bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the oral probiotics to control pain and stress disorders of cyclical mastalgia associated with fibrocystic breast changes; a randomised controlled trial
Authors: Davoodabadi Abdulhosein , Rohani Seyed Hamed , Hajian Abbas
Published: May 2021

ABSTRACT

Background:

Breast fibrocystic changes (FCC) is the most common benign breast lesion among females in productive age. Cyclical pain is the most common symptom of the lesion which decreases life quality and worsens stress disorders of sufferers. The study aimed to evaluate effects of oral probiotics to confront such pain and stress among females.

Method:

In this randomised, double-blind controlled trial finally 50 eligible women with cyclical mastalgia due to the FCC aged between 18 and 40 years were enrolled. They were allocated in placebo and probiotic receivers. Subjects in the latter received a daily capsule containing of 2 × 109 colony forming units of probiotic microorganisms. Patients underwent a 12 weeks survey. The Visual analog scaling instrument was applied to measure pain severity. Blood samples were sent to evaluate hs-CRP, total antioxidant capacity (TAC), malondialdehyde and total plasma gluthation. Stress disorders including of depression, anxiety and sleep quality also were investigated by standard relative questionnaires.

Results:

Probiotic receivers showed meaningful decrease in cyclical mastalgia (p < 0.01) after 12 weeks probiotic consumption. Additionally plasma level of hs-CRP (p = 0.03) decreased concurrently with significant increase in TAC (p = 0.04) level among probiotic receivers. Probiotics helped better recovery from depressive symptoms although influenced positively neither anxiety nor sleep quality.

Conclusion:

This study showed that oral probiotic consumption should be considered to control the pain in cyclical mastalgia contributing to FCC of the breast.

Highlights
High-resolution X-ray flash radiography of Ti characteristic lines with multilayer Kirkpatrick–Baez microscope at the Shenguang-II Update laser facility
Authors: Yi Shengzhen , Zhang Feng , Huang Qiushi , Wei Lai , Gu Yuqiu , Wang Zhanshan
Published: May 2021

High-resolution X-ray flash radiography of Ti characteristic lines with a multilayer Kirkpatrick–Baez microscope was developed on the Shenguang-II (SG-II) Update laser facility. The microscope uses an optimized multilayer design of Co/C and W/C stacks to obtain a high reflection efficiency of the Ti characteristic lines while meeting the precise alignment requirement at the Cu Kα line. The alignment method based on dual simulated balls was proposed herein, which simultaneously realizes an accurate indication of the center field of view and the backlighter position. The optical design, multilayer coatings, and alignment method of the microscope and the experimental result of Ti flash radiography of the Au-coned CH shell target on the SG-II Update are described.
Empiricalα–βrunout modelling of snow avalanches in the Catalan Pyrenees
Authors: Oller Pere , Baeza Cristina , Furdada Glòria
Published: May 2021

A variation in theα−βmodel which is a regression model that allows a deterministic prediction of the extreme runout to be expected in a given path, was applied for calculating avalanche runout in the Catalan Pyrenees. Present knowledge of major avalanche activity in this region and current mapping tools were used. The model was derived using a dataset of 97 ‘extreme’ avalanches that occurred from the end of 19th century to the beginning of 21st century. A multiple linear regression model was obtained using three independent variables: inclination of the avalanche path, horizontal length and area of the starting zone, with a good fit of the function (R2= 0.81). A larger starting zone increases the runout and a larger length of the path reduces the runout. The new updated equation predicts avalanche runout for a return period of ~100 years. To study which terrain variables explain the extreme values of the avalanche dataset, a comparative analysis of variables that influence a longer or shorter runout was performed. The most extreme avalanches were treated. The size of the avalanche path and the aspect of the starting zone showed certain association between avalanches with longer or shorter runouts.
The lichen genus Villophora (Teloschistaceae, Ascomycota)
Authors: Søchting Ulrik , Søgaard Majbrit Zeuthen , Sancho Leo Garcia , Arup Ulf
Published: May 2021

The Southern Hemisphere lichen genus Villophora in subfamily Teloschistoideae is analyzed based on DNA sequence data. Six species are described, five of which are new to science: V. darwiniana and V. wallaceana grow on lignum and bark in southern Patagonia and Tierra del Fuego; V. onas and V. patagonica are lichenicolous or saxicolous on rocks in southern Patagonia; V. rimicola is saxicolous in Antarctica. Based on a three-gene DNA analysis, Tayloriellina is shown to be closely related to Villophora, and Tayloriellina microphyllina is established as a new combination. A key is provided to all species of the two genera. Raesaeneniana maulensis is combined into Villophora.
Food addiction and weight in students with high academic performance
Authors: Tserne Tatyana A , Borisenkov Mikhail F , Popov Sergey V , Bakutova Larisa A , Jongte Lalremruati , Trivedi Amit K , Pecherkina Anna A , Dorogina Olga I , Martinson Ekaterina A , Vetosheva Valentina I , Gubin Denis G , Solovieva Svetlana V , Danilova Lina A , Turovinina Elena F , Symaniuk Elvira E
Published: May 2021

Objective:

The purpose of this study was to analyse the relationships between food addiction (FA), anthropometric characteristics and academic performance.

Design:

The average age (sd) of the participants was 17·5 (sd 2·7) years (64·1 % female). Each study participant indicated their sex, height, weight and academic performance and completed the Yale Food Addiction Scale.

Setting:

Syktyvkar, Kirov, Tyumen, Yekaterinburg, Russia; Aizawl, India.

Participants:

The study involved 3426 people.

Results:

FA was found in 8·7 % of participants from Russia and 14·6 % from India. In schoolchildren but not in university students, high academic performance was associated with a higher incidence rate of FA detection (OR = 1·16, 95 % CI 1·07, 1·26) and a lower BMI (OR = 0·72, 95 % CI 0·56, 0·94).

Conclusions:

These data showed an increased incidence rate of FA detection in adolescents with high academic performance.
Mothers’ perceptions on and learning from infant and young child-feeding videos displayed in Mother and Child Health Centers in Kenya: a qualitative and quantitative approach
Authors: Schneider Lauriina , Kosola Mikko , Uusimäki Kerttu , Ollila Sari , Lubeka Crippina , Kimiywe Judith , Mutanen Marja
Published: May 2021

Objective:

The objective was to explore mothers’ perceptions on educational videos on infant and young child-feeding practices, and to assess whether viewing frequencies would influence maternal knowledge, attitudes and feeding practices (KAP).

Design:

A set of forty-seven videos were displayed in health centres for 6 months. At 3 months, we conducted focus group discussions (FGD) with mothers and, at 6 months, administered KAP-questionnaire-based interviews to mothers. Using a quasi-experimental design, we compared groups according to video viewing frequencies.

Setting:

The study was conducted in a slum in Nairobi and a rural area in Machakos, Kenya. We installed TV screens in waiting rooms of six Mother and Child Health Centers, where mothers could choose to watch them.

Participants:

Forty-three mothers with children aged 0–48 months participated in six FGD and 547 mothers of children aged 0–23 months in KAP interviews.

Results:

The mothers from the FGD found the videos acceptable and beneficial. Videos enhanced mothers’ learning and empowered them to support others in learning. The KAP data showed that after adjustments, breast-feeding (P = 0·06), complementary feeding knowledge (P = 0·01), complementary feeding attitudes (P = 0·08) and hygiene knowledge and practices (P = 0·003) were better among mothers who had seen videos three to four times, or five or more times, compared with mothers who had seen the videos once or twice.

Conclusions:

Videos were an accepted form of education and were beneficial when watched repeatedly. The videos could be a good addition to current infant and young child-feeding education efforts in Kenya.
Taxes and the revaluation of household wealth
Authors: Wolff Edward N.
Published: May 2021

I compare pre-tax and post-tax wealth levels and trends after netting out implicit taxes on tax-deferred assets and accrued capital gains. The analysis covers 1983–2016 for net worth (NW) and augmented wealth (AW), which includes pension and Social Security wealth. Netting out implicit taxes substantially reduces growth in mean and median NW and AW. However, the upward trajectory in NW and AW inequality is basically unchanged from using post-tax values. I also introduce bequest wealth, the value of the estate including death benefits. It is notably more equal than NW and has grown faster over time.
Description of a training protocol to improve research reproducibility for dignity therapy: an interview-based intervention
Authors: Schoppee Tasha M. , Scarton Lisa , Bluck Susan , Yao Yingwei , Keenan Gail , Handzo George , Chochinov Harvey M. , Fitchett George , Emanuel Linda L. , Wilkie Diana J.
Published: May 2021

Background

Dignity Therapy (DT) has been implemented over the past 20 years, but a detailed training protocol is not available to facilitate consistency of its implementation. Consistent training positively impacts intervention reproducibility.

Objective

The objective of this article is to describe a detailed method for DT therapist training.

Method

Chochinov's DT training seminars included preparatory reading of the DT textbook, in-person training, and practice interview sessions. Building on this training plan, we added feedback on practice and actual interview sessions, a tracking form to guide the process, a written training manual with an annotated model DT transcript, and quarterly support sessions. Using this training method, 18 DT therapists were trained across 6 sites.

Results

The DT experts’ verbal and written feedback on the practice and actual sessions encouraged the trainees to provide additional attention to eight components: (1) initial framing (i.e., clarifying and organizing of the patient's own goals for creating the legacy document), (2) verifying the patient's understanding of DT, (3) gathering the patient's biographical information, (4) using probing questions, (5) exploring the patient's story thread, (6) refocusing toward the legacy document creation, (7) inviting the patient's expression of meaningful messages, and (8) general DT processes. Evident from the ongoing individual trainee mentoring was achievement and maintenance of adherence to the DT protocol.

Discussion

The DT training protocol is a process to enable consistency in the training process, across waves of trainees, toward the goal of maintaining DT implementation consistency. This training protocol will enable future DT researchers and clinicians to consistently train therapists across various disciplines and locales. Furthermore, we anticipate that this training protocol could be generalizable as a roadmap for implementers of other life review and palliative care interview-based interventions.
How Non-Majoritarian Institutions Make Silent Majorities Vocal: A Political Explanation of Authoritarian Populism
Authors: Zürn Michael
Published: May 2021

Why did we witness such a strong growth of anti-liberal forces twenty-five years after the triumph of liberalism? The answer is twofold. First, authoritarian populism has not sneaked into a given political space but is co-constitutive of a new cleavage in most modern societies. Authoritarian populists speak to the issues of this cleavage. Second, the rise of this new cleavage and authoritarian populists cannot be reduced to one of the two well-known explanations, namely the economic insecurity perspective and cultural backlash perspective. This current paper develops a political explanation that integrates struggles over policies with a focus on endogenous dynamics of political institutions in and beyond democracies. In this account, it is the historical compromise between labor and capital that has triggered a dynamic in which the rise of so-called non-majoritarian institutions (NMIs)—such as central banks, constitutional courts, and international organizations (IOs)—have locked in liberal policies in most consolidated democracies. This explanation brings together the party cartelization thesis with the observation that NMIs are a major target of contemporary populism. The explanatory model is probed by translating it into descriptive propositions and by showing step by step how the sequence unfolded in electoral democracies.
Knightian uncertainty in non-market institutional settings: the case of democracy and nonprofit civil society
Authors: Burns Scott , Manish G. P. , Nair Malavika
Published: May 2021

The implications of Knightian uncertainty are frequently discussed in the context of market-based institutional settings. Given money prices, entrepreneurs can engage in calculative action, in conjunction with ‘judgment’, to guide decision-making and bring about a coordination of production plans with consumer preferences. However, if the existence of Knightian uncertainty isubiquitous and applies to all human action, then what are its implications in non-market institutional settings? This paper explores questions related to the implications of Knightian uncertainty for two important non-market institutional settings: democratic government and the nonprofit or philanthropic sector, where there is an explicit lack of monetary calculation, yet nonprofit and political entrepreneurs still must use ‘judgment’ to deal with Knightian uncertainty. For instance, what are the implications of private property and privatized cost in the case of nonprofitsversusthe absence of private property and socialized cost in the case of democracy, in the presence of Knightian uncertainty? Which group of ‘consumers’ is likely to have their preferences satisfied when it comes to nonprofits (benefactors or beneficiaries) and democratic government (voters or lobbyists)? The paper, thus, points to the importance of further research on the implications of Knightian uncertainty in the hard case of non-market institutional settings.
Freedom of speech within political parties
Authors: Bhatia Udit , Wolkenstein Fabio
Published: May 2021

The expulsion of party members for the expression of dissent is a common practice in democratic states around the world, which can have momentous consequences for individual parties and the political system at large. In this article, we address the question of whether limitations on party members’ free speech can be defended on normative grounds. Drawing on a conception of parties that sees them as broader membership organisations that allow citizens to exercise political agency in a unique fashion, as well as on insights from the broader normative-theoretical literature on organisations, we build a strong presumptive case that interference with party members’ political freedoms is normatively problematic. Exploring numerous weighty arguments in favour of limiting freedom of speech within parties, we find that none of them provides a knock-down argument against our case. The argument we advance has important implications for contemporary theoretical debates about parties and partisanship, and for the regulation of parties’ internal affairs more generally.
Observations and Simulations of Dropout Events and Flux Decays in October 2013: Comparing MEO Equatorial With LEO Polar Orbit
Authors: Pierrard Viviane , Ripoll Jean‐Francois , Cunningham Gregory , Botek Edith , Santolik Ondrej , Thaller Scott , Kurth William S. , Cosmides Mélanie
Published: May 2021

We compare ESA PROBA‐V observations of electron flux at LEO with those from the NASA Van Allen Probes mostly at MEO for October 2013. Dropouts are visible at all energy during four storms from both satellites. Equatorially trapped electron fluxes are higher than at LEO by 102 (<1 MeV) to 105 (>2.5 MeV). We observe a quite isotropic structure of the outer belt during quiet times, contrary to the inner belt, and pitch angle dependence of high energy injection. We find a very good overlap of the outer belt at MEO and LEO at ∼0.5 MeV. We use test‐particle simulations of the energetic electrons trapped in the terrestrial magnetic field to study the outer radiation belt electron flux changes during geomagnetic storms. We show that the Dst (Disturbance storm time) effect during the main phase of a geomagnetic storm results in a betatron mechanism causing outward radial drift and a deceleration of the electrons. This outward drift motion is energy independent, pitch angle‐dependent, and represents a significant distance (∼1 L‐shell at L = 5 for moderate storms). At fixed L‐shell, this causes a decay of the LEO precipitating flux (adiabatic outward motion), followed by a return to the normal state (adiabatic inward motion) during main and recovery phases. Dst effect, associated with magnetopause shadowing and radial diffusion can explain the main characteristics of outer radiation belt electron dropouts in October 2013. We also use Fokker‐Planck simulations with event‐driven diffusion coefficients at high temporal resolution, to distinguish instantaneous loss from the gradual scattering that depopulates the slot region and the outer belt after storms. Simulations reproduce the slot formation and the gradual loss in the outer belt. The typical energy dependence of these losses leads to the absence of scattering for relativistic and ultra‐relativistic electrons in the outer belt, oppositely to dropouts.
A General Algorithm for the Linear and Quadratic Gradients of Physical Quantities Based on 10 or More Point Measurements
Authors: Shen Chao , Zhou Yufei , Ma Yonghui , Wang Xiaogang , Pu Zuyin , Dunlop M.
Published: May 2021

A novel algorithm for estimating both the linear and quadratic gradients of physical quantities based on multiple spacecraft observations using the least squares method is put forward. Using 10 or more spacecraft constellation measurements as input, this new algorithm can yield both the linear and quadratic gradients at the barycenter of the constellation. Iterations were used in the algorithm. Tests on cylindrical flux ropes, dipole magnetic field, and modeled geomagnetospheric field were carried out. The results of these tests indicate that the linear gradient obtained is of second‐order accuracy, while the quadratic gradient is of first‐order accuracy. The test on the modeled geomagnetospheric field showed that, the greater the number of spacecraft in the constellation, the greater the accuracy of the quadratic gradient calculated. However, the accuracy of the linear gradient obtained was independent of the number of spacecraft. The feasibility, reliability, and accuracy of this algorithm have been successfully verified. This algorithm could find wide applications in the design of future multiple spacecraft missions as well as in the analysis of multiple‐point measurement data.
Spatially explicit analysis identifies significant potential for bioenergy with carbon capture and storage in China
Authors: Xing Xiaofan , Wang Rong , Bauer Nico , Ciais Philippe , Cao Junji , Chen Jianmin , Tang Xu , Wang Lin , Yang Xin , Boucher Olivier , Goll Daniel , Peñuelas Josep , Janssens Ivan A. , Balkanski Yves , Clark James , Ma Jianmin , Pan Bo , Zhang Shicheng , Ye Xingnan , Wang Yutao , Li Qing , Luo Gang , Shen Guofeng , Li Wei , Yang Yechen , Xu Siqing
Published: May 2021

As China ramped-up coal power capacities rapidly while CO2 emissions need to decline, these capacities would turn into stranded assets. To deal with this risk, a promising option is to retrofit these capacities to co-fire with biomass and eventually upgrade to CCS operation (BECCS), but the feasibility is debated with respect to negative impacts on broader sustainability issues. Here we present a data-rich spatially explicit approach to estimate the marginal cost curve for decarbonizing the power sector in China with BECCS. We identify a potential of 222 GW of power capacities in 2836 counties generated by co-firing 0.9 Gt of biomass from the same county, with half being agricultural residues. Our spatially explicit method helps to reduce uncertainty in the economic costs and emissions of BECCS, identify the best opportunities for bioenergy and show the limitations by logistical challenges to achieve carbon neutrality in the power sector with large-scale BECCS in China.
Reduced adaptation of glutamatergic stress response is associated with pessimistic expectations in depression
Authors: Cooper Jessica A. , Nuutinen Makiah R. , Lawlor Victoria M. , DeVries Brittany A. M. , Barrick Elyssa M. , Hossein Shabnam , Cole Daniel J. , Leonard Chelsea V. , Hahn Evan C. , Teer Andrew P. , Shields Grant S. , Slavich George M. , Ongur Dost , Jensen J. Eric , Du Fei , Pizzagalli Diego A. , Treadway Michael T.
Published: May 2021

Stress is a significant risk factor for the development of major depressive disorder (MDD), yet the underlying mechanisms remain unclear. Preclinically, adaptive and maladaptive stress-induced changes in glutamatergic function have been observed in the medial prefrontal cortex (mPFC). Here, we examine stress-induced changes in human mPFC glutamate using magnetic resonance spectroscopy (MRS) in two healthy control samples and a third sample of unmedicated participants with MDD who completed the Maastricht acute stress task, and one sample of healthy control participants who completed a no-stress control manipulation. In healthy controls, we find that the magnitude of mPFC glutamate response to the acute stressor decreases as individual levels of perceived stress increase. This adaptative glutamate response is absent in individuals with MDD and is associated with pessimistic expectations during a 1-month follow-up period. Together, this work shows evidence for glutamatergic adaptation to stress that is significantly disrupted in MDD.
Feature-specific reaction times reveal a semanticisation of memories over time and with repeated remembering
Authors: Lifanov Julia , Linde-Domingo Juan , Wimber Maria
Published: May 2021

Memories are thought to undergo an episodic-to-semantic transformation in the course of their consolidation. We here test if repeated recall induces a similar semanticisation, and if the resulting qualitative changes in memories can be measured using simple feature-specific reaction time probes. Participants studied associations between verbs and object images, and then repeatedly recalled the objects when cued with the verb, immediately and after a two-day delay. Reaction times during immediate recall demonstrate that conceptual features are accessed faster than perceptual features. Consistent with a semanticisation process, this perceptual-conceptual gap significantly increases across the delay. A significantly smaller perceptual-conceptual gap is found in the delayed recall data of a control group who repeatedly studied the verb-object pairings on the first day, instead of actively recalling them. Our findings suggest that wake recall and offline consolidation interact to transform memories over time, strengthening meaningful semantic information over perceptual detail.
Superconductivity emerging from a stripe charge order in IrTe2 nanoflakes
Authors: Park Sungyu , Kim So Young , Kim Hyoung Kug , Kim Min Jeong , Kim Taeho , Kim Hoon , Choi Gyu Seung , Won C. J. , Kim Sooran , Kim Kyoo , Talantsev Evgeny F. , Watanabe Kenji , Taniguchi Takashi , Cheong Sang-Wook , Kim B. J. , Yeom H. W. , Kim Jonghwan , Kim Tae-Hwan , Kim Jun Sung
Published: May 2021

Superconductivity in the vicinity of a competing electronic order often manifests itself with a superconducting dome, centered at a presumed quantum critical point in the phase diagram. This common feature, found in many unconventional superconductors, has supported a prevalent scenario in which fluctuations or partial melting of a parent order are essential for inducing or enhancing superconductivity. Here we present a contrary example, found in IrTe2 nanoflakes of which the superconducting dome is identified well inside the parent stripe charge ordering phase in the thickness-dependent phase diagram. The coexisting stripe charge order in IrTe2 nanoflakes significantly increases the out-of-plane coherence length and the coupling strength of superconductivity, in contrast to the doped bulk IrTe2. These findings clarify that the inherent instabilities of the parent stripe phase are sufficient to induce superconductivity in IrTe2 without its complete or partial melting. Our study highlights the thickness control as an effective means to unveil intrinsic phase diagrams of correlated van der Waals materials.
Structure and nature of ice XIX
Authors: Salzmann Christoph G. , Loveday John S. , Rosu-Finsen Alexander , Bull Craig L.
Published: May 2021

Ice is a material of fundamental importance for a wide range of scientific disciplines including physics, chemistry, and biology, as well as space and materials science. A well-known feature of its phase diagram is that high-temperature phases of ice with orientational disorder of the hydrogen-bonded water molecules undergo phase transitions to their ordered counterparts upon cooling. Here, we present an example where this trend is broken. Instead, hydrochloric-acid-doped ice VI undergoes an alternative type of phase transition upon cooling at high pressure as the orientationally disordered ice remains disordered but undergoes structural distortions. As seen with in-situ neutron diffraction, the resulting phase of ice, ice XIX, forms through a Pbcn-type distortion which includes the tilting and squishing of hexameric clusters. This type of phase transition may provide an explanation for previously observed ferroelectric signatures in dielectric spectroscopy of ice VI and could be relevant for other icy materials.
Masked graph modeling for molecule generation
Authors: Mahmood Omar , Mansimov Elman , Bonneau Richard , Cho Kyunghyun
Published: May 2021

De novo, in-silico design of molecules is a challenging problem with applications in drug discovery and material design. We introduce a masked graph model, which learns a distribution over graphs by capturing conditional distributions over unobserved nodes (atoms) and edges (bonds) given observed ones. We train and then sample from our model by iteratively masking and replacing different parts of initialized graphs. We evaluate our approach on the QM9 and ChEMBL datasets using the GuacaMol distribution-learning benchmark. We find that validity, KL-divergence and Fréchet ChemNet Distance scores are anti-correlated with novelty, and that we can trade off between these metrics more effectively than existing models. On distributional metrics, our model outperforms previously proposed graph-based approaches and is competitive with SMILES-based approaches. Finally, we show our model generates molecules with desired values of specified properties while maintaining physiochemical similarity to the training distribution.
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa
Authors: Benavente Ernest Diez , Manko Emilia , Phelan Jody , Campos Monica , Nolder Debbie , Fernandez Diana , Velez-Tobon Gabriel , Castaño Alberto Tobón , Dombrowski Jamille G. , Marinho Claudio R. F. , Aguiar Anna Caroline C. , Pereira Dhelio Batista , Sriprawat Kanlaya , Nosten Francois , Moon Robert , Sutherland Colin J. , Campino Susana , Clark Taane G.
Published: May 2021

Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described. Determinants of antimalarial drug susceptibility for P. vivax in the region have not been characterised. Our genomic analysis of global P. vivax (n = 558) establishes South Asian isolates (n = 92) as a distinct subpopulation, which shares ancestry with some East African and South East Asian parasites. Signals of positive selection are linked to drug resistance-associated loci including pvkelch10, pvmrp1, pvdhfr and pvdhps, and two loci linked to P. vivax invasion of reticulocytes, pvrbp1a and pvrbp1b. Significant identity-by-descent was found in extended chromosome regions common to P. vivax from India and Ethiopia, including the pvdbp gene associated with Duffy blood group binding. Our investigation provides new understanding of global P. vivax population structure and genomic diversity, and genetic evidence of recent directional selection in this important human pathogen.
Slippery damper of an overlay for arresting and manipulating droplets on nonwetting surfaces
Authors: Han Xing , Li Wei , Zhao Haibo , Li Jiaqian , Tang Xin , Wang Liqiu
Published: May 2021

In diverse processes, such as fertilization, insecticides, and cooling, liquid delivery is compromised by the super-repellency of receiving surfaces, including super-hydro-/omni-phobic and superheated types, a consequence of intercalated air pockets or vapor cushions that promote droplet rebounds as floating mass-spring systems. By simply overlaying impacting droplets with a tiny amount of lubricant (less than 0.1 vol% of the droplet), their interfacial properties are modified in such a way that damper-roller support is attached to the mass-spring system. The overlayers suppress the out-of-plane rebounds by slowing the departing droplets through viscous dissipation and sustain the droplets’ in-plane mobility through self-lubrication, a preferential state for scenarios such as shedding of liquid in spray cooling and repositioning of droplets in printing. The footprint of our method can be made to be minimal, circumventing surface contamination and toxification. Our method enables multifunctional and dynamic control of droplets that impact different types of nonwetting surfaces.
Giant enhancement of THz-frequency optical nonlinearity by phonon polariton in ionic crystals
Authors: Lu Yao , Zhang Qi , Wu Qiang , Chen Zhigang , Liu Xueming , Xu Jingjun
Published: May 2021

The field of nonlinear optics has grown substantially in past decades, leading to tremendous progress in fundamental research and revolutionized applications. Traditionally, the optical nonlinearity for a light wave at frequencies beyond near-infrared is observed with very high peak intensity, as in most materials only the electronic nonlinearity dominates while ionic contribution is negligible. However, it was shown that the ionic contribution to nonlinearity can be much larger than the electronic one in microwave experiments. In the terahertz (THz) regime, phonon polariton may assist to substantially trigger the ionic nonlinearity of the crystals, so as to enhance even more the nonlinear optical susceptibility. Here, we experimentally demonstrate a giant second-order optical nonlinearity at THz frequency, orders of magnitude higher than that in the visible and microwave regimes. Different from previous work, the phonon-light coupling is achieved under a phase-matching setting, and the dynamic process of nonlinear THz generation is directly observed in a thin-film waveguide using a time-resolved imaging technique. Furthermore, a nonlinear modification to the Huang equations is proposed to explain the observed nonlinearity enhancement. This work brings about an effective approach to achieve high nonlinearity in ionic crystals, promising for applications in THz nonlinear technologies.
Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex
Authors: Lu Defen , Shang Guijun , He Xiaojing , Bai Xiao-chen , Zhang Xuewu
Published: May 2021

Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for neuronal axon guidance and other processes. Despite extensive investigations, the overall architecture of and the molecular interactions in the Sema3/plexin/neuropilin complex are incompletely understood. Here we present the cryo-EM structure of a near intact extracellular region complex of Sema3A, PlexinA4 and Neuropilin 1 (Nrp1) at 3.7 Å resolution. The structure shows a large symmetric 2:2:2 assembly in which each subunit makes multiple interactions with others. The two PlexinA4 molecules in the complex do not interact directly, but their membrane proximal regions are close to each other and poised to promote the formation of the intracellular active dimer for signaling. The structure reveals a previously unknown interface between the a2b1b2 module in Nrp1 and the Sema domain of Sema3A. This interaction places the a2b1b2 module at the top of the complex, far away from the plasma membrane where the transmembrane regions of Nrp1 and PlexinA4 embed. As a result, the region following the a2b1b2 module in Nrp1 must span a large distance to allow the connection to the transmembrane region, suggesting an essential role for the long non-conserved linkers and the MAM domain in neuropilin in the semaphorin/plexin/neuropilin complex.
How can artificial intelligence models assist PD-L1 expression scoring in breast cancer: results of multi-institutional ring studies
Authors: Wang Xinran , Wang Liang , Bu Hong , Zhang Ningning , Yue Meng , Jia Zhanli , Cai Lijing , He Jiankun , Wang Yanan , Xu Xin , Li Shengshui , Xiao Kaiwen , Yan Kezhou , Tian Kuan , Han Xiao , Huang Junzhou , Yao Jianhua , Liu Yueping
Published: May 2021

Programmed death ligand-1 (PD-L1) expression is a key biomarker to screen patients for PD-1/PD-L1-targeted immunotherapy. However, a subjective assessment guide on PD-L1 expression of tumor-infiltrating immune cells (IC) scoring is currently adopted in clinical practice with low concordance. Therefore, a repeatable and quantifiable PD-L1 IC scoring method of breast cancer is desirable. In this study, we propose a deep learning-based artificial intelligence-assisted (AI-assisted) model for PD-L1 IC scoring. Three rounds of ring studies (RSs) involving 31 pathologists from 10 hospitals were carried out, using the current guideline in the first two rounds (RS1, RS2) and our AI scoring model in the last round (RS3). A total of 109 PD-L1 (Ventana SP142) immunohistochemistry (IHC) stained images were assessed and the role of the AI-assisted model was evaluated. With the assistance of AI, the scoring concordance across pathologists was boosted to excellent in RS3 (0.950, 95% confidence interval (CI): 0.936–0.962) from moderate in RS1 (0.674, 95% CI: 0.614–0.735) and RS2 (0.736, 95% CI: 0.683–0.789). The 2- and 4-category scoring accuracy were improved by 4.2% (0.959, 95% CI: 0.953–0.964) and 13% (0.815, 95% CI: 0.803–0.827) (p < 0.001). The AI results were generally accepted by pathologists with 61% “fully accepted” and 91% “almost accepted”. The proposed AI-assisted method can help pathologists at all levels to improve the PD-L1 assay (SP-142) IC assessment in breast cancer in terms of both accuracy and concordance. The AI tool provides a scheme to standardize the PD-L1 IC scoring in clinical practice.
Treatment scheduling effects on the evolution of drug resistance in heterogeneous cancer cell populations
Authors: Patwardhan Gauri A. , Marczyk Michal , Wali Vikram B. , Stern David F. , Pusztai Lajos , Hatzis Christos
Published: May 2021

The effect of scheduling of targeted therapy combinations on drug resistance is underexplored in triple-negative breast cancer (TNBC). TNBC constitutes heterogeneous cancer cell populations the composition of which can change dynamically during treatment resulting in the selection of resistant clones with a fitness advantage. We evaluated crizotinib (ALK/MET inhibitor) and navitoclax (ABT-263; Bcl-2/Bcl-xL inhibitor) combinations in a large design consisting of 696 two-cycle sequential and concomitant treatment regimens with varying treatment dose, duration, and drug holiday length over a 26-day period in MDA-MB-231 TNBC cells and found that patterns of resistance depend on the schedule and sequence in which the drugs are given. Further, we tracked the clonal dynamics and mechanisms of resistance using DNA-integrated barcodes and single-cell RNA sequencing. Our study suggests that longer formats of treatment schedules in vitro screening assays are required to understand the effects of resistance and guide more realistically in vivo and clinical studies.
Radiation recall dermatitis following letrozole administration in patient with a remote history of radiation therapy
Authors: Sweren Evan , Aravind Pathik , Dembinski Robert , Klein Catherine , Habibi Mehran , Kerns Michelle L.
Published: May 2021

We report the case of letrozole-induced radiation recall dermatitis (RRD) in a patient with a remote history of radiation therapy. There is only one previously known case of RRD triggered by letrozole in a patient with a recent (<3 month) history of radiation. Previously, only four other cases of aromatase-inhibitor-induced RRD have been reported. This case is significant for cancer care teams considering personalized treatments. In addition, improved long-term outcomes in cancer patients may lead to increases in and underdiagnoses of RRD. Likewise, RRD is patient specific, exacerbating health concerns, and can be difficult to recognize without proper awareness, documentation, and classification of triggering drugs. The authors hope to address these issues in this report.
Corrosion performance and degradation mechanism of a bi-metallic aluminum structure processed by wire-arc additive manufacturing
Authors: Azar Amin S. , Lekatou Angeliki , Sunding Martin F. , Graff Joachim S. , Tzima Nicky , Diplas Spyros
Published: May 2021

An Al-5Mg alloy (AA5083) block, deposited over an AA6061 substrate by wire-arc additive manufacturing, was electrochemically tested along two different cross-sectional planes by cyclic polarization in 3.5 wt.% NaCl. The deposited layers and the interlayer boundaries showed similar polarization behavior regardless of the cross-sectional direction. The corrosion of both the substrate and the deposited layers was mainly attributed to the presence of relatively coarse intermetallic Al(Fe, Mn)Si particles. In the substrate, corrosion was governed by deep crevices along the interfaces of directionally aligned Al(Fe, Mn)Si particles with the Al matrix. The deposited layers and the interlayer boundaries showed pitting around numerous Al(Fe, Mn)Si particles and/or Al(Fe, Mn, Cr, Ti)Si at the interlayer boundaries, which were much finer compared to those of the substrate. The abundance of the fine precipitates and their intergranular location caused surface material removal, which was more extensive along the interlayer boundaries. The perpendicularz-yandz-xplanes of the deposited block did not show significant differences in anodic polarization behavior. Differences were more distinct in the case of cathodic polarization. Some anisotropy in polarization behavior was noted through the thickness of thez-yplane that complies with the obtained tensile behavior.
Inhibition of nuclear factor (erythroid-derived 2)-like 2 promotes hepatic progenitor cell activation and differentiation
Authors: Bellanti Francesco , di Bello Giorgia , Iannelli Giuseppina , Pannone Giuseppe , Pedicillo Maria Carmela , Boulter Luke , Lu Wei-Yu , Tamborra Rosanna , Villani Rosanna , Vendemiale Gianluigi , Forbes Stuart J. , Serviddio Gaetano
Published: May 2021

The stem cell ability to self-renew and lead regeneration relies on the balance of complex signals in their microenvironment. The identification of modulators of hepatic progenitor cell (HPC) activation is determinant for liver regeneration and may improve cell transplantation for end-stage liver disease. This investigation used different models to point out the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) as a key regulator of the HPC fate. We initially proved that in vivo models of biliary epithelial cells (BECs)/HPC activation show hepatic oxidative stress, which activates primary BECs/HPCs in vitro. NRF2 downregulation and silencing were associated with morphological, phenotypic, and functional modifications distinctive of differentiated cells. Furthermore, NRF2 activation in the biliary tract repressed the ductular reaction in injured liver. To definitely assess the importance of NRF2 in HPC biology, we applied a xenograft model by inhibiting NRF2 in the human derived HepaRG cell line and transplanting into SCID/beige mice administered with anti-Fas antibody to induce hepatocellular apoptosis; this resulted in effective human hepatocyte repopulation with reduced liver injury. To conclude, NRF2 inhibition leads to the activation and differentiation of liver progenitors. This redox-dependent transcription factor represents a potential target to regulate the commitment of undifferentiated hepatic progenitors into specific lineages.
Aachen-Heerlen annotated steel microstructure dataset
Authors: Iren Deniz , Ackermann Marc , Gorfer Julian , Pujar Gaurav , Wesselmecking Sebastian , Krupp Ulrich , Bromuri Stefano
Published: May 2021

Studying steel microstructures yields important insights regarding its mechanical characteristics. Within steel, microstructures transform based on a multitude of factors including chemical composition, transformation temperatures, and cooling rates. Martensite-austenite (MA) islands in bainitic steel appear as blocky structures with abstract shapes that are difficult to identify and differentiate from other types of microstructures. In this regard, material science may benefit from machine learning models that are able to automatically and accurately detect these structures. However, the training process of the state-of-the-art machine learning models requires a large amount of high-quality data. In this dataset, we provide 1.705 scanning electron microscopy images along with a set of 8.909 expert-annotated polygons to describe the geometry of the MA islands that appear on the images. We envision that this dataset will be useful for material scientists to explore the relationship between the morphology of bainitic steel and mechanical characteristics. Moreover, computer vision researchers and practitioners may use this data for training state-of-the-art object segmentation models for abstract geometries such as MA islands.
Computational design of single-stranded DNA hairpin aptamers immobilized on a biosensor substrate
Authors: Jeddi Iman , Saiz Leonor
Published: May 2021

Aptamer interactions with a surface of attachment are central to the design and performance of aptamer-based biosensors. We have developed a computational modeling approach to study different system designs—including different aptamer-attachment ends, aptamer surface densities, aptamer orientations, and solvent solutions—and applied it to an anti MUC1 aptamer tethered to a silica biosensor substrate. Amongst all the system designs explored, we found that attaching the anti MUC1 aptamer through the 5′ terminal end, in a high surface density configuration, and solvated in a 0.8 M NaCl solution provided the best exposure of the aptamer MUC1 binding regions and resulted in the least amount of aptamer backbone fluctuations. Many of the other designs led to non-functional systems, with the aptamer collapsing onto the surface. The computational approach we have developed and the resulting analysis techniques can be employed for the rational design of aptamer-based biosensors and provide a valuable tool for improving biosensor performance and repeatability.
Prenatal exposures to mixtures of endocrine disrupting chemicals and children’s weight trajectory up to age 5.5 in the SELMA study
Authors: Svensson Katherine , Tanner Eva , Gennings Chris , Lindh Christian , Kiviranta Hannu , Wikström Sverre , Bornehag Carl-Gustaf
Published: May 2021

Exposure to endocrine disrupting chemicals (EDCs) may impact early growth, although information is limited on exposure to combination of multiple EDCs. We aimed to evaluate the effect of prenatal exposure to EDC mixtures on birthweight z-scores and childhood weight trajectories. Twenty-six proven and suspected EDCs, were analyzed in prenatal urine and blood samples from 1118 mothers participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study. Two growth parameters were estimated from each child’s weight trajectory from birth to 5.5 years of age: infant growth spurt rate and age at infant peak growth velocity (PGV). Weighted quantile sum (WQS) regression was used to estimate the mixture effect and identify chemicals of concern. A one-unit increase in the EDC mixture WQS index, was associated with decreased birthweight z-scores of 0.11 (95% CI − 0.16, − 0.06), slower infant growth spurt rate of 0.01 (95% CI − 0.03, − 0.01, on the log10 scale), and delayed age at infant PGV of 0.15 months (95% CI 0.07, 0.24) after adjusting for potential confounders. Stratified analysis by sex, showed that delayed age at infant PGV was mostly observed in girls with 0.51 months (95% CI 0.26, 0.76). Identified chemicals of concern included perfluorinated alkyl substances (PFAS), Triclosan, phthalates, non-phthalate plasticizers, bisphenols, polycyclic aromatic hydrocarbons, pesticides and PCBs. Prenatal exposure to EDC mixtures was associated with lower birthweight and altered infant weight gain trajectories.
Live cell dynamics of the NF-Y transcription factor
Authors: Priest David G. , Bernardini Andrea , Lou Jieqiong , Mantovani Roberto , Hinde Elizabeth
Published: May 2021

Transcription factors (TFs) are core players in the control of gene expression, evolutionarily selected to recognise a subset of specific DNA sequences and nucleate the recruitment of the transcriptional machinery. How TFs assemble and move in the nucleus to locate and bind their DNA targets and cause a transcriptional response, remains mostly unclear. NF-Y is a highly conserved, heterotrimeric TF with important roles in both housekeeping and lineage-specific gene expression, functioning as a promoter organiser. Despite a large number of biochemical, structural and genomic studies of NF-Y, there is a lack of experiments in single living cells; therefore, basic assumptions of NF-Y biology remain unproven in vivo. Here we employ a series of dynamic fluorescence microscopy methods (FLIM-FRET, NB, RICS and FRAP) to study NF-Y dynamics and complex formation in live cells. Specifically, we provide quantitative measurement of NF-Y subunit association and diffusion kinetics in the nucleus that collectively suggest NF-Y to move and bind chromatin as a trimeric complex in vivo.
Pulmonary effects of dexmedetomidine infusion in thoracic aortic surgery under hypothermic circulatory arrest: a randomized placebo-controlled trial
Authors: Kim Seongsu , Park Soo Jung , Nam Sang Beom , Song Suk-Won , Han Yeonseung , Ko Sangmin , Song Young
Published: May 2021

Dexmedetomidine has emerged as a promising organ protective agent. We performed prospective randomized placebo-controlled trial investigating effects of perioperative dexmedetomidine infusion on pulmonary function following thoracic aortic surgery with cardiopulmonary bypass and moderate hypothermic circulatory arrest. Fifty-two patients were randomized to two groups: the dexmedetomidine group received 1 µg/kg of dexmedetomidine over 20 min after induction of anesthesia, followed by 0.5 µg/kg/h infusion until 12 h after aortic cross clamp (ACC)-off, while the control group received the same volume of normal saline. The primary endpoints were oxygenation indices including arterial O2 partial pressure (PaO2) to alveolar O2 partial pressure ratio (a/A ratio), (A–a) O2 gradient, PaO2/FiO2 and lung mechanics including peak inspiratory and plateau pressures and compliances, which were assessed after anesthesia induction, 1 h, 6 h, 12 h, and 24 h after ACC-off. The secondary endpoints were serum biomarkers including interleukin-6, tumor necrosis factor-α, superoxide dismutase, and malondialdehyde (MDA). As a result, dexmedetomidine did not confer protective effects on the lungs, but inhibited elevation of serum MDA level, indicative of anti-oxidative stress property, and improved urine output and lower requirements of vasopressors.