bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sera of elderly obstructive sleep apnea patients alter blood–brain barrier integrity in vitro: a pilot study
Authors: Voirin Anne-Cloé , Celle Sébastien , Perek Nathalie , Roche Frédéric 
Published: July 2020

AbstractObstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of hypoxia during the night. The severity of the disorder can be evaluated using an apnea–hypopnea index (AHI). The physiological consequences are mainly cardiovascular and neuronal dysfunctions. One hypothesis to explain such associated neurological disorders is disruption of the blood–brain barrier (BBB), which protects the brain from endovascular cytotoxic compounds. We selected two subgroups of volunteers from the PROOF cohort study (France), a group of patients suffering newly diagnosed severe OSAS (AHI > 30/h) and a group showing no sleep apnea (AHI < 5/h). We exposed a human in vitro BBB model of endothelial cells (HBEC-5i) with sera of patients with and without OSAS. After exposure, we measured the apparent BBB permeability as well as tight junction and ABC transporter expression using whole cell ELISA. We showed that after incubation with sera from OSAS patients, there was a loss of integrity in the human in vitro BBB model; this was reflected by an increase in permeability (43%; p < 0.001) and correlated with a 50% and 40% decrease in tight junction protein expression of ZO-1 and claudin-5, respectively. At the same time, we observed an upregulation in Pgp protein expression (52%) and functionality, and a downregulation in BCRP expression (52%). Our results demonstrated that severe BBB disorder after exposure to sera from OSAS patients was reflected by an opening of the BBB.
A framework for understanding how activities associated with dog ownership relate to human well-being
Authors: Barcelos Ana Maria , Kargas Niko , Maltby John , Hall Sophie , Mills Daniel S. 
Published: July 2020

AbstractThere is notorious inconsistency regarding mental health benefits of dog ownership, partially due to repeated cross-sectional studies comparing dog owners and non-owners, without taking into account the heterogeneity of dog-owner dyads, especially the activities with which the owners are involved. This study aimed to develop a comprehensive framework of the most important dog human related activities and their impact on owner well-being. Six focus groups with 35 dog owners were conducted, and their audio transcripts thematically analysed. Dog human related activities and themes of activities were linked to their reported changes in well-being through matrix coding. A framework of 58 dog human related activities linked with their specific hedonic well-being, life satisfaction and eudaimonic well-being outcomes was generated. Most activities were reported to improve owner’s well-being, (e.g. human–dog tactile interaction increases owner’s self-esteem), and a minority was mainly associated with negative outcomes. The richness of the framework presented in this study reinforces the importance of assessing dog ownership well-being outcomes based on specific dog human related activities with which dog owners are involved. This new and systematic investigative approach should decrease inconsistencies in the field and facilitate mental health interventions and study designs of a higher level of evidence.
Mortality of Patients with Cushing’s Disease
Authors: Ntali Georgia , Hakami Osamah , Wattegama Milanka , Ahmed Shahzada , Karavitaki Niki 
Published: July 2020

AbstractCushing’s disease is a rare condition of cortisol excess attributed to a
pituitary adenoma with an annual incidence of 1.2–2.4 cases per million
population. It is associated with several co-morbidities leading to increased
mortality predominantly due to cardiovascular disease. Despite the advances in
its diagnosis and management, survival can be compromised even after apparent
successful treatment. Minimizing the duration and extent of exposure to
hypercortisolaemia by early diagnosis and rapid, effective therapeutic
interventions, as well as close monitoring and aggressive control of
cardiovascular risk factors are vital for improving outcomes of the
patients.
Resistance to Fracture of Zirconia Abutments with Different Angulations: Impact of Implant Platform Diameter
Authors: Saker Samah , AL-Zordk Walid , Özcan Mutlu 
Published: July 2020

Abstract
Objective The aim of this study was to assess the impact of implant platform diameters on ultimate force to failure of zirconia abutments with different angulation.
Materials and Methods Forty-two zirconia abutments with either 0 degree (ST) or 15-degree (AN) angulation were assembled on tapered internal connection titanium implants (Direct's Legacy; 13 mm Implant Direct, LLC, Las Vegas, United States) with a platform diameter of Ø3.0, Ø3.5, and Ø4.5 mm (14 per group). Zirconia crowns (Ceramill Zolid; Amann Girrbach GmbH) were fabricated and cemented using self-adhesive resin cement (MaxCem Elite, Kerr). The specimens were thermomechanically loaded (TCML= 6,000 cycles of 5 to 50°C for 2 minutes/cycle followed by cyclic loading 600,000 cycles) followed by static loading until fracture. The data of load (N) at which fracture occurred were statistically analyzed by using Kruskal–Wallis analysis of variance and Mann–Whitney U tests at 5% significance level.
Results Higher load to fracture was reported for zirconia crowns in straight abutments groups and a platform of 4.5, 3.5, and 3 mm diameter was 438.2± 85.4, 345.5± 71.3, and 331.1± 59.1 N, respectively. However, the groups restored with zirconia crowns in angulated abutments groups and a platform of 4.5, 3.5, or 3 mm diameter showed a fracture load of 411.4 ± 49.8, 354.2 ± 52.5, and 302.8 ± 52.5 N, respectively.
Conclusion Straight and angulated zirconia abutments presented similar load to fracture on 3 and 3.5 mm platform diameters yet being significantly less for 4.5 mm diameter.
Subject and agentivity in Teotitlán Zapotec
Authors: Uchihara Hiroto , Gutiérrez Ambrocio 
Published: July 2020

Abstract
In Teotitlán Zapotec, some, but not all, verbs undergo stem alternation in the 1st person forms, in addition to
the attachment of the pronominal enclitics that encode the subject argument. We argue that stem alternation and pronominal
cliticization are independent from one another and that each encodes different grammatical features, agent and subject,
respectively. The phenomenon discussed in this paper is peculiar in two respects. First, stem alternation as the exponent of the
agent is cross-linguistically rare (although it is common within the Otomanguean languages). Furthermore, the category of
agentivity has not been studied in detail in Zapotecan languages, but this paper shows the pervasiveness of agentivity in the
Teotitlán Zapotec grammar.
Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry
Authors: Chaparro María , Garre Ana , Mesonero Francisco , Rodríguez Cristina , Barreiro-de Acosta Manuel , Martínez-Cadilla Jesús , Arroyo María T , Manceñido Noemí , Sierra-Ausín Mónica , Vera-Mendoza Isabel , Casanova María José , Nos Pilar , González-Muñoza Carlos , Martínez Teresa , Boscá-Watts Maia , Calafat Margalida , Busquets David , Girona Eva , Llaó Jordina , Martín-Arranz María Dolores , Piqueras Marta , Ramos Laura , Surís Gerard , Bermejo Fernando , Carbajo Ana Y , Casas-Deza Diego , Fernández-Clotet Agnes , García María J , Ginard Daniel , Gutiérrez-Casbas Ana , Hernández Luis , Lucendo Alfredo J , Márquez Lucía , Merino-Ochoa Olga , Rancel Francisco J , Taxonera Carlos , López Sanromán Antonio , Rubio Saioa , Domènech Eugeni , Gisbert Javier P 
Published: July 2020

AbstractAimTo evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life.MethodsPatients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16.ResultsA total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1–0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3–0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1–0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3–1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events.ConclusionsTofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure.
Prevalence and Duration of Gastrointestinal Symptoms Before Diagnosis of Inflammatory Bowel Disease and Predictors of Timely Specialist Review: A Population-Based Study
Authors: Blackwell J , Saxena S , Jayasooriya N , Bottle A , Petersen I , Hotopf M , Alexakis C , Pollok R C 
Published: July 2020

Abstract

Background and Aims
Lack of timely referral and significant waits for specialist review amongst individuals with unresolved gastrointestinal [GI] symptoms can result in delayed diagnosis of inflammatory bowel disease [IBD].

Aims
To determine the frequency and duration of GI symptoms and predictors of timely specialist review before the diagnosis of both Crohn’s disease [CD] and ulcerative colitis [UC].

Methods
This is a case control study of IBD matched 1:4 for age and sex to controls without IBD using the Clinical Practice Research Datalink from 1998 to 2016.

Results
We identified 19 555 cases of IBD and 78 114 controls. One in four cases of IBD reported GI symptoms to their primary care physician more than 6 months before receiving a diagnosis. There was a significant excess prevalence of GI symptoms in each of the 10 years before IBD diagnosis. GI symptoms were reported by 9.6% and 10.4% at 5 years before CD and UC diagnosis respectively compared to 5.8% of controls. Amongst patients later diagnosed with IBD, &lt;50% received specialist review within 18 months from presenting with chronic GI symptoms. Patients with a previous diagnosis of irritable bowel syndrome [IBS] or depression were less likely to receive timely specialist review (IBS: hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.60–0.99, depression: HR = 0.77, 95% CI 0.60–0.98).

Conclusions
There is an excess of GI symptoms 5 years before diagnosis of IBD compared to the background population, probably attributable to undiagnosed disease. Previous diagnoses of IBS and depression are associated with delays in specialist review. Enhanced pathways are needed to accelerate specialist referral and timely IBD diagnosis.
Association between early treatment hospitals, serum cholesterol level and cardiovascular disease risk in dyslipidemia patients
Authors: Han Kyu-Tae , Kim Seung Ju 
Published: July 2020

Abstract

Background
Studies have shown the importance of managing chronic diseases, such as cardiovascular disease (CVD), at the primary treatment level. Here, we aimed to evaluate the association between medical treatment institutions and health outcomes in patients with dyslipidemia, a major risk of CVD, to provide evidence for increasing chronic disease management at the primary care level in Korea.

Methods
We used National Health Insurance Sampling cohort data, of which 37 506 patients were newly diagnosed with dyslipidemia during 2009–14. CVD risk and changes in serum cholesterol level after dyslipidemia diagnosis were outcome variable examined. A generalized estimating equation model was used to identify associations between initial medical institution, CVD risk and changes in serum cholesterol levels. The Cox proportional-hazard ratio was used to assess the association between initial medical institutions and detailed CVD risk. Subgroup analyses were conducted to assess CVD risk following treatment with prescription medication.

Results
Our analyses demonstrate that CVD risk was lower at primary care-level community health centers and clinics compared to tertiary hospitals, with a statistically significant difference observed in clinics. Ischemic heart disease was lower at community health centers and clinics. However, all medical institution types were associated with significantly lower serum cholesterol levels compared to the baseline.

Conclusions
Management of patients with dyslipidemia at primary care institutions was associated with reduced CVD risk and decreased serum cholesterol levels. Therefore, policymakers should strengthen the quality of healthcare at primary care institutions and educate patients that these institutions are appropriate for managing chronic disease.
Trends in active commuting to school from 2003 to 2017 among children and adolescents from Germany: the MoMo Study
Authors: Reimers Anne K , Marzi Isabel , Schmidt Steffen C E , Niessner Claudia , Oriwol Doris , Worth Annette , Woll Alexander 
Published: July 2020

Abstract

Background
Inactivity in children and adolescents is a global issue requiring interventions that target different domains of physical activity, such as active transport. The aim of this study was to assess the prevalence, historical trends and socio-demographic correlates of active commuting to school (ACS) in a nationwide sample of girls and boys from Germany.

Methods
Data of commuting behaviour and socio-demographic factors were collected, covering three measurement points from 2003 to 2017. The MoMo Study derived its data from a representative sample of children and adolescents aged 4–17 years who answered a questionnaire (N = 11 387). Statistically significant differences between Baseline, Wave 1 and Wave 2 were determined via 95% confidence intervals (CIs) for complex samples.

Results
Overall, ACS decreased from 84.4% at the first measurement point to 78.3% in the third measurement point. The proportion of cases in which children opted for passive modes of commuting increased predominantly in those aged 4–5 years, in children with a low-to-medium socio-economic status, and in children residing in small- or medium-sized towns. No gender differences were found in active commuting. The results of multinomial logistic regression identified age, migration background and residential area as correlates of walking for boys. For girls, the likelihood of walking, cycling and taking public transport instead of opting for motorized transport increased with age.

Conclusions
Intervention programmes to increase active transport in children and adolescents should target different age groups and also consider parental influence in determining the child’s choice of transport mode.
First insights into the phylogeography and demographic history of the common hermit crab Pagurus bernhardus (Linnaeus, 1758) (Decapoda: Anomura: Paguridae) across the Eastern Atlantic and North Sea
Authors: Rossel Sven , Deli Temim , Raupach Michael J 
Published: July 2020

AbstractThe common hermit crab Pagurus bernhardus (Linnaeus, 1758) is an abundant and ecologically important benthic crustacean in the northeastern Atlantic Ocean. While this species has been intensively studied in terms of its ecology, physiology, behavior, and larval development, knowledge about its population structure and demographic history is still lacking. We examined, for the first time, the genetic variability of P. bernhardus by analyzing two mitochondrial gene fragments (CO1 and 16S) from more than 150 specimens collected from various locations from the Iberian Peninsula to Norway. Our results provide evidence for a significant genetic structure according to the sampled regions for both genetic markers. Furthermore, a comprehensive demographic history reconstruction, mainly based on neutrality tests and a Bayesian Skyline Plot (CO1), revealed a recent demographic expansion of P. bernhardus that preceded the Last Glacial Maximum. Such pattern of retrieved demographic trend could have been likely a successive process to historical contraction of the species into potential climate refugia within the surveyed geographic spectrum.
Coming of age: morphometric variation in the hand skeletons of juvenile and adult Lesser Treeshrews (Scandentia: Tupaiidae: Tupaia minor Günther, 1876)
Authors: Woodman Neal , Miller-Murthy Ananth , Olson Link E , Sargis Eric J 
Published: July 2020

AbstractMorphometric analyses of the manus skeleton have proven useful in understanding species limits and morphological divergence among tupaiid treeshrews (Scandentia: Tupaiidae). Specimens in these studies are typically limited to mature individuals with fully erupted permanent dentition, which eliminates potentially confounding variation attributable to age, but also can exclude rare taxa and small island populations that are poorly represented in systematic collections. To determine the real limits associated with including immature animals in such studies, we used multivariate analyses to study sexual and age variation of the manus skeleton in two allopatric populations of the Lesser Treeshrew (Tupaia minor Günther, 1876) from the Malay Peninsula and from Borneo that we treated as separate samples. Individuals were aged using dental eruption of the permanent dentition. We also recorded the degree of epiphyseal fusion of the bones of the manus based on x-rays of study skins. We then tested our ability to distinguish the two populations using a series of discriminant function analyses of hand measurements from samples that included varying proportions of immature individuals and adults. We found no evidence of sexual dimorphism in hand proportions, permitting us to combine females and males in our samples. Epiphyseal fusion of the metacarpals and phalanges typically occurs by the time the third molars have completely erupted, and fusion of the distal epiphyses of the radius and ulna typically occurs by the time the permanent fourth premolars are in place. There is occasional asynchrony between dental age and epiphyseal fusion. In both populations, the hands of most infants and subadults provide morphometric values within the range of variation of adults, although they are typically distributed in the lower part of the adult range and have the potential to bias the sample toward lower mean size. The inclusion of infants and subadults when attempting to discriminate between two taxa generally results in lower rates of correct classifications, although the rates increase as the sample of immature individuals is limited to older subadults. As a general rule, we recommend that specimens of infants and subadults continue to be excluded from analyses when exploring taxonomic boundaries among treeshrews. In cases of extremely small sample sizes of adults, however, older subadults—in which the permanent third premolars are erupting or in place—can be used with appropriate caution.
A complex regulating pattern induced by the effects of predation and parasites on root vole (Microtus oeconomus) populations during the breeding season
Authors: Shang Guozhen , Yang Yuangang , Zhu Yahui , Wu Xueqing , Cao Yifan , Wu Yan , Bian Jianghui 
Published: July 2020

Abstract
Predators and parasites have synergistic effects on the phenotype of the species they share as prey and host. Experimental studies that incorporate the interactions between predation and parasitism are, however, scarce in small-mammal populations. Our previous work has shown that the combined effects of predation and coccidian infection reduce overwinter survival and population density in root voles (Microtus oeconomus). Here, we examined the separate and combined effects of these two drivers on the population growth of root voles during the breeding season. We carried out a two-level factorial experiment, in which we manipulated predator exclusion and the removal of parasites in enclosures and measured survival, fecal corticosterone metabolite (FCM) concentration, recruitment, and population density. An expected synergistic effect of predators and parasites on vole population was not found, due to no effect of parasites on FCM level and recruitment rate during the period of the experiment. Instead, we found phase-related effects of predation on demography. Predation reduced the survival rate of voles in spring, which was intensified by parasite infection. Predation risk reduced recruitment rate in early summer by elevating FCM levels. Consequently, both direct and indirect effects of predation lowered population density during the experimental period. In addition, for populations free of predators, the peak density that occurred in early autumn elevated FCM level of adult voles, which reduced recruitment rates and halted population growth. Moreover, predation, parasites, and density affected the quality of the offspring. Our study suggests that multiple regulation processes influence population fluctuations during the breeding season. We conclude that a population experiencing stress acts as a common interface through which interactions between intrinsic and extrinsic factors can be important determinants of fluctuations. We propose a new hypothesis of integrative stress effects to explain small-mammal population fluctuations.
Pulsed radiation therapy for the treatment of newly diagnosed glioblastoma
Authors: Almahariq Muayad F , Quinn Thomas J , Arden Jessica D , Roskos P T , Wilson George D , Marples Brian , Grills Inga S , Chen Peter Y , Krauss Daniel J , Chinnaiyan Prakash , Dilworth Joshua T 
Published: July 2020

AbstractBackgroundPulsed radiation therapy (PRT) has shown effective tumor control and superior normal-tissue sparing ability compared with standard radiotherapy (SRT) in preclinical models and retrospective clinical series. This is the first prospective trial to investigate PRT in the treatment of patients with newly diagnosed glioblastoma (GBM).MethodsThis is a single-arm, prospective study. Patients with newly diagnosed GBM underwent surgery, followed by 60 Gy of PRT with concurrent temozolomide (TMZ). Each day, a 2-Gy fraction was divided into ten 0.2-Gy pulses, separated by 3-minute intervals. Patients received maintenance TMZ. Neurocognitive function (NCF) and quality of life (QoL) were monitored for 2 years using the Hopkins Verbal Learning Test‒Revised and the European Organisation for Research and Treatment of Cancer QLQ-C30 QoL questionnaire. Change in NCF was evaluated based on a minimal clinically important difference (MCID) threshold of 0.5 standard deviation.ResultsTwenty patients were enrolled with a median follow-up of 21 months. Median age was 60 years. Forty percent underwent subtotal resection, and 60% underwent gross total resection. One patient had an isocitrate dehydrogenase (IDH)–mutated tumor. Median progression-free survival (PFS) and overall survival (OS) were 10.7 and 20.9 months, respectively. In a post-hoc comparison, median OS for the prospective cohort was longer, compared with a matched cohort receiving SRT (20.9 vs 14 mo, P = 0.042). There was no decline in QoL, and changes in NCF scores did not meet the threshold of an MCID.ConclusionsTreatment of newly diagnosed GBM with PRT is feasible and produces promising effectiveness while maintaining neurocognitive function and QoL. Validation of our results in a larger prospective trial warrants consideration.