bluuebunny/crossref_metadata_2025 huggingface dataset:
Potentials and perspectives of food self-sufficiency in urban areas—a case study from Leipzig
Authors: Rüschhoff Judith , Hubatsch Carl , Priess Jörg , Scholten Thomas , Egli Lukas
Published: November 2021

Regionalization of food systems is a potential strategy to support environmental, economic and social sustainability. However, local preconditions need to be considered to assess the feasibility of such a transformation process. To better understand the potentials and perspectives of food self-sufficiency in urban and peri-urban areas, we determined the food self-sufficiency level (SSL) of a German metropolitan region, i.e., the percentage of the food demand that could be potentially provided on existing agricultural land. Main input parameters were actual food demand, agricultural productivity and its temporal variability and land availability. Furthermore, we considered changes in diet, food losses and land management. Based on current diets and agricultural productivity, the administrative region of Leipzig achieved a mean SSL of 94%, ranging from 77 to 116%. Additionally, an area of 26,932 ha, representing 12% of the regionally available agricultural land, was needed for commodities that are not cultivated regionally. Changes in food demand due to a diet shift to a more plant-based diet and reduced food losses would increase the SSL by 29 and 17%, respectively. A shift to organic agriculture would decrease the SSL by 34% due to lower crop yields compared with conventional production. However, a combination of organic agriculture with less food loss and a more plant-based diet would lead to a mean SSL of 95% (75–115%). Our results indicate the feasibility of food system regionalization in the study area under current and potential near future conditions. Addressing a combination of multiple dimensions, for example plant-based and healthier diets combined with reduced food loss and organic farming, is the most favorable approach to increase food self-sufficiency in urban and peri-urban areas and simultaneously provide synergies with social and environmental objectives.
Jus ex bello and international humanitarian law: States’ obligations when withdrawing from armed conflict
Authors: Strauch Paul , Walton Beatrice
Published: November 2021

This article considers the international legal obligations relevant to States when withdrawing from situations of armed conflict. While a growing literature has focused on precisely when armed conflicts come to a legal end, as well as obligations triggered by the cessation of active hostilities, comparatively little attention has been paid to the legal implications of withdrawals from armed conflict and the contours of the obligations relevant to States in doing so. Following in the wake of just war scholarship endeavouring to distil jus ex bello principles, this article examines States’ obligations when ending their participation in armed conflicts from the perspective of international humanitarian law (IHL). It shows that while it is generally understood that IHL ceases to apply at the end of armed conflict, this is in reality a significant simplification; a number of obligations actually endure. Such rules act as exceptions to the general temporal scope of IHL and continue to govern withdrawing States, in effect straddling the in bello and post bellum phases of armed conflict. The article then develops three key end-of-participation obligations: obligations governing detention and transfer of persons, obligations imposed by Article 1 common to the four Geneva Conventions, and obligations relating to accountability and the consequences of conflict.
Study of an Equatorward Detachment of Auroral Arc From the Oval Using Ground‐Space Observations and the BATS‐R‐US–CIMI Model
Authors: Yadav Sneha , Shiokawa K. , Oyama S. , Inaba Y. , Takahashi N. , Seki K. , Keika K. , Chang Tzu‐Fang , Tam S. W. Y. , Wang B.‐J. , Kazama Y. , Wang S.‐Y. , Asamura K. , Kasahara S. , Yokota S. , Hori T. , Kasaba Y. , Tsuchiya F. , Kumamoto A. , Shoji M. , Kasahara Y. , Matsuoka A. , Matsuda S. , Jun C.‐W. , Imajo S. , Miyoshi Y. , Shinohara I.
Published: November 2021

We present observations of an equatorward detachment of the auroral arc from the main oval and magnetically conjugate measurements made by the Arase satellite in the inner magnetosphere. The all‐sky imager at Gakona (magnetic latitude = 63.6°N), Alaska, shows the detachment of the auroral arc in both red and green lines at local midnight (∼0130–0230 MLT) on 30 March 2017. The electron density derived from the Arase in‐situ observations shows that this arc occurred outside the plasmapause. At the arc crossing, the electron flux of energies ∼0.1–2 keV is found to be locally enhanced at L∼4.3–4.5. We estimated auroral intensities for both red and green lines by using the Arase low‐energy (0.1–19 keV) electron flux data. The peak latitude of the estimated intensity shows reasonably good correspondence with the observed intensity mapped at the ionospheric footprints of the Arase satellite. These findings indicate that the observed arc detachment at Gakona was associated with the localized enhancement of low‐energy electrons (∼0.1–2 keV) at the inner edge of the electron plasma sheet. Further, we employ the simulation results of the Community Coordinated Modeling Center (CCMC), the BATS‐R‐US–CIMI 3‐D MHD code to understand the conditions in the inner magnetosphere around the time of detachment. Although the simulation could not reproduce the lower‐energy component responsible for the arc detachment, it successfully reproduced two earthward convection events at the lower radial distance (R) (R ≤ ∼4) around the time of arc detachment and the features of enhanced convection in similarity with the observations.
Sensitivity of Steady State, Deep Ocean Dissolved Organic Carbon to Surface Boundary Conditions
Authors: Matsumoto Katsumi , Tanioka Tatsuro , Gilchrist Maya
Published: November 2021

We use the transport matrices of a data‐constrained circulation model to efficiently compute the steady state distribution of the deep ocean dissolved organic carbon (DOC) at a 1° horizontal resolution by propagating the surface DOC boundary conditions into the ocean interior. An equivalent simulation in the traditional forward modeling approach would be prohibitively computationally expensive. Our model simulates the total DOC as the sum of two DOC pools, the refractory and the semi‐labile. The model is able to simulate the large‐scale features of the deep ocean DOC without local sources or sinks of DOC in the ocean interior. The deep ocean DOC in the model is sensitive to the preformed DOC concentrations in the formation sites of deep and bottom waters, where observations are lacking. Furthermore, our model experiments indicate that the deep Atlantic DOC gradient is sensitive to the mixing of deep waters with different concentrations of preformed refractory DOC, the transport of semi‐labile DOC from the surface North Atlantic, and the decay rate of semi‐labile DOC. These, combined with the observation that much of the deep ocean DOC gradient is in the Atlantic, suggests that the semi‐labile DOC may be an important component of the deep Atlantic DOC. Finally, we show that DOC export depends substantially on the depth level where it is evaluated.
The Spectrum of Slip Behaviors of a Granular Fault Gouge Analogue Governed by Rate and State Friction
Authors: Rudolf M. , Rosenau M. , Oncken O.
Published: November 2021

Currently, it is unknown how seismic and aseismic slip influences the recurrence and magnitude of earthquakes. Modern seismic hazard assessment is therefore based on statistics combined with numerical simulations of fault slip and stress transfer. To improve the underlying statistical models we conduct low velocity shear experiments with glass micro‐beads as fault gouge analogue at confining stresses of 5–20 kPa. As a result, we show that characteristic slip events emerge, ranging from fast and large slip to small scale oscillating creep and stable sliding. In particular, we observe small scale slip events that occur immediately before large scale slip events for a specific set of experiments. Similar to natural faults we find a separation of scales by several orders of magnitude for slow events and fast events. Enhanced creep and transient dilatational events pinpoint that the granular analogue is close to failure. From slide‐hold‐slide tests, we find that the rate‐and‐state properties are in the same range as estimates for natural faults and fault rocks. The fault shows velocity weakening characteristics with a reduction of frictional strength between 0.8% and 1.3% per e‐fold increase in sliding velocity. Furthermore, the slip modes that are observed in the normal shear experiments are in good agreement with analytical solutions. Our findings highlight the influence of micromechanical processes on macroscopic fault behavior. The comprehensive data set associated with this study can act as a benchmark for numerical simulations and improve the understanding of observations of natural faults.
Study of Substorm‐Related Auroral Absorption: Latitudinal Width and Factors Affecting the Peak Intensity of Energetic Electron Precipitation
Authors: Nikolaev A. V. , Sergeev V. A. , Shukhtina M. A. , Spanswick E. , Rogov D. D. , Stepanov N. A.
Published: November 2021

Previously, suggesting a scenario of “injected and drifting electron cloud” to describe the enhancements and precipitations of energetic electrons during substorms we used the linear prediction filter (LPF) method to build the empirical dynamical model of auroral absorption in the middle of auroral zone, driven by the midlatitude positive bay (MPB) index time series. In this paper, to understand better the relationship between magnetic dipolarization, injection, and energetic electron precipitation, we quantitatively explore correlations between dipolarization proxies (MPB and SML indices, substorm current wedge (SCW) intensity, location, and size) and precipitation‐related auroral absorption in the morning maximum region for 148 isolated substorms. We confirm good correlation of precipitation peak values with dipolarization proxies and show that the absorption amplitude is most strongly controlled by total SCW current and its azimuthal size, and is also influenced by solar wind‐dependent background energetic electron flux in the conjugate plasma sheet. This result confirms the adequacy of our starting assumption that there is a close relationship between the intensities and size of substorm dipolarizations and energetic particle injections. To extend the latitudinal coverage, we computed the LPF response functions for individual riometers of NORSTAR array. Finding similar shapes and amplitudes of their response at latitudes 63°–69° in the regions where maximal precipitation is statistically observed, we suggest, test, and approve that the auroral absorption in the belt 63°–69° may be predicted using a set of LPFs determined empirically in the center of auroral zone for various magnetic local times.
Depth Dependent Focal Mechanisms of Volcanic Deep Low‐Frequency Earthquakes in Northeast Japan
Authors: Oikawa Genki , Aso Naofumi , Nakajima Junichi
Published: November 2021

Deep low‐frequency earthquakes (LFEs) in Northeast Japan occur beneath active volcanoes at depths of 10–40 km. These volcanic LFEs radiate low‐frequency seismic waves, with most energy at 2–8 Hz, despite their low magnitudes (M < 2). Although many previous studies have obtained various focal mechanisms with non‐double‐couple components and suggested physical processes related to magma, the universal physical process is poorly understood. Therefore, we comprehensively determined the focal mechanisms of 264 LFEs for 26 volcanic regions in Northeast Japan usingS/Pamplitude ratios. Many of the obtained solutions have large double‐couple components with small compensated linear vector dipole components. Such source mechanisms can be explained by shear slip on the bending fault. We observed that the plunge of the null axis is as small as 20–30º at depths of 15–25 km, whereas it becomes larger and more varied at depths of 25–35 km. We interpreted that the regional stress field is relatively homogeneous in the middle of the crust, whereas it may be altered near the Moho discontinuity due to thermal stress or other effects related to potential magmatic processes. In addition, after quantitatively investigating the possible triggering of LFEs due to static stress changes in both the 2008 Iwate‐Miyagi earthquake and the 2011 Tohoku earthquake, we concluded that LFEs might have been triggered by substantial stress changes caused by large earthquakes in some regions.
Using Dynamic Ocean Color Provinces to Elucidate Drivers of North Sea Hydrography and Ecology
Authors: Taylor Marc H. , Akimova Anna , Bracher Astrid , Kempf Alexander , Kühn Bernhard , Hélaouët Pierre
Published: November 2021

Ocean biogeochemical provinces have historically been used to characterize regions of similar biogeography, allowing for large‐scale comparisons and the definition of possible management units. Recent studies have shown that ocean color (OC) may be used as a proxy for a range of physical and biological parameters, allowing for a more direct approach in defining and monitoring provinces. The current work investigates whether OC‐derived provinces (area of a given OC type) can be identified in the North Sea and if they can provide insight into the system's dynamics. The analysis workflow was organized into three main steps: 1. OC type classification based on clustering of normalized reflectance spectra, 2. OC type characterization following match‐ups to other biological and physical covariates, and 3. Exploration of drivers of OC province dynamics. Based on data from 1997–2019, four main OC types were identified, which are shown to be related to bio‐optical, physical, and zooplankton community covariates. Atlantic‐associated OC types varied in their coverage of the North Sea on seasonal and interannual scales, with increased penetration related to periods of a weakened circulation. Interannual variability of OC province extent was also found to correlate with an index of the Subpolar Gyre. These results indicate that the dynamics of OC provinces in the North Sea are likely driven by the interaction between large‐scale circulation and local wind‐driven and baroclinic currents. The perspective offered by OC provinces helps elucidate spatiotemporal patterns of plankton and is proposed as a novel operational index for additional exploration of ecosystem functioning.
Characteristics of Raindrop Size Distributions in Chongqing Observed by a Dense Network of Disdrometers
Authors: Liu Xuancheng , Xue Lulin , Chen Baojun , Zhang Yixuan
Published: November 2021

This study investigates the characteristics of raindrop size distribution (RSD) including the temporal and spatial variabilities and the summer rain RSD features using 34 Parsivel disdrometers data from Jan. 2015 to Jan. 2016 in Chongqing, an inland municipality in Southwest China. The observed RSDs are fitted with the gamma distribution (N(D) = N0Dμe−λD) in this study. Rainfall in summer differs greatly from winter with larger rain rate, rain water content and variabilities. From winter to summer, raindrop sizes increase as the frequency of convective rain increases, and the diurnal variabilities of raindrop sizes are greatly enlarged. The spatial variabilities of N0, λ and μ are relatively weak and change little in summer. The summer rainfall RSD characteristics and parameter relationships in Chongqing are different from other regions (Nanjing, Beijing, Zhuhai and Daocheng) in China. A novel diagnosed relation between the shape parameter of the gamma distribution (μ) and the mean volume diameter (Dv) is proposed based on the large amount of observations, which allows for a wider range of the mean volume diameter of raindrops compared to traditional μ − λ relations in microphysics parameterizations.
ENSO and SAM Influence on the Generation of Long Episodes of Rossby Wave Packets During Southern Hemisphere Summer
Authors: Pérez Iago , Barreiro Marcelo , Masoller Cristina
Published: November 2021

This study assesses the impact of low‐frequency climate modes on Rossby Wave Packets (RWPs) during southern hemisphere summer. In particular, we focus on long‐lived RWPs (lifespan above 8 days) and determine how El Niño‐Southern Oscillation (ENSO) and the Southern Annular Mode (SAM) influence their statistics, that is, their duration, frequency of occurrence, and activity areas. We used daily mean meridional winds at 300 hPa from December to March between 1979 and 2020 from the ERA5 and NCEP‐DOE 2 reanalyses. We found that long‐lived wave packets, which are a small percentage of the total number of wave packets, show large interannual variability; there are years in which these types of waves do not occur and years that present up to 9 wave packets. This suggests that large‐scale circulation conditions set up by low‐frequency climate modes can modulate their occurrence. Classifying years according to SAM phases reveals that the occurrence of long‐lived RWPs is highest (lowest) during intense negative (positive) SAM events. ENSO influence, on the other hand, was found to be weak and not robust. Analysis of large scale circulation conditions shows that during negative SAM phases the jet shifts northward, strengthens in the Indian sector, and extends further into the Pacific basin, so that it acts as a better waveguide favoring the propagation of long‐lived RWPs. Conversely, during positive phases of SAM, the jet shifts southward and an anticyclonic center develops to the southwest of Australia blocking the jet and the progression of the wave packets.
Regional Patterns in Miocene‐Pliocene Aridity Across the Chinese Loess Plateau Revealed by High Resolution Records of Paleosol Carbonate and Occluded Organic Matter
Authors: Gallagher Timothy M. , Serach Lily , Sekhon Natasha , Zhang Hanzhi , Wang Hanlin , Ji Shunchuan , Chang Xi , Lu Huayu , Breecker Daniel O.
Published: November 2021

Paleosols preserved in the Red Clay depositional sequence of the Chinese Loess Plateau record information about vegetation and regional hydrology responses to global temperature variation throughout the late Miocene and Pliocene. Reconstructing spatial and temporal patterns of environmental change across the Loess Plateau from carbon isotopes of pedogenic carbonate (δ13Ccarb) is complicated because multiple factors affect δ13Ccarb values and higher resolution records do not exist along the northern margin of the Loess Plateau. To address these needs, we present paired carbon isotope records of pedogenic carbonate and occluded organic matter (δ13Corg) from 697 discrete nodules sampled from 119 different depths at the Jiaxian section, North Central China. Between 7.6 and 2.4 Ma, δ13Ccarb values increase by nearly 5‰, while δ13Corg values increase by 2.5‰. These increases are explained by a progressive decline in moisture availability through time, and there is no definitive evidence from these δ13C data for C4 vegetation at the Jiaxian site until after 3.6 Ma. Comparison of the Jiaxian record to other Loess Plateau sections reveals a consistent spatial gradient with δ13Ccarb values becoming higher and more variable to the N‐NW. Additionally, an independent index of monsoonal precipitation from a southern site corresponds to fluctuations in δ13Ccarb values at Jiaxian, while southern δ13Ccarb records remain more stable. These spatial patterns are explained by a progressive decline in moisture availability across the Loess Plateau through the Late Miocene and Pliocene, with δ13Ccarb values being more sensitive to moisture availability under consistently more arid conditions to the NW.
Poleward Shift in Tropical Cyclone Tracks in the Northwest Pacific During Warm Periods: Past and Future
Authors: Tao Shichen , Liu Kam‐biu , Yu Kefu , Shi Qi , Yan Hongqiang , Zhang Huiling , Wang Luo , Huang Zhongzhou , Chen Tegu
Published: November 2021

We used the top age of storm‐relocated coral blocks (SRCBs) from Xisha Islands and Huangyan Island, South China Sea (SCS), in combination with existing paleotempestology records and instrumental climatic data, to reconstruct the spatio‐temporal changes in tropical cyclone (TC) activity over the past millennium, and to project its future trends in the Northwestern Pacific region. We found a positive correlation between the frequencies of TCs, typhoons, and super‐typhoons and the NINO3.4 on the interannual timescale during 1945–2019. TCs latitude has a significant positive correlation with sea surface temperature, with a northward migration rate of 80 ± 11 km per decade during 1951–2019. Coral δ18O can well indicate the month of paleo‐TCs occurrence. The frequency of SRCBs (and by inference, TCs) is relatively low during relatively warm periods (RWP) but high during relatively cold periods (RCP) in the SCS. The spatio‐temporal pattern inferred from paleotempestology records further supports the notion of North‐South migration in TC activity as revealed by the instrumental record in this study. TC activity mainly affected relatively low latitudes (e.g., Philippines, Vietnam, and Hainan, Guangdong, Taiwan) during the RCP (AD 1450–1900), but it migrated from low latitudes towards higher latitudes during the RWP (AD 1000–1450), affecting locations such as Zhejiang, Jiangsu, and Shandong, southwestern Japan, the Korean Peninsula, and even Northeast China. Fujian and northern Guangdong may be in a transition zone of paleo‐TC activity between the North and the South in the past millennium. As global warming continues, the mean tracks and landfall locations of TCs will continue to migrate northward in this region.
Assessing the prognostic utility of smoldering multiple myeloma risk stratification scores applied serially post diagnosis
Authors: Visram Alissa , Rajkumar S. Vincent , Kapoor Prashant , Dispenzieri Angela , Lacy Martha Q. , Gertz Morie A. , Buadi Francis K. , Hayman Suzanne R. , Dingli David , Kourelis Taxiarchis , Gonsalves Wilson , Warsame Rahma , Muchtar Eli , Leung Nelson , Baughn Linda B. , Kyle Robert A. , Kumar Shaji
Published: November 2021

The Mayo-2018 smoldering multiple myeloma (SMM) risk score is used routinely in the clinical setting but has only been validated at diagnosis. In SMM patients, the progression risk decreases over time. However, the utility of applying risk stratification models after diagnosis is unknown. We retrospectively studied 704 SMM patients and applied the Mayo 2018 and IMWG-2020 risk stratification models at annual landmark timepoints up to 5 years post diagnosis. The Mayo-2018 and IMWG-2020 models reliably stratified patients based on progression risk when applied post diagnosis. The respective 2-year progression risk in Mayo-2018 high risk patients versus IMWG-2020 intermediate-high risk patients was 51% versus 62% at the 1-year landmark and 47% versus 45% at the 4-year landmark. We showed that patients categorized at Mayo-2018 high-risk at follow-up had a similar risk of progression if the baseline risk assessment was low-intermediate versus high-risk (HR 1.04, 95% CI 0.46–2.36, p = 0.931 at 5-year landmark). Patients migrating to a higher risk category during follow up had a higher progression risk compared to patients with stable/decreased risk categorization. Our findings support the use of these risk scores post-diagnosis and suggest that patients evolving to a high-risk category may benefit from early intervention therapeutic approaches.
Benefits and harms of annual, biennial, or triennial breast cancer mammography screening for women at average risk of breast cancer: a systematic review for the European Commission Initiative on Breast Cancer (ECIBC)
Authors: Canelo-Aybar Carlos , Posso Margarita , Montero Nadia , Solà Ivan , Saz-Parkinson Zuleika , Duffy Stephen W. , Follmann Markus , Gräwingholt Axel , Giorgi Rossi Paolo , Alonso-Coello Pablo
Published: November 2021

Background

Although mammography screening is recommended in most European countries, the balance between the benefits and harms of different screening intervals is still a matter of debate. This review informed the European Commission Initiative on Breast Cancer (BC) recommendations.

Methods

We searched PubMed, EMBASE, and the Cochrane Library to identify RCTs, observational or modelling studies, comparing desirable (BC deaths averted, QALYs, BC stage, interval cancer) and undesirable (overdiagnosis, false positive related, radiation related) effects from annual, biennial, or triennial mammography screening in women of average risk for BC. We assessed the certainty of the evidence using the GRADE approach.

Results

We included one RCT, 13 observational, and 11 modelling studies. In women 50–69, annual compared to biennial screening may have small additional benefits but an important increase in false positive results; triennial compared to biennial screening may have smaller benefits while avoiding some harms. In younger women (aged 45–49), annual compared to biennial screening had a smaller gain in benefits and larger harms, showing a less favourable balance in this age group than in women 50–69. In women 70–74, there were fewer additional harms and similar benefits with shorter screening intervals. The overall certainty of the evidence for each of these comparisons was very low.

Conclusions

In women of average BC risk, screening intervals have different trade-offs for each age group. The balance probably favours biennial screening in women 50–69. In younger women, annual screening may have a less favourable balance, while in women aged 70–74 years longer screening intervals may be more favourable.
Genomic analysis of childhood hearing loss in the Yoruba population of Nigeria
Authors: Adeyemo Adebolajo , Faridi Rabia , Chattaraj Parna , Yousaf Rizwan , Tona Risa , Okorie Samuel , Bharadwaj Thashi , Nouel-Saied Liz M. , Acharya Anushree , Schrauwen Isabelle , Morell Robert J. , Leal Suzanne M. , Friedman Thomas B. , Griffith Andrew J. , Roux Isabelle
Published: November 2021

Although variant alleles of hundreds of genes are associated with sensorineural deafness in children, the genes and alleles involved remain largely unknown in the Sub-Saharan regions of Africa. We ascertained 56 small families mainly of Yoruba ethno-lingual ancestry in or near Ibadan, Nigeria, that had at least one individual with nonsyndromic, severe-to-profound, prelingual-onset, bilateral hearing loss not attributed to nongenetic factors. We performed a combination of exome and Sanger sequencing analyses to evaluate both nuclear and mitochondrial genomes. No biallelic pathogenic variants were identified in GJB2, a common cause of deafness in many populations. Potential causative variants were identified in genes associated with nonsyndromic hearing loss (CIB2, COL11A1, ILDR1, MYO15A, TMPRSS3, and WFS1), nonsyndromic hearing loss or Usher syndrome (CDH23, MYO7A, PCDH15, and USH2A), and other syndromic forms of hearing loss (CHD7, OPA1, and SPTLC1). Several rare mitochondrial variants, including m.1555A>G, were detected in the gene MT-RNR1 but not in control Yoruba samples. Overall, 20 (33%) of 60 independent cases of hearing loss in this cohort of families were associated with likely causal variants in genes reported to underlie deafness in other populations. None of these likely causal variants were present in more than one family, most were detected as compound heterozygotes, and 77% had not been previously associated with hearing loss. These results indicate an unusually high level of genetic heterogeneity of hearing loss in Ibadan, Nigeria and point to challenges for molecular genetic screening, counseling, and early intervention in this population.
Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis
Authors: Yip Raymond K. H. , Rimes Joel S. , Capaldo Bianca D. , Vaillant François , Mouchemore Kellie A. , Pal Bhupinder , Chen Yunshun , Surgenor Elliot , Murphy Andrew J. , Anderson Robin L. , Smyth Gordon K. , Lindeman Geoffrey J. , Hawkins Edwin D. , Visvader Jane E.
Published: November 2021

Bone marrow is a preferred metastatic site for multiple solid tumours and is associated with poor prognosis and significant morbidity. Accumulating evidence indicates that cancer cells colonise specialised niches within the bone marrow to support their long-term propagation, but the precise location and mechanisms that mediate niche interactions are unknown. Using breast cancer as a model of solid tumour metastasis to the bone marrow, we applied large-scale quantitative three-dimensional imaging to characterise temporal changes in the bone marrow microenvironment during disease progression. We show that mouse mammary tumour cells preferentially home to a pre-existing metaphyseal domain enriched for type H vessels. Metastatic lesion outgrowth rapidly remodelled the local vasculature through extensive sprouting to establish a tumour-supportive microenvironment. The evolution of this tumour microenvironment reflects direct remodelling of the vascular endothelium through tumour-derived granulocyte-colony stimulating factor (G-CSF) in a hematopoietic cell-independent manner. Therapeutic targeting of the metastatic niche by blocking G-CSF receptor inhibited pathological blood vessel remodelling and reduced bone metastasis burden. These findings elucidate a mechanism of ‘host’ microenvironment hijacking by mammary tumour cells to subvert the local microvasculature to form a specialised, pro-tumorigenic niche.
The Chloranthus sessilifolius genome provides insight into early diversification of angiosperms
Authors: Ma Jianxiang , Sun Pengchuan , Wang Dandan , Wang Zhenyue , Yang Jiao , Li Ying , Mu Wenjie , Xu Renping , Wu Ying , Dong Congcong , Shrestha Nawal , Liu Jianquan , Yang Yongzhi
Published: November 2021

Most extant angiosperms belong to Mesangiospermae, which comprises eudicots, monocots, magnoliids, Chloranthales and Ceratophyllales. However, phylogenetic relationships between these five lineages remain unclear. Here, we report the high-quality genome of a member of the Chloranthales lineage (Chloranthus sessilifolius). We detect only one whole genome duplication within this species and find that polyploidization events in different Mesangiospermae lineage are mutually independent. We also find that the members of all floral development-related gene lineages are present in C. sessilifolius despite its extremely simplified flower. The AP1 and PI genes, however, show a weak floral tissue-specialized expression. Our phylogenomic analyses suggest that Chloranthales and magnoliids are sister groups, and both are together sister to the clade comprising Ceratophyllales and eudicots, while the monocot lineage is sister to all other Mesangiospermae. Our findings suggest that in addition to hybridization, incomplete lineage sorting may largely account for phylogenetic inconsistencies between the observed gene trees.
Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization
Authors: Lapuente Dennis , Fuchs Jana , Willar Jonas , Vieira Antão Ana , Eberlein Valentina , Uhlig Nadja , Issmail Leila , Schmidt Anna , Oltmanns Friederike , Peter Antonia Sophia , Mueller-Schmucker Sandra , Irrgang Pascal , Fraedrich Kirsten , Cara Andrea , Hoffmann Markus , Pöhlmann Stefan , Ensser Armin , Pertl Cordula , Willert Torsten , Thirion Christian , Grunwald Thomas , Überla Klaus , Tenbusch Matthias
Published: November 2021

Several effective SARS-CoV-2 vaccines are currently in use, but effective boosters are needed to maintain or increase immunity due to waning responses and the emergence of novel variants. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic plasmid DNA or mRNA priming result in systemic and mucosal immunity in mice. In contrast to two intramuscular applications of an mRNA vaccine, intranasal boosts with adenoviral vectors induce high levels of mucosal IgA and lung-resident memory T cells (TRM); mucosal neutralization of virus variants of concern is also enhanced. The mRNA prime provokes a comprehensive T cell response consisting of circulating and lung TRM after the boost, while the plasmid DNA prime induces mostly mucosal T cells. Concomitantly, the intranasal boost strategies lead to complete protection against a SARS-CoV-2 infection in mice. Our data thus suggest that mucosal booster immunizations after mRNA priming is a promising approach to establish mucosal immunity in addition to systemic responses.
CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease
Authors: Tsagkaraki Emmanouela , Nicoloro Sarah M. , DeSouza Tiffany , Solivan-Rivera Javier , Desai Anand , Lifshitz Lawrence M. , Shen Yuefei , Kelly Mark , Guilherme Adilson , Henriques Felipe , Amrani Nadia , Ibraheim Raed , Rodriguez Tomas C. , Luk Kevin , Maitland Stacy , Friedline Randall H. , Tauer Lauren , Hu Xiaodi , Kim Jason K. , Wolfe Scot A. , Sontheimer Erik J. , Corvera Silvia , Czech Michael P.
Published: November 2021

Obesity and type 2 diabetes are associated with disturbances in insulin-regulated glucose and lipid fluxes and severe comorbidities including cardiovascular disease and steatohepatitis. Whole body metabolism is regulated by lipid-storing white adipocytes as well as “brown” and “brite/beige” adipocytes that express thermogenic uncoupling protein 1 (UCP1) and secrete factors favorable to metabolic health. Implantation of brown fat into obese mice improves glucose tolerance, but translation to humans has been stymied by low abundance of primary human beige adipocytes. Here we apply methods to greatly expand human adipocyte progenitors from small samples of human subcutaneous adipose tissue and then disrupt the thermogenic suppressor gene NRIP1 by CRISPR. Ribonucleoprotein consisting of Cas9 and sgRNA delivered ex vivo are fully degraded by the human cells following high efficiency NRIP1 depletion without detectable off-target editing. Implantation of such CRISPR-enhanced human or mouse brown-like adipocytes into high fat diet fed mice decreases adiposity and liver triglycerides while enhancing glucose tolerance compared to implantation with unmodified adipocytes. These findings advance a therapeutic strategy to improve metabolic homeostasis through CRISPR-based genetic enhancement of human adipocytes without exposing the recipient to immunogenic Cas9 or delivery vectors.
Chronic nicotine increases midbrain dopamine neuron activity and biases individual strategies towards reduced exploration in mice
Authors: Dongelmans Malou , Durand-de Cuttoli Romain , Nguyen Claire , Come Maxime , Duranté Etienne K. , Lemoine Damien , Brito Raphaël , Ahmed Yahia Tarek , Mondoloni Sarah , Didienne Steve , Bousseyrol Elise , Hannesse Bernadette , Reynolds Lauren M. , Torquet Nicolas , Dalkara Deniz , Marti Fabio , Mourot Alexandre , Naudé Jérémie , Faure Philippe
Published: November 2021

Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related and unrelated to drug seeking and consumption. Using an intracranial self-stimulation reward-based foraging task, we investigated in mice the impact of chronic nicotine on midbrain dopamine neuron activity and its consequence on the trade-off between exploitation and exploration. Model-based and archetypal analysis revealed substantial inter-individual variability in decision-making strategies, with mice passively exposed to nicotine shifting toward a more exploitative profile compared to non-exposed animals. We then mimicked the effect of chronic nicotine on the tonic activity of dopamine neurons using optogenetics, and found that photo-stimulated mice adopted a behavioral phenotype similar to that of mice exposed to chronic nicotine. Our results reveal a key role of tonic midbrain dopamine in the exploration/exploitation trade-off and highlight a potential mechanism by which nicotine affects the exploration/exploitation balance and decision-making.
Population-specific brain [18F]-FDG PET templates of Chinese subjects for statistical parametric mapping
Authors: Wang Hongkai , Tian Yang , Liu Yang , Chen Zhaofeng , Zhai Haoyu , Zhuang Mingrui , Zhang Nan , Jiang Yuanfang , Gao Ya , Feng Hongbo , Zhang Yanjun
Published: November 2021

Statistical Parametric Mapping (SPM) is a computational approach for analysing functional brain images like Positron Emission Tomography (PET). When performing SPM analysis for different patient populations, brain PET template images representing population-specific brain morphometry and metabolism features are helpful. However, most currently available brain PET templates were constructed using the Caucasian data. To enrich the family of publicly available brain PET templates, we created Chinese-specific template images based on 116 [18F]-fluorodeoxyglucose ([18F]-FDG) PET images of normal participants. These images were warped into a common averaged space, in which the mean and standard deviation templates were both computed. We also developed the SPM analysis programmes to facilitate easy use of the templates. Our templates were validated through the SPM analysis of Alzheimer’s and Parkinson’s patient images. The resultant SPM t-maps accurately depicted the disease-related brain regions with abnormal [18F]-FDG uptake, proving the templates’ effectiveness in brain function impairment analysis.
A SARS-CoV-2 antigen rapid diagnostic test for resource limited settings
Authors: Frew Erica , Roberts Douglas , Barry Shelly , Holden Matthew , Restell Mand Amanda , Mitsock Emily , Tan Enqing , Yu Wei , Skog Johan
Published: November 2021

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 disease. RT-qPCR has been the primary method of diagnosis; however, the required infrastructure is lacking in many developing countries and the virus has remained a global challenge. More inexpensive and immediate test methods are required to facilitate local, regional, and national management strategies to re-open world economies. Here we have developed a SARS-CoV-2 antigen test in an inexpensive lateral flow format to generate a chromatographic result identifying the presence of the SARS-CoV-2 antigen, and thus an active infection, within a patient anterior nares swab sample. Our 15-min test requires no equipment or laboratory infrastructure to administer with a limit of detection of 2.0 × 102 TCID50/mL and 87.5% sensitivity, 100% specificity when tested against 40 known positive and 40 known negative patient samples established by a validated RT-qPCR test.
Droplet-based microfluidics platform for antifungal analysis against filamentous fungi
Authors: Iftikhar Sehrish , Vigne Aurélie , Sepulveda-Diaz Julia Elisa
Published: November 2021

Fungicides are extensively used in agriculture to control fungal pathogens which are responsible for significant economic impact on plant yield and quality. The conventional antifungal screening techniques, such as water agar and 96-well plates, are based on laborious protocols and bulk analysis, restricting the analysis at the single spore level and are time consuming. In this study, we present a droplet-based microfluidic platform that enables antifungal analysis of single spores of filamentous fungus Alternaria alternata. A droplet-based viability assay was developed, allowing the germination and hyphal growth of single A. alternata spores within droplets. The viability was demonstrated over a period of 24 h and the antifungal screening was achieved using Kunshi/Tezuma as antifungal agent. The efficacy results of the droplet-based antifungal analysis were compared and validated with the results obtained from conventional protocols. The percentage inhibitions assessed by the droplet-based platform were equivalent with those obtained by the other two methods, and the Pearson correlation analysis showed high correlation between the three assays. Taken together, this droplet-based microfluidic platform provides a wide range of potential applications for the analysis of fungicide resistance development as well as combinatorial screening of other antimicrobial agents and even antagonistic fungi.
Oxide nanowire microfluidics addressing previously-unattainable analytical methods for biomolecules towards liquid biopsy
Authors: Takahashi Hiromi , Baba Yoshinobu , Yasui Takao
Published: November 2021

Nanowire microfluidics using a combination of self-assembly and nanofabrication technologies is expected to provide bioanalytical methods for liquid biopsy, which are impossible to achieve with conventional technologies.
Electronic and optical properties of hydrogen-terminated biphenylene nanoribbons: a first-principles study
Authors: Shen Hong , Yang Riyi , Xie Kun , Yu Zhiyuan , Zheng Yuxiang , Zhang Rongjun , Chen Liangyao , Wu Bi-Ru , Su Wan-Sheng , Wang Songyou
Published: November 2021

Pristine biphenylene exhibits metallic properties. However, for 1D nanoribbons, a direct–indirect transition occurs in the band gap as the width increases, transforming the nanoribbons to endow them with metallic characteristics at a certain width.
Free-standing lamellar 3D architectures assembled from chitosan as a reusable titanium-immobilized affinity membrane for efficiently capturing phosphopeptides
Authors: Pan Lei , Ma Shujuan , Tang Ruizhi , Wu Wenrui , Ou Junjie , Li Cong , Shen Yehua
Published: November 2021

A series of Ti4+-chitosan membranes containing pyrogallol groups were fabricated and reused for the enrichment of phosphopeptides in biological samples, offering an inspiration to construct more sustainable materials.
Correction: Truncated S-MGBs: towards a parasite-specific and low aggregation chemotype
Authors: Brooke Daniel P. , McGee Leah M. C. , Giordani Federica , Cross Jasmine M. , Khalaf Abedawn I. , Irving Craig , Gillingwater Kirsten , Shaw Craig D. , Carter Katharine C. , Barrett Michael P. , Suckling Colin J. , Scott Fraser J.
Published: November 2021

Correction for ‘Truncated S-MGBs: towards a parasite-specific and low aggregation chemotype’ by Daniel P. Brooke et al., RSC Med. Chem., 2021, 12, 1391–1401, DOI: 10.1039/D1MD00110H.
Conformation-dependent antioxidant properties of β-carotene
Authors: Sandhiya L. , Zipse H.
Published: November 2021

The antioxidant capacity of β-carotene has been studied in terms of H-atom abstraction reactions using quantum chemical methods.
Understanding Cu(ii)-based systems for C(sp3)–H bond functionalization: insights into the synthesis of aza-heterocycles
Authors: Camats Marc , Favier Isabelle , Mallet-Ladeira Sonia , Pla Daniel , Gómez Montserrat
Published: November 2021

Carboxylate-assisted Cu(ii)-catalyzed relay towards the synthesis of imidazo[1,5-a]pyridines encompassing C(sp3)–H amination and cyclization of aldimines followed by C(sp2)–H cyanation, is reported.
Porphyrin-based donor–acceptor COFs as efficient and reusable photocatalysts for PET-RAFT polymerization under broad spectrum excitation
Authors: Zhu Yifan , Zhu Dongyang , Chen Yu , Yan Qianqian , Liu Chun-Yen , Ling Kexin , Liu Yifeng , Lee Dongjoo , Wu Xiaowei , Senftle Thomas P. , Verduzco Rafael
Published: November 2021

Porphyrin-based donor–acceptor COFs are effective heterogeneous photocatalysts for photoinduced electron transfer-reversible addition–fragmentation chain transfer (PET-RAFT), including for aqueous polymerizations and under red-light excitation.
Convergence of nonlinear numerical approximations for an elliptic linear problem with irregular data
Authors: Eymard Robert , Maltese David
Published: November 2021

This work is devoted to the study of the approximation, using two nonlinear numerical methods, of a linear elliptic problem with measure data and heterogeneous anisotropic diffusion matrix. Both methods show convergence properties to a continuous solution of the problem in a weak sense, through the change of variable u = ψ(v), where ψ is a well chosen diffeomorphism between (−1, 1) and ℝ, and v is valued in (−1, 1). We first study a nonlinear finite element approximation on any simplicial grid. We prove the existence of a discrete solution, and, under standard regularity conditions, we prove its convergence to a weak solution of the problem by applying Hölder and Sobolev inequalities. Some numerical results, in 2D and 3D cases where the solution does not belong to H1 (Ω), show that this method can provide accurate results. We then construct a numerical scheme which presents a convergence property to the entropy weak solution of the problem in the case where the right-hand side belongs to L1. This is achieved owing to a nonlinear control volume finite element (CVFE) method, keeping the same nonlinear reformulation, and adding an upstream weighting evaluation and a nonlinear p-Laplace vanishing stabilisation term.
Approach to Tremor Disorders
Authors: Lee Andrea , Sarva Harini
Published: November 2021

Tremor disorders are diverse and complex. Historical clues and examination features play a major role in diagnosing these disorders, but diagnosis can be challenging due to phenotypic overlap. Ancillary testing, such as neuroimaging or laboratory testing, is driven by the history and examination, and should be performed particularly when there are other neurological or systemic manifestations. The pathophysiology of tremor is not entirely understood, but likely involves multiple networks along with the cerebello-thalamo-cortical pathways. Treatment options include medications, botulinum toxin, surgery, and nonpharmacologic interventions utilizing physical and occupational therapies and assistive devices. Further work is needed in developing accurate diagnostic tests and better treatment options for tremor disorders.
Approach to Limb Weakness
Authors: Bhagavan Sachin M. , Ramaswamy Swathi B. , Mehta Tejas R. , Govindarajan Raghav
Published: November 2021

“Approach to limb weakness” provides an overview of the pathways of the motor system and the type of weakness seen with pathology at each level from the cortex to the muscle. This article provides the clinical pearls needed to identify different patterns of weakness and accurately localize the level of weakness. It offers important pointers that help distinguish among the different etiologies of weakness at each level, as well as various diagnostic approaches and treatments of diseases that lead to limb weakness. The diagnoses discussed are meant to be representative and not exhaustive, as a complete differential for each pattern of weakness is beyond the scope of this article.
Knowledge and attitudes towards periodontal health among Australians diagnosed with diabetes
Authors: Tuncer Eren , Darby Ivan
Published: November 2021

Diabetes and periodontitis are two major diseases affecting the Australian population. Despite the established interrelationship between the diseases, the knowledge of people with diabetes about this interrelationship is limited. This study investigated the knowledge of individuals with diabetes towards periodontal health in Australia. Adults diagnosed with diabetes participated in a survey asking about demographics, medical history, symptoms in the oral cavity, oral hygiene, attendance at the dentist and their knowledge of the interactions between periodontal disease and diabetes. The survey was completed by 113 participants, most of whom thought their diabetes was well controlled. Over half reported bleeding on brushing and one-third reported swollen gums. More than half (53.6%) the respondents were unaware of any complications of diabetes associated with the oral cavity, especially periodontal disease. Most respondents did not talk to their dentist about diabetes (53.6%), yet most wanted to know more about the effects of diabetes on gum health (75.3%). These findings demonstrate that, in this survey, adult Australians diagnosed with diabetes have limited knowledge about how periodontal disease affects them. These individuals, who are at a higher risk of periodontal disease, need to be better informed of the established bidirectional relationship between diabetes and oral health by all health professionals.