bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting the role of Krüppel homolog 1 in the metamorphosis and female reproduction of the cotton bollworm, Helicoverpa armigera
Authors: Zhang W.‐N. , Ma L. , Liu C. , Chen L. , Xiao H.‐J. , Liang G.‐M. 
Published: May 2018

AbstractIn insects, metamorphosis and reproduction are controlled by juvenile hormone (JH) and 20‐hydroxyecdysone (20E). Krüppel homolog 1 (Kr‐h1), a transcription factor, is regarded as a JH‐early inducible gene responsible for the repression of metamorphosis. However, the role of Kr‐h1 in reproduction of holometabolic insects is relatively less understood. In this study, we studied the role of Kr‐h1 in larvae–pupae transition and female reproduction in the major agricultural pest Helicoverpa armigera. Two HaKr‐h1 isoforms (HaKr‐h1α and HaKr‐h1ß) were identified, with HaKr‐h1α predominant in the cotton bollworm. In larvae, HaKr‐h1 was predominately expressed in the epidermis and markedly up‐regulated during the moult stage, whereas in adults HaKr‐h1 was mainly expressed in females and the highest transcription was detected in the ovaries. Considering the function of hormones in larval metamorphosis, we examined the modulation of gene expression in response to hormones, which showed that HaKr‐h1 was significantly induced by both JH analogue (JHA) and 20E. Knockdown of HaKr‐h1 in fifth‐instar larvae resulted in precocious metamorphosis from larvae to pupae. Moreover, a fluorescence immunoassay coupled with heterologous expression revealed that HaKr‐h1 was localized in the nucleus of oocyte membrane. In female adults, depletion of HaKr‐h1 severely repressed the transcription of vitellogenin, disrupted oocyte maturation and reduced the number of eggs laid, suggesting that HaKr‐h1 is required for vitellogenesis and egg production in H. armigera. The present study provides insight into the roles of HaKr‐h1 in JH‐mediated reproduction and highlights HaKr‐h1 as a target for suppression of lepidopteran pests.
Using ‘collective omics data’ for biomedical research training
Authors: Chaussabel Damien , Rinchai Darawan 
Published: April 2018

SummarySystems‐scale molecular profiling data accumulating in public repositories may constitute a useful resource for immunologists. It is for instance likely that information relevant to their chosen line of research be found among the more than 90,000 data series available in the NCBI Gene Expression Omnibus. Such ‘collective omics data’ may also be employed as source material for training purposes. This is the case when training curricula aim at the development of bioinformatics skills necessary for the analysis, interpretation or visualization of data generated on global scales. But ‘collective omics data’ may also be reused for training purposes to foster the development of the skills and ‘mental habits’ underpinning traditional reductionist science approaches. This review describes a small‐scale initiative involving investigators, for the most part immunologists, having engaged in a range of training activities relying on ‘collective omics data’.
Iterated local search and simulated annealing algorithms for the inventory routing problem
Authors: Alvarez Aldair , Munari Pedro , Morabito Reinaldo 
Published: May 2018

AbstractThis paper addresses the inventory routing problem (IRP), which consists in defining the customer visit schedule, the delivery quantities, and the vehicle routing plan to meet the demands of a set of customers over a given time horizon. We consider the variant with a single item, a single supplier, multiple vehicles, and a finite multiperiod planning horizon, minimizing the sum of inventory and travel costs. In addition, we address an alternative objective function that minimizes the logistic ratio, defined as the total travel cost divided by the total quantity delivered to customers. This second objective function, while more realistic in some logistics settings, poses a challenge for integer programming models and exact methods because of its nonlinearity. To our knowledge, no heuristic method has been proposed to address this objective in the IRP variant addressed in this paper. To solve this problem with each of these objective functions, we propose effective metaheuristic algorithms based on iterated local search and simulated annealing. Computational experiments show that these algorithms provide reasonably high‐quality solutions in relatively short running times for both objective functions when compared to other methods for well‐known instances from the literature. Moreover, the algorithms produce new best solutions for some of these instances.
Directing adipose‐derived stem cells into keratinocyte‐like cells: impact of medium composition and culture condition
Authors: Petry L. , Kippenberger S. , Meissner M. , Kleemann J. , Kaufmann R. , Rieger U.M. , Wellenbrock S. , Reichenbach G. , Zöller N. , Valesky E. 
Published: April 2018

AbstractBackgroundAdipose‐derived stem cells (ASC) are known to transdifferentiate into a wide range of different cell species in vitro including along the epidermal lineage. This property makes them a promising tool for regenerative medicine to restore the epidermal barrier.ObjectiveThis study is dedicated to identify in vitro conditions enabling transdifferentiation to a keratinocyte‐like phenotype. In particular, the impact of different culture conditions (media compositions, 2D, 3D cultures) and extracellular matrix (ECM) molecules was evaluated.MethodsAdipose‐derived stem cells derived from subcutaneous abdominal fat were characterized by stemness‐associated markers and subjected to different media. Epithelial differentiation in 2D cultures was monitored by pan‐cytokeratin expression using flow cytometry and immunocytochemistry. To evaluate the impact of different ECM molecules on epidermal stratification, 3D cultures were produced, lifted to the air–liquid interface (ALI) and examined by histological analysis and quantitative real‐time RT–PCR.ResultsWe identified a medium composition containing retinoic acid, hydrocortisone, ascorbic acid and BMP‐4 enabling maximum pan‐cytokeratin expression in 2D cultures. Moreover, adhesion to type IV collagen further promotes the pan‐cytokeratin expression. When cultures were lifted to the ALI, significant stratification was observed, particularly in supports coated with type IV collagen or fibronectin. Moreover, epidermal differentiation markers (involucrin, cytokeratin 1 and 14) become induced.ConclusionConditions with hampered wound healing such as non‐healing ulcers demand new treatment regimes. The here introduced optimized protocols for transdifferentiation of ASC into keratinocyte‐like cells may help to establish more effective treatment procedures.
Anxiety and depression in patients with moderate‐to‐severe psoriasis and comparison of change from baseline after treatment with guselkumab vs. adalimumab: results from the Phase 3 VOYAGE 2 study
Authors: Gordon K.B. , Armstrong A.W. , Han C. , Foley P. , Song M. , Wasfi Y. , You Y. , Shen Y.‐K. , Reich K. 
Published: April 2018

AbstractBackgroundAnxiety and depression are clinically significant comorbidities associated with psoriasis. Improvements in psoriasis are known to decrease anxiety and depression. Guselkumab, an anti‐interleukin‐23 monoclonal antibody, has demonstrated efficacy and safety for the treatment of moderate‐to‐severe psoriasis.ObjectiveAssess improvements in anxiety and depression with guselkumab vs. placebo and adalimumab using the Hospital Anxiety and Depression Scale (HADS).MethodsIn VOYAGE 2, a Phase 3, randomized, double‐blind, placebo‐ and adalimumab‐controlled study, patients received placebo (through week 16 followed by crossover to guselkumab), guselkumab, or adalimumab through week 24. HADS consists of two subscales measuring anxiety (HADS‐A) and depression (HADS‐D), with scores ranging from 0 to 21 and higher scores indicating more severe symptoms. Scores ≥8 indicate instrument‐defined anxiety or depression. Severity of psoriasis was assessed using the Psoriasis Area and Severity Index (PASI).ResultsAmong 989 patients randomized (with baseline HADS measurements), mean HADS‐A and HADS‐D scores were 6.8 ± 4.2 and 5.3 ± 4.2, respectively; 38.6% of patients reported HADS‐A ≥8 and 27.7% HADS‐D ≥8 at baseline. At week 16, a significantly greater proportion of guselkumab patients with baseline HADS‐A or HADS‐D ≥8 reported HADS‐A <8 (51.4% vs. 25.9%; P < 0.001) or HADS‐D <8 (59.2% vs. 27.0%; P < 0.001) vs. placebo patients. At week 24, a greater proportion of guselkumab patients with baseline HADS‐A or HADS‐D ≥8 reported HADS‐A <8 (58.4% vs. 42.9%; P = 0.028) or HADS‐D <8 (59.8% vs. 46.4%; P = 0.079) vs. adalimumab patients. PASI improvements correlated with improvement in anxiety (r = 0.27; P < 0.0001) and depression (r = 0.25; P < 0.0001) scores in patients with baseline HADS‐A or HADS‐D ≥8. Greater improvements in HADS were also observed at week 16 in guselkumab‐treated patients vs. placebo using a more stringent cut‐off of HADS ≥11.ConclusionGuselkumab treatment was associated with greater improvements in symptoms of anxiety and depression scores in patients with psoriasis compared with placebo and adalimumab.
Longitudinal subungual acanthoma: one denomination for various clinical presentations
Authors: Baran R. , Moulonguet I. , Goettmann‐Bonvallot S. , Encaoua R. , Robert C. 
Published: April 2018

AbstractBackgroundBenign subungual proliferation of the distal nail matrix and bed such as longitudinal keratosis, seborrhoeic keratosis or onychocytic matricoma should belong to a single spectrum of diseases.ObjectiveThis article intends to demonstrate clinically and histologically the different facets of Nail unit longitudinal acanthoma.MethodsWe report three new cases that present as a longitudinal melanonychia with thickening of the nail plate in two of them and as leukoxanthonychia in the third one. We compared them with the two original cases we described in 1999, reminiscent of seborrhoeic keratosis and all the new cases published since then.ResultsWe therefore consider that all these tumours belong to a single spectrum of diseases, we have called ‘nail unit longitudinal acanthoma’ which describes a histopathological process. The distinct clinical features of these tumours, melanonychia or leukoxanthonychia may be linked to their variable anatomic locations in different zones of the nail unit.
Long‐term real‐life safety profile and effectiveness of fumaric acid esters in psoriasis patients: a single‐centre, retrospective, observational study
Authors: Dickel H. , Bruckner T. , Altmeyer P. 
Published: April 2018

AbstractBackgroundFumaric acid esters (FAEs) are an established systemic treatment for moderate‐to‐severe psoriasis. However, the long‐term clinical safety and effectiveness of continuous FAE monotherapy and combination therapy have not been established.ObjectiveTo examine the long‐term safety and effectiveness of FAEs as monotherapy and in combination with phototherapy or methotrexate in patients with psoriasis treated at a single centre in Germany.MethodsThis monocentric, retrospective observational study, with a follow‐up period of up to 32.5 years, included 859 patients: 626 received FAE monotherapy, 123 received FAEs with concomitant phototherapy and 110 received FAEs with methotrexate.ResultsApproximately half of patients (49.0%) reported adverse events (566 total events), most of which involved the gastrointestinal tract. Serious adverse events were reported in 2.3% of patients, but none were deemed to have a causal relationship with any of the treatment regimens. Adverse events leading to treatment discontinuation were observed in 12.9% of patients. A median duration of 1 year was observed in all three treatment subcohorts (P = 0.70) from initiation of FAE treatment to a 50% response rate, where response was defined as achieving a cumulative static Physician's Global Assessment (PGA) score of ‘light’ and at least a 2‐point reduction in baseline PGA. A 50% response rate for the cumulative Psoriasis Area and Severity Index 75 was achieved in the FAE monotherapy subcohort after a median of 3 years of treatment, in the FAEs + phototherapy subcohort after 6.7 years and in the FAEs + methotrexate subcohort after 8.1 years (P = 0.001).ConclusionAccording to our data, FAEs as monotherapy or in combination with phototherapy or methotrexate are safe and beneficial for long‐term clinical use. However, multicentre, randomized controlled trials are required to establish the clinical value of monotherapy versus combination therapy and the optimal treatment duration.
Cutaneous melanoma in France in 2015 attributable to solar ultraviolet radiation and the use of sunbeds
Authors: Arnold M. , Kvaskoff M. , Thuret A. , Guénel P. , Bray F. , Soerjomataram I. 
Published: April 2018

AbstractBackgroundExposure to solar ultraviolet radiation (UVR) and the use of UV‐emitting tanning devices are associated with cutaneous malignant melanoma occurrence.ObjectiveThe aim of this study was to quantify the proportion and number of melanoma cases attributable to solar UVR exposure and sunbed use in France in 2015.MethodsPopulation attributable fractions (PAFs) and numbers of melanoma cases attributable to solar UVR exposure were estimated by age and sex using the incidence rates of a 1903 birth cohort as the primary reference. Further analyses were performed using the following: (i) contemporary melanoma incidence rates in low‐incidence regions within France and (ii) national melanoma incidence rates for the year 1980, as additional references. Assuming a 15‐year lag period, PAF and melanoma cases attributable to sunbed use were calculated using prevalence estimates from a cross‐sectional population survey and published relative risk estimates.ResultsIn 2015, an estimated 10 340 melanoma cases diagnosed in French adults were attributable to solar UVR exposure, corresponding to 83% of all melanomas and 3% of all cancer cases in that year. PAFs for melanoma were highest in the youngest age group (30–49 years) and higher in men than in women (89% vs. 79%). A total of 382 melanoma cases occurring in French adults in 2015 were attributed to the use of sunbeds, equivalent to 1.5% and 4.6% of all melanoma cases in men and women, respectively.ConclusionsA considerable proportion of melanoma cases in France in 2015 were attributable to solar UVR exposure, suggesting that targeted prevention strategies need to be implemented.
The effects of season and weather on healthcare utilization among patients with atopic dermatitis
Authors: Hamann C.R. , Andersen Y.M.F. , Engebretsen K.A. , Skov L. , Silverberg J.I. , Egeberg A. , Thyssen J.P. 
Published: April 2018

AbstractBackgroundPatient‐reported triggers for atopic dermatitis (AD) flares include changes in ultraviolet irradiation, humidity and temperature.ObjectivesTo identify the relationships between weather data and healthcare utilization in AD patients.MethodsUsing nationwide healthcare registries, clinic (1994–2012) and hospital visits (1977–2012) for AD treatment were calculated as well as monthly totals of topical corticosteroid (TCS) (1996–2012) and calcineurin inhibitor (TCI) prescriptions (2003–20012) filled by AD patients. We calculated monthly averages of temperature, atmospheric pressure, cloud cover and hours of bright sunlight and compared these variables to healthcare utilization endpoints, for the years 2000–2012 (n = 156 months), using linear regression models.ResultsIn Denmark, between the year 2000 and 2012, mean monthly totals of AD emergency room visits were 6, AD hospitalizations 32, AD outpatient visits 170, TCS prescriptions filled by AD patients 3811 and TCI prescriptions 2552. Healthcare utilization among AD patients was highest in winter/spring. Temperature was the environmental variable that had the strongest association with healthcare utilization: per 1°C lower monthly temperature, 2 more (95% confidence interval [CI] 1–4) AD clinic/hospital visits hospitalizations were observed, 18 (95% CI 9–26) more TCS prescriptions and 53 (95% CI 36–70) more TCI prescriptions were filled by patients with AD. Environmental variables were highly correlated. Associations between AD healthcare utilization and hours of cloud cover were generally positive, while those with hours of bright sunlight were generally inverse.ConclusionsAD healthcare utilization markers changed significantly with season. A decline in temperature correlated well with AD patients’ healthcare utilization, but a causative role could not be determined with certainty.
Subclinical enthesopathy of extensor digitorum tendon is highly prevalent and associated with clinical and ultrasound alterations of the adjacent fingernails in patients with psoriatic disease
Authors: Moya Alvarado P. , Roé Crespo E. , Muñoz‐Garza F.Z. , López‐Ferrer A. , Laiz Alonso A. , Vilarrassa Rull E. , Casademont i Pou J. , Puig Sanz L. 
Published: April 2018

AbstractBackgroundNail psoriasis disease is associated with an increased probability of psoriatic arthritis, and its clinical signs may have different correlates with the pathogenesis of adjacent bone destruction and have different prognostic value. Recent publications about psoriasis and nail psoriatic disease describe different ultrasonographic findings but the relationship between these ungueal alterations measured by ultrasonography and the presence of enthesopathy of the extensor digitorum has yet to be discovered.ObjectiveTo describe which ultrasonographic characteristics of nail psoriasis are associated with the presence of subclinical enthesopathy in patients with PsO and asymptomatic PsA.MethodsPatients with psoriasis and asymptomatic psoriatic arthritis were included in the prospective study. Demographic, clinical data and PASI and NAPSI indexes were recorded of all the patients in the assessment visit. The US assessment included Achilles tendon, extensor digitorum tendon and US scan of the nail plate, nail matrix, nail bed and adjacent skin over nail matrix of the five nails of each hand.ResultsForty‐eight patients were included in the study; 33 of them presented ultrasound evidence of extensor digitorum tendon enthesopathy. Nails of the patients with subclinical enthesopathy had a higher NAPSI and skin thickness than the nails of the patients without subclinical enthesopathy (P = 0.047). Patients with asymptomatic enthesopathy had significantly thicker proximal nail folds (1.44 ± 0.312 vs. 1.23 ± 0.27, P = 0.023). Nail beds and matrices were also thicker but the differences were not statistically significant (1.77 ± 0.27 vs. 1.74 ± 0.21, P = 0.66, and 1.79 ± 0.28 vs. 1.67 ± 0.19, P = 0.10, respectively). No statistically significant differences in the trilaminar structure were found between both groups. Patients with and without asymptomatic enthesopathy of extensor digitorum tendons did not statistically differ as regards ultrasonographic alterations of the Achilles tendons (60.6% vs. 46.4%, P 0.368).ConclusionEnthesopathy abnormalities can be detected by US in patients with psoriasis without musculoskeletal complaints frequently. There is a close relationship between subclinical enthesopathy of the extensor digitorum tendon and the presence of nail alterations. Further studies are required to research what implications have the presence of these ungual alterations measured by US, and how it affects later development of a PsA.
Mohs micrographic surgery for nail unit tumours: an update and a critical review of the literature
Authors: Lambertini M. , Piraccini B.M. , Fanti P.A. , Dika E. 
Published: April 2018

AbstractMohs micrographic surgery (MMS) is a good treatment option for epithelial neoplasms, especially when localized in areas where tissue conservation is crucial, such as the nail unit (NU). MMS is a method of radical excision offering high cure rates due to the margin control and functional preservation. Our aim is to provide a review on the use of MMS for the treatment of the most common nail tumours. We revised the current literature on the use of MMS to treat malignant neoplasms (Bowen's disease, squamous cell carcinoma, melanoma, basal cell carcinoma, keratoacanthoma, carcinoma cuniculatum) and benign neoplasms (onychomatricoma and glomus tumour). MMS represents a successful surgical option for nail tumours, firstly in terms of tissue conservation: the NU anatomy is complex and the preservation of the component structures is imperative for its functionality. Secondly, due to the surgical radicality, which is essential not only for the clearing of malignant tumours, but also for benign cases, in order to reduce recurrences. Although a conservative treatment of NU melanoma with MMS has been proposed, in our experience, the conservative approach with functional surgery is a good option for the treatment of non‐invasive melanoma (in situ and Ia).
Emerging concepts on the role of epigenetics in the relationships between nutrition and health
Authors: Stover P. J. , James W. P. T. , Krook A. , Garza C. 
Published: April 2018

AbstractUnderstanding the physiological and metabolic underpinnings that confer individual differences in responses to diet and diet‐related chronic disease is essential to advance the field of nutrition. This includes elucidating the differences in gene expression that are mediated through programming of the genome through epigenetic chromatin modifications. Epigenetic landscapes are influenced by age, genetics, toxins and other environmental factors, including dietary exposures and nutritional status. Epigenetic modifications influence transcription and genome stability are established during development with life‐long consequences. They can be inherited from one generation to the next. The covalent modifications of chromatin, which include methylation and acetylation, on DNA nucleotide bases, histone proteins and RNA are derived from intermediates of one‐carbon metabolism and central metabolism. They influence key physiological processes throughout life, and together with inherited DNA primary sequence, contribute to responsiveness to environmental stresses, diet and risk for age‐related chronic disease. Revealing diet–epigenetic relationships has the potential to transform nutrition science by increasing our fundamental understanding of: (i) the role of nutrients in biological systems, (ii) the resilience of living organisms in responding to environmental perturbations, and (iii) the development of dietary patterns that programme physiology for life‐long health. Epigenetics may also enable the classification of individuals with chronic disease for specific dietary management and/or for efficacious diet‐pharmaceutical combination therapies. These new emerging concepts at the interface of nutrition and epigenetics were discussed, and future research needs identified by leading experts at the 26th Marabou Symposium entitled ‘Nutrition, Epigenetics, Genetics: Impact on Health and Disease’.For a compilation of the general discussion at the marabou symposium, click here http://www.marabousymposium.org/.