bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of scaffold reshaping and disassembly in dynamin driven membrane fission
Authors: Pannuzzo Martina , McDargh Zachary A , Deserno Markus
Published: December 2018

The large GTPase dynamin catalyzes membrane fission in eukaryotic cells, but despite three decades of experimental work, competing and partially conflicting models persist regarding some of its most basic actions. Here we investigate the mechanical and functional consequences of dynamin scaffold shape changes and disassembly with the help of a geometrically and elastically realistic simulation model of helical dynamin-membrane complexes. Beyond changes of radius and pitch, we emphasize the crucial role of a third functional motion: an effective rotation of the filament around its longitudinal axis, which reflects alternate tilting of dynamin’s PH binding domains and creates a membrane torque. We also show that helix elongation impedes fission, hemifission is reached via a small transient pore, and coat disassembly assists fission. Our results have several testable structural consequences and help to reconcile mutual conflicting aspects between the two main present models of dynamin fission—the two-stage and the constrictase model.
A causal role for right temporo-parietal junction in signaling moral conflict
Authors: Obeso Ignacio , Moisa Marius , Ruff Christian C , Dreher Jean-Claude
Published: December 2018

The right temporo-parietal junction (rTPJ) has been proposed to play a key role in guiding human altruistic behavior, but its precise functional contribution to altruism remains unclear. We aimed to disentangle three possible functions of the rTPJ for human altruism, namely: implementing the motivation to help, signaling conflicts between moral and material values, or representing social reputation concerns. Our novel donation-decision task consisted of decisions requiring trade-offs of either positive moral values and monetary cost when donating to a good cause, or negative moral values and monetary benefits when sending money to a bad cause. Disrupting the rTPJ using transcranial magnetic stimulation did not change the general motivation to give or to react to social reputation cues, but specifically reduced the behavioral impact of moral-material conflicts. These findings reveal that signaling moral-material conflict is a core rTPJ mechanism that may contribute to a variety of human moral behaviors.
Neuronal variability and tuning are balanced to optimize naturalistic self-motion coding in primate vestibular pathways
Authors: Mitchell Diana E , Kwan Annie , Carriot Jerome , Chacron Maurice J , Cullen Kathleen E
Published: December 2018

It is commonly assumed that the brain’s neural coding strategies are adapted to the statistics of natural stimuli. Specifically, to maximize information transmission, a sensory neuron’s tuning function should effectively oppose the decaying stimulus spectral power, such that the neural response is temporally decorrelated (i.e. ‘whitened’). However, theory predicts that the structure of neuronal variability also plays an essential role in determining how coding is optimized. Here, we provide experimental evidence supporting this view by recording from neurons in early vestibular pathways during naturalistic self-motion. We found that central vestibular neurons displayed temporally whitened responses that could not be explained by their tuning alone. Rather, computational modeling and analysis revealed that neuronal variability and tuning were matched to effectively complement natural stimulus statistics, thereby achieving temporal decorrelation and optimizing information transmission. Taken together, our findings reveal a novel strategy by which neural variability contributes to optimized processing of naturalistic stimuli.
ScanFold: an approach for genome-wide discovery of local RNA structural elements—applications to Zika virus and HIV
Authors: Andrews Ryan J. , Roche Julien , Moss Walter N.
Published: December 2018

In addition to encoding RNA primary structures, genomes also encode RNA secondary and tertiary structures that play roles in gene regulation and, in the case of RNA viruses, genome replication. Methods for the identification of functional RNA structures in genomes typically rely on scanning analysis windows, where multiple partially-overlapping windows are used to predict RNA structures and folding metrics to deduce regions likely to form functional structure. Separate structural models are produced for each window, where the step size can greatly affect the returned model. This makes deducing unique local structures challenging, as the same nucleotides in each window can be alternatively base paired. We are presenting here a new approach where all base pairs from analysis windows are considered and weighted by favorable folding. This results in unique base pairing throughout the genome and the generation of local regions/structures that can be ranked by their propensity to form unusually thermodynamically stable folds. We applied this approach to the Zika virus (ZIKV) and HIV-1 genomes. ZIKV is linked to a variety of neurological ailments including microcephaly and Guillain–Barré syndrome and its (+)-sense RNA genome encodes two, previously described, functionally essential structured RNA regions. HIV, the cause of AIDS, contains multiple functional RNA motifs in its genome, which have been extensively studied. Our approach is able to successfully identify and model the structures of known functional motifs in both viruses, while also finding additional regions likely to form functional structures. All data have been archived at the RNAStructuromeDB (www.structurome.bb.iastate.edu), a repository of RNA folding data for humans and their pathogens.
Desafios no atendimento das metas do Plano Nacional de Educação pelo segmento público: elevação das taxas de matrícula na educação superior
Authors: Siebiger Ralf Hermes
Published: December 2018

Esse texto apresenta uma projeção estimativa bem como uma reflexão sobre as possibilidades de atendimento das metas estabelecidas no Plano Nacional de Educação (PNE) 2014-2024 (Lei 13.005/2014) em relação à elevação das taxas de matrícula na educação superior. Baseou-se em pesquisa documental por meio de levantamento de dados junto às sinopses estatísticas do Inep, estimativas populacionais da PNAD e projeções do IBGE, cotejando-as com as metas do atual PNE, traduzidas em números. Como resultados preliminares, evidencia-se o desafio de se alcançar as metas estabelecidas no PNE até 2024 - ano final da vigência do Plano – considerando que a lei estabelece que 40% das novas matrículas devam ser realizadas no segmento público.
Avaliação radiográfica da interface de reparo em resina bulk fill
Authors: Teixeira Ana Paula Araujo , Canedo Paula Mathias de Moraes , Gomes Rafael Soares
Published: December 2018

Objetivo: avaliar radiograficamente a interface de reparo em resina bulk fill (Opus bulk fill - FGM) com diferentes protocolos de adesão. Metodologia: foram confeccionados 30 corpos de prova em formato de cubo, nas dimensões de 4mm x 6mm. Os corpos foram randomizados e divididos entre os grupos: G1: ácido fosfórico a 37% (Dentsply) + adesivo (Ambar - FGM); G2: ácido fosfórico a 37% (Dentsply) + silano (Prosil- FGM) + adesivo (Ambar–FGM)  e G3: Adesivo auto-condicionante (Ambar universal -FGM). Após os tratamentos, os corpos foram posicionados em uma matriz metálica de 4mm x 8mm para receber novos incrementos de resina bulk fill. Para análise do reparo, as amostras foram submetidas a radiografias digitais (Micro Imagem), com disparo de 0,16 segundos. Aplicou-se o efeito de contraste filtro de tele MI para permitir a avaliação visual.  Para análise estatística foi utilizado o teste exato de Fisher.  Resultados: o grupo 2 apresentou em metade dos espécimes avaliados, uma interface não visível, porém, não diferiu estatisticamente dos outros grupos que em sua maioria apresentaram a interface visível em mais de 50% da extensão do reparo. Conclusão: os protocolos realizados na interface da resina bulk fill não foram suficientes para gerar diferenças entre as imagens dos grupos tratados.
Análise comparativa entre a coloração do azul de toluidina e a imunoexpressão da ciclina D1 em leucoplasias da mucosa bucal com diferentes graus de atipia
Authors: Silva Lorena Ferraz Santos , Ramalho Luciana Maria Pedreira
Published: December 2018

O câncer de boca ocupa uma posição de destaque em relação ao número total de casos registrados no Brasil. A displasia epitelial (DE) oral é um achado histopatológico associado a um risco aumentado de transformação maligna do epitélio oral. A falha nos mecanismos de sinalização celular, no controle do ciclo celular ou nos mecanismos para reparar danos celulares pode favorecer a processos que culminam com a progressão para o câncer. Objetivo – Avaliar comparativamente a resposta clínica da marcação do azul de toluidina (AT) e a imunoexpressão da proteína ciclina D1, uma proteína nuclear de grande importância como regulador da transição da fase G1 para fase S do ciclo celular, em leucoplasias oral (LO). Materiais e métodos – Avaliamos 12 pacientes que apresentavam, na cavidade bucal, lesões com diagnóstico clínico de LO. O estudo se desenvolveu em duas etapas: clínica e laboratorial. Foi feita marcação com AT e avaliação Imuno-histoquímica, respectivamente. Após análise quantitativa das lâminas, os dados obtidos foram analisados pelo programa BIOESTAT 2.0, por meio dos testes de Spearman e pelo teste de correlações múltiplas de Pearson. Resultados – Não foi observada relação entre a marcação clínica do AT, o grau de displasia da lesão e a imunoexpressão da Ciclina D1 em LO. Conclusão – 82% das lesões apresentaram DE em graus variados, confirmando a necessidade de se realizar o diagnóstico histopatológico das LO e o acompanhamento clínico posterior dos pacientes.
German Cancer Consortium (DKTK) – A national consortium for translational cancer research
Authors: Joos Stefan , Nettelbeck Dirk M. , Reil‐Held Anette , Engelmann Katja , Moosmann Alexandra , Eggert Angelika , Hiddemann Wolfgang , Krause Mechthild , Peters Christoph , Schuler Martin , Schulze‐Osthoff Klaus , Serve Hubert , Wick Wolfgang , Puchta Josef , Baumann Michael
Published: December 2018

The German Cancer Consortium (‘Deutsches Konsortium für Translationale Krebsforschung’, DKTK) is a long‐term cancer consortium, bringing together the German Cancer Research Center (DKFZ), Germany's largest life science research center, and the leading University Medical Center‐based Comprehensive Cancer Centers (CCCs) at seven sites across Germany. DKTK was founded in 2012 following international peer review and has positioned itself since then as the leading network for translational cancer research in Germany. DKTK is long term funded by the German Ministry of Research and Education and the federal states of each DKTK partner site. DKTK acts at the interface between basic and clinical cancer research, one major focus being to generate suitable multisite cooperation structures and provide the basis for including higher numbers of patients and facilitate effective collaborative forward and reverse translational cancer research. The consortium addresses areas of high scientific and medical relevance and develops critical infrastructures, for example, for omics technologies, clinical and research big data exchange and analysis, imaging, and clinical grade drug manufacturing. Moreover, DKTK provides a very attractive environment for interdisciplinary and interinstitutional training and career development for clinician and medical scientists.
A Stimuli‐Responsive Nanocomposite for 3D Anisotropic Cell‐Guidance and Magnetic Soft Robotics
Authors: Tognato Riccardo , Armiento Angela R. , Bonfrate Valentina , Levato Riccardo , Malda Jos , Alini Mauro , Eglin David , Giancane Gabriele , Serra Tiziano
Published: December 2018

Stimuli‐responsive materials have the potential to enable the generation of new bioinspired devices with unique physicochemical properties and cell‐instructive ability. Enhancing biocompatibility while simplifying the production methodologies, as well as enabling the creation of complex constructs, i.e., via 3D (bio)printing technologies, remains key challenge in the field. Here, a novel method is presented to biofabricate cellularized anisotropic hybrid hydrogel through a mild and biocompatible process driven by multiple external stimuli: magnetic field, temperature, and light. A low‐intensity magnetic field is used to align mosaic iron oxide nanoparticles (IOPs) into filaments with tunable size within a gelatin methacryloyl matrix. Cells seeded on top or embedded within the hydrogel align to the same axes of the IOPs filaments. Furthermore, in 3D, C2C12 skeletal myoblasts differentiate toward myotubes even in the absence of differentiation media. 3D printing of the nanocomposite hydrogel is achieved and creation of complex heterogeneous structures that respond to magnetic field is demonstrated. By combining the advanced, stimuli‐responsive hydrogel with the architectural control provided by bioprinting technologies, 3D constructs can also be created that, although inspired by nature, express functionalities beyond those of native tissue, which have important application in soft robotics, bioactuators, and bionic devices.
Tuning Hole Transport Layer Using Urea for High‐Performance Perovskite Solar Cells
Authors: Elbohy Hytham , Bahrami Behzad , Mabrouk Sally , Reza Khan Mamun , Gurung Ashim , Pathak Rajesh , Liang Mao , Qiao Qiquan , Zhu Kai
Published: December 2018

Interface engineering is critical to the development of highly efficient perovskite solar cells. Here, urea treatment of hole transport layer (e.g., poly(3,4‐ethylene dioxythiophene):polystyrene sulfonate (PEDOT:PSS)) is reported to effectively tune its morphology, conductivity, and work function for improving the efficiency and stability of inverted MAPbI3 perovskite solar cells (PSCs). This treatment has significantly increased MAPbI3 photovoltaic performance to 18.8% for the urea treated PEDOT:PSS PSCs from 14.4% for pristine PEDOT:PSS devices. The use of urea controls phase separation between PEDOT and PSS segments, leading to the formation of a unique fiber‐shaped PEDOT:PSS film morphology with well‐organized charge transport pathways for improved conductivity from 0.2 S cm−1 for pristine PEDOT:PSS to 12.75 S cm−1 for 5 wt% urea treated PEDOT:PSS. The urea‐treatment also addresses a general challenge associated with the acidic nature of PEDOT:PSS, leading to a much improved ambient stability of PSCs. In addition, the device hysteresis is significantly minimized by optimizing the urea content in the treatment.
Local Structure of High Performance TiOx Electron‐Selective Contact Revealed by Electron Energy Loss Spectroscopy
Authors: Mochizuki Takeya , Gotoh Kazuhiro , Kurokawa Yasuyoshi , Yamamoto Takahisa , Usami Noritaka
Published: December 2018

Recent increases in the power conversion efficiency of crystalline silicon (c‐Si) heterojunction (SHJ) solar cells are due to implementation of carrier‐selective contacts (CSCs) with high passivation performance and low contact resistivity. These electrical properties of CSCs significantly depend on the nature of the CSCs/c‐Si interface at the atomistic scale, and precise control of the interface with the SiOx interlayer is the key to obtaining superior electrical properties. It is shown that a TiOx/c‐Si structure with an interlayer prepared by nitric acid at room temperature shows the best performance among points with five different interlayer formation methods. The underlying mechanisms are investigated by combining high‐resolution transmission electron microscopy and electron energy loss (EEL) spectroscopy. The EEL spectra reveal that the Si:O ratio of an as‐deposited SiOx interlayer is nonstoichiometric (x < 2), which could contribute to lower contact resistivity. Furthermore, the as‐deposited SiOx leads to formation of a Ti containing SiOx layer with few oxygen vacancies after forming gas annealing, resulting in the significant enhancement of passivation performance. These results show that the control of the interlayer with atomistic scale is of crucial importance to realize higher power conversion efficiency of SHJ solar cells.
Decoloniality as a Framework for Indigenous Youth Suicide Prevention Pedagogy: Promoting Community Conversations About Research to End Suicide
Authors: Trout Lucas , McEachern Diane , Mullany Anna , White Lauren , Wexler Lisa
Published: December 2018

Indigenous youth suicide remains a substantial health disparity in circumpolar communities, despite prevention efforts through primary health care, public health campaigns, school systems, and social services. Innovations in prevention practice move away from expert‐driven approaches to emphasize local control through processes that utilize research evidence, but privilege self‐ determined action based on local and personal contexts, meanings, and frameworks for action. “Promoting Community Conversations About Research to End Suicide” is a community health intervention that draws on networks of Indigenous health educators in rural Alaska, who host learning circles in which research evidence is used to spark conversations and empower community members to consider individual and collective action to support vulnerable people and create health‐promoting conditions that reduce suicide risk. The first of nine learning circles focuses on narratives of local people who link the contemporary youth suicide epidemic to 20th century American colonialism, and situates prevention within this context. We describe the theoretical framework and feasibility and acceptability outcomes for this learning circle, and elucidate how the educational model engages community members in decolonial approaches to suicide prevention education and practice, thus serving as a bridge between Western and Indigenous traditions to generate collective knowledge and catalyze community healing.
SCAPER‐associated nonsyndromic autosomal recessive retinitis pigmentosa
Authors: Jauregui Ruben , Thomas Amanda L. , Liechty Benjamin , Velez Gabriel , Mahajan Vinit B. , Clark Lorraine , Tsang Stephen H.
Published: December 2018

Mutations in the gene SCAPER (S‐phase CyclinA Associated Protein residing in the Endoplasmic Reticulum) have recently been identified as causing syndromic autosomal recessive retinitis pigmentosa with the extraocular manifestations of intellectual disability and attention‐deficit/hyperactivity disorder. We present the case of an 11‐year‐old boy that presented to our clinic with the complaint of decreased night vision. Clinical presentation, family history, and diagnostic imaging were congruent with the diagnosis of autosomal recessive retinitis pigmentosa. Genetic testing of the patient and both parents via whole‐exome sequencing revealed the homozygous mutation c.2023‐2A>G in SCAPER. Unique to our patient's presentation is the absence of intellectual disability and attention‐deficit/hyperactivity disorder, suggesting that SCAPER‐associated retinitis pigmentosa can also present without systemic manifestations.
Peptide‐Coated Platinum Nanoparticles with Selective Toxicity against Liver Cancer Cells
Authors: Shoshan Michal S. , Vonderach Thomas , Hattendorf Bodo , Wennemers Helma
Published: December 2018

Peptide‐stabilized platinum nanoparticles (PtNPs) were developed that have significantly greater toxicity against hepatic cancer cells (HepG2) than against other cancer cells and non‐cancerous liver cells. The peptide H‐Lys‐Pro‐Gly‐dLys‐NH2 was identified by a combinatorial screening and further optimized to enable the formation of water‐soluble, monodisperse PtNPs with average diameters of 2.5 nm that are stable for years. In comparison to cisplatin, the peptide‐coated PtNPs are not only more toxic against hepatic cancer cells but have a significantly higher tumor cell selectivity. Cell viability and uptake studies revealed that high cellular uptake and an oxidative environment are key for the selective cytotoxicity of the peptide‐coated PtNPs.
Partial removal of protein associated with arabinoxylans: Impact on the viscoelasticity, crosslinking content, and microstructure of the gels formed
Authors: Mendez‐Encinas Mayra A. , Carvajal‐Millan Elizabeth , Yadav Madhav P. , López‐Franco Yolanda L. , Rascon‐Chu Agustín , Lizardi‐Mendoza Jaime , Brown‐Bojorquez Francisco , Silva‐Campa Erika , Pedroza‐Montero Martín
Published: December 2018

Arabinoxylans (AX) treated with protease and dialyzed (AXP) or only dialyzed (AXD) formed gels showing an increase in the elastic modulus G′ (1291 and 1419 Pa, respectively) and the ferulic acid dimers (3.34 and 3.10 μg/mg polysaccharide, respectively) and trimers (0.51 and 0.53 μg/mg polysaccharide, respectively) in comparison to AX gels (767 Pa, 0.56 and 0.12 μg/mg polysaccharide, respectively). Nevertheless, the G′ values and crosslinking contents were not different among the AXP and AXD gels, suggesting that the amount of protein removed (54%) does not affect these parameters. Confocal laser scanning microscopy analysis showed that AXP treatment promotes the homogeneity of the gels. In addition, scanning electron microscopy observations indicated that AXD and particularly AXP gels had a more compact microstructure. Thus, the partial removal of protein associated with AX does not impact the viscoelasticity and crosslinking content of the gels formed but could improve their microstructural characteristics. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47300.
Relationship on structure and properties of polyurethane modified Diels–Alder addition polymer
Authors: Liu Xu , Liu Fangbo , Liu Simeng , Cui Min , Deng Jianru
Published: December 2018

A series of linear and crosslinked polyurethane modified materials were prepared by Diels–Alder cycloaddition reaction. Based on raw materials, some novel equations were designed and effects of equation parameters on the mechanical properties of modified material were explored. It was demonstrated that tensile strength of modified materials and elongation at break were changed from 3.68 to 18.71 MPa, 200 to 866%, respectively. In addition, the optimal reaction temperature of retro‐Diels–Alder (r‐DA) reaction was determined by differential scanning calorimeter (DSC). Gel permeation chromatography (GPC) and tensile experiments were used to characterize the properties of repolymerized material after degradation. The results indicated the optimal temperature of r‐DA for linear and crosslinked polyurethane modified materials is 127 and 150 °C. Moreover, after decomposed, the product was slowly repolymerized at 60 °C, and can more effectively restore material strength under the action of the solvent to achieve self‐healing effect. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47355.
Family and neighborhood socioeconomic inequality in cryptorchidism and hypospadias: A nationwide study from Sweden
Authors: Li Xinjun , Sundquist Jan , Hamano Tsuyoshi , Sundquist Kristina
Published: December 2018

Objectives

To examine whether there is an association between neighborhood deprivation and incidence of cryptorchidism and hypospadias, after accounting for family‐level and individual‐level sociodemographic characteristics.

Methods

All boys born in Sweden between January 1, 2001 and December 31, 2010 were followed. Data were analyzed by multilevel logistic regression, with family‐level and individual‐level characteristics at the first level and level of neighborhood deprivation at the second level.

Results

During the study period, among a total of 497,584 boys, 8,584 (1.7%) and 3,704 (0.7%) were diagnosed with cryptorchidism and hypospadias, respectively. Cumulative rates for cryptorchidism and hypospadias increased with increasing levels of neighborhood deprivation. In the study population, 1.5 per 100 and 2.0 per 100 boys, in the least and most deprived neighborhoods were diagnosed with cryptorchidism and 0.7 per 100 and 0.9 per 100 boys were diagnosed with hypospadias. Incidence of hospitalization for cryptorchidism and hypospadias increased with increasing neighborhood‐level deprivation across all family‐level and individual‐level sociodemographic categories. The odds ratio (OR) for cryptorchidism and hypospadias for those living in high‐deprivation neighborhoods versus those living in low‐deprivation neighborhoods was 1.13 (95% confidence interval [CI] = 1.05–1.21) and 1.24 (95% CI = 1.12–1.37). High neighborhood deprivation remained significantly associated with higher odds of hypospadias after adjustment for family‐level and individual‐level sociodemographic characteristics (OR = 1.20, 95% CI = 1.08–1.35).

Conclusions

This study is the largest so far on neighborhood influences on cryptorchidism and hypospadias. Our results suggest that neighborhood deprivation is associated with a moderate incidence of hypospadias independent of family‐level and individual‐level sociodemographic characteristics.
Corporate sustainability in practice: An exploratory study of the sustainable development goals (SDGs)
Authors: Vildåsen Sigurd Sagen
Published: December 2018

Companies applying the sustainable development goals (SDGs) are likely to face a tension between business strategy and societal development. I develop this claim through inductive reasoning, drawing on an exploratory, and longitudinal case study of the company Plasto. The findings indicate that the SDGs framework is a well‐suited platform for debating social and environmental concerns with societal stakeholders. In addition, the framework facilitates organizational learning and internal collaboration. However, actors such as customers may see the generic nature of the SDGs as irrelevant when it comes to specific business operations. Following the inductive logic, I position the findings within ongoing debates in the field of corporate sustainability. Further research should acknowledge contradictory requirements from stakeholders as a theoretical starting point. This implies that the emerging management literature on paradox theory fits well to advance insights on SDG application in a business context.
Intrinsic and Extrinsic Heavy‐Atom Effects on the Multifaceted Emissive Behavior of Cyclic Triimidazole
Authors: Lucenti Elena , Forni Alessandra , Botta Chiara , Giannini Clelia , Malpicci Daniele , Marinotto Daniele , Previtali Andrea , Righetto Stefania , Cariati Elena
Published: December 2018

Considering that heavy halogen atoms can be used to tune the emissive properties of organic luminogens, the understanding of their role in photophysics is fundamental for materials engineering. Here, the extrinsic and intrinsic heavy‐atom effects on the photophysics of organic crystals were separately evaluated by comparing cyclic triimidazole (TT) with its monoiodo derivative (TTI) and its co‐crystal with diiodotetrafluorobenzene (TTCo). Crystals of TT showed room‐temperature ultralong phosphorescence (RTUP) originated from H‐aggregation. TTI and TTCo displayed two additional long‐lived components, the origin of which is elucidated through single‐crystal X‐ray and DFT/TDDFT studies. The results highlight the different effects of the I atom on the three phosphorescent emissions. Intrinsic heavy‐atom effects play a major role on molecular phosphorescence, which is displayed at room temperature only for TTI. The H‐aggregate RTUP and the I⋅⋅⋅N XB‐induced (XB=halogen bond) phosphorescence on the other side depend only on packing features.
Minimal residual disease by flow cytometry and allelic‐specific oligonucleotide real‐time quantitative polymerase chain reaction in patients with myeloma receiving lenalidomide maintenance: A pooled analysis
Authors: Gambella Manuela , Omedé Paola , Spada Stefano , Muccio Vittorio Emanuele , Gilestro Milena , Saraci Elona , Grammatico Sara , Larocca Alessandra , Conticello Concetta , Bernardini Annalisa , Gamberi Barbara , Troia Rossella , Liberati Anna Marina , Offidani Massimo , Rocci Alberto , Palumbo Antonio , Cavo Michele , Sonneveld Pieter , Boccadoro Mario , Oliva Stefania
Published: December 2018

Background

Minimal residual disease (MRD) is one of the most relevant prognostic factors in patients with multiple myeloma (MM); however, the impact of maintenance therapy on MRD levels remains unclear. Among patients with newly diagnosed MM (NDMM) who received lenalidomide maintenance until they developed disease progression, the role of MRD status as a predictor of progression‐free survival (PFS) was evaluated by multiparameter flow cytometry (MFC) and allelic‐specific oligonucleotide real‐time quantitative polymerase chain reaction (ASO‐RQ‐PCR) analysis.

Methods

Seventy‐three patients with NDMM enrolled in the RV‐MM‐EMN‐441 (clinical trials.gov identifier, NCT01091831) and RV‐MM‐COOP‐0556 (clinicaltrials.gov identifier, NCT01208766; European Myeloma Network EMN02/HO95 MM Trial) phase 3 trials who achieved at least a very good partial response after intensification/consolidation were included. The median patient age was 57 years (interquartile range, 53‐61 years), and all patients received lenalidomide maintenance until they developed progression. MRD was evaluated on bone marrow after intensification/consolidation, after 6 courses of maintenance, and every 6 months thereafter until clinical relapse using both ASO‐RQ‐PCR (sensitivity, 10−5) and MFC (sensitivity, from 10−4 to 10−5).

Results

After intensification/consolidation, 33 of 72 patients (46%) achieved a molecular complete response (m‐CR), and 44 of 70 (63%) achieved a flow complete response (flow‐CR). Almost 27% of patients who were MRD‐positive after consolidation became MRD‐negative during maintenance. After a median follow‐up of 38 months, PFS was prolonged in patients who achieved negative MRD status during maintenance according to results from both ASO‐RQ‐PCR analysis (hazard ratio, 0.29; 95% confidence interval, 0.14‐0.62; P = .0013) and MFC (hazard ratio, 0.19; 95% confidence interval, 0.09‐0.41; P < .001). The impact of negative MRD status on PFS was similar in all subgroups (ASCT and no‐ASCT; International Staging System stages I, II, and III; high‐risk and standard‐risk cytogenetics), and the two techniques were highly correlated.

Conclusions

MRD status is a stronger predictor of PFS than standard risk factors, and lenalidomide maintenance further increases the rate of negative MRD results.
A decision analysis comparing 3 active surveillance protocols for the treatment of patients with low‐risk prostate cancer
Authors: White Craig , Nimeh Tony , Gazelle G. Scott , Weinstein Milton C. , Loughlin Kevin R.
Published: December 2018

Background

Active surveillance (AS) is a viable management option for approximately 50% of men who are newly diagnosed with prostate cancer. To the authors’ knowledge, no direct comparisons between the different variants of AS protocols have been conducted to date. The authors developed a microsimulation decision model to evaluate which of 3 alternative AS protocols is optimal for men with low‐risk prostate cancer, and compared each of these with immediate treatment.

Methods

Men who were diagnosed with low‐risk prostate cancer at age 65 years were modeled as having been treated with either immediate therapy or via each of 3 AS protocols. Modeled AS protocols represent those in the literature; a modified AS protocol was included in a sensitivity analysis. Immediate therapy included radical prostatectomy, external‐beam radiotherapy, or brachytherapy. Outcome measures were quality‐adjusted life‐years (QALYs) and costs. Cost‐effectiveness analysis and deterministic and probabilistic sensitivity analyses were performed.

Results

Immediate therapy produced fewer QALYs than all variants of AS. Of the AS protocols evaluated, biennial biopsy was found to be the only efficient option, with an incremental cost‐effectiveness ratio of $3490 per QALY compared with immediate therapy. It delayed the need for curative therapy by a mean of 56 months, and was found to be preferred in >86.9% of cases in probabilistic sensitivity analysis. A modified version of low‐intensity AS dominated all other options.

Conclusions

For a 65‐year‐old man with low‐risk prostate cancer, AS with biennial biopsy appears to be highly cost‐effective compared with common alternatives. An AS protocol using triennial biopsy was found to dominate all other strategies and should be considered for men who are comfortable with a longer period between biopsies. The optimal strategy depends on a patient’s tolerance for periodic biopsies and comfort with delaying radical treatment. Physicians should incorporate these patient preferences into decision making.
The who, when, and why of primary adrenal malignancies: Insights into the epidemiology of a rare clinical entity
Authors: Chandrasekar Thenappan , Goldberg Hanan , Klaassen Zachary , Wallis Christopher J. D. , Woon Dixon T. S. , Herrera‐Caceres Jaime O. , Kulkarni Girish S. , Fleshner Neil E.
Published: December 2018

Background

Primary malignancies of the adrenal glands are rare. Epidemiologic assessment of primary adrenal malignancies is lacking and has been limited to case reports and series. Population‐level data can provide a better understanding of the incidence, distribution, and prognostic factors associated with these rare malignancies.

Methods

The Surveillance, Epidemiology, and End Results database (1973‐2013) was queried for all patients who were diagnosed with primary adrenal malignancies, categorized in 5 histologic groups: adrenocortical carcinoma (ACC), pheochromocytoma and paraganglioma (PH), neuroblastoma (NE), non‐Hodgkin lymphoma (NHL), and sarcoma (SA). Age‐adjusted incidence, distribution trends, and cancer‐specific survival (CSS) for each group were analyzed.

Results

In total, 4695 patients with primary adrenal malignancies were identified, including 2057 with ACC, 512 with PH, 1863 with NE, 202 with NHL, and 61 with SA. The age‐adjusted incidence of all 5 histologic subtypes was rising. Age at presentation differed substantially by histologic group: NE was the most prevalent during the first decade of life, whereas ACC predominated after age 30 years, and NHL outnumbered PH after age 70 years. Patient‐specific factors were not associated with advanced disease at the time of presentation. The 5‐year CSS rate for each histologic subtype was 38% for ACC, 69% for PH, 64% for NE, 38% for NHL, and 42% for SA. Survival outcomes for patients with ACC, NHL, PH and SA remained unchanged over the 40‐year study period. Multimodal therapy was associated with higher CSS in patients with NE.

Conclusions

This first population‐level analysis of all primary adrenal malignancies provides important initial data regarding presentation and clinical outcomes. Notably, except for patients with NE, the survival of patients with these rare cancers has not improved over the past 40 years.
Transcriptomics reveals complex kinetics of dorsal–ventral patterning gene expression in the mandibular arch
Authors: Sharma Praveer P. , MacLean Adam L. , Meinecke Lina , Clouthier David E. , Nie Qing , Schilling Thomas F.
Published: December 2018

The mandibular or first pharyngeal arch forms the upper and lower jaws in all gnathostomes. A gene regulatory network that defines ventral, intermediate, and dorsal domains along the dorsal–ventral (D–V) axis of the arch has emerged from studies in zebrafish and mice, but the temporal dynamics of this process remain unclear. To define cell fate trajectories in the arches we have performed quantitative gene expression analyses of D–V patterning genes in pharyngeal arch primordia in zebrafish and mice. Using NanoString technology to measure transcript numbers per cell directly we show that, in many cases, genes expressed in similar D–V domains and induced by similar signals vary dramatically in their temporal profiles. This suggests that cellular responses to D‐V patterning signals are likely shaped by the baseline kinetics of target gene expression. Furthermore, similarities in the temporal dynamics of genes that occupy distinct pathways suggest novel shared modes of regulation. Incorporating these gene expression kinetics into our computational models for the mandibular arch improves the accuracy of patterning, and facilitates temporal comparisons between species. These data suggest that the magnitude and timing of target gene expression help diversify responses to patterning signals during craniofacial development.
Do replicates of independent guppy lineages evolve similarly in a predator‐free laboratory environment?
Authors: Gotanda Kiyoko M. , Pack Amy , LeBlond Caroline , Hendry Andrew P.
Published: December 2018

The Trinidadian guppy is emblematic of parallel and convergent evolution, with repeated demonstrations that predation regime is a driver of adaptive trait evolution. A classic and foundational experiment in this system was conducted by John Endler 40 years ago, where male guppies placed into low‐predation environments in the laboratory evolved increased color in a few generations. However, Endler's experiment did not employ the now typical design for a parallel/convergent evolution study, which would employ replicates of different ancestral lineages. We therefore implemented an experiment that seeded replicate mesocosms with small founding populations of guppies originating from high‐predation populations of two very different lineages. The different mesocosms were maintained identically, and male guppy color was quantified every four months. After one year, we tested whether male color had increased, whether replicates within a lineage had parallel phenotypic trajectories, and whether the different lineages converged on a common phenotype. Results showed that male guppy color generally increased through time, primarily due to changes in melanic color, whereas the other colors showed inconsistent and highly variable trajectories. Most of the nonparallelism in phenotypic trajectories was among mesocosms containing different lineages. In addition to this mixture of parallelism and nonparallelism, convergence was not evident in that the variance in color among the mesocosms actually increased through time. We suggest that our results reflect the potential importance of high variation in female preference and stochastic processes such as drift and founder effects, both of which could be important in nature.
The conundrum of patients with obesity, exercise intolerance, elevated ventricular filling pressures and a measured ejection fraction in the normal range
Authors: Packer Milton
Published: December 2018

Patients with obesity, a reduced exercise capacity, increased cardiac filling pressures and a measured left ventricular ejection fraction in the normal range do not have a homogeneous disorder, but instead, exhibit one of three phenotypes. First, many obese people exhibit sodium retention, plasma volume expansion and cardiac enlargement, and some are likely to have heart failure that is related to hypervolaemia, even though cardiac index and circulating levels of natriuretic peptides are not meaningfully increased. Second, in some middle‐aged men and women (particularly those with minimal co‐morbidities), levels of natriuretic peptides increase markedly and can lower systemic vascular resistance, thus leading to high‐output heart failure (HOHF) and glomerular hyperfiltration. Third, older obese people, particularly women with multiple co‐morbidities, exhibit the syndrome of heart failure with a preserved ejection fraction (HFpEF). Despite degrees of plasma volume expansion similar to HOHF, these patients exhibit only modestly increased ventricular dimensions and circulating levels of natriuretic peptides (despite a high prevalence of atrial fibrillation), and glomerular function is characteristically impaired. A conceptual framework is proposed to distinguish among the three phenotypes seen in obese patients with exercise intolerance, increased ventricular filling pressures and a measured left ventricular ejection fraction in the normal range, since they may respond differently to therapeutic interventions. Efforts are needed to enhance the recognition of heart failure in obese people and to ensure that clinical trials that are designed to study patients with HFpEF actually enrol those who have the disease.
When lack of control enhances closeness to others: The case of unemployment and economic threat
Authors: Bukowski Marcin , de Lemus Soledad , Rodríguez‐Bailón Rosa , Willis Guillermo B. , Alburquerque Abraham
Published: December 2018

When personal control is threatened, people often turn to their own group and show negativity towards others. In three studies, we tested an alternative prediction that the salient lack of personal control (vs. control) experienced in the context of unemployment can lead to connectedness and more positive perception of similar others (e.g., members of groups affected by unemployment or the economic crisis). In two European countries, we found experimental (Study 1: Poland) and correlational (Study 2: Spain) evidence that a lowered sense of control of unemployed people was related to more favorable intergroup evaluations. Furthermore, when lack of control related to unemployment threat was experimentally induced, participants perceived a Greek outgroup more positively, and this effect was mediated by identification with and similarity to this group (Study 3). We discuss the role of the shared experience of collective uncontrollability in promoting positive intergroup relations.
A Dual‐Ion Battery with a Ferric Ferricyanide Anode Enabling Reversible Na+ Intercalation
Authors: Fan Jiaxin , Fang Yaobing , Xiao Qiangqiang , Huang Runyu , Li Li , Yuan Wenhui
Published: December 2018

Dual‐ion batteries have been developed as a promising technology in recent years, but their high self‐discharge rate leading to low coulombic efficiency (CE) limits their practical applications. This work provides a deft strategy to circumvent this issue by using FeFe(CN)6 as the anode material for hosting Na+ cations, in combination with a graphite cathode for accommodating the bis(trifluoromethanesulfonyl)imide anions (TFSI−). The relatively high bonding force between FeFe(CN)6 and Na+ can hinder self‐extraction of ions from the electrodes, thereby decreasing the self‐discharge rate. The FeFe(CN)6 nanospheres, synthesized by a facile solution reaction method, are well crystallized and dispersed. Na+ insertion into the FeFe(CN)6 cube is determined by cyclic voltammetry (CV), galvanostatic charge–discharge, and X‐ray diffraction tests, suggesting a reversible process. Under a current of 0.05 mA cm−2 the batteries present an acceptable discharge plateau within 1.5–0.7 V and a well‐defined capacity of 75.0 mAh g−1, with a high CE above 98.5% (±0.1%); under 0.2 mA cm−2, cells display a high cyclability of 83.0% capacity retention for 100 cycles, with an excellent CE exceeding 99.6% (±0.1%). Moreover, the batteries exhibit a low self‐discharge rate with a resting capacity decay of 0.32% h−1, outperforming many of the reported dual‐ion cells.
Dual‐energy CT iodine quantification for characterizing focal thyroid lesions
Authors: Lee Do Hyung , Lee Young Hen , Seo Hyung Suk , Lee Ki Yeol , Suh Sang‐il , Ryoo Inseon , You Sung‐Hye , Kim Byungjun , Yang Kyung‐Sook
Published: December 2018

Background

To determine the usefulness of dual‐energy CT (DECT) iodine quantification to classify the focal thyroid lesions.

Methods

We retrospectively enrolled a total of 76 cytopathologically confirmed focal thyroid lesions (mean size: 1.9 cm). After drawing a region of interest on the DECT‐derived iodine maps, the obtained iodine concentration values of thyroid nodules (IC_N) and normalized IC_N were compared between 3 groups: papillary thyroid carcinoma (PTC), benign nodule, and cyst.

Results

From all lesions, 46, 17, and 13 were assigned to the PTC, benign nodule, and cyst groups. IC_N was the highest in the benign nodule, lower in the PTC, and the lowest in the cyst (median [interquartile range]: 4.3 [3.13‐5.48], 3.15 [2.29‐4.01], 0.60 [0.33‐0.88], all P < .001). Similarly, the normalized IC_N values were all statistically different from each other (P < .05).The multi‐class area under the curves using the optimal cutoff values were 0.931 for IC_N and 0.918, 0.920 for normalized IC, respectively.

Conclusion

DECT iodine quantification could be helpful to classify the focal thyroid lesions.
Encoding of 3D head direction information in the human brain
Authors: Kim Misun , Maguire Eleanor A.
Published: December 2018

Head direction cells are critical for navigation because they convey information about which direction an animal is facing within an environment. To date, most studies on head direction encoding have been conducted on a horizontal two‐dimensional (2D) plane, and little is known about how three‐dimensional (3D) direction information is encoded in the brain despite humans and other animals living in a 3D world. Here, we investigated head direction encoding in the human brain while participants moved within a virtual 3D “spaceship” environment. Movement was not constrained to planes and instead participants could move along all three axes in volumetric space as if in zero gravity. Using functional magnetic resonance imaging (fMRI) multivoxel pattern similarity analysis, we found evidence that the thalamus, particularly the anterior portion, and the subiculum encoded the horizontal component of 3D head direction (azimuth). In contrast, the retrosplenial cortex was significantly more sensitive to the vertical direction (pitch) than to the azimuth. Our results also indicated that vertical direction information in the retrosplenial cortex was significantly correlated with behavioral performance during a direction judgment task. Our findings represent the first evidence showing that the “classic” head direction system that has been identified on a horizontal 2D plane also seems to encode vertical and horizontal heading in 3D space in the human brain.
Monitoring turbidity from above: Deploying small unoccupied aerial vehicles to image in‐stream turbidity
Authors: Ehmann Karyn , Kelleher Christa , Condon Laura E.
Published: December 2018

Small unoccupied aerial systems (sUASs) are increasingly applied to study hydrologic processes and water quality. Here, we evaluate a novel application of sUAS to stream turbidity monitoring, with the goal of extending analyses implemented with satellite remote sensing to enable high resolution, rapid collection of turbidity imagery along smaller waterbodies. To accomplish this, we collected multispectral imagery using two sUAS platforms under a range of environmental conditions along a local creek in Syracuse, NY. In addition, we collected in situ turbidity observations immediately after each flight along several transects along the creek, as well as within a clear plume created by a natural spring entering the main channel of the creek. The in situ turbidity values were compared with the mean and standard deviation of several single‐band and multiband indices extracted along similar transects from the sUAS flights. On the basis of data collected across several flights, we found optical metrics obtained from multispectral imagery correlated well with in situ turbidity measurements. Though many optical metrics yielded strong relationships considering only values within the main channel, values associated with the red band were strongly related to turbidity estimates from the main channel as well as lower turbidity values observed in the spring plume. Although there are still limitations of this approach associated with variable field conditions, results from this proof of concept analysis show that sUASs offer a promising avenue for cost‐effective turbidity monitoring.