Silljé H. H. W. , Dokter M. M. , van den Berg F. , Huizinga L. , Vriesema M. , Post J. , Anker S. D. , Cleland J. G. , Ng L. L. , Samani N. J. , Dickstein K. , Zannad F. , Lang C. C. , van Haelst P. L. , Gietema J. A. , Metra M. , Ameri P. , Canepa M. , van Veldhuisen D. J. , Voors A. A. , de Boer R. A.
Published: May 2020

Background

There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics.

Objectives

To explore the association between tumour biomarkers and HF outcomes.

Methods

In 2,079 patients of BIOSTAT‐CHF cohort, we measured six established tumour biomarkers: CA125, CA15‐3, CA19‐9, CEA, CYFRA 21‐1 and AFP.

Results

During a median follow‐up of 21 months, 555 (27%) patients reached the primary end‐point of all‐cause mortality. CA125, CYFRA 21‐1, CEA and CA19‐9 levels were positively correlated with NT‐proBNP quartiles (all P < 0.001, P for trend < 0.001) and were, respectively, associated with a hazard ratio of 1.17 (95% CI 1.12–1.23; P < 0.0001), 1.45 (95% CI 1.30–1.61; P < 0.0001), 1.19 (95% CI 1.09–1.30; P = 0.006) and 1.10 (95% CI 1.05–1.16; P < 0.001) for all‐cause mortality after correction for BIOSTAT risk model (age, BUN, NT‐proBNP, haemoglobin and beta blocker). All tumour biomarkers (except AFP) had significant associations with secondary end‐points (composite of all‐cause mortality and HF hospitalization, HF hospitalization, cardiovascular (CV) mortality and non‐CV mortality). ROC curves showed the AUC of CYFRA 21‐1 (0.64) had a noninferior AUC compared with NT‐proBNP (0.68) for all‐cause mortality (P = 0.08). A combination of CYFRA 21‐1 and NT‐proBNP (AUC = 0.71) improved the predictive value of the model for all‐cause mortality (P = 0.0002 compared with NT‐proBNP).

Conclusions

Several established tumour biomarkers showed independent associations with indices of severity of HF and independent prognostic value for HF outcomes. This demonstrates that pathophysiological pathways sensed by these tumour biomarkers are also dysregulated in HF.
Cerebral Perfusion Does Not Increase after Shunt Surgery for Normal Pressure Hydrocephalus
Authors: Virhammar Johan , Ahlgren André , Cesarini Kristina G. , Laurell Katarina , Larsson Elna‐Marie
Published: May 2020

BACKGROUND AND PURPOSE

Cerebral blood flow (CBF) has been reported to increase after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). The aims of this study were to investigate if CBF, measured using the noninvasive perfusion MRI method arterial spin labeling (ASL), increased after shunt surgery, if postoperative change in CBF correlated with improvement in symptoms, and if baseline CBF data correlated with postoperative outcome.

METHODS

Twenty‐three patients with iNPH were prospectively included and examined with MRI of the brain and clinical tests of symptoms at baseline. Eighteen of the patients were treated with shunt implantation and were reexamined with clinical tests and MRI 3 months postoperatively. The MRI protocol included a pseudo‐continuous ASL sequence for perfusion imaging. The perfusion was measured in 12 manually drawn regions of interest (ROIs).

RESULTS

In the whole sample, CBF did not increase after shunting in any ROI. Preoperative CBF in medial frontal cortex correlated with an improvement in urinary incontinence after shunt surgery, r = .53, P = .022. There were no correlations between change in CBF and change in clinical symptoms postoperatively.

CONCLUSIONS

The clinical value of ASL in the work‐up of patients with iNPH is uncertain. In this study, ASL could not predict outcome after shunt surgery and there were no correlations between change in CBF and change in clinical symptoms after shunt surgery.
Activity of four nematicides against Meloidogyne incognita race 2 on tomato plants
Authors: Yue Xiangguo , Li Fahui , Wang Bingtai
Published: May 2020

Meloidogyne incognita is one of the most important causes of disease in protected vegetable cultivation in North China Plain, but chemical control options for it are currently limited. In the present study, we measured activity of four nematicides with M. incognita race 2 in the laboratory and greenhouse pots. Fluensulfone and fluopyram had a greater negative effect on the motility of M. incognita second‐stage juveniles (J2) than avermectin B1a (AV‐B1a) and fosthiazate had, especially at low concentration, with respective EC50 values of 0.29, 0.13, 0.68 and 2.48 mg/L. AV‐B1a significantly and uniquely inhibited egg hatching, which indicated that it was the only nematicide that could readily be transported across the eggshell. In greenhouse pots, fluensulfone (10 mg−1) and fluopyram (1 and 10 mg−1) caused the greatest inhibition of formation of galls in tomato roots, with decreases of 98.6%, 96.2% and 99.2%, respectively. This indicated that some M. incognita J2 lost their root penetration ability without losing their motility.
Patient‐specific finite element models of the human mandible: Lack of consensus on current set‐ups
Authors: Merema Bram Barteld Jan , Kraeima Joep , Glas Haye H. , Spijkervet Fred K. L. , Witjes Max J. H.
Published: May 2020

The use of finite element analysis (FEA) has increased rapidly over the last decennia and has become a popular tool to design implants, osteosynthesis plates and prostheses. With increasing computer capacity and the availability of software applications, it has become easier to employ the FEA. However, there seems to be no consensus on the input variables that should be applied to representative FEA models of the human mandible. This review aims to find a consensus on how to define the representative input factors for a FEA model of the human mandible. A literature search carried out in the PubMed and Embase database resulted in 137 matches. Seven papers were included in this current study. Within the search results, only a few FEA models had been validated. The material properties and FEA approaches varied considerably, and the available validations are not strong enough for a general consensus. Further validations are required, preferably using the same measuring workflow to obtain insight into the broad array of mandibular variations. A lot of work is still required to establish validated FEA settings and to prevent assumptions when it comes to FEA applications.
Can Needs‐Based Grants Improve Local Transit Performance? Varying Effects by Level of Control
Authors: Pasha Obed , Poister Theodore H.
Published: May 2020

Needs‐based grant programs are budgeting systems that tie grant dollars to the needs of the grantees as determined by objective indicators. Although performance improvement is not an explicit goal of such grants, the associated awards could work as incentives for grantees to meet the grant criteria. In other words, grantees seek to improve their performance to fulfill the criteria, even though the grant‐makers intend such grants to support the existing operational needs of the grantees. This study tests these assertions in the context of the small transit intensive cities (STIC) grant that was established as a needs‐based grant system by the federal government to support small local transit agencies operating with unusually high service demands. This study argues that these systems would have a stronger impact on indicators over which grantees have more control. This study tests these assertions using a difference‐in‐differences analysis of 290 transit agencies over 17 years. The findings show that STIC is effective in improving grantee performance, at least on the indicators which are more amenable to control.
Simultaneous occurrence of cutaneous mastocytosis and juvenile xanthogranuloma in a child: Random or true association?
Authors: Vergara‐de‐la‐Campa Laura , Torrelo Antonio , Isabel Sánchez‐Moya Ana , Recuero‐Pradillo María , Mollejo Manuela , Matito Almudena
Published: May 2020

Juvenile xanthogranuloma (JXG) and cutaneous mastocytosis (CM) are two distinct conditions that have rarely been reported in association. We report a child with CM and disseminated JXG, who showed a significant decrease in serum tryptase levels and regression of JXG lesions over time. Due to the paucity of reports, a true association between these two conditions has not been validated, although a potential induction of histiocytic lesions by mast cell degranulation has been proposed.
Oral hairy leukoplakia in a child using a corticosteroid nasal spray
Authors: Costa Fernanda Herrera , Costa Victor , León Jorge Esquiche , Anbinder Ana Lia , Ribeiro‐Silva Alfredo , Kaminagakura Estela
Published: May 2020

We report a case of atypical oral hairy leukoplakia (OHL) in a 9‐year‐old immunocompetent girl treated with fluticasone propionate nasal spray for allergic rhinitis. The OHL in childhood is uncommon and should be included in a differential diagnosis of white lesions in the oral mucosa.