bluuebunny/crossref_metadata_2025_split huggingface dataset:
Search for Early Pancreatic Cancer Blood Biomarkers in Five European Prospective Population Biobanks Using Metabolomics
Authors: Fest Jesse , Vijfhuizen Lisanne S , Goeman Jelle J , Veth Olga , Joensuu Anni , Perola Markus , Männistö Satu , Ness-Jensen Eivind , Hveem Kristian , Haller Toomas , Tonisson Neeme , Mikkel Kairit , Metspalu Andres , van Duijn Cornelia M , Ikram Arfan , Stricker Bruno H , Ruiter Rikje , van Eijck Casper H J , van Ommen Gert-Jan B , ʼt Hoen Peter A C 
Published: May 2019

Abstract
Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between 1 month and 17 years after sampling (N = 356) and age- and sex-matched controls (N = 887) were collected from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian Biobank, Rotterdam Study). We applied proton nuclear magnetic resonance–based metabolomics on the Nightingale platform. Logistic regression identified two interesting hits: glutamine (P = 0.011) and histidine (P = 0.012), with Westfall–Young family-wise error rate adjusted P values of 0.43 for both. Stratification in quintiles showed a 1.5-fold elevated risk for the lowest 20% of glutamine and a 2.2-fold increased risk for the lowest 20% of histidine. Stratification by time to diagnosis suggested glutamine to be involved in an earlier process (2 to 5 years before diagnosis), and histidine in a process closer to the actual onset (<2 years). Our data did not support the branched-chain amino acids identified earlier in several US cohorts as potential biomarkers for pancreatic cancer. Thus, although we identified glutamine and histidine as potential biomarkers of biological interest, our results imply that a study at this scale does not yield metabolomic biomarkers with sufficient predictive value to be clinically useful per se as prognostic biomarkers.
Longitudinal Metabolic Impacts of Perinatal Exposure to Phthalates and Phthalate Mixtures in Mice
Authors: Neier Kari , Cheatham Drew , Bedrosian Leah D , Gregg Brigid E , Song Peter X K , Dolinoy Dana C 
Published: May 2019

Abstract
Developmental exposures to phthalates are suspected to contribute to risk of metabolic syndrome. However, findings from human studies are inconsistent, and long-term metabolic impacts of early-life phthalate and phthalate mixture exposures are not fully understood. Furthermore, most animal studies investigating metabolic impacts of developmental phthalate exposures have focused on diethylhexyl phthalate (DEHP), whereas newer phthalates, such as diisononyl phthalate (DINP), are understudied. We used a longitudinal mouse model to evaluate long-term metabolic impacts of perinatal exposures to three individual phthalates, DEHP, DINP, and dibutyl phthalate (DBP), as well as two mixtures (DEHP+DINP and DEHP+DINP+DBP). Phthalates were administered to pregnant and lactating females through phytoestrogen-free chow at the following exposure levels: 25 mg of DEHP/kg of chow, 25 mg of DBP/kg of chow, and 75 mg of DINP/kg of chow. One male and female per litter (n = 9 to 13 per sex per group) were weaned onto control chow and followed until 10 months of age. They underwent metabolic phenotyping at 2 and 8 months, and adipokines were measured in plasma collected at 10 months. Longitudinally, females perinatally exposed to DEHP only had increased body fat percentage and decreased lean mass percentage, whereas females perinatally exposed to DINP only had impaired glucose tolerance. Perinatal phthalate exposures also modified the relationship between body fat percentage and plasma adipokine levels at 10 months in females. Phthalate-exposed males did not exhibit statistically significant differences in the measured longitudinal metabolic outcomes. Surprisingly, perinatal phthalate mixture exposures were statistically significantly associated with few metabolic effects and were not associated with larger effects than single exposures, revealing complexities in metabolic effects of developmental phthalate mixture exposures.
Umbilical Cord miRNAs in Small-for-Gestational-Age Children and Association With Catch-Up Growth: A Pilot Study
Authors: Mas-Parés Berta , Xargay-Torrent Sílvia , Bonmatí Alexandra , Lizarraga-Mollinedo Esther , Martínez-Calcerrada José Maria , Carreras-Badosa Gemma , Prats-Puig Anna , de Zegher Francis , Ibáñez Lourdes , López-Bermejo Abel , Bassols Judit 
Published: May 2019

Abstract

Context
Catch-up growth in infants who are small for gestational age (SGA) is a risk factor for the development of cardiometabolic diseases in adulthood. The basis and mechanisms underpinning catch-up growth in newborns who are SGA are unknown.

Objective
To identify umbilical cord miRNAs associated with catch-up growth in infants who are SGA and study their relationship with offspring’s cardiometabolic parameters.

Design
miRNA PCR panels were used to study the miRNA profile in umbilical cord tissue of five infants who were SGA with catch-up (SGA-CU), five without catch-up (SGA-nonCU), and five control infants [appropriate for gestational age (AGA)]. The miRNAs with the smallest nominal P values were validated in 64 infants (22 AGA, 18 SGA-nonCU, and 24 SGA-CU) and correlated with anthropometric parameters at 1 (n = 64) and 6 years of age (n = 30).

Results
miR-501-3p, miR-576-5p, miR-770-5p, and miR-876-3p had nominally significant associations with increased weight, height, weight catch-up, and height catch-up at 1 year, and miR-374b-3p, miR-548c-5p, and miR-576-5p had nominally significant associations with increased weight, height, waist, hip, and renal fat at 6 years. Multivariate analysis suggested miR-576-5p as a predictor of weight catch-up and height catch-up at 1 year, as well as weight, waist, and renal fat at 6 years. In silico studies suggested that miR-576-5p participates in the regulation of inflammatory, growth, and proliferation signaling pathways.

Conclusions
Umbilical cord miRNAs could be novel biomarkers for the early identification of catch-up growth in infants who are SGA. miR-576-5p may contribute to the regulation of postnatal growth and influence the risk for cardiometabolic diseases associated with a mismatch between prenatal and postnatal weight gain.
Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes
Authors: Hjort Rebecka , Löfvenborg Josefin E , Ahlqvist Emma , Alfredsson Lars , Andersson Tomas , Grill Valdemar , Groop Leif , Sørgjerd Elin P , Tuomi Tiinamaija , Åsvold Bjørn Olav , Carlsson Sofia 
Published: May 2019

Abstract

Objective
We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes.

Methods
We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP).

Results
The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO.

Conclusions
Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.
Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation‒Positive Child
Authors: Dutta Pinaki , Reddy Kavita S , Rai Ashutosh , Madugundu Anil K , Solanki Hitendra S , Bhansali Anil , Radotra Bishan D , Kumar Narendra , Collier David , Iacovazzo Donato , Gupta Prakamya , Raja Remya , Gowda Harsha , Pandey Akhilesh , Devgun Jagtar Singh , Korbonits Márta 
Published: May 2019

AbstractContextInactivating germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are linked to pituitary adenoma predisposition. Here, we present the youngest known patient with AIP-related pituitary adenoma.Case DescriptionThe patient presented at the age of 4 years with pituitary apoplexy and left ptosis with severe visual loss following a 1-year history of abdominal pain, headaches, and rapid growth. His IGF-1 level was 5× the upper limit of normal, and his random GH level was 1200 ng/mL. MRI showed a 43 × 24 × 35‒mm adenoma with suprasellar extension invading the left cavernous sinus (Knosp grade 4). After transsphenoidal surgery, histology showed a grade 2A sparsely granulated somatotropinoma with negative O6-methylguanine-DNA methyltransferase and positive vascular endothelial growth factor staining. Genetic testing identified a heterozygous germline nonsense AIP mutation (p.Arg81Ter). Exome sequencing of the tumor revealed that it had lost the entire maternal chromosome-11, rendering it hemizygous for chromosome-11 and therefore lacking functional copies of AIP in the tumor. He was started on octreotide, but because the tumor rapidly regrew and IGF-1 levels were unchanged, temozolomide was initiated, and intensity-modulated radiotherapy was administered 5 months after surgery. Two months later, bevacizumab was added, resulting in excellent tumor response. Although these treatments stabilized tumor growth over 4 years, IGF-1 was normalized only after pegvisomant treatment, although access to this medication was intermittent. At 3.5 years of follow-up, gamma knife treatment was administered, and pegvisomant dose increase was indicated.ConclusionMultimodal treatment with surgery, long-acting octreotide, radiotherapy, temozolomide, bevacizumab, and pegvisomant can control genetically driven, aggressive, childhood-onset somatotropinomas.
Reflecting in the Vernacular
Authors: Williams Richard David 
Published: May 2019

Abstract
In early modern North India, knowledge systems developed simultaneously in multiple “classical” and “vernacular” languages. This article examines the processes of multilingual knowledge transmission through an analysis of a Brajbhasha (classical Hindi) music treatise, the Sangitadarpana (“Mirror of Music”) of Harivallabha (ca. 1653). Harivallabha was translating a recent Sanskrit work of the same name: an old-fashioned treatise that nonetheless proved extremely influential in Persian and other Sanskrit works, as well as in miniature painting. This article examines the implications of the vernacular rendering of the Sangitadarpana and Harivallabha's seminal influence on the musicological intellectual culture that followed in his wake. Drawing on other translations and treatises in other forms of Hindi and Bengali, the article also considers the limits of Brajbhasha's circulation, and the wider implications of using a vernacular language for reading, listening, visual, and performance practices.
Within-individual behavioural variability and division of labour in social insects
Authors: Jeanson Raphaël 
Published: May 2019

ABSTRACTDivision of labour, whereby individuals divide the workload in a group, is a recurrent property of social living. The current conceptual framework for division of labour in social insects is provided by the response-threshold model. This model posits that the differences between individuals (i.e. between-individual variability) in responsiveness to task-associated stimuli is a key feature for task specialisation. The consistency of individual behaviours (i.e. within-individual variability) in task performance represents an additional but little-considered component driving robust patterns of division of labour. On the one hand, the presence of workers with a high level of within-individual variability presumably allows colonies to rapidly adapt to external fluctuations. On the other hand, a reduced degree of within-individual variability promotes a stricter specialisation in task performance, thereby limiting the costs of task switching. The ideal balance between flexibility and canalisation probably varies depending on the developmental stage of the colony to satisfy its changing needs. Here, I introduce the main sources of within-individual variability in behaviours in social insects and I review neural correlates accompanying the changes in behavioural flexibility. I propose the hypothesis that the positive scaling between group size and the intensity of task specialisation, a relationship consistently reported both within and between taxa, may rely on reduced within-individual variability via self-organised processes linked to the quality of brood care. Overall, I emphasise the need for a more comprehensive characterisation of the response dynamics of individuals to better understand the mechanisms shaping division of labour in social insects.
Renal cystic lesions characterization using spectral detector CT (SDCT): Added value of spectral results
Authors: Kessner Rivka , Große Hokamp Nils , Ciancibello Les , Ramaiya Nikhil , Herrmann Karin A. 
Published: May 2019

Objectives:
To evaluate the added value of spectral results derived from Spectral Detector CT (SDCT) to the characterization of renal cystic lesions (RCL).

Methods:
This retrospective study was approved by the local Institutional review board. 70 consecutive patients who underwent abdominopelvic SDCT and had at least one RCL were included. 84 RCL were categorized as simple, complex or neoplastic based on attenuation values on single-phase post-contrast images. Attenuation values were measured in each lesion on standard conventional CT images (stCI) and virtual monoenergetic images of 40keV and 100keV. A spectral curve slope was calculated and intra lesional iodine concentration (IC) was measured using iodine-density maps. Reference standard was established using histopathologic correlation, prior and follow-up imaging. Analysis of variance (ANOVA) was used to compare between the groups.

Results:
Mean attenuation values for benign simple and complex RCL differed significantly (42 ± 16 vs 8 ± 3 HU; p &lt; 0.001). IC was almost identical in benign simple and complex RCL (0.23 ± 0.04 mg ml−1 vs 0.24 ± 0.04 mg ml−1), while IC in neoplastic RCL was significantly higher (2.10 ± 0.08 mg ml−1 ; p &lt; 0.001). The mean spectral curve slope did not differ significantly between simple and complex RCL (0.30 ± 0.03 vs 0.33 ± 0.05) but was significantly higher in neoplastic RCL (2.60 ± 0.10; p &lt; 0.001).

Conclusions:
Spectral results of SDCT are highly promising in distinguishing benign complex RCL from enhancing neoplastic RCL based on single-phase post-contrast imaging only.

Advances in knowledge:
SDCT can assist in differentiating between benign complex and neoplastic renal cystic lesions.
Revisiting the excitation/inhibition imbalance hypothesis of ASD through a clinical lens
Authors: Port Russell G , Oberman Lindsay M , Roberts Timothy PL 
Published: May 2019

Autism spectrum disorder (ASD) currently affects 1 in 59 children, although the aetiology of this disorder remains unknown. Faced with multiple seemingly disparate and noncontiguous neurobiological alterations, Rubenstein and Merzenich hypothesized that imbalances between excitatory and inhibitory neurosignaling (E/I imbalance) underlie ASD. Since this initial statement, there has been a major focus examining this exact topic spanning both clinical and preclinical realms.
The purpose of this article is to review the clinical neuroimaging literature surrounding E/I imbalance as an aetiology of ASD. Evidence for E/I imbalance is presented from several complementary clinical techniques including magnetic resonance spectroscopy, magnetoencephalography and transcranial magnetic stimulation. Additionally, two GABAergic potential interventions for ASD, which explicitly attempt to remediate E/I imbalance, are reviewed.
The current literature suggests E/I imbalance as a useful framework for discussing the neurobiological etiology of ASD in at least a subset of affected individuals. While not constituting a completely unifying aetiology, E/I imbalance may be relevant as one of several underlying neuropathophysiologies that differentially affect individuals with ASD. Such statements do not diminish the value of the E/I imbalance concept—instead they suggest a possible role for the characterization of E/I imbalance, as well as other underlying neuropathophysiologies, in the biologically-based subtyping of individuals with ASD for potential applications including clinical trial enrichment as well as treatment triage.
Ocular findings in patients with novel A/H1N1 infection: an observational cross-sectional study
Authors: Mehta Salil , Vas Conrad Rui 
Published: May 2019

Background: The systemic findings of novel A (H1N1) influenza have been well documented but data on ocular lesions is scarce. We report the systemic and ophthalmoscopic findings of 14 patients with proven H1N1 infection. Methods: An observational non-interventional retrospective study. During a period of nine years, 14 patients (six female and eight males), were referred for an ophthalmic evaluation. All patients underwent a detailed systemic and ocular evaluation. Results: Three patients (21.4 %) showed ocular lesions in the form of a unilateral intraretinal hemorrhage. Of these, one patient (7.1%) had a large disc hemorrhage and an area of retinal whitening, consistent with ischemia in the macular area. Conclusions: Physicians dealing with H1N1 infection should be aware of these findings and may include an ocular evaluation as part of their protocol.
ГЕНДЕРНЫЕ ОСОБЕННОСТИ ВОСПРИЯТИЯ СУПРУГАМИ ДРУГ ДРУГА И УДОВЛЕТВОРЕННОСТЬ БРАКОМ
Authors: Gurieva Svetlana Dzakhotovna , Ilina Tatyana Igorevna 
Published: May 2019

Актуальность. Необходимым условием гармоничного функционирования личности в обществе представляется ощущение психологического благополучия, одной из важных составляющих которого является удовлетворенность браком. Особый интерес исследования, состоит в том, что объектом исследования здесь является супружеская пара, а не отдельная личность. В нашем случае речь идет о гетеросексуальной паре, что позволяет говорить о гендерных различиях в восприятии тех или иных аспектов брака.Основной целью исследования было изучение взаимосвязи между удовлетворенностью браком и близостью взаимных представлений супругов. Кроме того, мы рассматривали проблему различий в том, насколько точно мужчины и женщины склонны формировать для себя образ супруга. Дизайн исследования позволил определить «ошибку восприятия», состоящую в разнице между образами супругов и сопоставить ее с уровнем удовлетворенности браком.Предмет: гендерные особенности формирования образа супруга и его связи с удовлетворенностью браком.Выборка. В исследовании приняли участие 36 гетеросексуальных семейных пар, все – жители г. Санкт-Петербурга, которым было предложено ответить на вопросы комплекса психодиагностических методик, опираясь на собственную самооценку, а затем – от лица своего супруга. Из ответов для каждого испытуемого было составлено по два «портрета». Сопоставление портретов позволило вычислить уровень ошибки восприятия, для каждой пары и соотнести его с уровнем удовлетворенности браком.Методики исследования: «Удовлетворенность браком» (В.В. Столин, Т.Л. Романова, Г.П. Бутенко), «Семантический дифференциал» (Ч.Осгуд), «Ведущий ресурс»( по теории Дж. П. Фландерса), типы отношений к окружающим (Опросник Т. Лири).Результаты: выявлены специфические различия в восприятии супруга в мужской и женской частях выборки. Так, обнаружено, что в большинстве случаев, мужчины склонны гораздо точнее составлять образ супруги, чем женщины – образ мужа. Это обстоятельство следует учитывать в практической работе с семейными парами, не отрицая при этом индивидуальных особенностей.
Localización del punto óptimo de partida en el problema de ruteo vehicular con capacidad restringida (CVRP)
Authors: Solarte Guillermo Roberto , Soto Mejía José , Muñoz Guerrero Luis Eduardo 
Published: May 2019

Contexto: Esta investigación resuelve el problema de encontrar el punto óptimo de localización de una flota de vehículos recolectores de basura y las rutas óptimas para minimizar el costo de su recolección, en 144 barrios del municipio de Dosquebradas, Risaralda (Colombia), utilizando 8 vehículos con capacidad homogénea de 25 toneladas de la empresa Serviciudad.
Métodos: Primero, se utilizó una heurística de barrido (Ospina Toro y Orrego, 2016) para encontrar un buen punto de partida para los vehículos de recolección y generar rutas iniciales de buena calidad. Posteriormente, estas rutas iniciales alimentan el algoritmo genético modificado de Chu-Beasley (Solarte, Castillo y Rodríguez, 2015) teniendo en cuenta la capacidad de carga del vehículo (Rondon et al., 2010). Finalmente, para garantizar un resultado óptimo, el mejor encontrado en la fase anterior es tratado nuevamente con una metaheurística tabú (Bodas, 2017).
Resultados: Se diseñó una nueva metodología, denominada híbrida CSGTR (Clustering, sweep, genetic, tabu routing) que permitió aprovechar las ventajas de la clusterización (Rueda et al., 2017) antes del ruteo de vehículos (Hernández, 2017), incluyendo modelos heurísticos como la técnica de barrido (Ospina Toro y Orrego, 2016) y metaheurísticos como los algoritmos de Chu-Beasley y tabú (Grajales, Hincapié y Montoya, 2017). La aplicación de la metodología CSGTR permitió reducir el tiempo y los costos de los recorridos de los camiones recolectores de basura en el municipio de Dosquebradas, Risaralda (Colombia).
Conclusiones: La metodología hibrida CSGTR para resolver el problema de ubicación de flotas de vehículos y generación de rutas de recolección se presenta como un enfoque alternativo, con mejores resultados que el enfoque previo.