bluuebunny/crossref_metadata_2025_split huggingface dataset:
Indirubin and NAD+ prevent mitochondrial ischaemia/reperfusion damage in fatty livers
Authors: Teodoro João Soeiro , Varela Ana Teresa , Duarte Filipe Valente , Gomes Ana Patrícia , Palmeira Carlos Marques , Rolo Anabela Pinto 
Published: March 2018

AbstractBackgroundFatty livers are considerably more susceptible to acute stressors, such as ischaemia/reperfusion (I/R). As the incidence of I/R is high due to surgical events and some pathologies, there is an urgent need to find strategies against I/R injury (I/RI) in fatty livers. We postulate that an acute pretreatment with indirubin‐3′‐oxime (Ind) or NAD+ prevents mitochondrial dysfunction associated with warm I/RI in fatty livers.Materials and MethodsZucker fatty rats were subjected to warm ischaemia and 12 hours of reperfusion. Ind or NAD+ was administered in the hepatic artery 30 minutes before ischaemia. Hepatic mitochondrial isolation was performed, and functional assays as well as molecular analysis were performed.ResultsPretreatment decreased markers of liver injury while preserving mitochondrial cytochrome c content, which is related to the prevention of calcium‐induced mitochondrial permeability transition (mPT), the decline in mitochondrial respiratory state 3 and ATP content. The generation of reactive oxygen species (ROS) was also diminished. Inhibition of GSK‐3ß by Ind resulted in the prevention of cyclophilin‐D (CypD) phosphorylation, unabling it to bind to the adenine nucleotide translocator (ANT), thus, preventing mPT induction. Furthermore, deacetylation of CypD at Lys residue by sirtuin 3 (SIRT3) caused its dissociation from ANT, contributing to an increase in mPT threshold in NAD+‐pretreated animals.ConclusionsPretreatment with Ind or NAD+ protects fatty livers by maintaining mitochondrial calcium homoeostasis, thus, preserving mitochondrial function and energetic balance. As such, CypD might be a new protective target against I/RI in fatty livers.
The start of a new wave: Developments in proteasome inhibition in multiple myeloma
Authors: Yong Kwee , Gonzalez‐McQuire Sebastian , Szabo Zsolt , Schoen Paul , Hajek Roman 
Published: March 2018

AbstractMultiple myeloma (MM) accounts for 10% of hematological cancers. Stem cell transplantation remains the cornerstone of first‐line treatment for eligible patients, but historically, pharmaceutical treatment options for MM have been limited. The proteasome was identified as a target for MM therapy in the early 2000s and, in 2004, the boronic acid proteasome inhibitor bortezomib gained European approval. Bortezomib now plays a major role in MM treatment, but the duration of its use can be limited by toxicities such as peripheral neuropathy and the development of resistance. A new generation of proteasome inhibitors has since entered the treatment landscape: carfilzomib, an epoxyketone‐based agent with a distinct mode of action, high clinical efficacy, and lower levels of peripheral neuropathy compared with bortezomib, received approval in 2015 for use in patients with relapsed and/or refractory MM (RRMM). Ixazomib, a second‐generation, orally administered, boronic acid proteasome inhibitor, has also been approved for use in patients with RRMM. In just over a decade, proteasome inhibitor‐based regimens have become an integral component of MM treatment; with more proteasome inhibitors in development, this remains a vibrant research area with potential to improve the lives of patients with MM in the years to come.
How ecology shapes exploitation: a framework to predict the behavioural response of human and animal foragers along exploration–exploitation trade‐offs
Authors: Monk Christopher T. , Barbier Matthieu , Romanczuk Pawel , Watson James R. , Alós Josep , Nakayama Shinnosuke , Rubenstein Daniel I. , Levin Simon A. , Arlinghaus Robert 
Published: April 2018

AbstractUnderstanding how humans and other animals behave in response to changes in their environments is vital for predicting population dynamics and the trajectory of coupled social‐ecological systems. Here, we present a novel framework for identifying emergent social behaviours in foragers (including humans engaged in fishing or hunting) in predator–prey contexts based on the exploration difficulty and exploitation potential of a renewable natural resource. A qualitative framework is introduced that predicts when foragers should behave territorially, search collectively, act independently or switch among these states. To validate it, we derived quantitative predictions from two models of different structure: a generic mathematical model, and a lattice‐based evolutionary model emphasising exploitation and exclusion costs. These models independently identified that the exploration difficulty and exploitation potential of the natural resource controls the social behaviour of resource exploiters. Our theoretical predictions were finally compared to a diverse set of empirical cases focusing on fisheries and aquatic organisms across a range of taxa, substantiating the framework's predictions. Understanding social behaviour for given social‐ecological characteristics has important implications, particularly for the design of governance structures and regulations to move exploited systems, such as fisheries, towards sustainability. Our framework provides concrete steps in this direction.
Demand for neurological services in Central Eastern Europe: a 10‐year national survey in Hungary
Authors: Oberfrank F. , Ajtay A. , Bereczki D. 
Published: March 2018

Background and purposeIn order to plan neurological capacities at a national level for the next decade, the current use of neurological services should be evaluated. We analyzed the utilization of neurological services in Hungary, a country with a single‐payer health insurance system covering the whole population.MethodsWe created a database from medical reports submitted to the National Health Insurance Fund from all hospitals and outpatient services between 2004 and 2013. The number of subjects presenting to the neurological healthcare system and their major diagnoses by 10th International Classification of Diseases categories were analyzed. The overall healthcare service utilization of these patients was also estimated.ResultsOf the 10 million inhabitants, 2.9 million people used an inpatient or outpatient neurological service at least once over the 10‐year period. Annually, 1% of the population was admitted to neurological inpatient wards and 6% of the population used some neurological outpatient service. Major reasons for using neurological services were: cerebrovascular diseases (I60–I69; 1.2 million patients), episodic and paroxysmal disorders (G40–G47; 1.3 million patients) and general symptoms and signs (R50–R56; 1.3 million patients). The 2.9 million people had 12.7 million hospital admissions to any ward and 365.7 million outpatient visits to any specialist during the 10 years.ConclusionsThe demand for neurological services is high in Hungary; close to 30% of the population used an inpatient or outpatient neurological service at least once during this 10‐year period. Results from this project provide data for international comparisons and help to ensure better informed and more focused resource allocation.
Dose optimization of tacrolimus with therapeutic drug monitoring and CYP3A5 polymorphism in patients with myasthenia gravis
Authors: Chen D. , Hou S. , Zhao M. , Sun X. , Zhang H. , Yang L. 
Published: April 2018

Background and purposeTacrolimus is beneficial for treatment of myasthenia gravis (MG) and has a narrow therapeutic range. Therefore, therapeutic drug monitoring is essential for tacrolimus to optimize dosage and prevent adverse reactions. However, no studies have explored the factors influencing tacrolimus blood concentration in patients with MG. Thus, we aimed to analyze these factors and discuss how to optimize tacrolimus dosage for MG treatment.MethodsData regarding clinical characteristics, therapeutic drugs and adverse reactions of patients with MG who received tacrolimus were collected from 2013 to 2015 at Beijing Hospital. Tacrolimus whole‐blood concentrations were measured by chemiluminescent microparticle immunoassay and CYP3A5*3 gene polymorphism was detected by digital fluorescence molecule hybridization fluorescence. Regression analysis was applied to analyze the factors influencing blood concentrations and adverse reactions.ResultsIt was shown that there was a correlation between concentration and dosage. Furthermore, co‐administration of proton pump inhibitor and clarithromycin and CYP3A5*3 gene polymorphism could significantly increase the tacrolimus whole‐blood levels. Adverse reactions were related to blood concentration, CYP3A5 genetic polymorphisms and combined medication though logistic regression analysis.ConclusionsThe concentration of tacrolimus is affected by many factors. Therapeutic drug monitoring and detection of CYP3A5 gene polymorphism was essential for dosage optimization in patients with MG.
Common data elements for epilepsy mobile health systems
Authors: Goldenholz Daniel M. , Moss Robert , Jost David A. , Crone Nathan E. , Krauss Gregory , Picard Rosalind , Caborni Chiara , Cavazos Jose E. , Hixson John , Loddenkemper Tobias , Salazar Tracy Dixon , Lubbers Laura , Harte‐Hargrove Lauren C. , Whittemore Vicky , Duun‐Henriksen Jonas , Dolan Eric , Kasturia Nitish , Oberemk Mark , Cook Mark J. , Lehmkuhle Mark , Sperling Michael R. , Shafer Patricia O. 
Published: March 2018

SummaryObjectiveCommon data elements (CDEs) are currently unavailable for mobile health (mHealth) in epilepsy devices and related applications. As a result, despite expansive growth of new digital services for people with epilepsy, information collected is often not interoperable or directly comparable. We aim to correct this problem through development of industry‐wide standards for mHealth epilepsy data.MethodsUsing a group of stakeholders from industry, academia, and patient advocacy organizations, we offer a consensus statement for the elements that may facilitate communication among different systems.ResultsA consensus statement is presented for epilepsy mHealth CDEs.SignificanceAlthough it is not exclusive, we believe that the use of a minimal common information denominator, specifically these CDEs, will promote innovation, accelerate scientific discovery, and enhance clinical usage across applications and devices in the epilepsy mHealth space. As a consequence, people with epilepsy will have greater flexibility and ultimately more powerful tools to improve their lives.
A guide to studying human dermal adipocytes in situ
Authors: Nicu Carina , Pople Jennifer , Bonsell Laura , Bhogal Ranjit , Ansell David M. , Paus Ralf 
Published: March 2018

AbstractDermal white adipose tissue (DWAT) is a main component of human skin, composed of individual lipid‐laden mesenchymal cells known as dermal adipocytes (DAs). Besides their well‐known role in lipid storage and release, DAs also promote skin immunity, wound healing and hair follicle cycling and are important players in cutaneous neuroendocrinology. The ever‐growing insights into DWAT functions, albeit mostly in mice, have invited speculation that it may be involved in multiple skin diseases ranging from fibrosis to alopecia and psoriasis, thus designating human DWAT a clinically relevant, but as yet insufficiently investigated skin compartment. Therefore, this practical, user‐friendly guide aims to introduce the techniques available to study human DWAT in situ and ex vivo, including immunohistochemistry, immunofluorescence microscopy and analysis via quantitative immunohistomorphometry. Here, we provide information on a collection of stains comprising pre‐adipocyte (Pref1) and mature adipocyte markers (Perilipin1, Caveolin1), as well as various lipid (OilRedO, BODIPY) and histochemical stains (H&E, trichrome) available for use on human DWAT. We offer the reader guidelines on fixing, processing and staining human DAs and highlight caveats and solutions to common problems that one may encounter when studying this fascinating skin compartment. We also suggest standard methods for conducting quantitative immunohistomorphometry on human DWAT and its individual adipocytes to quantify cell size, number, lipid content and fluorescence intensity of adipose‐specific markers. Finally, we briefly introduce in situ hybridization, transmission electron microscopy and essentials of magnetic resonance imaging imaging as additional tools for instructively interrogating this largest, but still least‐known compartment of human skin.
Community activities predict disability and mortality in community‐dwelling older adults
Authors: Okura Mika , Ogita Mihoko , Yamamoto Miki , Nakai Toshimi , Numata Tomoko , Arai Hidenori 
Published: March 2018

AimWith aging, it is important to maintain older community dwellers’ regular engagement with familiar community activities (CA) engaged in close to home to protect them from frailty. Thus, the present study aimed to examine whether CA items or CA score were associated with mortality or the need for care under the new long‐term care insurance service requirements over 3 years among community‐dwelling older Japanese adults.MethodsWe analyzed cohort data for older adults from a prospective cohort study in Kami town, Japan. The response rate to the self‐reported questionnaire was 94.3% (n = 5094), and we followed these participants for 3 years. Our final sample comprised 5076 older adults. Missing data were filled in using multiple imputation. We used seven items to assess CA: (i) volunteer activity; (ii) regional activity related to the neighborhood; (iii) visiting friends; (iv) hobbies or favorite lessons; (v) earning an income; (vi) farm work and growing vegetables; and (vii) shopping daily by oneself. The Kihon Checklist and new long‐term care insurance service certifications were used as the frailty screening and disability indices, respectively.ResultsDuring the follow‐up survey, 705 participants obtained new long‐term care insurance service certifications and 262 died. Using the receiver operating characteristic curve, the desirable cut‐off of the CA score to predict disability and mortality was at least two items for all elderly age groups in rural areas.ConclusionsCA items and CA score could predict disability and mortality in community‐dwelling older adults in Japanese rural areas. Therefore, it is recommended that older adults from all age groups participate in CA. Geriatr Gerontol Int 2018; 18: 1114–1124.
Employment Growth by Firm Size During the Recent Crisis in Italy: A Multifactor Partitioning Analysis
Authors: Bianchi Annamaria , Biffignandi Silvia 
Published: March 2018

AbstractThe effects on employment growth in firms, grouped by size class, of the economic crisis that began in 2008 are analysed using multifactor partitioning (MFP). Italy's employment growth is decomposed into four explanatory factors: the stage in the business cycle; the effect of firm size; industry composition; and regional distribution; together with the interactions among these four effects. The interpretation of these effects is facilitated by the introduction within the MFP framework of a new decomposition of several key elements. The results show that the adopted approach and the suggested decompositions are useful to study the effect of size on employment change. This effect is found to be negative only for micro units (with less than 10 employees). For the other classes, it is positive. The observed negative changes in these classes are mainly due to the business cycle and an unfavourable industrial composition.
A Method to Create a Horizontal Resistance Layer by Injection of a Viscous Fluid: PLAID
Authors: de Lange W.J. , Vink J.P.M. 
Published: March 2018

AbstractWe present a method to create a horizontal resistance layer at desired depth below soil surface to decrease seepage over a relatively large area. The layer is produced in a continuous process by means of numerous temporary screens of wells. Between each pair of screens groundwater flow is forced in horizontal direction. In the center of such flow, along virtual parallel flow lines, a chemical, viscous and dense fluid is injected that produces a clogging substance within several hours. The impact of density is overcome by the forced flow between screens. The impact of viscosity on the flow distribution is handled by adaptation of the fluxes and heads at the filters in the screens. The resulting procedure includes multistep injection and is supported by model simulations. Though a small‐scale proof of concept has been successful, the composition of the optimal chemical mixture needs further research.
Complex influence of climate on the distribution and body size of an Alpine species
Authors: Baroni Daniele , Masoero Giulia 
Published: March 2018

AbstractAlpine species with a limited distribution can act as sentinels of climate change, but first we have to identify their climate‐sensitive traits. Here, we adopted a multi‐level approach to define the influence of climate on the geographical distribution and body size of a steno‐endemic Alpine grasshopper, theStenobothrus ursulaeNadig, 1986.We built a species distribution model (SDM) with the following climatic predictors: precipitation seasonality, precipitation of the wettest month, mean temperature of the driest quarter and isothermality. The model provides a satisfactory representation of the species geographical range, but it also identifies areas suitable in terms of climate in which the species was not found. Therefore, we suggest that climatic and geographic barriers combined with a poor dispersal ability might have limited its distribution.We measured 309 individuals collected across the whole geographical range. Our results show that increasing elevation was linked both to a decline inS. ursulaebody length (converse Bergmann's rule) and to a decline in sexual size dimorphism (converse Rensch's rule). We demonstrate also that the same climatic predictors that describe the species distribution affect its morphological variation.Our results suggest that climate affects this species distribution and body size with opposite effects: suitable climatic conditions are found at high elevations, and the fitness‐related trait (i.e. body size) declines with elevations. In the future, distribution and/or morphology of the species might change in order to successfully cope with the changing climate, but its very limited dispersal ability constitutes an issue of concern.
Clinical and dermoscopic response predictors in psoriatic patients undergoing narrowband ultraviolet B phototherapy: results from a prospective study
Authors: Errichetti Enzo , Stinco Giuseppe 
Published: March 2018

AbstractBackgroundAlthough disease severity, gender, body weight, and previous treatments have all been reported to affect clinical response of psoriasis vulgaris to narrowband ultraviolet B (NB‐UVB) therapy, little information about possible local (lesional) influencing factors is available.ObjectiveTo assess correlations between clinical/dermoscopic findings of psoriatic plaques and therapeutic response to NB‐UVB phototherapy in order to find positive and/or negative response predictor factors to such a treatment.MethodsFor each target lesion, we calculated local psoriasis severity index and assessed dermoscopic findings at the baseline. After 8 weeks of treatment, we evaluated clinical improvement of each lesion, correlating the therapeutic outcome with initial clinical and dermoscopic features.ResultsNinety‐eight target lesions from 27 patients were included in the study. After 8 weeks of therapy, 31 lesions experienced no/limited improvement, while partial response was observed in 40 plaques and optimal response in 27 lesions. Regarding clinical variables, we found an association between poor therapeutic outcomes and both legs localization and more marked lesion scaling/infiltration. Similarly, globular vessels on dermoscopy were more commonly associated with no/limited response as well as lesions localized on the legs, particularly those showing treatment resistance. Conversely, the presence of dotted vessels carried a higher probability for getting improvement.ConclusionTherapeutic response of psoriasis vulgaris to NB‐UVB treatment may be negatively affected by local clinical factors, that is, significant scaling/infiltration and legs localization, and dermoscopy may be useful in highlighting possible response predictors, with globular and dotted vessels associated with bad and good outcomes, respectively.
A retrospective study of the characteristics of patients with early‐onset compared to adult‐onset hidradenitis suppurativa
Authors: Dessinioti Clio , Tzanetakou Vassiliki , Zisimou Chrisa , Kontochristopoulos George , Antoniou Christina 
Published: March 2018

AbstractBackgroundThe mean age of onset of hidradenitis suppurativa (HS) is between 20 and 24 years. Very few data about patients with early‐onset HS exist.ObjectiveTo investigate the association of early‐onset HS with the clinical characteristics: age, gender, body mass index (BMI), smoking, family history of HS, Hurley stage, and number of areas affected.MethodsThis was a retrospective study of the reported early age at HS onset (≤17 years old) with clinical characteristics and with the severity of HS at first consultation visit.ResultsIn 166 patients, 42 patients (25.3%) reported early‐onset HS. Compared to adult‐onset HS, patients with early‐onset HS were younger (mean age: 37 years vs. 27 years, P < 0.0001), had a significantly younger mean age of onset (28.2 years old vs. 14.5 years old, respectively, P < 0.0001), longer mean disease duration (8.8 years vs. 12.6 years, respectively, P = 0.011) and were less frequently smokers (P < 0.001), whereas there was no association with gender (P = 0.177) or BMI (0.086). Patients with a family history had increased risk for early‐onset HS (OR: 2.45, 95% CI: 1.08–5.56). Early‐onset HS was not associated with Hurley stage (OR: 1.12, 95% CI: 0.33–3.74) or with the number of body areas affected (OR: 1.54, 95% CI: 0.49–4.83).ConclusionEarly‐onset HS was frequent and associated with a family history of HS. There was no difference in the severity of HS in adult life for patients with an onset of HS at ≤17 years, compared to patients with adult‐onset, which may be reassuring information for these younger patients.
Complex portfolio selection via convex mixed‐integer quadratic programming: a survey
Authors: Mencarelli Luca , D'Ambrosio Claudia 
Published: April 2018

AbstractIn this paper, we review convex mixed‐integer quadratic programming approaches to deal with single‐objective single‐period mean‐variance portfolio selection problems under real‐world financial constraints. In the first part, after describing the original Markowitz's mean‐variance model, we analyze its theoretical and empirical limitations, and summarize the possible improvements by considering robust and probabilistic models, and additional constraints. Moreover, we report some recent theoretical convexity results for the probabilistic portfolio selection problem. In the second part, we overview the exact algorithms proposed to solve the single‐objective single‐period portfolio selection problem with quadratic risk measure.