bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatigue Profiles in Patients with Multiple Sclerosis are Based on Severity of Fatigue and not on Dimensions of Fatigue
Authors: Beckerman Heleen , Eijssen Isaline CJM , van Meeteren Jetty , Verhulsdonck Marion C , de Groot Vincent 
Published: March 2020

AbstractFatigue related to Multiple Sclerosis (MS) is considered a multidimensional symptom, manifesting in several dimensions such as physical, cognitive, and psychosocial fatigue. This study investigated in 264 patients with severe primary MS-related fatigue (median MS duration 6.8 years, mean age 48.1 years, 75% women) whether subgroups can be distinguished based on these dimensions. Subsequently, we tested whether MS-related fatigue consists of a single common unidimensional factor. Subscale scores on four self-reported fatigue questionnaires, including the Checklist of Individual Strength, the Modified Fatigue Impact Scale, the Fatigue Severity Scale and the SF36 vitality, were used in a cluster analysis to identify patients with similar fatigue characteristics. Next, all 54 items were included in exploratory factor analysis to test unidimensionality. Study results show that in patients with a treatment indication for primary MS-related fatigue, fatigue profiles are based on severity and not on the various dimensions of fatigue. The three profiles found, suggested one underlying fatigue dimension, but this could not be confirmed. Factor analysis of all 54 items resulted in 8 factors, confirming the multidimensional construct of the included fatigue questionnaires.
Influence of Competing Risks on Estimates of Recurrence Risk and Breast Cancer-specific Mortality in Analyses of the Early Breast Cancer Trialists Collaborative Group
Authors: Saleh Ramy R. , Nadler Michelle B. , Desnoyers Alexandra , Rodin Danielle L. , Abdel-Qadir Husam , Amir Eitan 
Published: March 2020

AbstractEarly-stage breast cancer (BC) is a curable disease with many patients dying of causes other than BC. The influence of non-BC death and other competing risks on the interpretation of Kaplan-Meier (KM)-based analyses for BC-specific outcomes are unknown. We searched the Oxford University website to identify all meta-analyses published by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) between 2005 and 2018. The potential influence of competing risks was estimated using a validated multivariable linear model that predicts the difference between KM and cumulative incidence function (CIF) on estimates of BC-specific outcomes. The initial search identified 14 EBCTCG papers, 10 (71%) reported data on BC and competing events. Eight (80%) had a relative difference between KM and the competing risk adjusted estimates exceeding 10%. The median relative difference was 28.4% for local-recurrence; 16.8% for distant-recurrence, and 6.7% for BC-specific mortality. There was a 18.9% relative difference between KM and CIF adjusted analyses beyond 10 years. The use of KM-based methods when competing risks are present biases risk estimates in studies of early BC especially for uncommon outcomes such as local recurrence. The use of CIF to calculate BC-specific outcomes may be preferable in this setting.
Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting
Authors: Pinigin Konstantin V. , Kondrashov Oleg V. , Jiménez-Munguía Irene , Alexandrova Veronika V. , Batishchev Oleg V. , Galimzyanov Timur R. , Akimov Sergey A. 
Published: March 2020

AbstractLiquid-ordered lipid domains represent a lateral inhomogeneity in cellular membranes. These domains have elastic and physicochemical properties different from those of the surrounding membrane. In particular, their thickness exceeds that of the disordered membrane. Thus, elastic deformations arise at the domain boundary in order to compensate for the thickness mismatch. In equilibrium, the deformations lead to an incomplete register of monolayer ordered domains: the elastic energy is minimal if domains in opposing monolayers lie on the top of each other, and their boundaries are laterally shifted by about 3 nm. This configuration introduces a region, composed of one ordered and one disordered monolayers, with an intermediate bilayer thickness. Besides, a jump in a local monolayer curvature takes place in this intermediate region, concentrating here most of the elastic stress. This region can participate in a lateral sorting of membrane inclusions by offering them an optimal bilayer thickness and local curvature conditions. In the present study, we consider the sorting of deformable lipid inclusions, undeformable peripheral and deeply incorporated peptide inclusions, and undeformable transmembrane inclusions of different molecular geometry. With rare exceptions, all types of inclusions have an affinity to the ordered domain boundary as compared to the bulk phases. The optimal lateral distribution of inclusions allows relaxing the elastic stress at the boundary of domains.
Domestic dogs are mammalian reservoirs for the emerging zoonosis flea-borne spotted fever, caused by Rickettsia felis
Authors: Ng-Nguyen Dinh , Hii Sze-Fui , Hoang Minh-Trang Thi , Nguyen Van-Anh Thi , Rees Robert , Stenos John , Traub Rebecca Justine 
Published: March 2020

AbstractRickettsia felis is an obligate intracellular bacterium that is being increasingly recognized as an etiological agent of human rickettsial disease globally. The agent is transmitted through the bite of an infected vector, the cat flea, Ctenocephalides felis, however there is to date, no consensus on the pathogen’s vertebrate reservoir, required for the maintenance of this agent in nature. This study for the first time, demonstrates the role of the domestic dog (Canis familiaris) as a vertebrate reservoir of R. felis. The ability of dogs to sustain prolonged periods of rickettsemia, ability to remain asymptomatically infected with normal haematological parameters and ability to act as biological vehicles for the horizontal transmission of R. felis between infected and uninfected fleas provides indication of their status as a mammalian reservoir of this emerging zoonosis.
Changes in the salivary electrolytic dynamic after sucrose exposure in children with Early Childhood Caries
Authors: de Sousa Emerson Tavares , Lima-Holanda Aline Tavares , Nobre-dos-Santos Marinês 
Published: March 2020

AbstractThis study sought to explore if the effect of 20% sucrose rinse (SR) on the salivary electrolytic concentration of calcium (Ca2+), phosphate (Pi) and fluoride (F−) in children with Early Childhood Caries (ECC) is different from healthy children. Here, fifty-eight preschoolers aged 3 to 5 years were divided into 2 groups: caries-free (CF) and with ECC. Changes in saliva flow rate, pH and buffering capacity (BC), as well as in concentrations of Ca2+, Pi, and F−, and the degree of saturation in relation to hydroxyapatite (DSS HAp) and fluorapatite (DSS FAp) were evaluated. The pre-rinse [Ca2+] was higher in the ECC group in the CF group. A significant increase in [Ca2+] was demonstrated after SR in the CF group (p = 0.05). The [Pi] was reduced by 18% after SR in the ECC group (p = 0.007). The [F-] reduced in both groups after SR (p < 0.000). There was a moderate positive correlation between [Ca2+] and the DSS HAp and DSS FAp. Multivariate analysis showed that children with a higher [Ca2+] in pre-rinse saliva are more likely to have ECC. In conclusion, the effect of a 20% sucrose rinse on the electrolytic concentration of Ca2+, Pi and F- was different when children with ECC were compared with CF children.
The Two-Species Model of transketolase explains donor substrate-binding, inhibition and heat-activation
Authors: Wilkinson Henry C. , Dalby Paul A. 
Published: March 2020

AbstractWe recently characterised a low-activity form of E. coli transketolase, TKlow, which also binds the cofactor thiamine pyrophosphate (TPP) with an affinity up to two-orders of magnitude lower than the previously known high TPP-affinity and high-activity form, TKhigh, in the presence of Mg2+. We observed previously that partial oxidation was responsible for increased TKhigh activity, while low-activity TKlow was unmodified. In the present study, the fluorescence-based cofactor-binding assay was adapted to detect binding of the β-hydroxypyruvate (HPA) donor substrate to wild-type transketolase and a variant, S385Y/D469T/R520Q, that is active towards aromatic aldehydes. Transketolase HPA affinity again revealed the two distinct forms of transketolase at a TKhigh:TKlow ratio that matched those observed previously via TPP binding to each variant. The HPA dissociation constant of TKlow was comparable to the substrate-inhibition dissociation constant, KiHPA, determined previously. We provide evidence that KiHPA is a convolution of binding to the low-activity TKlow-TKlow dimer, and the TKlow subunit of the partially-active TKhigh-TKlow mixed dimer, where HPA binding to the TKlow subunit of the mixed dimer results in inhibition of the active TKhigh subunit. Heat-activation of transketolase was similarly investigated and found to convert the TKlow subunit of the mixed dimer to have TKhigh-like properties, but without oxidation.
Immune-mediated febrile response in female rats: Role of central hypothalamic mediators
Authors: Brito Haissa Oliveira , Radulski Débora , Wilhelms Daniel Björk , Stojakovic Andrea , Brito Luciane Maria Oliveira , Gil da Costa Rui Miguel , Trindade Edvaldo , Engblom David , Franco Celia Regina Cavichiolo , Zampronio Aleksander Roberto 
Published: March 2020

AbstractLipopolysaccharide (LPS) induces fever through cytokines like receptor-activator of nuclear factor κB ligand (RANKL), triggering mediators like prostaglandins (PG), endothelin-1 (ET-1), corticotrophin-releasing factor (CRF), substance P (SP) and endogenous opioids. LPS-induced fever is reduced in females compared with males except in ovariectomized (OVX) females which show increased fever mediated by PG. The present study aimed to identify the mediators involved in fever in intact and OVX female rats. Fever was induced with LPS (50 μg/kg) intraperitoneally or CRF (2.5 μg), ET-1 (1 pg), morphine (10 μg) and SP (500 ng) intracerebroventricularly in sham-operated and OVX rats. The role of RANKL was evaluated with osteoprotegerin (OPG, 1 μg, intracerebroventricularly). Expression of RANK, CRFI/II, ETB, μ-opioid (MOR) and NK1 receptors was evaluated by confocal microscopy. Besides LPS, only morphine induced fever in OVX rats while all mediators induced fever in sham-operated animals. OPG abolished LPS-induced fever in OVX but not sham-operated animals. Overall, fever involves similar central mediators in cycling females and males but only morphine induced fever in OVX females. Importantly, RANK/RANKL participates in LPS-induced fever in OVX females, as in males but not in cycling females.
Gene expression variation in the brains of harvester ant foragers is associated with collective behavior
Authors: Friedman Daniel Ari , York Ryan Alexander , Hilliard Austin Travis , Gordon Deborah M. 
Published: March 2020

AbstractNatural selection on collective behavior acts on variation among colonies in behavior that is associated with reproductive success. In the red harvester ant (Pogonomyrmex barbatus), variation among colonies in the collective regulation of foraging in response to humidity is associated with colony reproductive success. We used RNA-seq to examine gene expression in the brains of foragers in a natural setting. We find that colonies differ in the expression of neurophysiologically-relevant genes in forager brains, and a fraction of these gene expression differences are associated with two colony traits: sensitivity of foraging activity to humidity, and forager brain dopamine to serotonin ratio. Loci that were correlated with colony behavioral differences were enriched in neurotransmitter receptor signaling & metabolic functions, tended to be more central to coexpression networks, and are evolving under higher protein-coding sequence constraint. Natural selection may shape colony foraging behavior through variation in gene expression.
Ebselen as template for stabilization of A4V mutant dimer for motor neuron disease therapy
Authors: Chantadul Varunya , Wright Gareth S. A. , Amporndanai Kangsa , Shahid Munazza , Antonyuk Svetlana V. , Washbourn Gina , Rogers Michael , Roberts Natalie , Pye Matthew , O’Neill Paul M. , Hasnain S. Samar 
Published: March 2020

AbstractMutations to the gene encoding superoxide dismutase-1 (SOD1) were the first genetic elements discovered that cause motor neuron disease (MND). These mutations result in compromised SOD1 dimer stability, with one of the severest and most common mutations Ala4Val (A4V) displaying a propensity to monomerise and aggregate leading to neuronal death. We show that the clinically used ebselen and related analogues promote thermal stability of A4V SOD1 when binding to Cys111 only. We have developed a A4V SOD1 differential scanning fluorescence-based assay on a C6S mutation background that is effective in assessing suitability of compounds. Crystallographic data show that the selenium atom of these compounds binds covalently to A4V SOD1 at Cys111 at the dimer interface, resulting in stabilisation. This together with chemical amenability for hit expansion of ebselen and its on-target SOD1 pharmacological chaperone activity holds remarkable promise for structure-based therapeutics for MND using ebselen as a template.
The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain
Authors: Nakamura Seiko , Matsui Aiko , Akabane Shiori , Tamura Yasushi , Hatano Azumi , Miyano Yuriko , Omote Hiroshi , Kajikawa Mizuho , Maenaka Katsumi , Moriyama Yoshinori , Endo Toshiya , Oka Toshihiko 
Published: March 2020

AbstractLETM1 is a mitochondrial inner membrane protein that is required for maintaining the mitochondrial morphology and cristae structures, and regulates mitochondrial ion homeostasis. Here we report a role of LETM1 in the organization of cristae structures. We identified four amino acid residues of human LETM1 that are crucial for complementation of the growth deficiency caused by gene deletion of a yeast LETM1 orthologue. Substituting amino acid residues with alanine disrupts the correct assembly of a protein complex containing LETM1 and prevents changes in the mitochondrial morphology induced by exogenous LETM1 expression. Moreover, the LETM1 protein changes the shapes of the membranes of in vitro-reconstituted proteoliposomes, leading to the formation of invaginated membrane structures on artificial liposomes. LETM1 mutant proteins with alanine substitutions fail to facilitate the formation of invaginated membrane structures, suggesting that LETM1 plays a fundamental role in the organization of mitochondrial membrane morphology.
PV power intra‐day predictions using PDE models of polynomial networks based on operational calculus
Authors: Zjavka Ladislav 
Published: March 2020

Precise daily forecasts of photo‐voltaic (PV) power production are necessary for its planning, utilisation and integration into the electrical grid. PV power is conditioned by the current amount of specific solar radiation components. Numerical weather prediction systems are usually run every 6 h and provide only rough local prognoses of cloudiness with a delay. Statistical methods can predict PV power, considering a specific plant situation. Their intra‐day models are usually more precise if rely only on the latest data observations and power measurements. Differential polynomial neural network (D‐PNN) is a novel neuro‐computing technique based on analogies with brain pulse signal processing. D‐PNN decomposes the general partial differential equation (PDE), being able to describe the local atmospheric dynamics, into specific sub‐PDEs in its nodes. These are converted using adapted procedures of operational calculus to obtain the Laplace images of unknown node functions, which are inverse L‐transformed to obtain the originals. D‐PNN can select from dozens of input variables to produce applicable sum PDE components which can extend, one by one, its composite models towards the optima. The PDE models are developed with historical spatial data from the estimated optimal numbers of the last days for each 1–9‐h inputs‐output time‐shift to predict clear sky index in the trained time‐horizon.
Auswirkungen lärmmindernder Maßnahmen auf die Häufigkeit von Lärmbelästigung, Schlafstörungen und Herz-Kreislauf-Erkrankungen – eine Modellrechnung
Authors: Seidler Andreas , Hegewald Janice , Schubert Melanie , Popp Christian , Moebus Susanne 
Published: March 2020

Zusammenfassung
Ziel Schwellenwerte zu lärmbedingten Gesundheitsgefährdungen liegen derzeit bei Verkehrslärmpegeln von 70 Dezibel (dB) am Tag und 60 dB in der Nacht. Nach aktuellen wissenschaftlichen Erkenntnissen gewährleisten diese Schwellenwerte keinen hinreichenden Gesundheitsschutz. Ziel dieser Modellrechnung ist es, die Auswirkungen von 3 Szenarien konkreter Lärmminderungsmaßnahmen auf Lärmbelästigung, Schlafstörungen und Herz-Kreislauf-Erkrankungen getrennt voneinander zu schätzen.
Methodik Für Straßen- und Bahnlärm werden 3 Lärmminderungsmaßnahmen (Pegelsenkungen) modelliert: (1) gewichtete 24 Stunden-Mittelungspegel LDEN von maximal 65 dB bzw. nächtliche Mittelungspegel LNight von 55 dB, (2) LDEN von maximal 60 dB bzw. LNight von 50 dB, (3) eine generelle Senkung von Straßen- und Bahnlärmpegel um 3 dB. Effekte der Maßnahmen (1) bis (3) werden exemplarisch für die Studienpopulation der NORAH-Studie zu Krankheitsrisiken (Rhein-Main-Gebiet) ermittelt. Dabei werden die gesundheitlichen Folgen zum einen auf Grundlage der WHO Noise Guidelines (2018), zum anderen auf Grundlage der NORAH-Studie zu Krankheitsrisiken abgeschätzt.
Ergebnisse Die Modellrechnungen zeigen, dass Lärmminderungsmaßnahme (1) die Zahl durch Verkehrslärm hoch Belästigter und stark durch nächtlichen Verkehrslärm Schlafgestörter sowie die Zahl an einer verkehrslärmbedingten Herz-Kreislauf-Erkrankung erkrankender Menschen um etwa 5–10% senken könnte. Eine Lärmminderung nach (2) könnte eine Verringerung verkehrslärmbedingter Herz-Kreislauf-Erkrankungen von mindestens etwa 10% erzielen; nach den WHO Noise Guidelines wäre sogar eine Verringerung straßenlärmbedingter ischämischer Herzkrankheiten um mehr als 30% erreichbar. Diese Maßnahmen würden besonders der hoch lärmbelasteten Bevölkerung nützen – einer ohnehin aufgrund ihrer eingeschränkten sozioökonomischen Ressourcen vulnerablen Personengruppe. Mit der generellen Absenkung von Verkehrslärmpegeln um 3 dB ließe sich die Häufigkeit von Lärmbelästigungen und verkehrslärmbedingten Schlafstörungen insbesondere bei den gering bis mittelgradig Lärmexponierten verringern.
Schlussfolgerungen Aufgrund der unterschiedlichen Zielrichtungen bzw. Zielgruppen der untersuchten Lärmminderungsmaßnahmen sollte die Einführung und Umsetzung konkreter Pegelgrenzwerte durch eine Verringerung des Verkehrslärms im Bereich unterhalb der Pegelgrenzwerte ergänzt werden.
The Effect of Physical Exercise on the Retina and Choroid
Authors: Szalai Irén , Pálya Fanni , Csorba Anita , Tóth Miklós , Somfai Gabor Mark 
Published: March 2020

AbstractThere is only limited information available on the effects of physical exercise on the posterior pole. Retinal circulation is autoregulated similarly to the brain vasculature in order to provide constant flow and thus constant nutrition of the inner retinal structures while the choroid is mostly controlled by the sympathetic nervous system. The available data show that physical exercise may indeed have a positive effect on the retina and visual function. The assessment of retinal structure could serve as a marker in sports medicine, whereas physical activity could exert a positive protective effect against diseases such as diabetic retinopathy or age-related macular degeneration. According to our theory, similar to the term “trained heart” used in cardiology and sports medicine, the term “trained eye” could also be coined. This latter term would help to further emphasize the beneficial effects of physical exercise that works protectively not only for the cardiovascular but for the visual system as well, and thus could further help in the fight against avoidable blindness worldwide.
Iminyl-Radical-Triggered C–C Bond Cleavage of Cycloketone Oxime Derivatives: Generation of Distal Cyano-Substituted Alkyl Radicals and Their Functionalization
Authors: Xiao Tiebo , Zhou Lei , Huang Hongtai , Anand Devireddy 
Published: March 2020

Alkyl nitriles are versatile building blocks in organic synthesis because the cyano group can be easily converted into other functional groups. Iminyl-radical-triggered C–C bond cleavage of cycloketone oxime­ derivatives provides a practical route to access distal cyano-substituted alkyl radicals, which has given chemists a new radical reaction platform for the synthesis of diverse alkyl nitriles. This review provides an overview of various types of radical cyanoalkylation via ring opening of cycloketone oxime derivatives.1	Introduction2	C–C Bond Formation2.1	Alkenes as Radical Acceptors2.2	Aromatic Rings as Radical Acceptors2.3	Organometallic Reagents as Radical Acceptors2.4	Cyanoalkyl-Radical-Triggered Cyclization Reactions2.5	Miscellaneous3	C–Heteroatom Bond Formation3.1	C–O Bond Formation3.2	C–N Bond Formation3.3	C–S Bond Formation3.4	C–Halogen Bond Formation3.5	C–B Bond Formation4	Conclusion
Treatment Complications of Atrial Fibrillation and Their Management
Authors: Mattia Allan , Newman Joshua , Manetta Frank 
Published: March 2020

AbstractAtrial fibrillation (AF) is a rhythm disturbance defined by irregular, rapid electrical, and mechanical activation of the atria, which causes unsynchronized atrial contraction and promotes thromboembolism. AF is the most common sustained arrhythmia. Its prevalence and incidence are increasing due to aging and improved survival from acute heart diseases. This article is a review on AF management from both a surgical and catheter-based perspective. While both treatment approaches to AF have been shown to be successful in the management of AF, they are not without their own inherent complications. This article seeks to review some of these complications and help to guide treatment.
CT Validation of Intraoperative Implant Position and Knee Alignment as Determined by the MAKO Total Knee Arthroplasty System
Authors: Sires James D. , Wilson Christopher J. 
Published: March 2020

AbstractRobotic-assisted technology in total knee arthroplasty (TKA) aims to increase implantation accuracy, with real-time data being used to estimate intraoperative component alignment. Postoperatively, Perth computed tomography (CT) protocol is a valid measurement technique in determining both femoral and tibial component alignments. The aim of this study was to evaluate the accuracy of intraoperative component alignment by robotic-assisted TKA through CT validation. A total of 33 patients underwent TKA using the MAKO robotic-assisted TKA system. Intraoperative measurements of both femoral and tibial component placements, as well as limb alignment as determined by the MAKO software were recorded. Independent postoperative Perth CT protocol was obtained (n = 29) and compared with intraoperative values. Mean absolute difference between intraoperative and postoperative measurements for the femoral component were 1.17 degrees (1.10) in the coronal plane, 1.79 degrees (1.12) in the sagittal plane, and 1.90 degrees (1.88) in the transverse plane. Mean absolute difference between intraoperative and postoperative measurements for the tibial component were 1.03 degrees (0.76) in the coronal plane and 1.78 degrees (1.20) in the sagittal plane. Mean absolute difference of limb alignment was 1.29 degrees (1.25), with 93.10% of measurements ≤3 degrees of postoperative CT measurements. Overall, intraoperatively measured component alignment as estimated by the MAKO robotic-assisted TKA system is comparable to CT-based measurements.