bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current patterns of beta‐blocker prescription in cardiac amyloidosis: an Italian nationwide survey
Authors: Tini Giacomo , Cappelli Francesco , Biagini Elena , Musumeci Beatrice , Merlo Marco , Crotti Lia , Cameli Matteo , Di Bella Gianluca , Cipriani Alberto , Marzo Francesca , Guerra Federico , Forleo Cinzia , Gagliardi Christian , Zampieri Mattia , Carigi Samuela , Vianello Pier Filippo , Mandoli Giulia Elena , Ciliberti Giuseppe , Lichelli Luca , Mariani Davide , Porcari Aldostefano , Russo Domitilla , Licordari Roberto , Ponziani Alberto , Porto Italo , Perfetto Federico , Autore Camillo , Rapezzi Claudio , Sinagra Giafranco , Canepa Marco 
Published: May 2021

AbstractAimsThe use of beta‐blocker therapy in cardiac amyloidosis (CA) is debated. We aimed at describing patterns of beta‐blocker prescription through a nationwide survey.Methods and resultsFrom 11 referral centres, we retrospectively collected data of CA patients with a first evaluation after 2016 (n = 642). Clinical characteristics at first and last evaluation were collected, with a focus on medical therapy. For patients in whom beta‐blocker therapy was started, stopped, or continued between first and last evaluation, the main reason for beta‐blocker management was requested. Median age of study population was 77 years; 81% were men. Arterial hypertension was found in 58% of patients, atrial fibrillation (AF) in 57%, and coronary artery disease in 16%. Left ventricular ejection fraction was preserved in 62% of cases, and 74% of patients had advanced diastolic dysfunction. Out of the 250 CA patients on beta‐blockers at last evaluation, 215 (33%) were already taking this therapy at first evaluation, while 35 (5%) were started it, in both cases primarily because of high‐rate AF. One‐hundred‐nineteen patients (19%) who were on beta‐blocker at first evaluation had this therapy withdrawn, mainly because of intolerance in the presence of heart failure with advanced diastolic dysfunction. The remaining 273 patients (43%) had never received beta‐blocker therapy. Beta‐blockers usage was similar between CA aetiologies. Patients taking vs. not taking beta‐blockers differed only for a greater prevalence of arterial hypertension, coronary artery disease, AF, and non‐restrictive filling pattern (P < 0.01 for all) in the former group.ConclusionsBeta‐blockers prescription is not infrequent in CA. Such therapy may be tolerated in the presence of co‐morbidities for which beta‐blockers are routinely used and in the absence of advanced diastolic dysfunction.
DEIT: Dempster Shafer Theory‐based edge‐centric Internet of Things‐specific trust model
Authors: Bhargava Arpita , Verma Shekhar 
Published: May 2021

AbstractThe potential benefits of edge‐centric Internet of Things (IoT) come with increased security threats and because the edge devices may be compromised into sending or forwarding wrong information. To negate the effect of wrong information on inference, such messages need to be identified. Identification and dropping of messages in the network as early as possible would minimize the communication overhead. Trust values of nodes help in the early identification of such messages. In this work, the Dempster Shafer Theory (DST)‐based edge‐centric IoT‐specific Trust Model (DEIT) is designed to compute trust to include the specific characteristics of IoT. Edge servers use DEIT to compute trust value of edge devices in the network. In DEIT, DST combines the available trust messages. DIET also uses the degradation variable, credibility variable, punishment variable, re‐compensating variable, and pardoning variable to compute final trust value. The computed trust value assists the edges in taking correct decisions. Simulation results demonstrate that it can immediately capture two major types of misbehavior, namely, information drop and modification under both sparse and dense traffic conditions. Through scenarios in the results section, the depiction of various possible misbehaviors has been discussed. Scenario 1 and 2 discuss a situation where a malicious edge device misbehaves in two ways, namely, dropping and modification of information, respectively. In scenario 3 and 4, situations are discussed when the trust opinion of the trusted and distrusted devices are neutralized with time using the degradation factor to illustrate and compare changes in trust values in two different situation.
Music‐based interventions for people living with dementia, targeting behavioral and psychological symptoms: A scoping review
Authors: Sousa Lídia , Neves Maria J. , Moura Bárbara , Schneider Justine , Fernandes Lia 
Published: May 2021

AbstractIntroductionDementia care is a major public health issue worldwide. The management of behavioral and psychological symptoms (BPSD) is one of the hardest challenges in this context. Non‐pharmacological strategies, like music‐based interventions (Mbi), seem promising options, being considered low‐risk, widely available and inclusive. This scoping review aimed at mapping all Mbi used in dementia care, targeting BPSD, and debriefing its components, structure and rationale. Music therapy and other therapeutic music activities were included.MethodsThe Arksey and O'Malley framework, Cochrane recommendations and PRISMA checklist were followed. Embase, PubMed, PsycINFO, ASSIA and Humanities Index were searched from first records until the 31st of March 2020. Snowballing process and screening of relevant journals were also undertaken. A panel of experts critically guided the evidence synthesis.ResultsOverall, 103 studies (34 RCT; 12 NRT; 40 Before/After studies and 17 Case Studies) met inclusion criteria. Basic elements of the Mbi, the rationale supporting its development and hypothesis tested were mostly underreported, thus hampering cross‐study comparisons and generalizations. Despite this, available evidence indicates that: it is feasible to deliver Mbi to PwD at very different stages and in different settings ‐ from community to the acute setting ‐ even for non‐music therapists; positive or neutral effects in BPSD are often reported but not without exception; individualization seems a critical factor mediating Mbi effects.ConclusionsDetailed intervention and research reporting are essential to interpretation, replication and translation into practice. Ten years after the publication of specific reporting guidelines, this goal is not yet fully achieved in music in dementia care.
Large‐scale reconfiguration of connectivity patterns among attentional networks during context‐dependent adjustment of cognitive control
Authors: Li Yilu , Wang Yanqing , Yu Fangwen , Chen Antao 
Published: May 2021

AbstractThe ability to adjust our behavior flexibly depending on situational demands and changes in the environment is an important characteristic of cognitive control. Previous studies have proved that this type of adaptive control plays a crucial role in selective attention, but have barely explored whether and how attentional networks support adaptive control. In the present study, a Stroop task with a different proportion of incongruent trials was used to investigate the brain activity and connectivity of six typical attentional control networks (i.e., the fronto‐parietal network (FPN), cingulo‐opercular network (CON), default mode network (DMN), dorsal attention network (DAN), and ventral attention network/salience network (VAN/SN)) in the environment with changing control demand. The behavioral analysis indicated a decreased Stroop interference (incongruent vs. congruent trial response time [RT]) with the increase in the proportion of incongruent trials within a block, indicating that cognitive control was improved there. The fMRI data revealed that the attenuate Stroop interference was accompanied by the activation of frontal and parietal regions, such as bilateral dorsolateral prefrontal cortex and anterior cingulate cortex. Crucially, the improved cognitive control induced by the increased proportion of incongruent trials was associated with the enhanced functional connectivity within the five networks, and a greater connection between CON with the DAN/SN, and between DMN with the CON/DAN/SN. Meanwhile, however, the functional coupling between the FPN and VAN was decreased. These results suggest that flexible regulations of cognitive control are implemented by the large‐scale reconfiguration of connectivity patterns among the attentional networks.
Are drug prices subject to creative destruction? Evidence from the US, 1997–2017
Authors: Lichtenberg Frank R. 
Published: May 2021

AbstractThere are several types of pharmaceutical competition. In addition to competition among producers of the same chemical substance (“within‐substance competition”), there may be competition among producers of different chemical substances in the same chemical subgroup (“between‐substance competition”). There have been numerous econometric studies of the effect of within‐substance competition on drug prices, but empirical evidence about the effect of between‐substance competition is far more limited. The primary objective of this study is to assess the impact of the entry of new drugs in a drug's therapeutic class on branded drug prices, generic drug prices, and the generic market share, using publicly‐available US data for the period 1997–2017. Two methods are used to estimate the effects of between‐substance and within‐substance competition on those variables. The first method is standard 2‐way fixed effects estimation based on aggregate data. The second method, based on micro data, is estimation using the DID_MULTIPLEGT procedure developed by de Chaisemartin et al. (2021), which does not rely on, and allows us to test for, “parallel trends.” Between‐substance competition does not appear to have any effect on brand‐name drug prices, although our inability to fully account for rebates may bias the estimates towards zero. (There is also little evidence for an effect of within‐substance competition on brand‐name drug prices.) However, between‐substance competition has a significant negative effect on generic drug prices. We estimate that the 1985–2005 increase in the number of substances ever registered in a drug's ATC4 chemical subgroup reduced the 2017 price of generic drugs by 42%. (The ratio of the generic‐price reduction attributable to rising between‐substance competition to the generic‐price reduction attributable to rising within‐substance competition also happens to be 42%.) A striking finding is that the entry of imitators has no effect on the prices of brand‐name drugs, but the entry of innovators has a significant negative effect on the prices of generic drugs in the same ATC4 chemical subgroup. In addition, between‐substance competition has a significant positive effect on the generic market share: the 1985–2005 increase in the number of substances ever registered in a drug's ATC4 chemical subgroup increased the 2017 generic market share by 15.0 percentage points. Due to its effects on generic drug prices and the generic market share, the 1985–2005 increase in between‐substance competition reduced the average 2017 price of drugs that were already sold in 1997 by 35%. We estimate that 36% of 2017 expenditure on drugs that were first registered during 1986–2005 was offset by reduced 2017 expenditure on drugs that were sold in both 1997 and 2017.
Intrinsic osteoinductivity of PCL‐DA/PLLA semi‐IPN shape memory polymer scaffolds
Authors: Arabiyat Ahmad S. , Pfau Michaela R. , Grunlan Melissa A. , Hahn Mariah S. 
Published: May 2021

AbstractEngineering osteoinductive, self‐fitting scaffolds offers a potential treatment modality to repair irregularly shaped craniomaxillofacial bone defects. Recently, we innovated on osteoinductive poly(ε‐caprolactone)‐diacrylate (PCL‐DA) shape memory polymers (SMPs) to incorporate poly‐L‐lactic acid (PLLA) into the PCL‐DA network, forming a semi‐interpenetrating network (semi‐IPN). Scaffolds formed from these PCL‐DA/PLLA semi‐IPNs display stiffnesses within the range of trabecular bone and accelerated degradation relative to scaffolds formed from slowly degrading PCL‐DA SMPs. Herein, we demonstrate for the first time that PCL‐DA/PLLA semi‐IPN SMP scaffolds show increased intrinsic osteoinductivity relative to PCL‐DA. We also confirm that application of a bioinspired polydopamine (PD) coating further improves the osteoinductive capacity of these PCL‐DA/PLLA semi‐IPN SMPs. In the absence of osteogenic supplements, protein level assessment of human mesenchymal stem cells (h‐MSCs) cultured in PCL‐DA/PLLA scaffolds revealed an increase in expression of osteogenic markers osterix, bone morphogenetic protein‐4 (BMP‐4), and collagen 1 alpha 1 (COL1A1), relative to PCL‐DA scaffolds and osteogenic medium controls. Likewise, the expression of runt‐related transcription factor 2 (RUNX2) and BMP‐4 was elevated in the presence of PD‐coating. In contrast, the chondrogenic and adipogenic responses associated with the scaffolds matched or were reduced relative to osteogenic medium controls, indicating that the scaffolds display intrinsic osteoinductivity.
Regular Strength and Sprint Training Counteracts Bone Aging: A 10‐Year Follow‐Up in Male Masters Athletes
Authors: Suominen Tuuli H , Alén Markku , Törmäkangas Timo , Degens Hans , Rittweger Jörn , Heinonen Ari , Suominen Harri , Korhonen Marko T 
Published: May 2021

ABSTRACTCross‐sectional and interventional studies suggest that high‐intensity strength and impact‐type training provide a powerful osteogenic stimulus even in old age. However, longitudinal evidence on the ability of high‐intensity training to attenuate age‐related bone deterioration is currently lacking. This follow‐up study assessed the role of continued strength and sprint training on bone aging in 40‐ to 85‐year‐old male sprinters (n = 69) with a long‐term training background. Peripheral quantitative computed tomography (pQCT)‐derived bone structural, strength, and densitometric parameters of the distal tibia and tibia midshaft were assessed at baseline and 10 years later. The groups of well‐trained (actively competing, sprint training including strength training ≥2 times/week; n = 36) and less‐trained (<2 times/week, no strength training, switched to endurance training; n = 33) athletes were formed according to self‐reports at follow‐up. Longitudinal changes in bone traits in the two groups were examined using linear mixed models. Over the 10‐year period, group‐by‐time interactions were found for distal tibia total bone mineral content (BMC), trabecular volumetric bone mineral density (vBMD), and compressive strength index, and for mid‐tibia cortical cross‐sectional area, medullary area, total BMC, and BMC at the anterior and posterior sites (polar mass distribution analysis) (p < 0.05). These interactions reflected maintained (distal tibia) or improved (mid‐tibia) bone properties in the well‐trained and decreased bone properties in the less‐trained athletes over the 10‐year period. Depending on the bone variable, the difference in change in favor of the well‐trained group ranged from 2% to 5%. The greatest differences were found in distal tibia trabecular vBMD and mid‐tibia posterior BMC, which remained significant (p < 0.05) after adjustment for multiple testing. In conclusion, our longitudinal findings indicate that continued strength and sprint training is associated with maintained or even improved tibial properties in middle‐aged and older male sprint athletes, suggesting that regular, intensive exercise counteracts bone aging. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Microstructure Determines Apparent-Level Mechanics Despite Tissue-Level Anisotropy and Heterogeneity of Individual Plates and Rods in Normal Human Trabecular Bone
Authors: Yu Y Eric , Hu Yizhong Jenny , Zhou Bin , Wang Ji , Guo X Edward 
Published: May 2021

ABSTRACT
Trabecular plates and rods determine apparent elastic modulus and yield strength of trabecular bone, serving as important indicators of bone's mechanical integrity in health and disease. Although trabecular bone's apparent-level mechanical properties have been widely reported, tissue mechanical properties of individual trabeculae have not been fully characterized. We systematically measured tissue mineral density (TMD)–dependent elastic modulus of individual trabeculae using microindentation and characterized its anisotropy as a function of trabecular type (plate or rod), trabecular orientation in the global coordinate (longitudinal, oblique, or transverse along the anatomic loading axis), and indentation direction along the local trabecular coordinate (axial or lateral). Human trabecular bone samples were scanned by micro-computed tomography for TMD and microstructural measurements. Individual trabecula segmentation was used to decompose trabecular network into individual trabeculae, where trabecular type and orientation were determined. We performed precise, selective indentation of trabeculae in each category using a custom-built, microscope-coupled microindentation device. Co-localization of TMD at each indentation site was performed to obtain TMD-to-modulus correlations. We found significantly higher TMD and tissue modulus in trabecular plates than rods. Regardless of trabecular type and orientation, axial tissue modulus was consistently higher than lateral tissue modulus, with ratios ranging from 1.13 to 1.41. Correlations between TMD and tissue modulus measured from axial and lateral indentations were strong but distinct: axial correlation predicted higher tissue modulus than lateral correlation at the same TMD level. To assess the contribution of experimentally measured anisotropic tissue properties of individual trabeculae to apparent-level mechanics, we constructed non-linear micro-finite element models using a new set of trabecular bone samples and compared model predictions to mechanical testing measurements. Heterogeneous anisotropic models accurately predicted apparent elastic modulus but were no better than a simple homogeneous isotropic model. Variances in tissue-level properties may therefore contribute nominally to apparent-level mechanics in normal human trabecular bone. © 2021 American Society for Bone and Mineral Research (ASBMR).
Local current analysis on defective zigzag graphene nanoribbons devices for biosensor material applications
Authors: Shao Jingjing , Paulus Beate , Tremblay Jean Christophe 
Published: May 2021

AbstractIn this contribution, we aim at investigating the mechanism of biosensing in graphene‐based materials from first principles. Inspired by recent experiments, we construct an atomistic model composed of a pyrene molecule serving as a linker fragment, which is used in experiment to attach certain aptamers, and a defective zigzag graphene nanoribbons (ZGNRs). Density functional theory including dispersive interaction is employed to study the energetics of the linker absorption on the defective ZGNRs. Combining non‐equilibrium Green's function and the Landauer formalism, the total current‐bias voltage dependence through the device is evaluated. Modifying the distance between the linker molecule and the nanojunction plane reveals a quantitative change in the total current‐bias voltage dependence, which correlates to the experimental measurements. In order to illuminate the geometric origin of these variation observed in the considered systems, the local currents through the device are investigated using the method originally introduced by Evers and co‐workers. In our new implementation, the numerical efficiency is improved by applying sparse matrix storage and spectral filtering techniques, without compromising the resolution of the local currents. Local current density maps qualitatively demonstrate the local variation of the interference between the linker molecule and the nanojunction plane.
Genotyping, antifungal susceptibility, enzymatic activity, and phenotypic variation in Candida albicans from esophageal candidiasis
Authors: Jafarian Hadis , Gharaghani Maral , Seyedian Seyed Saeed , Mahmoudabadi Ali Zarei 
Published: May 2021

AbstractBackgroundEsophageal candidiasis is the most frequent form of esophagitis. The pathogenicity of Candida spp. is related to a combination of microbial factors, hydrolytic enzyme secretion and phenotypic switching. This study was designed to investigate esophageal candidiasis, antifungal activity, enzymatic activity patterns, phenotyping, and genotyping profiles of Candida albicans species.MethodsNine hundred thirty‐three visited patients were evaluated, and esophageal biopsies from patients were included in this study during 2019–2020. Direct smear, Gram staining, and culture on CHROMagar were performed for each sample. Isolated species were identified with conventional procedures and PCR‐RFLP. Susceptibility to antifungals was determined according to CLSI guidelines. ABC typing, phenotype switching, hemolysin, proteinase, phospholipase, and esterase activity were also determined with the appropriate protocols.ResultsTwenty‐three (2.5%) patients (mean age 55.2 years) were diagnosed with esophageal candidiasis. The species isolated were 19(82.6%) C. albicans, 3(13.1%) C. glabrata, and 1(4.3%) C. tropicalis. Genotype A (57.9%) was the predominant type in C. albicans isolates. 50% of C. albicans isolates exhibited a white phenotype. A high level of phospholipase (47.4%), hemolysin (68.4%), and proteinase activity (36.8%) was observed in the C. albicans isolates. Only three C. glabrata isolates displayed non‐wild type susceptibility to voriconazole and itraconazole.ConclusionThis study shows that C. albicans are still the most frequent isolates from patients with esophageal candidiasis. The predominance of genotype A, the white phenotype, and strong hemolysin activity may indicate a high prevalence of pathogenicity in these isolates. Sensitivity to antifungal drugs was greatest for amphotericin and fluconazole.
Inhibiting PHD2 in human periodontal ligament cells via lentiviral vector-mediated RNA interference facilitates cell osteogenic differentiation and periodontal repair
Authors: Cui Di , Chen Changxing , Luo Binyan , Yan Fuhua 
Published: May 2021

AbstractPeriodontal defect regeneration in severe periodontitis remains a challenging task in clinic owing to poor survival of seed cells caused by the remaining oxidative stress microenvironment. Recently, the reduction of prolyl hydroxylase domain-containing protein 2 (PHD2), a primary cellular oxygen sensor, has shown an incredible extensive effect on skeletal muscle tissue regeneration by improving cell resistance to reactive oxygen species, whereas its role in periodontal defect repair is unclear. Here, through lentivirus vector-mediated RNA interference, the PHD2 gene in human periodontal ligament cells (hPDLCs) is silenced, leading to hypoxia-inducible factor-1α stabilization in normoxia. In vitro, PHD2 silencing not only exhibited a satisfactory effect on cell proliferation, but also induced distinguished osteogenic differentiation of hPDLCs. Real-time polymerase chain reaction and Western blotting revealed significant up-regulation of osteocalcin, alkaline phosphatase (ALP), runt-related transcription factor 2, and collagen type I (COL I). Under oxidative stress conditions, COL I and ALP expression levels, suppressed by 100 μM H2O2, were elevated by PHD2-gene-silencing in hPDLCs. In vivo, periodontal fenestration defects were established in 18 female Sprague-Dawley rats aged 6 wk old, followed by implantation of PHD2 silencing hPDLCs in situ for 21 d. Persistent and stable silencing of PHD2 in hPDLCs promoted better new bone formation according to microcomputed tomography 3D reconstruction and related bone parameter analysis. This work demonstrates the therapeutic efficiency of PHD2 gene interference in osteogenic differentiation and periodontal defect repair for highly efficient periodontal regeneration.