bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daytime melatonin and light independently affect human alertness and body temperature
Authors: Lok Renske , van Koningsveld Minke J. , Gordijn Marijke C. M. , Beersma Domien G. M. , Hut Roelof A. 
Published: April 2019

AbstractLight significantly improves alertness during the night (Cajochen, Sleep Med Rev, 11, 2007 and 453; Ruger et al., AJP Regul Integr Comp Physiol, 290, 2005 and R1413), but results are less conclusive at daytime (Lok et al., J Biol Rhythms, 33, 2018 and 589). Melatonin and core body temperature levels at those times of day may contribute to differences in alerting effects of light. In this experiment, the combined effect of daytime exogenous melatonin administration and light intensity on alertness, body temperature, and skin temperature was studied. The goal was to assess whether (a) alerting effects of light are melatonin dependent, (b) soporific effects of melatonin are mediated via the thermoregulatory system, and (c) light can improve alertness after melatonin‐induced sleepiness during daytime. 10 subjects (5 females, 5 males) received melatonin (5 mg) in dim (10 lux) and, on a separate occasion, in bright polychromatic white light (2000 lux). In addition, they received placebo both under dim and bright light conditions. Subjects participated in all four conditions in a balanced order, yielding a balanced within‐subject design, lasting from noon to 04:00 pm. Alertness and performance were assessed half hourly, while body temperature and skin temperature were measured continuously. Saliva samples to detect melatonin concentrations were collected half hourly. Melatonin administration increased melatonin concentrations in all subjects. Subjective sleepiness and distal skin temperature increased after melatonin ingestion. Bright light exposure after melatonin administration did not change subjective alertness scores, but body temperature and proximal skin temperature increased, while distal skin temperature decreased. Light exposure did not significantly affect these parameters in the placebo condition. These results indicate that (a) exogenous melatonin administration during daytime increases subjective sleepiness, confirming a role for melatonin in sleepiness regulation, (b) bright light exposure after melatonin ingestion significantly affected thermoregulatory parameters without altering subjective sleepiness, therefore temperature changes seem nonessential for melatonin‐induced sleepiness, (c) subjective sleepiness was increased by melatonin ingestion, but bright light administration was not able to improve melatonin‐induced sleepiness feelings nor performance. Other (physiological) factors may therefore contribute to differences in alerting effects of light during daytime and nighttime.
Vibration‐based structural state identification by a 1‐dimensional convolutional neural network
Authors: Zhang Youqi , Miyamori Yasunori , Mikami Shuichi , Saito Takehiko 
Published: April 2019

AbstractDeep learning has ushered in many breakthroughs in vision‐based detection via convolutional neural networks (CNNs), but the vibration‐based structural damage detection by CNN remains being refined. Thus, this study proposes a simple one‐dimensional CNN that detects tiny local structural stiffness and mass changes, and validates the proposed CNN on actual structures. Three independent acceleration databases are established based on a T‐shaped steel beam, a short steel girder bridge (in test field), and a long steel girder bridge (in service). The raw acceleration data are not pre‐processed and are directly used as the training and validation data. The well‐trained CNN almost perfectly identifies the locations of small local changes in the structural mass and stiffness, demonstrating the high sensitivity of the proposed simple CNN to tiny structural state changes in actual structures. The convolutional kernels and outputs of the convolutional and max pooling layers are visualized and discussed as well.
Non‐involuting congenital hemangiomas (NICH) with postnatal atypical growth: A case series
Authors: Cossio María L. , Dubois Josée , McCuaig Catherine C. , Coulombe Jérôme , Hatami Afshin , Marcoux Danielle , Ondrejchak Sandra , Powell Julie 
Published: April 2019

AbstractBackgroundNon‐involuting congenital hemangiomas (NICH) are fully formed vascular tumors at birth, with a distinctive clinical, radiologic, and histopathological profile, and classically lack expansion or involution over time. We describe a series of NICH cases with atypical postnatal growth.MethodsThe authors retrospectively analyzed all NICH cases diagnosed from 2007 to 2017. We reviewed charts and photographic databases from our Vascular Anomalies Clinic. We included in the study all NICH with an atypical postnatal growth. Clinical data, imaging, and histopathology were analyzed.ResultsEighty cases of NICH were identified. Nine presented with atypical postnatal growth after a stable period, at ages from 2 to 10 years (mean: 5.3 years). Two patients had associated pain; 5 patients showed new red papules on the surface of the lesion; 2 reported bleeding from the papules; and 1 developed a pyogenic granuloma. All patients had Doppler ultrasound and/or MRI compatible with NICH, and a confirmatory biopsy was performed in 4 cases. In treatment, 2 patients received endovascular embolization, and one required further surgery.ConclusionsNon‐involuting congenital hemangiomas (NICH) may develop significant postnatal growth over time (10% in our series), requiring closer follow‐up for longer periods. The development of red papules, pyogenic granulomas, and superficial bleeding may be observed. Since this is a small series, we were not able to establish risk factors for NICH with postnatal growth.
Socioeconomic and Gender Health Disparities in Diabetes: The Lower Middle Income Case of Ghana
Authors: Dagadu Helena E. 
Published: April 2019

While literature theorizing the relationship between socioeconomic status (SES), gender, and health outcomes is robust in high‐income countries, there is less scholarship examining how SES affects men and women in lower middle income countries (LMICs). Focusing on the LMIC case of Ghana, I use Wave 1 of the World Health Organization Study on Global Aging and Adult Health (SAGE) to examine the relationship between SES and diabetes among Ghanaian women and men. Specifically, I examine how key SES measures such as educational attainment, employment status, and income singly and collectively predict the odds of diabetes for Ghanaian men and women. I also examine the explanatory value of the reversal hypothesis, which posits that those of high SES experience higher rates of non‐communicable diseases. Overall, I find that while Ghanaian men experience increased odds of diabetes with increased education, Ghanaian women have higher odds of diabetes compared to men regardless of educational attainment. Understanding health patterns in LMICs like Ghana is important for sociological inquiry on health disparities seeking to incorporate more global perspectives.
Patient-reported outcomes in the RELIGHT clinical trial of ranibizumab in diabetic macular oedema
Authors: Chakravarthy Usha , Pearce Ian , Banerjee Sanjiv , Burton Benjamin J L , Downey Louise , Gale Richard , Patel Jignesh , Patra Sudeshna , Sivaprasad Sobha , Stevenson Michael , Lupton Susanne 
Published: April 2019

Background/aimsThe RELIGHT clinical trial used an individualised treatment regimen of ranibizumab to treat diabetic macular oedema (DMO). We report findings from two patient-reported outcome instruments.MethodsThe National Eye Institute Visual Function Questionnaire (NEI-VFQ) was administered before starting treatment (M0) and at M6, 12 and 18. The Macular Disease Society Treatment Satisfaction Questionnaire (MacTSQ) was administered 1 month after treatment start (M1) and at M6, 12 and 18. Relationships between best-corrected visual acuity (BCVA) in the study eye (SE) and the status of the eye at baseline (as better or worse eye by BCVA) and the two instrument measures were investigated.ResultsBCVA in the SE correlated strongly with the NEI-VFQ composite scores and the majority of the subscales but not with the MacTSQ subscales. Statistically significant improvements were observed in the majority of the subscales of the NEI-VFQ at M6, 12 and 18. For the MacTSQ, improvements between baseline M6, 12 and 18 were seen for subscale 1 but only reached statistical significance at M12. In subscale 2, the changes in mean scores were statistically significant at all timepoints.ConclusionsAlthough ranibizumab treatment in DMO over an 18-month period resulted in improvements in visual functioning and patient satisfaction, no correlation was found between the instruments used to measure these outcomes. Our finding of a lack of correlation between BCVA and the MacTSQ suggests the presence of psychophysical factors not measured by traditional means.
Atrial fibrillation type and renal dysfunction as important predictors of left atrial thrombus
Authors: Kapłon-Cieślicka Agnieszka , Budnik Monika , Gawałko Monika , Peller Michał , Gorczyca Iwona , Michalska Anna , Babiarz Aldona , Bodys Aleksandra , Uliński Robert , Żochowski Maciej , Scisło Piotr , Kochanowski Janusz , Filipiak Krzysztof J , Opolski Grzegorz 
Published: April 2019

ObjectiveWe aimed to identify predictors of left atrial appendage (LAA) thrombus in patients with atrial fibrillation (AF) and to enhance the prognostic value of the CHA2DS2-VASc score.MethodsDerivation cohort included 1033 consecutive AF patients referred for catheter ablation or direct current cardioversion, in whom transoesophageal echocardiography (TOE) was performed prior to the procedure. Logistic regression analysis was used to identify predictors of LAA thrombus on TOE. Receiver operating characteristic (ROC) curves were constructed to compare the newly developed score with the CHA2DS2and CHA2DS2-VASc scores in the derivation and the validation (n=320) cohort.ResultsOn TOE, LAA thrombus was present in 59 (5.7%) patients in the derivation cohort. Aside from variables encompassed by the CHA2DS2-VASc score, LAA thrombus predictors included AF type (persistent/’permanent’ vs paroxysmal) and renal dysfunction. These predictors were incorporated into the CHA2DS2-VASc score. In ROC analysis, area under the curve (AUC) for the new score (CHA2DS2-VASc-RAF score) was significantly higher (0.81) than those for the CHA2DS2and CHA2DS2-VASc scores (0.71 and 0.70, respectively). In the validation cohort, the CHA2DS2-VASc-RAF score also performed significantly better (AUC of 0.88) than the CHA2DS2and CHA2DS2-VASc scores (AUC of 0.63 and 0.60, respectively).ConclusionIn real-world AF patients with majority on oral anticoagulation, LAA thrombus was found in approximately 6%. Two variables not included in the CHA2DS2-VASc score (AF type and renal dysfunction) proved strong, independent predictors of LAA thrombus and might improve thromboembolic risk stratification.
Sex-based associations with microvascular injury and outcomes after ST-segment elevation myocardial infarction
Authors: Maznyczka Annette Marie , Carrick David , Carberry Jaclyn , Mangion Kenneth , McEntegart Margaret , Petrie Mark C , Eteiba Hany , Lindsay Mitchell , Hood Stuart , Watkins Stuart , Davie Andrew , Mahrous Ahmed , Ford Ian , Welsh Paul , Sattar Naveed , Oldroyd Keith G , Berry Colin 
Published: April 2019

ObjectivesWe aimed to assess for sex differences in invasive parameters of acute microvascular reperfusion injury and infarct characteristics on cardiac MRI after ST-segment elevation myocardial infarction (STEMI).MethodsPatients with STEMI undergoing emergency percutaneous coronary intervention (PCI) were prospectively enrolled. Index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured in the culprit artery post-PCI. Contrast-enhanced MRI was used to assess infarct characteristics, microvascular obstruction and myocardial haemorrhage, 2 days and 6 months post-STEMI. Prespecified outcomes were as follows: (i) all-cause death/first heart failure hospitalisation and (ii) cardiac death/non-fatal myocardial infarction/urgent coronary revascularisation (major adverse cardiovascular event, MACE) during 5- year median follow-up.ResultsIn 324 patients with STEMI (87 women, mean age: 61 ± 12.19 years; 237 men, mean age: 59 ± 11.17 years), women had anterior STEMI less often, fewer prescriptions of beta-blockers at discharge and higher baseline N-terminal pro-B-type natriuretic peptide levels (all p < 0.05). Following emergency PCI, fewer women than men had Thrombolysis in Myocardial Infarction (TIMI) myocardial perfusion grades ≤ 1 (20% vs 32%, p = 0.027) and women had lower corrected TIMI frame counts (12.94 vs 17.65, p = 0.003). However, IMR, CFR, microvascular obstruction, myocardial haemorrhage, infarct size, myocardial salvage index, left ventricular remodelling and ejection fraction did not differ significantly between sexes. Female sex was not associated with MACE or all-cause death/first heart failure hospitalisation.ConclusionThere were no sex differences in microvascular pathology in patients with acute STEMI. Women had less anterior infarcts than men, and beta-blocker therapy at discharge was prescribed less often in women.Trial registration numberNCT02072850.
Nutrient intake and dietary quality changes within a personalized lifestyle intervention program for metabolic syndrome in primary care
Authors: Brauer Paula , Royall Dawna , Li Airu , Rodrigues Ariellia , Green Jennifer , Macklin Sharon , Craig Alison , Pasanen Jennifer , Brunelle Lucie , Maitland Scott , Dhaliwal Rupinder , Klein Doug , Tremblay Angelo , Rheaume Caroline , Mutch David M. , Jeejeebhoy Khursheed 
Published: April 2019

A team-based 12-month lifestyle program for the treatment of metabolic syndrome (MetS) (involving physicians, registered dietitians (RDs), and kinesiologists) was previously shown to reverse MetS in 19% of patients (95% confidence interval, 14% to 24%). This work evaluates changes in nutrient intake and diet quality over 12 months (n = 205). Individualized diet counselling was provided by 14 RDs at 3 centres. Two 24-h recalls, the Canadian Healthy Eating Index (HEI-C), and the Mediterranean Diet Score (MDS) were completed at each time point. Total energy intake decreased by 145 ± 586 kcal (mean ± SD) over 3 months with an additional 76 ± 452 kcal decrease over 3–12 months. HEI-C improved from 58 ± 15 to 69 ± 12 at 3 months and was maintained at 12 months. Similarly, MDS (n = 144) improved from 4.8 ± 1.2 to 6.2 ± 1.9 at 3 months and was maintained at 12 months. Changes were specific to certain food groups, with increased intake of fruits, vegetables, and nuts and decreased intake of “other foods” and “commercial baked goods” being the most prominent changes. There was limited change in intake of olive oil, fish, and legumes. Exploratory analysis suggested that poorer diet quality at baseline was associated with greater dietary changes as assessed by HEI-C. Novelty Multiple dietary assessment tools provided rich information on food intake changes in an intervention for metabolic syndrome. Improvements in diet were achieved by 3 months and maintained to 12 months. The results provide a basis for further dietary change implementation studies in the Canadian context.
Genome-Wide Association Studies of Endometrial Cancer: Latest Developments and Future Directions
Authors: O'Mara Tracy A. , Glubb Dylan M. , Kho Pik Fang , Thompson Deborah J. , Spurdle Amanda B. 
Published: April 2019

Abstract
Endometrial cancer, the most commonly diagnosed cancer of the female reproductive tract in developed countries, has a heritable component. To date, 16 genetic risk regions have been robustly discovered by genome-wide association studies (GWAS) of endometrial cancer. Post-GWAS analyses including expression quantitative trait loci analysis and laboratory-based functional studies have been successful in identifying genes and pathways involved in endometrial carcinogenesis. Mendelian randomization analysis studies have confirmed factors causal for endometrial cancer risk, including increased body mass index and early onset of menarche. In this review, we summarize findings from GWAS and post-GWAS analyses of endometrial cancer. We discuss clinical implications of these findings, current knowledge gaps, and future directions for the study of endometrial cancer genetics.
The FOXM1 Inhibitor RCM-1 Decreases Carcinogenesis and Nuclear β-Catenin
Authors: Shukla Samriddhi , Milewski David , Pradhan Arun , Rama Nihar , Rice Kathryn , Le Tien , Flick Matthew J. , Vaz Sara , Zhao Xueheng , Setchell Kenneth D. , Logarinho Elsa , Kalinichenko Vladimir V. , Kalin Tanya V. 
Published: April 2019

Abstract
The oncogenic transcription factor FOXM1 has been previously shown to play a critical role in carcinogenesis by inducing cellular proliferation in multiple cancer types. A small-molecule compound, Robert Costa Memorial drug-1 (RCM-1), has been recently identified from high-throughput screen as an inhibitor of FOXM1 in vitro and in mouse model of allergen-mediated lung inflammation. In the present study, we examined antitumor activities of RCM-1 using tumor models. Treatment with RCM-1 inhibited tumor cell proliferation as evidenced by increased cell-cycle duration. Confocal imaging of RCM-1–treated tumor cells indicated that delay in cellular proliferation was concordant with inhibition of FOXM1 nuclear localization in these cells. RCM-1 reduced the formation and growth of tumor cell colonies in the colony formation assay. In animal models, RCM-1 treatment inhibited growth of mouse rhabdomyosarcoma Rd76-9, melanoma B16-F10, and human H2122 lung adenocarcinoma. RCM-1 decreased FOXM1 protein in the tumors, reduced tumor cell proliferation, and increased tumor cell apoptosis. RCM-1 decreased protein levels and nuclear localization of β-catenin, and inhibited protein–protein interaction between β-catenin and FOXM1 in cultured tumor cells and in vivo. Altogether, our study provides important evidence of antitumor potential of the small-molecule compound RCM-1, suggesting that RCM-1 can be a promising candidate for anticancer therapy.
IL15-Based Trifunctional Antibody-Fusion Proteins with Costimulatory TNF-Superfamily Ligands in the Single-Chain Format for Cancer Immunotherapy
Authors: Beha Nadine , Harder Markus , Ring Sarah , Kontermann Roland E. , Müller Dafne 
Published: April 2019

Abstract
IL15 and costimulatory receptors of the tumor necrosis superfamily (TNFRSF) have shown great potential to support and drive an antitumor immune response. However, their efficacy as monotherapy is limited. Here, we present the development of a novel format for a trifunctional antibody-fusion protein that combines and focuses the activity of IL15/TNFSF-ligand in a targeting-mediated manner to the tumor site. The previously reported format consisted of a tumor-directed antibody (scFv), IL15 linked to an IL15Rα-fragment (RD), and the extracellular domain of 4-1BBL, where noncovalent trimerization of 4-1BBL into its functional unit led to a homotrimeric molecule with 3 antibody and 3 IL15-RD units. To reduce the size and complexity of the molecule, we have now designed a second format, where 4-1BBL is introduced as single-chain (sc), that is 3 consecutively linked 4-1BBL ectodomains. Thus, a monomeric trifunctional fusion protein presenting only 1 functional unit of each component was generated. Interestingly, the in vitro activity on T-cell stimulation was conserved or even enhanced for the soluble and target-bound molecule, respectively. Also, in a lung tumor mouse model, comparable antitumor effects were observed. Furthermore, corroborating the concept, OX40L and GITRL were also successfully incorporated into the novel single-chain format and the advantage of target-bound trifunctional versus corresponding combined bifunctional fusion proteins demonstrated by measuring T-cell proliferation and cytotoxic potential in vitro and antitumor effects of RD_IL15_scFv_scGITRL in a lung tumor mouse model in vivo. Thus, the trifunctional antibody-fusion protein single-chain format constitutes a promising innovative platform for further therapeutic developments.
Mechanisms of Lymphoma Clearance Induced by High-Dose Alkylating Agents
Authors: Lossos Chen , Liu Yunpeng , Kolb Kellie E. , Christie Amanda L. , Van Scoyk Alexandria , Prakadan Sanjay M. , Shigemori Kay , Stevenson Kristen E. , Morrow Sara , Plana Olivia D. , Fraser Cameron , Jones Kristen L. , Liu Huiyun , Pallasch Christian P. , Modiste Rebecca , Nguyen Quang-De , Craig Jeffrey W. , Morgan Elizabeth A. , Vega Francisco , Aster Jon C. , Sarosiek Kristopher A. , Shalek Alex K. , Hemann Michael T. , Weinstock David M. 
Published: April 2019

AbstractThe extraordinary activity of high-dose cyclophosphamide against some high-grade lymphomas was described nearly 60 years ago. Here we address mechanisms that mediate cyclophosphamide activity in bona fide human double-hit lymphoma. We show that antibody resistance within the bone marrow (BM) is not present upon early engraftment but develops during lymphoma progression. This resistance required a high tumor:macrophage ratio, was recapitulated in spleen by partial macrophage depletion, and was overcome by multiple, high-dose alkylating agents. Cyclophosphamide induced endoplasmic reticulum (ER) stress in BM-resident lymphoma cells in vivo that resulted in ATF4-mediated paracrine secretion of VEGFA, massive macrophage infiltration, and clearance of alemtuzumab-opsonized cells. BM macrophages isolated after cyclophosphamide treatment had increased phagocytic capacity that was reversed by VEGFA blockade or SYK inhibition. Single-cell RNA sequencing of these macrophages identified a “super-phagocytic” subset that expressed CD36/FCGR4. Together, these findings define a novel mechanism through which high-dose alkylating agents promote macrophage-dependent lymphoma clearance.Significance:mAbs are effective against only a small subset of cancers. Herein, we recapitulate compartment-specific antibody resistance and define an ER stress–dependent mechanism induced by high-dose alkylating agents that promotes phagocytosis of opsonized tumor cells. This approach induces synergistic effects with mAbs and merits testing across additional tumor types.See related commentary by Duval and De Palma, p. 834.This article is highlighted in the In This Issue feature, p. 813