bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severity of retinopathy of prematurity was associated with a higher risk of cerebral dysfunction in young adults born extremely preterm
Authors: Jacobson Lena , Vollmer Brigitte , Kistner Anna , Böhm Birgitta 
Published: July 2020

AbstractAimThis Swedish study evaluated whether the severity of retinopathy of prematurity (ROP) in extremely preterm infants was related to their overall outcome in young adulthood.MethodsWe followed 39 individuals born between 1988 and 1993 at less than 28 gestational weeks, included in the Stockholm Neonatal Project. A total of 19 were treated for severe ROP, and 20 had no or mild ROP. They were assessed for general cognitive abilities and mental health at 18 years of age and compared with 23 term‐born controls. Visual acuity was examined at 21‐25 years. They were asked about their education and everyday life.ResultsThe 19 individuals with severe treated ROP had lower visual acuity and higher risk for intellectual deficits, cerebral palsy and neuropsychiatric diagnoses than those with no or mild ROP and the term controls. Three were visually impaired, none were blind. They were less physically active than the other groups and had more problems finding their way around. However, nine were at university.ConclusionYoung adults treated for severe ROP had more problems resulting from cerebral dysfunction than those with no or mild ROP and term‐born controls. Retinal and brain pathologies in the extremely preterm infant constitute different expressions of neurovascular disease.
Translational engagement of lysophosphatidic acid receptor 1 in skin fibrosis: from dermal fibroblasts of patients with scleroderma to tight skin 1 mouse
Authors: Ledein Laetitia , Léger Bertrand , Dees Clara , Beyer Christian , Distler Alfiya , Vettori Serena , Boukaiba Rachid , Bidouard Jean Pierre , Schaefer Matthias , Pernerstorfer Josef , Ruetten Hartmut , Jagerschmidt Alexandre , Janiak Philip , Distler Jörg H.W. , Distler Oliver , Illiano Stéphane 
Published: July 2020

Background and PurposeGenetic deletion and pharmacological studies suggest a role for lysophosphatidic acid (LPA1) receptor in fibrosis. We investigated the therapeutic potential in systemic sclerosis (SSc) of a new orally active selective LPA1 receptor antagonist using dermal fibroblasts from patients and an animal model of skin fibrosis.Experimental ApproachDermal fibroblast and skin biopsies from systemic sclerosis patients were used. Myofibroblast differentiation, gene expression and cytokine secretion were measured following LPA and/or SAR100842 treatment. Pharmacolgical effect of SAR100842 was assessed in the tight skin 1 (Tsk1) mouse model.Key ResultsSAR100842 is equipotent against various LPA isoforms. Dermal fibroblasts and skin biopsies from patients with systemic sclerosis expressed high levels of LPA1 receptor. The LPA functional response (Ca2+) in systemic sclerosis dermal fibroblasts was fully antagonized with SAR100842. LPA induced myofibroblast differentiation in systemic sclerosis dermal and idiopathic pulmonary fibrosis lung fibroblasts and the secretion of inflammatory markers and activated Wnt markers. Results from systemic sclerosis dermal fibroblasts mirror those obtained in a mouse Tsk1 model of skin fibrosis. Using a therapeutic protocol, SAR100842 consistently reversed dermal thickening, inhibited myofibroblast differentiation and reduced skin collagen content. Inflammatory and Wnt pathway markers were also inhibited by SAR100842 in the skin of Tsk1 mice.Conclusion and ImplicationsThe effects of SAR100842 on LPA‐induced inflammation and on mechanisms linked to fibrosis like myofibroblast differentiation and Wnt pathway activation indicate that LPA1 receptor activation plays a key role in skin fibrosis. Our results support the therapeutic potential of LPA1 receptor antagonists in systemic sclerosis.
Effects of local forearm skin heating on skin properties
Authors: Mayrovitz Harvey N. 
Published: July 2020

AbstractThis study investigated impacts of local skin heating on skin properties and tested whether skin changes depended on heat‐induced hyperaemia. It was reasoned that heat‐induced vasodilation impacts accompanying interstitial fluid changes. Forearm skin was locally heated from a baseline of 35°C to 40–42°C in 30 young adults (15 females, 15 males, 24.9 ± 2.1 years) and non‐heated in 10 others (5 females, 5 males, 25.2 ± 1.3 years. Skin blood flow (SBF) was continuously measured using a laser Doppler method and skin tissue dielectric constant (TDC), stratum corneum capacitance (SCC) and transepidermal water loss (TEWL) were measured before and after maintained heat for 12 min. TDC values were determined to effective measurement depths of 1.5 mm (TDC15) and 2.5 mm (TDC25). Results showed a large heat‐induced hyperaemia, with SBF increasing on average 8.8‐fold from its baseline of 35°C. Heating also caused significant increases in TDC, SCC and TEWL that, compared to preheating, increased approximately 1.1‐fold, 3.1‐fold and 4.5‐fold. None of these skin changes correlated with the magnitude of the SBF hyperaemic response. Absence of this correlation may indicate that in young healthy adults, increased capillary filtration due to heat‐induced arteriolar vasodilation is rapidly accommodated by postcapillary reabsorption, enhanced lymphatic activity and TEWL processes. An alternate explanation is that heating caused increased red cell oscillations that were detected as part of the laser Doppler increase without representing increased capillary flux. The major determinant of the Increases in TDC, SCC and TEWL is likely a consequence of heat‐induced eccrine gland activation. Studies of older persons or those with depressed function are warranted.
Effect of setmelanotide, a melanocortin‐4 receptor agonist, on obesity in Bardet‐Biedl syndrome
Authors: Haws Robert , Brady Sheila , Davis Elisabeth , Fletty Kristina , Yuan Guojun , Gordon Gregory , Stewart Murray , Yanovski Jack 
Published: July 2020

AbstractAimTo report an analysis of ~1 year of setmelanotide treatment for obesity and hunger, as well as metabolic and cardiac outcomes, in individuals with Bardet‐Biedl syndrome (BBS).Materials and methodsIndividuals aged 12 years and older with BBS received once‐daily setmelanotide. The dose was titrated every 2 weeks to establish the individual therapeutic dose (≤3 mg); treatment continued for an additional 10 weeks. Participants who lost 5 kg or more (or ≥5% of body weight if <100 kg at baseline) continued into the 52‐week extension phase. The primary outcome was mean percent change from baseline in body weight at 3 months. Hunger scores and safety were secondary outcomes.ResultsFrom February 2017 and February 2018, 10 individuals were screened; eight completed the 3‐month treatment phase and seven completed the extension phase. Mean percent change in body weight from baseline to 3 months was −5.5% (90% CI, −9.3% to −1.6%; n = 8); change from baseline was −11.3% (90% CI, −15.5% to −7.0%; n = 8) at 6 months and −16.3% (90% CI, −19.9% to −12.8%; n = 7) at 12 months. All participants reported at least one treatment‐emergent adverse event (AE), most commonly injection‐site reaction. No AEs led to study withdrawal or death. Most, morning, and average hunger scores were reduced across time points.ConclusionsSetmelanotide reduced body weight and hunger in individuals with BBS and had a safety profile consistent with previous reports. Setmelanotide may be a treatment option in individuals with BBS‐associated obesity and hyperphagia.
Using a newly introduced framework to measure ecological stressor interactions
Authors: Tekin Elif , Diamant Eleanor S. , Cruz‐Loya Mauricio , Enriquez Vivien , Singh Nina , Savage Van M. , Yeh Pamela J. 
Published: July 2020

AbstractUnderstanding how stressors combine to affect population abundances and trajectories is a fundamental ecological problem with increasingly important implications worldwide. Generalisations about interactions among stressors are challenging due to different categorisation methods and how stressors vary across species and systems. Here, we propose using a newly introduced framework to analyse data from the last 25 years on ecological stressor interactions, for example combined effects of temperature, salinity and nutrients on population survival and growth. We contrast our results with the most commonly used existing method – analysis of variance (ANOVA) – and show that ANOVA assumptions are often violated and have inherent limitations for detecting interactions. Moreover, we argue that rescaling – examining relative rather than absolute responses – is critical for ensuring that any interaction measure is independent of the strength of single‐stressor effects. In contrast, non‐rescaled measures – like ANOVA – find fewer interactions when single‐stressor effects are weak. After re‐examining 840 two‐stressor combinations, we conclude that antagonism and additivity are the most frequent interaction types, in strong contrast to previous reports that synergy dominates yet supportive of more recent studies that find more antagonism. Consequently, measuring and re‐assessing the frequency of stressor interaction types is imperative for a better understanding of how stressors affect populations.
P‐glycoprotein overactivity in epileptogenic developmental lesions measured in vivo using (R)‐[11C]verapamil PET
Authors: Ilyas‐Feldmann Maria , Asselin Marie‐Claude , Wang Shaonan , McMahon Adam , Anton‐Rodriguez José , Brown Gavin , Hinz Rainer , Duncan John S. , Sisodiya Sanjay M. , Koepp Matthias 
Published: July 2020

AbstractObjectiveOverexpression of the drug transporter P‐glycoprotein (P‐gp) is thought to be involved in drug‐resistance in epilepsy by extrusion of antiepileptic drugs (AEDs). We used positron emission tomography (PET) and the P‐gp substrate radiotracer (R)‐[11C]verapamil (VPM) together with the third‐generation P‐gp inhibitor tariquidar (TQD) to evaluate P‐gp function in individuals with drug‐resistant epileptogenic developmental lesions.MethodsTwelve healthy controls (7 male, median age 45, range 35‐55 years), and two patients with epileptogenic developmental lesions (2 male, aged 24 and 62 years) underwent VPM‐PET scans before and 60 minutes after a 30‐minute infusion of 2 and 3 mg/kg TQD. The influx rate constant, VPM‐K1, was estimated from the first 10 minutes of dynamic data using a single‐tissue compartment model with a VPM plasma input function. Statistical parametric mapping (SPM) analysis was used to compare individual patients with the healthy controls.ResultsAt baseline, SPM voxel‐based analysis revealed significantly lower uptake of VPM corresponding to the area of the epileptogenic developmental lesion compared to 12 healthy controls (P < .048). This was accentuated following P‐gp inhibition with TQD. After TQD, the uptake of VPM was significantly lower in the area of the epileptogenic developmental lesion compared to controls (P < .002).SignificanceThis study provides further evidence of P‐gp overactivity in patients with drug‐resistant epilepsy, irrespective of the type of lesion. Identifying P‐gp overactivity as an underlying contributor to drug‐resistance in individual patients will enable novel treatment strategies aimed at overcoming or reversing P‐gp overactivity.
Microtubule‐associated proteins and emerging links to primary cilium structure, assembly, maintenance, and disassembly
Authors: Conkar Deniz , Firat‐Karalar Elif Nur 
Published: July 2020

The primary cilium is a microtubule‐based structure that protrudes from the cell surface in diverse eukaryotic organisms. It functions as a key signaling center that decodes a variety of mechanical and chemical stimuli and plays fundamental roles in development and homeostasis. Accordingly, structural and functional defects of the primary cilium have profound effects on the physiology of multiple organ systems including kidney, retina, and central nervous system. At the core of the primary cilium is the microtubule‐based axoneme, which supports the cilium shape and acts as the scaffold for bidirectional transport of cargoes into and out of cilium. Advances in imaging, proteomics, and structural biology have revealed new insights into the ultrastructural organization and composition of the primary cilium, the mechanisms that underlie its biogenesis and functions, and the pathologies that result from their deregulation termed ciliopathies. In this viewpoint, we first discuss the recent studies that identified the three‐dimensional native architecture of the ciliary axoneme and revealed that it is considerably different from the well‐known '9 + 0' paradigm. Moving forward, we explore emerging themes in the assembly and maintenance of the axoneme, with a focus on how microtubule‐associated proteins regulate its structure, length, and stability. This far more complex picture of the primary cilium structure and composition, as well as the recent technological advances, open up new avenues for future research.
Preclinical insights into the gut‐skeletal muscle axis in chronic gastrointestinal diseases
Authors: Ehlers Luise , Bannert Karen , Rohde Sarah , Berlin Peggy , Reiner Johannes , Wiese Mats , Doller Julia , Lerch Markus M. , Aghdassi Ali A. , Meyer Fatuma , Valentini Luzia , Agrifoglio Ottavia , Metges Cornelia C. , Lamprecht Georg , Jaster Robert 
Published: July 2020

AbstractMuscle wasting represents a constant pathological feature of common chronic gastrointestinal diseases, including liver cirrhosis (LC), inflammatory bowel diseases (IBD), chronic pancreatitis (CP) and pancreatic cancer (PC), and is associated with increased morbidity and mortality. Recent clinical and experimental studies point to the existence of a gut‐skeletal muscle axis that is constituted by specific gut‐derived mediators which activate pro‐ and anti‐sarcopenic signalling pathways in skeletal muscle cells. A pathophysiological link between both organs is also provided by low‐grade systemic inflammation. Animal models of LC, IBD, CP and PC represent an important resource for mechanistic and preclinical studies on disease‐associated muscle wasting. They are also required to test and validate specific anti‐sarcopenic therapies prior to clinical application. In this article, we review frequently used rodent models of muscle wasting in the context of chronic gastrointestinal diseases, survey their specific advantages and limitations and discuss possibilities for further research activities in the field. We conclude that animal models of LC‐, IBD‐ and PC‐associated sarcopenia are an essential supplement to clinical studies because they may provide additional mechanistic insights and help to identify molecular targets for therapeutic interventions in humans.
The systemic inflammatory response following hand instrumentation versus ultrasonic instrumentation—A randomized controlled trial
Authors: Johnston William , Paterson Michael , Piela Krystyna , Davison Emily , Simpson Annabel , Goulding Marilyn , Ramage Gordon , Sherriff Andrea , Culshaw Shauna 
Published: July 2020

AbstractObjectiveThis study sought to investigate whether the immediate systemic inflammatory response following full‐mouth debridement differs following use of hand compared with ultrasonic instruments.MethodsThirty‐nine periodontitis patients were randomized to treatment with full‐mouth debridement using either hand or ultrasonic instrumentation completed within 24 hr. Serum and periodontal clinical parameters were collected at baseline, day 1, day 7 and day 90 post‐treatment. Differences in systemic inflammatory markers were assessed using general linear models at each timepoint, corrected for age, gender, smoking status, body mass index and baseline levels of each marker.ResultsAcross all patients, serum C‐reactive protein increased at day 1, with no differences between hand and ultrasonic groups (p(adjusted) = .22). There was no difference between groups in interleukin‐6 (p(adjusted) = .29) or tumour necrosis factor α (p(adjusted) = .53) at day 1. Inflammatory markers returned to baseline levels by day 7. Treatment resulted in equal and marked improvements in clinical parameters in both groups; however, total treatment time was on average shorter for ultrasonic instruments (p(adjusted) = .002).ConclusionsUltrasonic instrumentation resulted in shorter treatment time with comparable clinical outcomes. Levels of serum C‐reactive protein at day 1 were similar following debridement with hand or ultrasonic instruments.
Loss of metabolic flexibility as a result of overexpression of pyruvate dehydrogenase kinases in muscle, liver and the immune system: Therapeutic targets in metabolic diseases
Authors: Jeon Jae‐Han , Thoudam Themis , Choi Eun Jung , Kim Min‐Ji , Harris Robert A , Lee In‐Kyu 
Published: July 2020

AbstractGood health depends on the maintenance of metabolic flexibility, which in turn is dependent on the maintenance of regulatory flexibility of a large number of regulatory enzymes, but especially the pyruvate dehydrogenase complex (PDC), because of its central role in carbohydrate metabolism. Flexibility in regulation of PDC is dependent on rapid changes in the phosphorylation state of PDC determined by the relative activities of the pyruvate dehydrogenase kinases (PDKs) and the pyruvate dehydrogenase phosphatases. Inactivation of the PDC by overexpression of PDK4 contributes to hyperglycemia, and therefore the serious health problems associated with diabetes. Loss of regulatory flexibility of PDC occurs in other disease states and pathological conditions that have received less attention than diabetes. These include cancers, non‐alcoholic fatty liver disease, cancer‐induced cachexia, diabetes‐induced nephropathy, sepsis and amyotrophic lateral sclerosis. Overexpression of PDK4, and in some situations, the other PDKs, as well as under expression of the pyruvate dehydrogenase phosphatases, leads to inactivation of the PDC, mitochondrial dysfunction and deleterious effects with health consequences. The possible basis for this phenomenon, along with evidence that overexpression of PDK4 results in phosphorylation of “off‐target” proteins and promotes excessive transport of Ca2+ into mitochondria through mitochondria‐associated endoplasmic reticulum membranes are discussed. Recent efforts to find small molecule PDK inhibitors with therapeutic potential are also reviewed.
Sex differences in sarcopenia and frailty among community‐dwelling Korean older adults with diabetes: The Korean Frailty and Aging Cohort Study
Authors: Kang Sunyoung , Oh Tae Jung , Cho Be Long , Park Yong Soon , Roh Eun , Kim Hyeon Ju , Lee Sam‐Gyu , Kim Bong Jo , Kim Miji , Won Chang Won , Jang Hak Chul 
Published: July 2020

AbstractAims/IntroductionWe aimed to examine the prevalence of sarcopenia and frailty in Korean older adults with diabetes compared with individuals without diabetes.Materials and MethodsWe analyzed the data of 2,403 participants aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study. Sarcopenia was defined using the Asian Working Group for Sarcopenia and the Foundation for the National Institutes of Health. Frailty was assessed by the Cardiovascular Health Study frailty phenotype criteria.ResultsThe mean age of the participants was 76.0 ± 3.9 years, and 47.2% were men. The prevalence of diabetes was 30.2% in men and 25.8% in women. Adults with diabetes showed a lower muscle mass index (appendicular skeletal muscle mass/body mass index) and handgrip strength in both sexes, but only the women showed decreased physical performance. Women with diabetes presented a higher prevalence of sarcopenia diagnosed by the Foundation for the National Institutes of Health criteria, and frailty compared with participants without diabetes (sarcopenia 14.7% vs 8.5%, P = 0.001; frailty 9.5% vs 4.9%, P = 0.003). Men in the high and middle tertiles for homeostatic model assessment of insulin resistance presented a significantly higher prevalence of sarcopenia, compared with men in the low tertile homeostatic model assessment of insulin resistance (high tertile 16.6%, middle tertile 13.3%, low tertile 8.6%).ConclusionsIn older adults with diabetes, muscle mass index and muscle strength were lower than in those without diabetes. However, the prevalence of sarcopenia and frailty was higher and physical performance was lower only in women with diabetes.
Nesidiocoris tenuis as a pest in Northwest Europe: Intervention threshold and influence of Pepino mosaic virus
Authors: Moerkens Rob , Pekas Apostolos , Bellinkx Stijn , Hanssen Inge , Huysmans Marlies , Bosmans Lien , Wäckers Felix 
Published: July 2020

AbstractThe use of Nesidiocoris tenuis (Hemiptera: Miridae) as a biocontrol agent is controversial as it is considered a pest in Northwest European tomato greenhouses, due to its tendency to damage the plant and fruit. Necessary chemical plant protection products to control N. tenuis have toxic side effects on important beneficials like Macrolophus pygmaeus (Hemiptera: Miridae), which jeopardizes the whole IPM programme. In this study, several commercial tomato greenhouses were monitored for mirid populations. The relationship between the number of N. tenuis individuals and plant damage was assessed in function of availability of prey and interaction with M. pygmaeus. These greenhouse data were used to determine a practical density intervention threshold. Next, the hypothesis that a Pepino mosaic virus (PepMV) infection increases plant and fruit damage by N. tenuis (as has been shown for M. pygmaeus) was tested. Plant damage occurred when the average number of predatory bugs in the head of the plant exceeded 16 per ten plants. Plant damage increased in severity at increasing predatory bug densities, independent of the availability of prey and M. pygmaeus presence. Plant and fruit damage were not affected by the presence of PepMV, as was shown for fruit damage in previous studies for M. pygmaeus. Our study provides a practical density intervention threshold for growers in greenhouse crops. Simple monitoring of the number of predatory bugs in the head of the plant can be used to take specific biocontrol actions. It was also shown that only the predatory bug N. tenuis itself causes damage, and there is no interaction with PepMV.
Epidemiology of Polypodium hydriforme in American Paddlefish
Authors: Okamura Beth , Hartigan Ashlie , Long Paul F. , Ruggeri Paolo , Smith‐Easter Katie , Schooley Jason D. 
Published: July 2020

AbstractPolypodium hydriforme is a parasitic cnidarian that develops within the eggs of acipenseriform fish in the Old and New Worlds. Currently regarded as monotypic, P. hydriforme has been studied largely in the context of caviar production in Russian sturgeon species. We report the first robust epidemiological study of P. hydriforme in North American acipenseriform fish. We sampled infection prevalences (in 2017 and 2018) and intensities (in 2017) during annual surveys of American Paddlefish, Polyodon spathula, caught during spawning migration in north‐eastern Oklahoma. Egg masses were characterized for the presence and intensity of P. hydriforme infection. Prevalences were similar in 2017 and 2018 (49% and 45%, respectively). Generally, a small number of eggs were infected per egg mass, but a few were heavily infected. Longer, heavier and older fish are more likely to be infected and to harbour more severe infections. In addition, infection is linked to decreases in roe fat weight independently of fish length, weight, age or roe weight. Infection thus diminishes Paddlefish energy reserves (roe fat) which could in turn impact host fitness. Our results raise questions about the impacts of infection on caviar production and Paddlefish conservation and suggest insights on infection dynamics and parasite strategies.