bluuebunny/crossref_metadata_2025 huggingface dataset:
An auxin-inducible, GAL4-compatible, gene expression system forDrosophila
Authors: McClure Colin D. , Hassan Amira , Aughey Gabriel N. , Butt Khushbakht , Estacio-Gómez Alicia , Duggal Aneisha , Sia Chee Ying , Barber Annika F. , Southall Tony D.
Published: January 2021

The ability to control transgene expression, both spatially and temporally, is essential for studying model organisms. InDrosophila, spatial control is primarily provided by the GAL4/UAS system, whilst temporal control relies on a temperature-sensitive GAL80 (which inhibits GAL4) and drug-inducible systems. However, these are not ideal. Shifting temperature can impact on many physiological and behavioural traits, and the current drug-inducible systems are either leaky, toxic, incompatible with existing GAL4-driver lines, or do not generate effective levels of expression. Here we describe the Auxin-inducible Gene Expression System (AGES). AGES relies on the auxin-dependent degradation of a ubiquitously expressed GAL80, and therefore, is compatible with existing GAL4-driver lines. Water-soluble auxin is added to fly food at a low, non-lethal, concentration, which induces expression comparable to uninhibited GAL4 expression. The system works in both larvae and adults, providing a stringent, non-lethal, cost-effective, and convenient method for temporally controlling GAL4 activity inDrosophila.
A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques
Authors: Hassan Ahmed O. , Feldmann Friederike , Zhao Haiyan , Curiel David T. , Okumura Atsushi , Tang-Huau Tsing-Lee , Case James Brett , Meade-White Kimberly , Callison Julie , Lovaglio Jamie , Hanley Patrick W. , Scott Dana P. , Fremont Daved H. , Feldmann Heinz , Diamond Michael S.
Published: January 2021

The deployment of a vaccine that limits transmission and disease likely will be required to end the Coronavirus Disease 2019 (COVID-19) pandemic. We recently described the protective activity of an intranasally-administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S) in the upper and lower respiratory tract of mice expressing the human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we show the immunogenicity and protective efficacy of this vaccine in non-human primates. Rhesus macaques were immunized with ChAd-Control or ChAd-SARS-CoV-2-S and challenged one month later by combined intranasal and intrabronchial routes with SARS-CoV-2. A single intranasal dose of ChAd-SARS-CoV-2-S induced neutralizing antibodies and T cell responses and limited or prevented infection in the upper and lower respiratory tract after SARS-CoV-2 challenge. As this single intranasal dose vaccine confers protection against SARS-CoV-2 in non-human primates, it is a promising candidate for limiting SARS-CoV-2 infection and transmission in humans.
C-phycocyanin as a highly attractive model system in protein crystallography: unique crystallization properties and packing-diversity screening
Authors: Sarrou Iosifina , Feiler Christian G. , Falke Sven , Peard Nolan , Yefanov Oleksandr , Chapman Henry
Published: January 2021

The unique crystallization properties of the antenna protein C-phycocyanin (C-PC) from the thermophilic cyanobacterium Thermosynechococcus elongatus are reported and discussed. C-PC crystallizes in hundreds of significantly different conditions within a broad pH range and in the presence of a wide variety of precipitants and additives. Remarkably, the crystal dimensions vary from a few micrometres, as used in serial crystallography, to several hundred micrometres, with a very diverse crystal morphology. More than 100 unique single-crystal X-ray diffraction data sets were collected from randomly selected crystals and analysed. The addition of small-molecule additives revealed three new crystal packings of C-PC, which are discussed in detail. The high propensity of this protein to crystallize, combined with its natural blue colour and its fluorescence characteristics, make it an excellent candidate as a superior and highly adaptable model system in crystallography. C-PC can be used in technical and methods development approaches for X-ray and neutron diffraction techniques, and as a system for comprehending the fundamental principles of protein crystallography.
Crystal structures of the selenoprotein glutathione peroxidase 4 in its apo form and in complex with the covalently bound inhibitor ML162
Authors: Moosmayer Dieter , Hilpmann André , Hoffmann Jutta , Schnirch Lennart , Zimmermann Katja , Badock Volker , Furst Laura , Eaton John K. , Viswanathan Vasanthi S. , Schreiber Stuart L. , Gradl Stefan , Hillig Roman C.
Published: January 2021

Wild-type human glutathione peroxidase 4 (GPX4) was co-expressed with SBP2 (selenocysteine insertion sequence-binding protein 2) in human HEK cells to achieve efficient production of this selenocysteine-containing enzyme on a preparative scale for structural biology. The protein was purified and crystallized, and the crystal structure of the wild-type form of GPX4 was determined at 1.0 Å resolution. The overall fold and the active site are conserved compared with previously determined crystal structures of mutated forms of GPX4. A mass-spectrometry-based approach was developed to monitor the reaction of the active-site selenocysteine Sec46 with covalent inhibitors. This, together with the introduction of a surface mutant (Cys66Ser), enabled the crystal structure determination of GPX4 in complex with the covalent inhibitor ML162 [(S)-enantiomer]. The mass-spectrometry-based approach described here opens the path to further co-complex crystal structures of this potential cancer drug target in complex with covalent inhibitors.
The accuracy of protein models automatically built into cryo-EM maps with ARP/wARP
Authors: Chojnowski Grzegorz , Sobolev Egor , Heuser Philipp , Lamzin Victor S.
Published: January 2021

Recent developments in cryogenic electron microscopy (cryo-EM) have enabled structural studies of large macromolecular complexes at resolutions previously only attainable using macromolecular crystallography. Although a number of methods can already assist in de novo building of models into high-resolution cryo-EM maps, automated and reliable map interpretation remains a challenge. Presented here is a systematic study of the accuracy of models built into cryo-EM maps using ARP/wARP. It is demonstrated that the local resolution is a good indicator of map interpretability, and for the majority of the test cases ARP/wARP correctly builds 90% of main-chain fragments in regions where the local resolution is 4.0 Å or better. It is also demonstrated that the coordinate accuracy for models built into cryo-EM maps is comparable to that of X-ray crystallographic models at similar local cryo-EM and crystallographic resolutions. The model accuracy also correlates with the refined atomic displacement parameters.
rac-11-Selena-12,13-diazabicyclo[10.3.0]pentadeca-10a(13a),12-dien-1-ol
Authors: Detert Heiner , Schollmeyer Dieter
Published: January 2021

The title compound, C12H20N2OSe, crystallizes in strands of enantiomeric molecules connected via O—H...N hydrogen bonds. There are only slight deviations from an ideal gauche conformation in the decamethylene chain, indicating just a little strain.
More drought leads to a greater significance of biocrusts to soil multifunctionality
Authors: Su Yan‐gui , Liu Jie , Zhang Yuan‐ming , Huang Gang
Published: January 2021

Soil biocrusts, as the fundamental component of drylands, alter soil microbial and plant community compositions, thus profoundly affecting soil multifunctionality (SMF). Biocrust development regulates microbial composition and eco‐physiological effects, but there have been limited assessments regarding how biocrust development impacts SMF through microbial communities and plant species.

We investigated the geographical patterns of plant diversity, soil bacterial diversity, biocrust development and SMF along an aridity gradient, spanning 2,200 km in northern China, and evaluated how biocrust development modulated multiple soil functions related to carbon, nitrogen and phosphorus cycles.

Plant species richness and SMF decreased linearly with increasing aridity (1‐AI), but the relationship of soil bacterial diversity and biocrust development index (BSCDI) with aridity differed between arid region and semi‐arid region.

Plant diversity and soil bacterial diversity increased linearly with BSCDI in arid regions, but decreased linearly with BSCDI in semi‐arid regions.

Both plant species and soil bacterial diversity exerted positive effects on SMF in arid regions, but soil bacterial diversity, rather than plant species, did not explain any variation in SMF in semi‐arid regions. Most importantly, biocrust development exerted direct effects on SMF in arid regions, but only indirect effects through changing soil microbial biomass carbon in semi‐arid regions.

Our findings suggest that the effects and influencing pathways of biocrusts on SMF are different between arid and semi‐arid regions, these results give a comprehensive view of how biocrust development facilitates soil multifunctionality improvement and ultimately promotes a deeper understanding of the dependence of biodiversity‐SMF relationship on aridity.

A free Plain Language Summary can be found within the Supporting Information of this article.
Decomposing fecundity and evaluating demographic influence of multiple broods in a migratory bird
Authors: Tenan Simone , Becker Detlef , Tolkmitt Dirk , Schaub Michael
Published: January 2021

Relevance of breeding season fecundity as a driver of population dynamics has been highlighted by many studies. Despite that, knowledge about how brood type specific (i.e. first, second or replacement) fecundity affects demography of multiple‐brooded species is limited. In fact, estimation of brood type specific fecundity is often challenging due to imperfect detection of nesting attempts.

We examined the demographic contribution and the feedback on population density of different components of fecundity, along with other vital rates, in a facultative multiple‐brooded migratory bird.

We used a novel formulation of a fecundity model that allows incorporating reproductive data for which information on the type of brood was unknown in some cases, and embedded it into an integrated population model (IPM) to obtain consensual estimates of all demographic rates, including brood type specific fecundities, reproductive success probabilities and proportion of breeding pairs that performed a second or replacement brood. We then conducted transient life table response experiments on IPM estimates to account for non‐stationary environments. We applied the model to two 20‐year datasets collected in a Swiss and a German local population of wrynecks Jynx torquilla.

Brood type specific fecundities and temporal patterns of brood type specific probabilities of success, number of successful and unsuccessful first broods, probability of starting a second or a replacement brood and proportion of pairs that performed a second or a replacement brood differed between the two populations. However, changes in immigration rate and apparent survival were the dominant contributors to temporal variation and large sequential changes in realized population growth rates in both populations. In the Swiss population we also found that second brood fecundity declined when population size increased.

Our study provides insight into the reproductive processes that affect population dynamics and mediate density‐dependent fecundity in a migratory bird. In addition, the analytical approach proposed can be used in other studies of multiple‐brooded species to maximize the use of available fecundity data through the estimation of unknown brood types, thus favouring a better understanding of the demographic contribution of brood type specific fecundity.
Wintering bird communities are tracking climate change faster than breeding communities
Authors: Lehikoinen Aleksi , Lindström Åke , Santangeli Andrea , Sirkiä Päivi M. , Brotons Lluís , Devictor Vincent , Elts Jaanus , Foppen Ruud P. B. , Heldbjerg Henning , Herrando Sergi , Herremans Marc , Hudson Marie‐Anne R. , Jiguet Frédéric , Johnston Alison , Lorrilliere Romain , Marjakangas Emma‐Liina , Michel Nicole L. , Moshøj Charlotte M. , Nellis Renno , Paquet Jean‐Yves , Smith Adam C. , Szép Tibor , van Turnhout Chris
Published: January 2021

Global climate change is driving species' distributions towards the poles and mountain tops during both non‐breeding and breeding seasons, leading to changes in the composition of natural communities. However, the degree of season differences in climate‐driven community shifts has not been thoroughly investigated at large spatial scales.

We compared the rates of change in the community composition during both winter (non‐breeding season) and summer (breeding) and their relation to temperature changes.

Based on continental‐scale data from Europe and North America, we examined changes in bird community composition using the community temperature index (CTI) approach and compared the changes with observed regional temperature changes during 1980–2016.

CTI increased faster in winter than in summer. This seasonal discrepancy is probably because individuals are less site‐faithful in winter, and can more readily shift their wintering sites in response to weather in comparison to the breeding season. Regional long‐term changes in community composition were positively associated with regional temperature changes during both seasons, but the pattern was only significant during summer due to high annual variability in winter communities. Annual changes in community composition were positively associated with the annual temperature changes during both seasons.

Our results were broadly consistent across continents, suggesting some climate‐driven restructuring in both European and North American avian communities. Because community composition has changed much faster during the winter than during the breeding season, it is important to increase our knowledge about climate‐driven impacts during the less‐studied non‐breeding season.
Tropical deforestation reduces plant mating quality by shifting the functional composition of pollinator communities
Authors: Torres‐Vanegas Felipe , Hadley Adam S. , Kormann Urs G. , Jones F. Andrew , Betts Matthew G. , Wagner Helene H.
Published: January 2021

Deforestation can impact the quality of pollen received by target plants (i.e. delivery of incompatible pollen, self‐pollen or pollen from closely related individuals). Such reductions in plant mating quality may be direct, when deforestation reduces plant population size and the availability of pollen donors, or indirect, when decreased mating quality results, for example, from shifts in the composition of the pollinator community. As most flowering plants depend on animal pollinators for reproduction, there is a need to understand the direct and indirect links between deforestation, pollinator community composition and plant mating quality.

We quantified the direct, pollen donor‐mediated and indirect, pollinator‐mediated effects of deforestation on mating quality inHeliconia tortuosa, a tropical herb pollinated by low‐ and high‐mobility hummingbirds. We used a confirmatory path analysis to test the hypothesis that deforestation (amount of forest cover and forest patch size) influenced mating quality (haplotype diversity of pollen pools, outcrossing and biparental inbreeding) directly and indirectly through functional shifts in the composition of pollinator communities (proportion of high‐mobility hummingbirds).

We found that deforestation triggered functional shifts in the composition of pollinator communities, as the proportion of high‐mobility hummingbirds increased significantly with the amount of forest cover and forest patch size. The composition of the pollinator community affected mating quality, as the haplotype diversity of pollen pools increased significantly with the proportion of high‐mobility hummingbirds, while biparental inbreeding decreased significantly. Although we did not detect any significant direct, pollen donor‐mediated effects of deforestation on mating quality, reductions in the amount of forest cover and forest patch size resulted in functional shifts that filtered out high‐mobility hummingbirds from the pollinator community, thereby reducing mating quality indirectly.

Synthesis. Deforestation primarily influenced plant mating quality through a cascading effect mediated by functional shifts in the composition of the pollinator community. Our results indicate that plant mating quality strongly depends on the composition of local pollinator communities. Functional shifts that filter out highly mobile and effective pollinators may reduce the transfer of genetically diverse pollen loads from unrelated plants. Such shifts may have pronounced effects on plant population dynamics and disrupt genetic connectivity.
Local‐scale climatic refugia offer sanctuary for a habitat‐forming species during a marine heatwave
Authors: Verdura Jana , Santamaría Jorge , Ballesteros Enric , Smale Dan A. , Cefalì Maria Elena , Golo Raül , de Caralt Sònia , Vergés Alba , Cebrian Emma
Published: January 2021

Gradual climate change and discrete extreme climatic events have driven shifts in the structure of populations and the distribution of species in many marine ecosystems. The most profound impacts of recent warming trends have been generally observed at species' warm edges and on large conspicuous species. However, given that different species and populations exhibit different responses to warming, and that responses are highly variable at regional scales, there is a need to broaden the evidence to include less conspicuous species and to focus on both local‐ and regional‐scale processes.

We examined the population dynamics of canopy‐forming seaweed populations situated at the core range of their distribution during a regional marine heatwave (MHW) event that occurred in the Mediterranean Sea in 2015, to determine between‐site variability in relation to the intensity of the MHW. We combined field observations with a thermo‐tolerance experiment to elucidate mechanisms underlying observed responses.

Despite our study populations are located in the species core range, the MHW was concomitant with a high mortality and structural shifts in only one of the two surveyed populations, most likely due to differences in habitat characteristics between sites (e.g. degree of shelter and seawater transfer). The experiment showed high mortalities at temperatures of 28°C, having the most severe implications for early life stages and fertility, which is consistent with warming being the cause of population changes in the field. Crucially, the regional‐scale quantification of the MHW (as described by satellite‐derived SSTs) did not capture local‐scale variation in MHW conditions at the study sites, which likely explained variation in population‐level responses to warming.

Synthesis. Enclosed and semi‐enclosed seas, such as the Mediterranean Sea, often highly impacted by human perturbations, are also global hotspots for ocean warming and are highly susceptible to future MHWs. Our findings highlight that local‐scale variability in the magnitude of extreme climatic events can lead to local extinctions of already fragmented populations of habitat‐forming seaweeds, even towards the species' core range. However, our results highlight the potential for local‐scale climatic refugia, which could be identified and managed to safeguard the persistence of canopy‐forming seaweeds.
The influence of pre‐heat treatment of skim milk on key quality attributes of fat filled milk powder made therefrom
Authors: Finnegan Eoin W , Mahomud Md. Sultan , Murphy Eoin G , O'Mahony James A
Published: January 2021

Key quality aspects of fat filled milk powders (FFMPs) produced with skim milk pre‐heated at 93 °C × 60 s and 105 °C × 15 s (medium whey protein nitrogen index; WPNI), and 116 °C × 60 s and 136 °C × 15 s (high WPNI) were examined. The 136 °C × 15 s treatment produced a FFMP with threefold higher free fat, showed significantly (P < 0.05) lower solubility in coffee and exhibited extensive flecking on rehydration in water. Insoluble materials were observed using microscopy; flecks generated upon rehydration in water were composed of fat, whereas flecks/sediment in coffee were composed of undissolved powder particles.
A role for the endocannabinoid enzymes monoacylglycerol and diacylglycerol lipases in cue‐induced cocaine craving following prolonged abstinence
Authors: Mitra Swarup , Gobira Pedro H. , Werner Craig T. , Martin Jennifer A. , Iida Madoka , Thomas Shruthi A. , Erias Kyra , Miracle Sophia , Lafargue Charles , An Chunna , Dietz David M.
Published: January 2021

Following exposure to drugs of abuse, long‐term neuroadaptations underlie persistent risk to relapse. Endocannabinoid signaling has been associated with drug‐induced neuroadaptations, but the role of lipases that mediate endocannabinoid biosynthesis and metabolism in regulating relapse behaviors following prolonged periods of drug abstinence has not been examined. Here, we investigated how pharmacological manipulation of lipases involved in regulating the expression of the endocannabinoid 2‐AG in the nucleus accumbens (NAc) influence cocaine relapse via discrete neuroadaptations. At prolonged abstinence (30 days) from cocaine self‐administration, there is an increase in the NAc levels of diacylglycerol lipase (DAGL), the enzyme responsible for the synthesis of the endocannabinoid 2‐AG, along with decreased levels of monoacylglycerol lipase (MAGL), which hydrolyzes 2‐AG. Since endocannabinoid‐mediated behavioral plasticity involves phosphatase dysregulation, we examined the phosphatase calcineurin after 30 days of abstinence and found decreased expression in the NAc, which we demonstrate is regulated through the transcription factor EGR1. Intra‐NAc pharmacological manipulation of DAGL and MAGL with inhibitors DO‐34 and URB‐602, respectively, bidirectionally regulated cue‐induced cocaine seeking and altered the phosphostatus of translational initiation factor, eIF2α. Finally, we found that cocaine seeking 30 days after abstinence leads to decreased phosphorylation of eIF2α and reduced expression of its downstream target NPAS4, a protein involved in experience‐dependent neuronal plasticity. Together, our findings demonstrate that lipases that regulate 2‐AG expression influence transcriptional and translational changes in the NAc related to drug relapse vulnerability.
Multidimensional Reasoning Can Promote 3‐Year‐Old Children’s Performance on the Dimensional Change Card Sort Task
Authors: Bardikoff Nicole , Sabbagh Mark A.
Published: January 2021

An important aspect of executive functioning is the ability to flexibly switch between behavioral rules. This study explored how considering the multidimensionality of objects affects behavioral rule switching in 3‐year‐old children. In Study 1 (N = 40), children who participated in a brief game separating and aggregating an object’s dimensions (i.e., color and shape) showed improved performance on the Dimensional Change Card Sort (DCCS), a measure of behavioral rule switching, relative to controls. In Study 2 (N = 80) DCCS performance improved even when the initial practice involved a different dimension (pattern and shape). Thus, practice thinking about multidimensionality can affect 3‐year‐olds’ DCCS performance and therefore may play an important role in the development of flexible thinking.
Different Cre systems induce differential microRNA landscapes and abnormalities in the female reproductive tracts of Dgcr8 conditional knockout mice
Authors: Kim Yeon Sun , Yang Seung Chel , Park Mira , Choi Youngsok , DeMayo Francesco J. , Lydon John P. , Kim Hye‐Ryun , Lim Hyunjung Jade , Song Haengseok
Published: January 2021

Objectives

The female reproductive tract comprises several different cell types. Using three representative Cre systems, we comparatively analysed the phenotypes of Dgcr8 conditional knockout (cKO) mice to understand the function of Dgcr8, involved in canonical microRNA biogenesis, in the female reproductive tract.

Materials and Methods

Dgcr8f/f mice were crossed with Ltficre/+, Amhr2cre/+ or PRcre/+ mice to produce mice deficient in Dgcr8 in epithelial (Dgcr8ed/ed), mesenchymal (Dgcr8md/md) and all the compartments (Dgcr8td/td) in the female reproductive tract. Reproductive phenotypes were evaluated in Dgcr8 cKO mice. Uteri and/or oviducts were used for small RNA‐seq, mRNA‐seq, real‐time RT‐PCR, and/or morphologic and histological analyses.

Result

Dgcr8ed/ed mice did not exhibit any distinct defects, whereas Dgcr8md/md mice showed sub‐fertility and oviductal smooth muscle deformities. Dgcr8td/td mice were infertile due to anovulation and acute inflammation in the female reproductive tract and suffered from an atrophic uterus with myometrial defects. The microRNAs and mRNAs related to immune modulation and/or smooth muscle growth were systemically altered in the Dgcr8td/td uterus. Expression profiles of dysregulated microRNAs and mRNAs in the Dgcr8td/td uterus were different from those in other genotypes in a Cre‐dependent manner.

Conclusions

Dgcr8 deficiency with different Cre systems induces overlapping but distinct phenotypes as well as the profiles of microRNAs and their target mRNAs in the female reproductive tract, suggesting the importance of selecting the appropriate Cre driver to investigate the genes of interest.
Insect fatalities at wind turbines as biodiversity sinks
Authors: Voigt Christian C.
Published: January 2021

Evidence is accumulating that insects are frequently killed by operating wind turbines, yet it is poorly understood if these fatalities cause population declines and changes in assemblage structures on various spatial scales. Current observations suggest that mostly hill‐topping, swarming, and migrating insects interact with wind turbines. Recently, the annual loss of insect biomass at wind turbines was estimated for Germany to amount 1,200 t for the plant growth period, which equates to about 1.2 trillion killed insects per year, assuming 1 mg insect body mass. Accordingly, a single turbine located in the temperate zone might kill about 40 million insects per year. Furthermore, Scheimpflug Lidar measurements at operating wind turbines confirm a high insect activity in the risk zone of turbines. These numbers and observations are alarming, yet they require further consolidation, particularly across all continents and climate zones where wind energy industry is expanding. We need to understand (a) how attraction of insects to wind turbines affect fatality rates and interactions of insect predators with wind turbines. (b) We have to connect insect fatalities at wind turbines with source populations and evaluate if these fatalities add to the decline of insect populations and potentially the extinction of species. (c) We need to assess how fatalities at wind turbines change insect‐mediated ecosystem services. An ever‐growing global wind energy industry with high densities of wind turbines may have long‐lasting effects on insects and associated trophic links if negative impacts on insects are not considered during the erection and operation of wind turbines.
Efficacy and tolerability of VCD chemotherapy in a UK real‐world dataset of elderly transplant‐ineligible newly diagnosed myeloma patients
Authors: Rampotas Alexandros , Djebbari Faouzi , Panitsas Fotios , Lees Charlotte , Tsagkaraki Ismini , Gomes Ana Rita , Prideaux Steve , Chen Lucia , Prodger Catherine , Khera Akhil , Gray Nicola , Ellis Lauren , Sangha Gavinda , Lim Wen Yuen , Eyre Toby A. , Moore Sally , Ramasamy Karthik , Kothari Jaimal
Published: January 2021

Objective

There are limited data on the efficacy and tolerability of VCD chemotherapy in transplant‐non‐eligible (TNE) newly diagnosed myeloma (NDMM) patients. In this retrospective study, we set out to evaluate this triplet combination in this setting across Thames Valley Cancer Network (UK).

Methods

The primary end point was overall response rate (ORR). Secondary outcomes included event‐free survival (EFS), overall survival (OS) and adverse events (AEs).

Results

In a total cohort of 158 patients, ORR for total cohort was 72.1%. Median EFS was 10.5 months, and for subgroups by age (<75:11.7 vs ≥75:10.3 months, P = .124), by Charlson Co‐morbidity Index (CCI) (<5:11.1 vs ≥5:8.2 months, P = .345). The 4‐month landmark analysis showed the following median EFS results: by cumulative bortezomib dose (≥26 mg/m2: 9.0 months vs <26 mg/m2: 6.4, P = .13), by cumulative cyclophosphamide dose (≥7000 mg: 9.2 vs <7000 mg: 7.0 months, P = .02) and by cumulative dexamethasone dose (>600 mg: 7.8 vs ≤600 mg: 8.3 months, P = .665). Median OS was 46.9 months. The incidence rate of AE was as follows: any grade (76.8%), ≥G3 (27.1%), ≥G3 haematological AEs (7.9%), any grade infections (31.1%) and ≥G3 infections (11.9%).

Conclusion

This study demonstrated a good ORR achieved from fixed duration VCD, which was reasonably well tolerated. This was followed by modest median EFS. We envisage that the latter may be improved in this patient group with the use of a higher cumulative bortezomib dose (≥26 mg/m2) which showed a trend for improved EFS although without statistical significance (P = .13), and with the use of a higher cumulative cyclophosphamide doses (≥7000 mg, P = .02), subject to tolerability and close monitoring.
An Improved In Situ Zircon U‐Pb Dating Method at High Spatial Resolution (≤ 10 μm Spot) by LA‐MC‐ICP‐MS and its Application
Authors: Lin Meng , Zhang Guibin , Li Nan , Li Huijuan , Wang Jiaxing
Published: January 2021

In situ small‐spot U‐Pb geochronology is essential for measuring zircon crystals containing micrometre‐scale heterogeneities, abundant inclusions, inevitable cracks and narrow growth zones, all of which are especially common in metamorphic zircons. We present a high spatial resolution (≤ 10 μm diameter) laser ablation‐multi‐collector‐inductively coupled plasma‐mass spectrometry (LA‐MC‐ICP‐MS) U‐Pb dating method using a Nu Plasma II mass spectrometer coupled with a GeoLas HD laser ablation system, which is capable of analysing zircon crystals with a wide range of U contents through two analytical modes (mixed‐mode for 10 μm ablation and IC‐mode for 5 μm ablation). We examined Pb/U down‐hole fractionation (DHF) as a function of different laser settings under small‐spot ablation, and how it controls the accuracy and precision of U‐Pb ages of zircon reference materials. After DHF correction using Iolite software (version 3.71), five measurement sessions (with different laser fluence and/or laser pulse settings) for the two analytical modes yielded accurate and precise U‐Pb ages for four zircon reference materials (Plešovice, 91500, GJ‐1 and Temora‐2). Further determinations of U‐Pb ages of three metamorphic zircon samples (~ 14 to 2000 Ma) from the Himalaya, North China Craton and North Qaidam were conducted, the results of which confirm the effectiveness and feasibility of this small‐spot ablation method for natural zircons with multiple growth zones.
The reputational basis of policy success in comparative perspective: Evidence from the education sector in Peru and Bolivia
Authors: Salazar‐Morales Diego Alonso
Published: January 2021

This article, building on the emerging theoretical corpus of “reputation theory” provides an alternative explanation about how successful policies are obtained in contexts of bureaucratic weakness and volatile politics. The argument is that politicians choose to intervene in delivering successful policies based on how contributable such policies are to construct their political reputations. The findings suggest that in both countries, less tenured politicians face higher incentives to build their reputations, so they choose to deliver better policies to accumulate “successful experiences” as vitae for electoral purposes. Tenured politicians, in turn, opt for inaction or strategic delivery, to preserve their already won political reputations. The present article brings evidence from the education sector of Peru and Bolivia, a sector that has been at the core of these countries' priorities for decades. Through a mixed methods approach involving a panel regression and in‐depth interviews, results obtained largely confirm this article's claims.
Corruption experiences and attitudes to political, interpersonal, and domestic violence
Authors: Gillanders Robert , van der Werff Lisa
Published: January 2021

It is understood that corruption can change the incentives to engage in political violence. However, the scope for corruption to change attitudes toward the permissibility of violence has received less attention. Drawing on Moral Foundations Theory, we argue that experiences of corruption in the social environment are likely to shape individual attitudes toward violent behavior. Using Afrobarometer data, we document a statistically significant and sizable relationship between an individual's experience of paying bribes and their attitudes to political, interpersonal, and domestic violence. These relationships are evident, and not significantly different, for men and women and are robust to the inclusion of variables capturing the local incidence of corruption, local norms regarding violence, and a proxy for the local incidence of violence with the community. Corruption is associated with permissive attitudes to violence even after controlling for the perceived legitimacy of the police and courts.
Research of both γ‐irradiation and La2O3 addition on structural and magnetoresistivity of Bi‐2223 bulk superconductors
Authors: Ağıl Hasan , Ozoglu Sevgi
Published: January 2021

In this study, we investigate the effects of both gamma irradiation and the addition of lanthanum oxide (La2O3) on the Bi1.85Pb0.35Sr2Ca2Cu3Oy (Bi‐2223) bulk superconductors. Pure and lanthanum‐added samples prepared by the solid‐state reaction method were analyzed before and after gamma irradiation using various methods such as X‐ray powder diffraction (XRD), the temperature dependence of resistivity under magnetic field (ρ‐T). Bi‐2223 + x La2O3 samples with x = 0.0, 1.0 and 5.0 wt% were fabricated. The synthesized samples were then subjected to gamma irradiation at different intensities, and the effects of radiation on the structural, electrical, and magnetic properties of the materials were examined. For this purpose, Bi‐2223 superconductors in the form of discs were produced and cut into two pieces. One piece was exposed to gamma radiation under high vacuum conditions. The phase analyzes of the materials were carried out by XRD. Then, electrical analysis of the materials was made by measuring resistance under a magnetic field.
Per aspera ad astra: The big challenge of consumers' insurance literacy
Authors: Cucinelli Doriana , Lippi Andrea , Soana Maria Gaia
Published: January 2021

This paper is a pioneering study on the determinants of customers' insurance knowledge in the Italian market. The analysis considers differences between life and non‐life insurance. Our findings show that socio‐economic variables (specifically family income and financial fragility) and financial literacy play a fundamental role in explaining consumers' insurance knowledge. This result is confirmed for both life and non‐life insurance. Among socio‐demographic factors, gender, the number of children under 18 and the level of education are determinants of global insurance knowledge. However, distinguishing between life and non‐life insurance knowledge, we find the level of education affects the former, while gender and age influence the latter.
Trimester‐specific thromboelastic values and coagulation activation markers in pregnancy compared across trimesters and compared to the nonpregnant state
Authors: Shamshirsaz Amir A. , Fox Karin A. , Erfani Hadi , Bruzdoski Karen , Kostousov Vadim , Clark Steven L. , Hensch Lisa , Hui Shiu‐Ki (Rocky) , Teruya Jun
Published: January 2021

Introduction

Rotational thromboelastometry (ROTEM) rapidly identifies deficits underlying coagulopathy during massive hemorrhage. Prompt coagulopathy correction is balanced with the risk of blood product overutilization, making the ability to quickly target therapy highly desirable. However, data about ROTEM reference ranges in pregnancy are limited. We hypothesized that ROTEM parameters change across trimesters of pregnancy and differ from the nonpregnant state. Also, we sought to identify which hemostatic test best predicts coagulation activation during pregnancy.

Methods

A prospective cohort study in healthy pregnant patients in the first (n = 34), second (n = 34), and third trimesters (n = 41) against healthy, nonpregnant controls (n = 33) was performed. Citrated blood was collected, and ROTEM, complete blood count, and plasma‐based assays of coagulation were performed. Mean ± SD or median [IQR] were compared across trimesters and between each trimester against the nonpregnant state. ROTEM parameters vs. plasma‐based assays were also compared.

Results

Maximum clot firmness and A10 in FIBTEM correlated strongly with fibrinogen level. INTEM and EXTEM values demonstrated only weak to modest correlation with corresponding tests using plasma assays. Thrombin antithrombin complex (TAT) increased from the first trimester onward, whereas other coagulation activation markers did not show difference compared with control group.

Conclusion

Rotational thromboelastometry parameters differ variably across trimesters of pregnancy and compared with the nonpregnant state. The development and use of pregnancy‐specific values are critical to the proper clinical interpretation of ROTEM in women with serious hemorrhage during different stages in pregnancy. TAT was the earliest laboratory marker for coagulation activation among others.
Gestational weight gain and childhood body mass index across three generations: Results from the 1993 Pelotas (Brazil) Birth Cohort
Authors: Schneider Bruna C. , Menezes Ana M. B. , Wehrmeister Fernando C. , Gonçalves Helen
Published: January 2021

Background

Gestational weight gain (GWG) has been associated with the accumulation of body fat in offspring, but little is known about the intergenerational relationship.

Objective

To assess the effect of GWG in grandmothers and mothers on the child's body mass index (BMI).

Methods

This is a sub‐study nested in the 1993 Pelotas (Brazil) Birth Cohort at 22 years follow‐up visit. We calculated the BMI‐for‐age z‐score (BAZ) and evaluated overweight (>2 SD in ≤5 years of age and >1 SD for >5 years of age for BAZ). Grandmothers' and mothers' GWG were calculated as the difference between weight in the beginning of pregnancy and the last recorded weight before delivery. We standardized the GWG by adjusting for pre‐gestational BMI. We also categorized GWG as adequate, excessive, or insufficient, in accordance with the Institute of Medicine (2009). Linear and logistic regressions stratified by child's age (≤2 years; 2.01‐5 years; >5 years) were used. Structural equations were modelled to calculate the total, indirect, and direct effects of grandmothers' and mothers' GWG on children's BAZ.

Results

Nine hundred and forty‐six out of 1113 children evaluated were 5 years of age or under. There was an indirect effect (through maternal birthweight, maternal pre‐gestational BMI, maternal GWG, and child birthweight) of grandmother GWG on grandchild BAZ, from 2.01 to 5 years of age [β = 0.12 95%CI: 0.04‐0.20 (P < 0.01)]. Maternal GWG directly increased the child's BAZ at >5 years of age [β = 0.34 95%CI: 0.15‐0.53 (P < 0.001)].

Conclusions

GWG's effect on BMI does seem to be transmitted across three generations. Managing this will require health education during the gestational period for women and their families.
PACT: A protocol for assessment, mechanism‐based case formulation and treatment planning
Authors: Hagmayer York , Witteman Cilia , Claes Laurence
Published: January 2021

Background

Proponents of clinical case formulations argue that the causes and mechanisms contributing to and maintaining a patient's problems should be analysed and integrated into a case conceptualization, on which treatment planning ought to be based. Empirical evidence shows that an individualized treatment based on a case formulation is at least sometimes better than a standardized evidence‐based treatment.

Methods

We argue that it is likely to improve decisions when two conditions hold: (a) knowing about the mechanisms underlying the patient's problems makes a difference for treatment, and (b) the case formulation is based on valid knowledge about mechanisms of psychopathology.

Results

We propose a protocol for assessment, case formulation and treatment planning (PACT), which incorporates transdiagnostic accounts of psychopathology. PACT describes a 5‐step decision making process, which aims to help clinicians to decide when to resort to evidence‐based treatments and when to construct a case formulation to individualize the treatment.

Conclusion

We show how PACT works in practice by discussing treatment planning for a clinical case involving symptoms of social anxiety, depression and post‐traumatic stress disorder.
Envisioning a community‐centric approach to impact assessments in subsistence marketplaces
Authors: Venugopal Srinivas
Published: January 2021

What does a community‐centric approach to impact assessment look like? That is the central question addressed in this article. Our community‐centric perspective provides an alternative to discipline‐centric approaches to impact assessment that emphasize specific methodological gold‐standards (e.g., randomized controlled trials [RCTs] in development economics). Disciplinary approaches to impact assessment owe their principal allegiance to the discipline's knowledge‐creation norms. Consequently, the concerns, interests, and voices of community members are not fully captured in the impact assessment process. In this article, we flip the conventional perspective to offer a community‐centric view of impact assessment that places the concerns, interests and voices of community members front and center. We present the case for why we need a community‐centric approach to impact assessment and clarify its axiological content, theoretical perspective, and methodological stance. Specifically, we advocate for a relational axiology, a system‐theoretic perspective, and a phenomenological methodology.
Outcomes of a walking exercise intervention in postpartum women with disordered sleep
Authors: Liu Yu‐Hsiang , Chang Ching‐Feng , Hung Hsuan‐Man , Chen Chung‐Hey
Published: January 2021

Aim

Good sleep quality is essential to physical and mental‐health‐related quality of life. The purpose of this study was to evaluate the effects of a walking exercise in relieving sleep quality, fatigue, and depression in new mothers during the postpartum period.

Methods

This quasi‐experimental study was conducted at a teaching hospital in southern Taiwan. One hundred and four eligible postpartum women with poor sleep quality (Postpartum Sleep Quality Scale; PSQS score ≧16) were assigned to either the experimental group (n= 50) or the control group (n= 54) according to their individual preferences. The participants in the experimental group participated in a 12‐week stride walking exercise intervention. The control group did not receive any exercise intervention. The PSQS, Postpartum Fatigue Scale, and Edinburgh Postnatal Depression Scale were used to assess outcomes.

Results

Repeated measures ANOVA demonstrated that the experimental group participants perceived milder physical symptoms associated with sleep inefficiency at 4‐week posttest (F= 7.25,p < 0.01) than their control group peers. However, no significant differences were found between two groups in terms of either fatigue or depression at 4‐week and 12‐week posttest.

Conclusion

Significant improvement in the physical symptoms associated with sleep inefficiency was observed. The findings may be used to encourage postpartum women with disordered sleep to incorporate 20–30 min of stride walking into their regular routine to improve sleep quality.
Cost analysis of four types of surgeries for pelvic organ prolapse in a Japanese population
Authors: Myoga Mai , Sho Tomoko , Aoki Hitomi , Ishizuka Takaki , Nakajima Daisuke , Yoshimura Kazuaki
Published: January 2021

Introduction and Hypothesis

To compare the perioperative costs analysis between laparoscopic/transvaginal and the mesh/non–mesh surgeries for pelvic organ prolapse (POP) in Japan.

Materials and Methods

From April 2013 to April 2017, 890 patients who underwent POP surgeries were enrolled in this study. Regarding transvaginal native tissue repair (TV‐NTR: transvaginal hysterectomy with colpocleisis), transvaginal mesh surgery (TVM), laparoscopic native tissue repair (L‐NTR: laparoscopic hysterectomy and uterosacral ligament colposuspension), and laparoscopic sacrocolpopexy (LSC), a retrospective observational study was performed. Patients' age, operation time, blood loss, perioperative complications, length of hospital stay, pre‐/postoperative quality of life (QOL) scores, were reviewed from the medical records. The net income, which was calculated by using the income (the operation/anesthesia fee) and the costs (the labor and consumables costs for operation/anesthesia), was evaluated.

Results

The operation fees of the L‐NTR ($4250) and the LSC ($4833) groups were higher than that of the TV‐NTR ($2652) and the TVM ($2913) groups. The labor costs and consumables costs of operation were higher in the LSC ($1589) and the L‐NTR ($1500) groups than the TV‐NTR ($180) and the TVM ($178) groups. The consumables costs for anesthesia in the four groups were equal. The operation hours were significantly shorter in the TV‐NTR and the TVM groups than the L‐NTR and the LSC groups.

Conclusions

We found that TVM operation was an economically excellent and the most efficient POP operation with shorter operation time and less consumables.
Red light imaging for programmed cell death visualization and quantification in plant–pathogen interactions
Authors: Landeo Villanueva Sergio , Malvestiti Michele C. , van Ieperen Wim , Joosten Matthieu H. A. J. , van Kan Jan A. L.
Published: January 2021

Studies on plant–pathogen interactions often involve monitoring disease symptoms or responses of the host plant to pathogen‐derived immunogenic patterns, either visually or by staining the plant tissue. Both these methods have limitations with respect to resolution, reproducibility, and the ability to quantify the results. In this study we show that red light detection by the red fluorescent protein (RFP) channel of a multipurpose fluorescence imaging system that is probably available in many laboratories can be used to visualize plant tissue undergoing cell death. Red light emission is the result of chlorophyll fluorescence on thylakoid membrane disassembly during the development of a programmed cell death process. The activation of programmed cell death can occur during either a hypersensitive response to a biotrophic pathogen or an apoptotic cell death triggered by a necrotrophic pathogen. Quantifying the intensity of the red light signal enables the magnitude of programmed cell death to be evaluated and provides a readout of the plant immune response in a faster, safer, and nondestructive manner when compared to previously developed chemical staining methodologies. This application can be implemented to screen for differences in symptom severity in plant–pathogen interactions, and to visualize and quantify in a more sensitive and objective manner the intensity of the plant response on perception of a given immunological pattern. We illustrate the utility and versatility of the method using diverse immunogenic patterns and pathogens.