bluuebunny/crossref_metadata_2025 huggingface dataset:
A core set of patient-reported outcomes for population-based cancer survivorship research: a consensus study
Authors: Ramsey Imogen , Corsini Nadia , Hutchinson Amanda D. , Marker Julie , Eckert Marion
Published: August 2020

Purpose

Core outcome sets aim to improve the consistency and quality of research by providing agreed-upon recommendations regarding what outcomes should be measured as a minimum for a population and setting. This study aimed to identify a core set of patient-reported outcomes (PROs) representing the most important issues impacting on cancer survivors’ long-term health, functioning, and quality of life, to inform population-based research on cancer survivorship.

Methods

In phase I, a list of 46 outcomes was generated through focus groups (n = 5) with cancer survivors (n = 40) and a review of instruments for assessing quality of life in cancer survivorship. In phase II, 69 national experts in cancer survivorship practice, research, policy, and lived experience participated in a two-round Delphi survey to refine and prioritise the listed outcomes into a core outcome set. A consensus meeting was held with a sub-sample of participants to discuss and finalise the included outcomes.

Results

Twelve outcome domains were agreed upon for inclusion in the core outcome set: depression, anxiety, pain, fatigue, cognitive problems, fear of cancer recurrence or progression, functioning in everyday activities and roles, financial toxicity, coping with cancer, overall bother from side effects, overall quality of life, and overall health status.

Conclusions

We established a core set of PROs to standardise assessment of cancer survivorship concerns at a population level.

Implications for Cancer Survivors

Adoption of the core outcome set will ensure that survivorship outcomes considered important by cancer survivors are assessed as a minimum in future studies. Furthermore, its routine use will optimise the comparability, quality, and usefulness of the data cancer survivors provide in population-based research.
Comparison of Free Zinc Levels Determined by Fluorescent Probes in THP1 Cells Using Microplate Reader and Flow Cytometer
Authors: Alker Wiebke , Haase Hajo
Published: August 2020

Free zinc is involved in signal transduction within mammalian cells, acting as a second messenger. Gold standard for its analysis is currently the use of metal-responsive fluorescent probes. The present study elucidates the impact of instrumentation used for measuring the resulting fluorescence. The free zinc concentration of THP-1 cells loaded with the fluorescent probes Zinpyr-1 (ZP1) or Fluozin-3 AM (FZ3) was determined using a microplate reader (MPR) and a flow cytometer (FC). Depending on the instrumentation, either low nanomolar (MPR) or picomolar (FC) concentrations of free zinc were observed. The concentrations measured from identical samples by MPR were about 40 (ZP1) or 165 (FZ3) times higher compared with FC. These results demonstrate that the choice of instrumentation has a fundamental impact on the determination of intracellular free zinc concentrations by low molecular weight fluorescent probes.
Risk factors for pancreas and lung neuroendocrine neoplasms: a case–control study
Authors: Giraldi Luca , Vecchioni Alessia , Carioli Greta , Bilotta Mirna , La Rosa Stefano , Imperatori Andrea , Volante Marco , Brizzi Maria Pia , Inzani Frediano , Petrone Gianluigi , Schinzari Giovanni , Bianchi Antonio , Margaritora Stefano , Alfieri Sergio , La Vecchia Carlo , Boccia Stefania , Rindi Guido
Published: August 2020

Purpose

Neuroendocrine neoplasia (NEN) has been displaying an incremental trend along the last two decades. This phenomenon is poorly understood, and little information is available on risk factor for neuroendocrine neoplasia development. Aim of this work is to elucidate the role of potentially modifiable risk factors for pancreatic and pulmonary NEN.

Methods

We conducted a case–control study on 184 patients with NEN (100 pancreas and 84 lung) and 248 controls. The structured questionnaire included 84 queries on socio-demographic, behavioral, dietary and clinical information.

Results

Increased risk was associated with history of cancer (“other tumor”, lung OR = 7.18; 95% CI: 2.55–20.20 and pancreas OR = 5.88; 95% CI: 2.43–14.22; “family history of tumor”, lung OR = 2.66; 95% CI: 1.53–4.64 and pancreas OR = 1.94; 95% CI: 1.19–3.17; “family history of lung tumor”, lung OR = 2.56; 95% CI: 1.05–6.24 and pancreas OR = 2.60; 95% CI: 1.13–5.95). Type 2 diabetes mellitus associated with an increased risk of pancreatic NEN (OR = 3.01; 95% CI: 1.15–7.89).

Conclusions

Besides site-specific risk factors, there is a significant link between neuroendocrine neoplasia and cancer in general, pointing to a shared cancer predisposition.
Diskurse Sozialer Arbeit und „Big Data“
Authors: Kloss Tilman
Published: August 2020

Der Beitrag setzt sich mit der Frage auseinander, über welche Themen in Rezensionen zu Publikationen im Bereich der Sozialen Arbeit gesprochen wird und welche davon miteinander diskutiert werden. Beispielsweise wird sichtbar, dass die Stichwörter Kind und Jugend eine inhaltliche Nähe zu Prävention, Psychotherapie und psychische Störung aufweisen. Darauf bezogen wird exemplarisch eine vorsichtige Kontextualisierung der Ergebnisse vorgenommen. Zudem wird gezeigt, welchen Mehrwert dieses methodische Vorgehen entfalten kann und wo wiederum dessen Grenzen liegen.
Reynolds number and wind tunnel wall effects on the flow field around a generic UHBR engine high-lift configuration
Authors: Ullah Junaid , Prachař Aleš , Šmíd Miroslav , Seifert Avraham , Soudakov Vitaly , Lutz Thorsten , Krämer Ewald
Published: August 2020

RANS simulations of a generic ultra-high bypass ratio engine high-lift configuration were conducted in three different environments. The purpose of this study is to assess small scale tests in an atmospheric closed test section wind tunnel regarding transferability to large scale tests in an open-jet wind tunnel. Special emphasis was placed on the flow field in the separation prone region downstream from the extended slat cut-out. Validation with wind tunnel test data shows an adequate agreement with CFD results. The cross-comparison of the three sets of simulations allowed to identify the effects of the Reynolds number and the wind tunnel walls on the flow field separately. The simulations reveal significant blockage effects and corner flow separation induced by the test section walls. By comparison, the Reynolds number effects are negligible. A decrease of the incidence angle for the small scale model allows to successfully reproduce the flow field of the large scale model despite severe wind tunnel wall effects.
A biosensor based on a modified S-taper fiber for target protein detection
Authors: Liu Xiaoqi , Liu Yange , Wang Zhi
Published: August 2020

A biosensor based on a modified S-taper fiber was proposed and experimentally demonstrated for antigen detection. Antibody was immobilized over the activated S-taper waist, where the fiber detected the interaction between the antibody and target antigen. Compared with a unmodified S-taper fiber structure, the silanized fiber had a detection limit of approximately 8.33 × 10−5 RIU when the concentration of antigen solution was changed 1%. The antibody and antigen binding processing was monitored in real time by analyzing and investigating the transmission spectral characteristics of the modified S-taper fiber. The cost-effectiveness, real-time detection, and high integration properties of the fiber enable its use in a modal interferometer for biosensing applications including disease diagnosis and biological specificity recognition.
Spaceborne Middle‐ and Far‐Infrared Observations Improving Nighttime Ice Cloud Property Retrievals
Authors: Saito Masanori , Yang Ping , Huang Xianglei , Brindley Helen E. , Mlynczak Martin G. , Kahn Brian H.
Published: August 2020

Two upcoming missions are scheduled to provide novel spaceborne observations of upwelling far‐infrared spectra. In this study, the accuracy of ice cloud property retrievals using spaceborne middle‐to‐far‐infrared (MIR‐FIR) measurements is examined toward a better understanding of retrieval biases and uncertainties. Theoretical sensitivity studies demonstrate that the MIR‐FIR spectra are sensitive to ice cloud properties, thereby providing a robust means for retrieving cloud properties under nighttime conditions. However, the temperature dependence of the ice refractive index and relevant ice particle shape models need to be incorporated into the retrieval procedure to avoid systematic biases in inferring cloud optical thickness and effective particle radius. Furthermore, prior information of subpixel cloud fractions is essential to mitigation of substantial systematic retrieval biases due to inconsistent subpixel cloud fractions.
First Direct Observational Evidence for Secondary Gravity Waves Generated by Mountain Waves Over the Andes
Authors: Kogure Masaru , Yue Jia , Nakamura Takuji , Hoffmann Lars , Vadas Sharon L. , Tomikawa Yoshihiro , Ejiri Mitsumu K. , Janches Diego
Published: August 2020

A mountain wave with a significant brightness temperature amplitude and ~500 km horizontal wavelength was observed over the Andes on 24–25 July 2017 in Atmospheric Infrared Sounder (AIRS)/Aqua satellite data. In the Modern‐Era Retrospective Analysis for Research and Applications, version 2 (MERRA‐2), reanalysis data, the intense eastward wind flowed over the Andes. Visible/Infrared Imaging Radiometer Suite (VIIRS)/Suomi‐NPP (National Polar‐orbiting Partnership) did not detect the mountain waves; however, it observed concentric ring‐like waves in the nightglow emissions at ~87 km with ~100 km wavelengths on the same night over and leeward of the Southern Andes. A ray tracing analysis showed that the mountain waves propagated to the east of the Andes, where concentric ring‐like waves appeared above a region of mountain wave breaking. Therefore, the concentric ring‐like waves were likely secondary waves generated by momentum deposition that accompanied mountain wave breaking. These results provide the first direct evidence for secondary gravity waves generated by momentum deposition.
Magnetic Field Imaging of Salt Structures at Nordkapp Basin, Barents Sea
Authors: Paoletti V. , Milano M. , Baniamerian J. , Fedi M.
Published: August 2020

We show that high‐resolution aeromagnetic surveys, although rarely employed in the research of salt structures, may be an effective and low‐cost tool for mapping diapirism. A multiscale analysis of a high‐resolution magnetic data set at Nordkapp Basin in the Barents Sea, allows a clear reconstruction of the main salt diapirs of the basin using Multiridge and Compact Depth from Extreme Points methods. We provide a 3‐D model of the diapirs extended from 500 to 4,000 m below sea level, characterized by a general low magnetization contrast no larger than −0.08 A/m. The 3‐D model is consistent with the salt top depth estimated by 2‐D seismics, with borehole data and with the 2‐D gravity model of the Uranus diapir. Our imaging shows the capability of the magnetic method that gives new and comprehensive pictures of salt diapirism.
3‐D Tomography of the Ionospheric Anomalies Immediately Before and After the 2011 Tohoku‐Oki (Mw9.0) Earthquake
Authors: Muafiry Ihsan Naufal , Heki Kosuke
Published: August 2020

A dense network of ground global navigation satellite system receivers detected ionospheric total electron content (TEC) changes starting ~40 min before the 2011 Tohoku‐oki (Mw9.0) earthquake around the ruptured fault, together with the long‐lasting postseismic TEC drop. In this paper, we robustly estimate three‐dimensional (3‐D) distribution of both preseismic and postseismic ionospheric anomalies of the 2011 Tohoku‐oki earthquake by tomographic inversions of electron density anomalies. We set up >6,000 blocks, as large as 1.0° (east‐west) × 0.9° (north‐south) × 60 km (vertical), over the Japanese Islands, the Sea of Japan, and the Korean Peninsula, up to 870 km altitude. By using TEC anomalies of pairs exceeding ~1,300 stations and eight satellites obtained using reference curves, we estimated electron density anomalies within individual blocks. The results showed that the preseismic and postseismic anomalies do not overlap in space. The preseismic anomalies are composed of low (~300 km height) positive and high (~600 km height) negative anomalies. They occurred above the land of NE Japan without extending offshore, suggesting its origin related to surface electric charges. On the other hand, the postseismic electron depletion occurred offshore above the region where large coseismic uplift took place. These results demonstrate that the preseismic and postseismic ionospheric anomalies are independent not only temporarily but also spatially and certainly in underlying physical mechanisms. We propose a simple model to explain how surface charges redistribute ionospheric electrons to make the observed preseismic electron density anomalies.
A 250‐Year, Decadally Resolved, Radiocarbon Time History in the Gulf of Maine Reveals a Hydrographic Regime Shift at the End of the Little Ice Age
Authors: Lower‐Spies Erin E. , Whitney Nina M. , Wanamaker Alan D. , Griffin Shelly M. , Introne Douglas S. , Kreutz Karl J.
Published: August 2020

In order to document relative changes in water mass contributions in the Gulf of Maine (GoM), we used the shell material of the long‐lived ocean quahog (Arctica islandica). A multicentury, crossdated master shell growth chronology facilitated the reconstruction of a radiocarbon Δ14C history prior to the radiocarbon bomb‐pulse of the 1950s. This reconstruction reveals a highly variable Δ14C series (mean = −56.6 ± 8.0‰ (1σ); N = 34) from CE 1685 to 1935. Δ14C values indicate a rapid shift ca. 1860 CE in source waters to the GoM. From CE 1685 to 1860, GoM waters were dominated by an admixture of Warm Slope Water primarily composed of tropical Atlantic surface waters/Gulf Stream Waters, and Scotian Shelf Water. This water regime was followed by a rapid Δ14C transition to a Labrador Slope Water endmember after CE 1860, with an apparent decrease in Scotian Shelf Water. Together, this shift is likely related to broader changes in the Arctic and the Labrador Sea, and a short‐term strengthening of the Atlantic meridional overturning circulation. Labrador Slope Water dominating GoM hydrography in the 1900s is verified by the similarities between this record and other coral‐ and shell‐derived Δ14C records influenced by waters with Labrador Sea origin. This suggests that GoM radiocarbon variability broadly reflects large‐scale ocean circulation processes in the Northwestern Atlantic. The lack of Δ14C values much below the Labrador Slope Water endmember suggests that the interior GoM gets very little to no Antarctic Intermediate Water as other studies had previously suggested.
Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation
Authors: Sharma Mohit , Fonseca Felipe Paiva , Hunter Keith D. , Radhakrishnan Raghu
Published: August 2020

The integrity of the basal stem cell layer is critical for epithelial homoeostasis. In this paper, we review the expression of oral mucosal stem cell markers (OM-SCMs) in oral submucous fibrosis (OSF), oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF. While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF, the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness. The vacillating expression patterns of OM-SCMs confirm the role of keratins 5, 14, 19, CD44, β1-integrin, p63, sex-determining region Y box (SOX2), octamer-binding transcription factor 4 (Oct-4), c-MYC, B-cell-specific Moloney murine leukaemia virus integration site 1 (Bmi-1) and aldehyde dehydrogenase 1 (ALDH1) in OSF, OPMDs and OSCC. The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.
Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8+ T cell responses
Authors: Kim Seon-Hee , Singh Rohit , Han Chungyong , Cho Eunjung , Kim Yu I. , Lee Don G. , Kim Young H. , Kim Sang Soo , Shin Dong Hoon , You Hye Jin , Lee Hyeon-Woo , Kwon Byoung S. , Choi Beom K.
Published: August 2020

The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy. However, the adverse side effects associated with agonist antibodies have hindered their clinical development. Here, we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs. We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1+CD8+ T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8+ T cells, which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB induction. However, repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes (TDLNs) of mice due to recruitment and accumulation of macrophages via the CD8+ T cell-IFN-γ axis. This was accompanied by excessive lymph node swelling, which impaired the sequential activation of CD8+ T cells. Our data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing, which should be considered during the clinical development of immunomodulating therapy.
Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site
Authors: Chebib Jobran , Jackson Benjamin C. , López-Cortegano Eugenio , Tautz Diethard , Keightley Peter D.
Published: August 2020

For over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals. We found that individuals within strains are not isogenic, and there are differences in the levels of genetic variation that are explained by differences in the genetic distance from the colony nucleus. In addition, we employ a novel approach to mutation rate estimation based on the observed genetic variation and the expected site frequency spectrum at equilibrium, given a fully inbred breeding design. We find that it provides a reasonable per nucleotide mutation rate estimate when mice come from the colony nucleus (~7.9 × 10−9 in C3H/HeN), but substantially inflated estimates when mice come from production colonies.
Molecular layer interneurons in the cerebellum encode for valence in associative learning
Authors: Ma Ming , Futia Gregory L. , de Souza Fabio M. Simoes , Ozbay Baris N. , Llano Isabel , Gibson Emily A. , Restrepo Diego
Published: August 2020

The cerebellum plays a crucial role in sensorimotor and associative learning. However, the contribution of molecular layer interneurons (MLIs) to these processes is not well understood. We used two-photon microscopy to study the role of ensembles of cerebellar MLIs in a go-no go task where mice obtain a sugar water reward if they lick a spout in the presence of the rewarded odorant and avoid a timeout when they refrain from licking for the unrewarded odorant. In naive animals the MLI responses did not differ between the odorants. With learning, the rewarded odorant elicited a large increase in MLI calcium responses, and the identity of the odorant could be decoded from the differential response. Importantly, MLIs switched odorant responses when the valence of the stimuli was reversed. Finally, mice took a longer time to refrain from licking in the presence of the unrewarded odorant and had difficulty becoming proficient when MLIs were inhibited by chemogenetic intervention. Our findings support a role for MLIs in learning valence in the cerebellum.
Entropy of a bacterial stress response is a generalizable predictor for fitness and antibiotic sensitivity
Authors: Zhu Zeyu , Surujon Defne , Ortiz-Marquez Juan C. , Huo Wenwen , Isberg Ralph R. , Bento José , van Opijnen Tim
Published: August 2020

Current approaches explore bacterial genes that change transcriptionally upon stress exposure as diagnostics to predict antibiotic sensitivity. However, transcriptional changes are often specific to a species or antibiotic, limiting implementation to known settings only. While a generalizable approach, predicting bacterial fitness independent of strain, species or type of stress, would eliminate such limitations, it is unclear whether a stress-response can be universally captured. By generating a multi-stress and species RNA-Seq and experimental evolution dataset, we highlight the strengths and limitations of existing gene-panel based methods. Subsequently, we build a generalizable method around the observation that global transcriptional disorder seems to be a common, low-fitness, stress response. We quantify this disorder using entropy, which is a specific measure of randomness, and find that in low fitness cases increasing entropy and transcriptional disorder results from a loss of regulatory gene-dependencies. Using entropy as a single feature, we show that fitness and quantitative antibiotic sensitivity predictions can be made that generalize well beyond training data. Furthermore, we validate entropy-based predictions in 7 species under antibiotic and non-antibiotic conditions. By demonstrating the feasibility of universal predictions of bacterial fitness, this work establishes the fundamentals for potentially new approaches in infectious disease diagnostics.
Single-cell RNA sequencing identifies shared differentiation paths of mouse thymic innate T cells
Authors: Lee Minji , Lee Eunmin , Han Seong Kyu , Choi Yoon Ha , Kwon Dong-il , Choi Hyobeen , Lee Kwanghwan , Park Eun Seo , Rha Min-Seok , Joo Dong Jin , Shin Eui-Cheol , Kim Sanguk , Kim Jong Kyoung , Lee You Jeong
Published: August 2020

Invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT), and γδ T cells are innate T cells that acquire memory phenotype in the thymus and share similar biological characteristics. However, how their effector differentiation is developmentally regulated is still unclear. Here, we identify analogous effector subsets of these three innate T cell types in the thymus that share transcriptional profiles. Using single-cell RNA sequencing, we show that iNKT, MAIT and γδ T cells mature via shared, branched differentiation rather than linear maturation or TCR-mediated instruction. Simultaneous TCR clonotyping analysis reveals that thymic maturation of all three types is accompanied by clonal selection and expansion. Analyses of mice deficient of TBET, GATA3 or RORγt and additional in vivo experiments corroborate the predicted differentiation paths, while human innate T cells from liver samples display similar features. Collectively, our data indicate that innate T cells share effector differentiation processes in the thymus.
ABHD4-dependent developmental anoikis safeguards the embryonic brain
Authors: László Zsófia I. , Lele Zsolt , Zöldi Miklós , Miczán Vivien , Mógor Fruzsina , Simon Gabriel M. , Mackie Ken , Kacskovics Imre , Cravatt Benjamin F. , Katona István
Published: August 2020

A specialized neurogenic niche along the ventricles accumulates millions of progenitor cells in the developing brain. After mitosis, fate-committed daughter cells delaminate from this germinative zone. Considering the high number of cell divisions and delaminations taking place during embryonic development, brain malformations caused by ectopic proliferation of misplaced progenitor cells are relatively rare. Here, we report that a process we term developmental anoikis distinguishes the pathological detachment of progenitor cells from the normal delamination of daughter neuroblasts in the developing mouse neocortex. We identify the endocannabinoid-metabolizing enzyme abhydrolase domain containing 4 (ABHD4) as an essential mediator for the elimination of pathologically detached cells. Consequently, rapid ABHD4 downregulation is necessary for delaminated daughter neuroblasts to escape from anoikis. Moreover, ABHD4 is required for fetal alcohol-induced apoptosis, but not for the well-established form of developmentally controlled programmed cell death. These results suggest that ABHD4-mediated developmental anoikis specifically protects the embryonic brain from the consequences of sporadic delamination errors and teratogenic insults.
Inherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses
Authors: Evans Rhys D. R. , Antonelou Marilina , Sathiananthamoorthy Sanchutha , Rega Marilena , Henderson Scott , Ceron-Gutierrez Lourdes , Barcenas-Morales Gabriela , Müller Christoph A. , Doffinger Rainer , Walsh Stephen B. , Salama Alan D.
Published: August 2020

Increased extracellular sodium activates Th17 cells, which provide protection from bacterial and fungal infections. Whilst high salt diets have been shown to worsen autoimmune disease, the immunological consequences of clinical salt depletion are unknown. Here, we investigate immunity in patients with inherited salt-losing tubulopathies (SLT). Forty-seven genotyped SLT patients (with Bartter, Gitelman or EAST Syndromes) are recruited. Clinical features of dysregulated immunity are recorded with a standardised questionnaire and immunological investigations of IL-17 responsiveness undertaken. The effects of altering extracellular ionic concentrations on immune responses are then assessed. Patients are hypokalaemic and hypomagnesaemic, with reduced interstitial sodium stores determined by 23Na-magnetic resonance imaging. SLT patients report increased mucosal infections and allergic disease compared to age-matched controls. Aligned with their clinical phenotype, SLT patients have an increased ratio of Th2:Th17 cells. SLT Th17 and Tc17 polarisation is reduced in vitro, yet STAT1 and STAT3 phosphorylation and calcium flux following T cell activation are unaffected. In control cells, the addition of extracellular sodium (+40 mM), potassium (+2 mM), or magnesium (+1 mM) reduces Th2:Th17 ratio and augments Th17 polarisation. Our results thus show that the ionic environment typical in SLT impairs IL-17 immunity, but the intracellular pathways that mediate salt-driven Th17 polarisation are intact and in vitro IL-17 responses can be reinvigorated by increasing extracellular sodium concentration. Whether better correction of extracellular ions can rescue the immunophenotype in vivo in SLT patients remains unknown.
Experience-dependent resonance in amygdalo-cortical circuits supports fear memory retrieval following extinction
Authors: Ozawa Minagi , Davis Patrick , Ni Jianguang , Maguire Jamie , Papouin Thomas , Reijmers Leon
Published: August 2020

Learned fear and safety are associated with distinct oscillatory states in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC). To determine if and how these network states support the retrieval of competing memories, we mimicked endogenous oscillatory activity through optogenetic stimulation of parvalbumin-expressing interneurons in mice during retrieval of contextual fear and extinction memories. We found that exogenously induced 4 Hz and 8 Hz oscillatory activity in the BLA exerts bi-directional control over conditioned freezing behavior in an experience- and context-specific manner, and that these oscillations have an experience-dependent ability to recruit distinct functional neuronal ensembles. At the network level we demonstrate, via simultaneous manipulation of BLA and mPFC, that experience-dependent 4 Hz resonance across BLA-mPFC circuitry supports post-extinction fear memory retrieval. Our findings reveal that post-extinction fear memory retrieval is supported by local and interregional experience-dependent resonance, and suggest novel approaches for interrogation and therapeutic manipulation of acquired fear circuitry.
Plasticity of muscle synergies through fractionation and merging during development and training of human runners
Authors: Cheung Vincent C. K. , Cheung Ben M. F. , Zhang Janet H. , Chan Zoe Y. S. , Ha Sophia C. W. , Chen Chao-Ying , Cheung Roy T. H.
Published: August 2020

Complex motor commands for human locomotion are generated through the combination of motor modules representable as muscle synergies. Recent data have argued that muscle synergies are inborn or determined early in life, but development of the neuro-musculoskeletal system and acquisition of new skills may demand fine-tuning or reshaping of the early synergies. We seek to understand how locomotor synergies change during development and training by studying the synergies for running in preschoolers and diverse adults from sedentary subjects to elite marathoners, totaling 63 subjects assessed over 100 sessions. During development, synergies are fractionated into units with fewer muscles. As adults train to run, specific synergies coalesce to become merged synergies. Presences of specific synergy-merging patterns correlate with enhanced or reduced running efficiency. Fractionation and merging of muscle synergies may be a mechanism for modifying early motor modules (Nature) to accommodate the changing limb biomechanics and influences from sensorimotor training (Nurture).
Asymmetric elastoplasticity of stacked graphene assembly actualizes programmable untethered soft robotics
Authors: Wang Shuai , Gao Yang , Wei Anran , Xiao Peng , Liang Yun , Lu Wei , Chen Chinyin , Zhang Chi , Yang Guilin , Yao Haimin , Chen Tao
Published: August 2020

There is ever-increasing interest yet grand challenge in developing programmable untethered soft robotics. Here we address this challenge by applying the asymmetric elastoplasticity of stacked graphene assembly (SGA) under tension and compression. We transfer the SGA onto a polyethylene (PE) film, the resulting SGA/PE bilayer exhibits swift morphing behavior in response to the variation of the surrounding temperature. With the applications of patterned SGA and/or localized tempering pretreatment, the initial configurations of such thermal-induced morphing systems can also be programmed as needed, resulting in diverse actuation systems with sophisticated three-dimensional structures. More importantly, unlike the normal bilayer actuators, our SGA/PE bilayer, after a constrained tempering process, will spontaneously curl into a roll, which can achieve rolling locomotion under infrared lighting, yielding an untethered light-driven motor. The asymmetric elastoplasticity of SGA endows the SGA-based bi-materials with great application promise in developing untethered soft robotics with high configurational programmability.
The fundamentals of cultural adaptation: implications for human adaptation
Authors: Fogarty Laurel , Kandler Anne
Published: August 2020

The process of human adaptation to novel environments is a uniquely complex interplay between cultural and genetic changes. However, mechanistically, we understand little about these processes. To begin to untangle these threads of human adaptation we use mathematical models to describe and investigate cultural selective sweeps. We show that cultural sweeps differ in important ways from the genetic equivalents. The models show that the dynamics of cultural selective sweeps and, consequently, their differences from genetic sweeps depend critically on cultural transmission mechanisms. Further, we consider the effect of processes unique to culture such as foresight and innovations in response to an environmental change on adaptation. Finally we show that a ‘cultural evolutionary rescue’, or the survival of an endangered population by means of cultural adaptation, is possible. We suggest that culture might make a true, genetic, evolutionary rescue plausible for human populations.
Author Correction: Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors: First Italian Clinical Trial
Authors: Ravaioli Matteo , De Pace Vanessa , Angeletti Andrea , Comai Giorgia , Vasuri Francesco , Baldassarre Maurizio , Maroni Lorenzo , Odaldi Federica , Fallani Guido , Caraceni Paolo , Germinario Giuliana , Donadei Chiara , Malvi Deborah , Del Gaudio Massimo , Bertuzzo Valentina Rosa , Siniscalchi Antonio , Ranieri Vito Marco , D’Errico Antonietta , Pasquinelli Gianandrea , Morelli Maria Cristina , Pinna Antonio Daniele , Cescon Matteo , La Manna Gaetano
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Spatiotemporal dynamics of hemorrhagic fever with renal syndrome in Jiangxi province, China
Authors: Yang Shu , Gao Yuan , Liu Xiaobo , Liu Xiaoqing , Liu Yangqing , Metelmann Soeren , Yuan Chenying , Yue Yujuan , Chen Shengen , Liu Qiyong
Published: August 2020

Historically, Jiangxi province has had the largest HFRS burden in China. However, thus far, the comprehensive understanding of the spatiotemporal distributions of HFRS is limited in Jiangxi. In this study, seasonal decomposition analysis, spatial autocorrelation analysis, and space–time scan statistic analyses were performed to detect the spatiotemporal dynamics distribution of HFRS cases from 2005 to 2018 in Jiangxi at the county scale. The epidemic of HFRS showed the characteristic of bi-peak seasonality, the primary peak in winter (November to January) and the second peak in early summer (May to June), and the amplitude and the magnitude of HFRS outbreaks have been increasing. The results of global and local spatial autocorrelation analysis showed that the HFRS epidemic exhibited the characteristic of highly spatially heterogeneous, and Anyi, Fengxin, Yifeng, Shanggao, Jing’an and Gao’an county were hot spots areas. A most likely cluster, and two secondary likely clusters were detected in 14-years duration. The higher risk areas of the HFRS outbreak were mainly located in Jiangxi northern hilly state, spreading to Wuyi mountain hilly state as time advanced. This study provided valuable information for local public health authorities to design and implement effective measures for the control and prevention of HFRS.
Robust design from systems physics
Authors: Klishin Andrei A. , Kirkley Alec , Singer David J. , van Anders Greg
Published: August 2020

A crucial challenge in engineering modern, integrated systems is to produce robust designs. However, quantifying the robustness of a design is less straightforward than quantifying the robustness of products. For products, in particular engineering materials, intuitive, plain language terms of strong versus weak and brittle versus ductile take on precise, quantitative meaning in terms of stress–strain relationships. Here, we show that a “systems physics” framing of integrated system design produces stress–strain relationships in design space. From these stress–strain relationships, we find that both the mathematical and intuitive notions of strong versus weak and brittle versus directly characterize the robustness of designs. We use this to show that the relative robustness of designs against changes in problem objectives has a simple graphical representation. This graphical representation, and its underlying stress–strain foundation, provide new metrics that can be applied to classes of designs to assess robustness from feature- to system-level.
Synchrotron radiation Ca K-edge 2D-XANES spectroscopy for studying the stratigraphic distribution of calcium-based consolidants applied in limestones
Authors: Monico Letizia , Cartechini Laura , Rosi Francesca , De Nolf Wout , Cotte Marine , Vivani Riccardo , Maurich Celeste , Miliani Costanza
Published: August 2020

In Heritage Science, the evaluation of stone consolidation treatments by investigating the nature of in situ newly formed products and their penetration depth within the consolidated matrix is a grand challenge. A number of analytical methods have been proposed, but, currently, most of them are not able to supply a full overview of the spatial, structural and compositional information of the newly formed crystalline and amorphous phases with a submicrometric lateral resolution. Here, we examined, the capabilities of synchrotron radiation (SR)-based two-dimensional X-ray absorption near-edge structure (2D-XANES) spectroscopy at Ca K-edge for determining the structural and compositional properties of the compounds formed after the application of a calcium acetoacetate-based consolidant on a porous carbonatic stone (limestone) and for investigating their stratigraphic distribution at the submicrometric scale length. We evaluated advantages and drawbacks of three Ca K-edge 2D-XANES-based approaches: (i) transmission mode full-field-XANES (FF-XANES) imaging; (ii) micro-X-ray fluorescence (μ-XRF) mapping above the Ca K-edge combined with the acquisition of XRF mode μ-XANES spectra at a limited number of spots; (iii) full-spectral µ-XANES (FS µ-XANES) mapping in XRF mode and its variant called selectively induced X-ray emission spectroscopy (SIXES) mapping. Overall, Ca K-edge 2D-XANES spectroscopy provided accurate qualitative and semi-quantitative information on the newly formed calcium carbonates (i.e., amorphous calcium carbonate, vaterite and calcite) and their stratigraphic distribution at the submicrometric scale, thus opening a new scenario to study the carbonatation process of calcium-based consolidants in limestones.
Insights into the molecular-level effects of atmospheric and room-temperature plasma on mononucleotides and single-stranded homo- and hetero-oligonucleotides
Authors: Wang Liyan , Zhao Hongxin , He Dong , Wu Yinan , Jin Lihua , Li Guo , Su Nan , Li Heping , Xing Xin-Hui
Published: August 2020

Atmospheric and room-temperature plasma (ARTP) has been successfully developed as a useful mutation tool for mutation breeding of various microbes and plants as well animals by genetic alterations. However, understanding of the molecular mechanisms underlying the biological responses to ARTP irradiation is still limited. Therefore, to gain a molecular understanding of how irradiation with ARTP damages DNA, we irradiated the artificially synthesized mononucleotides of dATP, dTTP, dGTP, and dCTP, and the oligonucleotides of dA8, dT8, dG8, dC8, and dA2dT2dG2dC2 as chemical building blocks of DNA with ARTP for 1–4 min, identified the mononucleotide products using 31P- and 1H-nuclear magnetic resonance spectroscopy (NMR), and identified the oligonucleotide products using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) during ARTP treatment. The observed 31P-and 1H-NMR spectrum signals for the plasma-treated and untreated mononucleotides indicated that dATP was less stable to plasma irradiation than the other mononucleotides. The oligonucleotides after treatment with ARTP were found to have been broken into small fragments as shown by mass spectrometry, with the cleaved bonds and produced fragments identified according to their expected spectral m/z values or molecular weights derived from their m/z values. The stabilities of the oligonucleotides differed to ARTP irradiation, with dT8 being the most stable and was more beneficial to stabilizing single-stranded oligonucleotide structures compared to the other base groups (A, G, and C). This was consistent with the average potential energy level obtained by the molecular dynamic simulation of the oligonucleotides, i.e., dT8 > dC8 > dA8 > dG8 > dA2dT2dG2dC2. In summary, we found that ARTP treatment caused various structural changes to the oligonucleotides that may account for the wide and successful applications reported for ARTP-induced mutation breeding of various organisms.
Floquet engineering of topological metal states and hybridization of edge states with bulk states in dimerized two-leg ladders
Authors: Jangjan Milad , Hosseini Mir Vahid
Published: August 2020

We consider asymmetric and symmetric dimerized two-leg ladders, comprising of four different lattice points per unit cell, illuminated by circularly polarized light. In the asymmetric dimerized ladder case, rungs are not perpendicular to the ladder’s legs whereas the rungs are perpendicular to the legs for the symmetric one. Using the Floquet theory, we obtain an effective Hamiltonian to study topological properties of the systems. Depending on the dimerization strength and driving amplitude, it is shown that topologically protected edge states manifest themselves not only as a zero-energy band within the gap between conduction and valence band but also as finite-energy curved bands inside the gap of subbands. The latter one can penetrate into bulk states and hybridize with the bulk states revealing hybridized Floquet topological metal phase with delocalized edge states in the asymmetric ladder case. However, in the symmetric ladder, the finite-energy edge states while remaining localized can coexist with the extended bulk states manifesting Floquet topological metal phase.
Growth retardation-responsive analysis of mRNAs and long noncoding RNAs in the liver tissue of Leiqiong cattle
Authors: Kong Lingxuan , Liu Guangbin , Deng Ming , Lian Zhiquan , Han Yinru , Sun Baoli , Guo Yongqing , Liu Dewu , Li Yaokun
Published: August 2020

As an important type of non-coding RNA molecule, long non-coding RNAs (lncRNAs) have varied roles in many biological processes, and have been studied extensively over the past few years. However, little is known about lncRNA-mediated regulation during cattle growth and development. Therefore, in the present study, RNA sequencing was used to determine the expression level of mRNAs and lncRNAs in the liver of adult Leiqiong cattle under the condition of growth retardation and normal growth. We totally detected 1,124 and 24 differentially expressed mRNAs and lncRNAs, respectively. The differentially expressed mRNAs were mainly associated with growth factor binding, protein K63-linked ubiquitination and cellular protein metabolic process; additionally, they were significantly enriched in the growth and development related pathways, including PPAR signaling pathway, vitamin B6 metabolism, glyoxylate and dicarboxylate metabolism. Combined analysis showed that the co-located differentially expressed lncRNA Lnc_002583 might positively influence the expression of the corresponding genes IFI44 and IFI44L, exerting co-regulative effects on Leiqiong cattle growth and development. Thus, we made the hypothesis that Lnc_002583, IFI44 and IFI44L might function synergistically to regulate the growth of Leiqiong cattle. This study provides a catalog of Leiqiong cattle liver mRNAs and lncRNAs, and will contribute to a better understanding of the molecular mechanism underlying growth regulataion.
Sex-specific effects of the histone variant H2A.Z on fear memory, stress-enhanced fear learning and hypersensitivity to pain
Authors: Ramzan Firyal , Creighton Samantha D. , Hall Meaghan , Baumbach Jennet , Wahdan Malak , Poulson Sandra J. , Michailidis Vassilia , Stefanelli Gilda , Narkaj Klotilda , Tao Cindy S. , Khan Dure , Steininger Carl F. D. , Walters Brandon J. , Monks D. Ashley , Martin Loren J. , Zovkic Iva B.
Published: August 2020

Emerging evidence suggests that histone variants are novel epigenetic regulators of memory, whereby histone H2A.Z suppresses fear memory. However, it is not clear if altered fear memory can also modify risk for PTSD, and whether these effects differ in males and females. Using conditional-inducible H2A.Z knockout (cKO) mice, we showed that H2A.Z binding is higher in females and that H2A.Z cKO enhanced fear memory only in males. However, H2A.Z cKO improved memory on the non-aversive object-in-place task in both sexes, suggesting that H2A.Z suppresses non-stressful memory irrespective of sex. Given that risk for fear-related disorders, such as PTSD, is biased toward females, we examined whether H2A.Z cKO also has sex-specific effects on fear sensitization in the stress-enhanced fear learning (SEFL) model of PTSD, as well as associated changes in pain sensitivity. We found that H2A.Z cKO reduced stress-induced sensitization of fear learning and pain responses preferentially in female mice, indicating that the effects of H2A.Z depend on sex and the type of task, and are influenced by history of stress. These data suggest that H2A.Z may be a sex-specific epigenetic risk factor for PTSD susceptibility, with implications for developing sex-specific therapeutic interventions.
Optimization of subsampling, decontamination, and DNA extraction of difficult peat and silt permafrost samples
Authors: Saidi-Mehrabad Alireza , Neuberger Patrick , Cavaco Maria , Froese Duane , Lanoil Brian
Published: August 2020

This study aims to act as a methodological guide for contamination monitoring, decontamination, and DNA extraction for peaty and silty permafrost samples with low biomass or difficult to extract DNA. We applied a biological tracer, either only in the field or both in the field and in the lab, via either spraying or painting. Spraying in the field followed by painting in the lab resulted in a uniform layer of the tracer on the core sections. A combination of bleaching, washing, and scraping resulted in complete removal of the tracer leaving sufficient material for DNA extraction, while other widely used decontamination methods did not remove all detectable tracer. In addition, of four widely used commercially available DNA extraction kits, only a modified ZymoBIOMICS DNA Microprep kit was able to acquire PCR amplifiable DNA. Permafrost chemical parameters, age, and soil texture did not have an effect on decontamination efficacy; however, the permafrost type did influence DNA extraction. Based on these findings, we developed recommendations for permafrost researchers to acquire contaminant-free DNA from permafrost with low biomass.
The satellite observed glacier mass changes over the Upper Indus Basin during 2000–2012
Authors: Abdullah Tariq , Romshoo Shakil Ahmad , Rashid Irfan
Published: August 2020

Decadal glacier thickness changes over the Upper Indus Basin in the Jammu and Kashmir Himalaya were estimated using the TanDEM-X and SRTM-C Digital Elevation Models (DEMs) from 2000 to 2012. In the study area 12,243 glaciers having 19,727 ± 1,054 km2 area have thinned on an average of − 0.35 ± 0.33 m a−1 during the observation period. The highest thinning of − 1.69 ± 0.60 m a−1 was observed in the Pir Panjal while as the marginal thinning of − 0.11 ± 0.32 m a−1 was observed for the glaciers in the Karakoram. The observed glacier thickness changes indicated a strong influence of the topographic parameters. Higher thickness reduction was observed on the glaciers situated at lower altitudes (− 1.40 ± 0.53 m a−1) and with shallower slopes (− 1.52 ± 0.40 m a−1). Significantly higher negative thickness changes were observed from the glaciers situated on the southern slopes (− 0.55 ± 0.37 m a−1). The thickness loss was higher on the debris-covered glaciers (− 0.50 ± 0.38 m a−1) than on the clean glaciers (− 0.32 ± 0.33 m a−1). The cumulative glacier mass loss of − 70.32 ± 66.69 Gt was observed during the observation period, which, if continued, would significantly affect the sustainability of water resources in the basin.