bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainability concerns on consumers’ attitude towards short food supply chains: an empirical investigation
Authors: Wang Meng , Kumar Vikas , Ruan Ximing , Saad Mohammed , Garza-Reyes Jose Arturo , Kumar Anil
Published: March 2021

While industrialized agro-food supply systems have gained tremendous success in recent decades, it has been increasingly criticized for its adverse environmental and social impact. Amongst this criticism, Short Food Supply Chains (SFSCs) have emerged as a promising sustainable alternative to the industrialized agri-food supply systems. In recent years there have been some attempts to explore the relationship between SFSCs and sustainability, but these are mostly theoretical discussions and lacks empirical validation. This study, therefore, attempts to provide empirical validation of the SFSCs and sustainability linkages. Additionally, from the theoretical perspective, our work extends the traditional triple bottom line constructs and explores two extra dimensions of sustainability in the food supply chain system, namely, governance and culture, thus exploring five dimensions of sustainability. Furthermore, while SFSCs have proven to improve farmers’ livelihoods and reconnect producers with consumers, little or no attention has been given to understand the consumers' attitudes towards the SFSC practices. Therefore, this study aims to explore the customers’ attitudes towards participating in SFSCs through the concept of a moral economy and personal relationship. Based on the 532 valid responses from Chinese consumers, our study shows that all five pillars of sustainability, moral economy and Chinese relationship have a positive influence on consumers’ participation in SFSCs. With its intuitive benefits, the economic pillar emerged as the most approved factor by the participants. Interestingly our findings show that the social aspect is less prominent than others, which is contrary to existing studies conducted in developed countries.
Attitudes to Cryptocurrencies: A Comparative Study Between Sweden and Japan
Authors: Grassman Rickard , Bracamonte Vanessa , Davis Matthew , Sato Maki
Published: March 2021

In this paper, we explore how cryptocurrencies have been received in Sweden and Japan, and what specific attitudes and discourses may reveal about the ethical implications surrounding this new technology. By way of topic modelling prevalent discourses on social media among users of cryptocurrencies, and teasing out the more culturally situated significance in such interactions through discourse analysis, our aim is to unpack the way certain tropes and traces around the notion of autonomy may provide a fruitful lens through which we may discern how this technology has been received in each respective country. The ultimate aim of the paper is to shed light on the attitudes that inform the way this technology is perceived and the cultural and ideological nuances that this brings to the fore, as well as how this culturally nuanced view may help us better discern the potential advantages and ethical challenges associated with this new technology.
Diabetic retinopathy detection and classification using capsule networks
Authors: Kalyani G. , Janakiramaiah B. , Karuna A. , Prasad L. V. Narasimha
Published: March 2021

Nowadays, diabetic retinopathy is a prominent reason for blindness among the people who suffer from diabetes. Early and timely detection of this problem is critical for a good prognosis. An automated system for this purpose contains several phases like identification and classification of lesions in fundus images. Machine learning techniques based on manual extraction of features and automatic extraction of features with convolution neural network have been presented for diabetic retinopathy detection. The recent developments like capsule networks in deep learning and their significant success over traditional machine learning methods for a variety of applications inspired the researchers to apply them for diabetic retinopathy diagnosis. In this paper, a reformed capsule network is developed for the detection and classification of diabetic retinopathy. Using the convolution and primary capsule layer, the features are extracted from the fundus images and then using the class capsule layer and softmax layer the probability that the image belongs to a specific class is estimated. The efficiency of the proposed reformed network is validated concerning four performance measures by considering the Messidor dataset. The constructed capsule network attains an accuracy of 97.98%, 97.65%, 97.65%, and 98.64% on the healthy retina, stage 1, stage 2, and stage 3 fundus images.
A survival analysis in the assessment of the influence of the SARS-CoV-2 pandemic on the probability and intensity of decline in the value of stock indices
Authors: Bieszk-Stolorz Beata , Dmytrów Krzysztof
Published: March 2021

The aim of the study is to assess the strength of the world stock exchanges reaction to the SARS-CoV-2 coronavirus pandemic at the turn of 2019–2020. We analyze the risk and intensity of the decline in the values of the basic stock indices by means of selected methods of survival analysis. The spreading pandemic within a few months covered all continents and had a significant impact on the socio-economic situation of all countries. We studied the time of the 20% drop in stock market indices. This is a value that is taken as a sign of a crisis. In order to assess the probability of indices’ value decrease, we use the Kaplan–Meier’s estimator. We determine the risk of decline by means of a logit model and the intensity of the decline by means of an empirical hazard estimator and the Cox proportional hazard model. The intensity and risk of the decline of stock indices varied from continent to continent. The obtained results show that the intensity is highest in the fourth and eighth week after the peak and is the highest on European exchanges and then American and Asian exchanges (including Australia). The risk of falling the stock indices’ prices is the highest in America, followed by Europe, Asia and Australia, and lowest in Africa. Half of the analyzed indices record a 20% drop in value after 52 days (median duration). The study is a prelude to further analyses related to the crisis and the normalization of the situation on world stock exchanges. It allows to learn about the impact of the pandemic on the economic situation and to detect the differences between the continents.
Rational functions, cotangent sums and Eichler integrals
Authors: Franke Johann
Published: March 2021

With the help of so called pre-weak functions, we formulate a very general transformation law for some holomorphic functions on the upper half plane and motivate the term of a generalized Eisenstein series with real-exponent Fourier expansions. Using the transformation law in the case of negative integers k, we verify a close connection between finite cotangent sums of a specific type and generalized L-functions at integer arguments. Finally, we expand this idea to Eichler integrals and period polynomials for some types of modular forms.
Hospital Admission and Readmission Among US Patients Receiving Umeclidinium/Vilanterol or Tiotropium as Initial Maintenance Therapy for Chronic Obstructive Pulmonary Disease
Authors: Slade David , Ray Riju , Moretz Chad , Germain Guillaume , Laliberté François , Shen Qin , Duh Mei Sheng , MacKnight Sean D. , Hahn Beth
Published: March 2021

Introduction

Patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations are at risk of further readmissions, increased treatment costs, and excess mortality. This study evaluated inpatient admissions and readmissions in patients receiving initial maintenance therapy with umeclidinium/vilanterol (UMEC/VI) versus tiotropium (TIO).

Methods

This retrospective, matched cohort study identified patients with COPD who initiated maintenance therapy with UMEC/VI or TIO from Optum’s de-identified Clinformatics Data Mart database between January 1, 2013, and December 31, 2018 (index date defined as earliest dispensing). Eligibility criteria included: ≥ 1 medical claim for COPD pre-index or on the index date; ≥ 12 months of continuous eligibility pre-index; age ≥ 40 years at index; no pre- or post-index asthma diagnosis; and no pre-index claims for medications containing inhaled corticosteroids, long-acting β2-agonists, or long-acting muscarinic antagonists. Outcomes included time to first on-treatment COPD-related inpatient admission, rate of on-treatment COPD-related admissions, and rate of all-cause and COPD-related readmissions within 30 and 90 days. Propensity score matching was used to adjust for potential confounders.

Results

Matched UMEC/VI and TIO cohorts each included 7997 patients and were balanced on baseline characteristics (mean age 70.9 years; female 47.1–47.6%). Over 12 months, patients initiating UMEC/VI had significantly reduced risk (hazard ratio [95% CI]: 0.87 [0.79, 0.96]; p = 0.006) and rates (rate ratio [95% CI]: 0.80 [0.72, 0.92]; p = 0.008) of COPD-related inpatient admissions compared with TIO. While all-cause readmission rates were similar between treatment cohorts, readmission rates among patients with an initial admission length of stay of 1–3 days were numerically lower for UMEC/VI versus TIO (30-day readmissions: 10.5% vs. 12.4%; 90-day readmissions: 15.5% vs. 19.8%). Similar patterns were observed for COPD-related readmissions.

Conclusions

These findings highlight the real-world benefits of dual therapy with UMEC/VI versus TIO in reducing inpatient admissions and readmissions in patients with COPD, which may translate to lower healthcare costs.
International Investment Law and Arbitration
Authors: Lim C. L. , Ho Jean , Paparinskis Martins
Published: March 2021

International investment law and arbitration is a rapidly evolving field, and can be difficult for students to acquire a firm understanding of, given the considerable number of published awards and legal writings. The first edition of this text, cited by courts in Singapore and Colombia, overcame this challenge by interweaving extracts from these arbitral decisions, treaties and scholarly works with concise, up-to-date and reliable commentary. Now fully updated and with a new chapter on arbitrators, the second edition retains this practical structure along with the carefully curated end-of-chapter questions and readings. The authors consider the new chapter an essential revision to the text, and a discussion which is indispensable to understanding the present calls for reform of investment arbitration. The coverage of the book has also been expanded, with the inclusion of over sixty new awards and judicial decisions, comprising both recent and well-established jurisprudence. This textbook will appeal to graduates studying international investment law and international arbitration, as well as being of interest to practitioners in this area.
The fluid limit of a random graph model for a shared ledger
Authors: King Christopher
Published: March 2021

A shared ledger is a record of transactions that can be updated by any member of a group of users. The notion of independent and consistent record-keeping in a shared ledger is important for blockchain and more generally for distributed ledger technologies. In this paper we analyze a stochastic model for the shared ledger known as the tangle, which was devised as the basis for the IOTA cryptocurrency. The model is a random directed acyclic graph, and its growth is described by a non-Markovian stochastic process. We first prove ergodicity of the stochastic process, and then derive a delay differential equation for the fluid model which describes the tangle at high arrival rate. We prove convergence in probability of the tangle process to the fluid model, and also prove global stability of the fluid model. The convergence proof relies on martingale techniques.
Model-independent pricing with insider information: a skorokhod embedding approach
Authors: Acciaio Beatrice , Cox Alexander M. G. , Huesmann Martin
Published: March 2021

In this paper we consider the pricing and hedging of financial derivatives in a model-independent setting, for a trader with additional information, or beliefs, on the evolution of asset prices. In particular, we suppose that the trader wants to act in a way which is independent of any modelling assumptions, but that she observes market information in the form of the prices of vanilla call options on the asset. We also assume that both the payoff of the derivative, and the insider’s information or beliefs, which take the form of a set of impossible paths, are time-invariant. In this way we accommodate drawdown constraints, as well as information/beliefs on quadratic variation or on the levels hit by asset prices. Our setup allows us to adapt recent work of [12] to prove duality results and a monotonicity principle. This enables us to determine geometric properties of the optimal models. Moreover, for specific types of information, we provide simple conditions for the existence of consistent models for the informed agent. Finally, we provide an example where our framework allows us to compute the impact of the information on the agent’s pricing bounds.
From the hospital toilet to the ward: A pilot study on microbe dispersal to multiple hospital surfaces following hand drying using a jet air dryer versus paper towels
Authors: Moura Ines B. , Ewin Duncan , Wilcox Mark H.
Published: March 2021

Using a bacteriophage to represent microbial contamination, we investigated virus transmission to the hospital environment following hand drying. The use of paper towels resulted in lower rates of virus contamination on hands and clothing compared with a jet air dryer and, consequently, lower contamination of multiple hospital surfaces.
Reflections on the Role of Ubuntu as an Antidote to Afro-Phobia
Authors: Kaungu Gideon Muchiri
Published: March 2021

This article argues that xenophobic acts towards black foreigners remain a human rights challenge in South Africa. Foreign nationals, mostly black Africans, continue to experience physical attacks, discrimination and looting of businesses, as well as targeted crime. Prevalent xenophobic attitudes continue to trouble the conscience of all well-meaning South Africans. There is ample evidence that xenophobia has morphed into afro-phobia, the hatred of black foreigners. Xenophobia continues to evolve and attackers are increasingly linking the presence of foreign nationals to socio-economic challenges facing the country. This article argues that, even though South Africa's Constitution does not expressly identify Ubuntu as a national value, it does recognize customary law and many of its provisions are anchored in Ubuntu philosophy. This article proposes Ubuntu, or African “humanness” whose “natural home” should be located in South Africa, as a pragmatic social intervention and a morally sustainable solution to address xenophobia that would be acceptable to both South Africans and foreign nationals.
Unfolding Africa's Impact on the Development of International Refugee Law
Authors: Palacios-Arapiles Sara
Published: March 2021

This article traces the contributions of African states to the development of international refugee law and explores the role African human rights supervisory bodies have played in the interpretation and application of this field of law. While Africa's contributions to international refugee law are often overlooked, this article sets out to identify Africa's involvement in the drafting process of the UN Refugee Convention and its 1967 Protocol. It also explores the legal framework for refugees in Africa, in particular the OAU Refugee Convention and the Bangkok Principles on Status and Treatment of Refugees, and the extent to which these two instruments have enriched international refugee law. The article argues that some of their provisions may provide evidence of customary rules of international law. Lastly, it examines some of the authoritative pronouncements made by African human rights supervisory bodies, in so far as they adopt a progressive approach to interpreting the rights of refugees and asylum-seekers.
Effects of full-time v. part-time grazing on seasonal changes in milk coagulation properties and fatty acid composition
Authors: Akert Franziska S. , Kreuzer Michael , Kunz Carmen , Reidy Beat , Berard Joel
Published: March 2021

For this research communication our objective was to investigate to what extent milk coagulation properties and milk fatty acid (FA) composition were affected by different feeding systems, season and their interaction. Eighteen cows in total were subjected to one of three different feeding system treatments: full-time grazing or part-time grazing combined with indoor feeding of fresh grass with low or high concentrate supplementation. Milk was sampled in spring, summer and autumn. Milk coagulation time was 15.0, 19.0 and 17.7 min, coagulation dynamics 1.67, 3.41 and 1.79 min, and curd firmness 52.7, 32.4 and 47.0 mm in spring, summer and autumn, respectively. Thus, milk coagulation properties of the milk were lower during summer. There were strong seasonal effects on milk FA proportions, but there were not always changes with progressing season, or changes were different with respect to the impact of the feeding systems (system × season interaction). The milk fat was favourably rich in oleic acid, conjugated linoleic acid and α-linolenic acid and had a low n-6/n-3 fatty acid ratio in all systems. Factors like seasonal variations in grass composition and the energy balance of the cows were considered relevant for the milk FA composition. Overall, seasonal variations in milk quality were less pronounced with part-time grazing with fresh grass indoors as compared to full-time grazing without concentrate.
Providing instrumental support to older parents of multi-child families in China: are there different within-family patterns?
Authors: Chen Jia , Zhou Xiaochen , Lu Nan
Published: March 2021

Older parents in China rely heavily on their adult children for instrumental assistance. In different multi-child families, multiple offspring may co-operate in providing instrumental support to older parents in distinct ways in terms of how much support they provide on average and how much differentiation exists between them when they provide such support within a family. We aimed to identify different within-family patterns in relation to multiple offspring's instrumental support to an older parent in Chinese multi-child families, and to investigate potential predictors for different within-family patterns. Using data from the China Family Panel Studies (2016), we had a working sample of 5,790 older adults aged 60+ (mean = 68.54, standard deviation = 6.60). We employed latent profile analysis (LPA) to classify within-family patterns and multinomial logistic regression to investigate predictors. Our findings identified three within-family patterns: dissociated (59.10%), highly differentiated (29.60%) and united-filial (11.30%). Older parents in the highly differentiated families tended to be older, mothers, divorced/widowed and to have poorer physical health compared to their counterparts in the dissociated families. In contrast, the composition characteristics of multiple adult children played more important roles in determining the united-filial within-family pattern. The united-filial families were more likely to have fewer adult children, at least one adult daughter and at least one co-residing adult child.
Evaluating traditional and complementary medicines: Where do we go from here?
Authors: Lin Lydia Wenxin , Ananthakrishnan Aparna , Teerawattananon Yot
Published: March 2021

Traditional and complementary medicines are increasingly considered possible options for prevention and symptomatic treatment of the novel coronavirus, COVID-19. With renewed attention on these therapies from researchers and policy makers alike, the well-documented challenges of evaluating their safety and efficacy are once again of global concern. Between 2005 and 2018, the World Health Organization conducted a series of surveys, in which 88 percent of responding member states confirmed that their biggest challenge in traditional medicine was the need for technical guidance on research and evaluation. As a first step in pursuing this need, our commentary summarizes thirteen international and regional guidance documents by three broad categories on evaluating safety, efficacy, and product quality for market-based approval and distribution of these treatments. We highlight the paucity of updated international recommendations on these subjects and identify gaps that could inform the current evidence base. All available guidance note the need for evidence surrounding the efficacy of these treatments and practices but are also quick to caution against methodological difficulties in the conduct of such evaluations. Evidence suggests that improved evaluation methods on efficacy and effectiveness are crucial toward expanding future research into establishing the cost-effectiveness of these therapies, in the context of shifting acceptance, interest, and integration of traditional medicines into health systems, and as another step toward Universal Health Coverage.
The Measure of Her Actions: A Quantitative Assessment of Anglo-Jewish Women's Litigation at the Exchequer of the Jews, 1219–81
Authors: Cavell Emma
Published: March 2021

Taking a chiefly quantitative approach to Jewish women's litigation at the Exchequer of the Jews between in the period 1219–81, this article represents the first exploration of Jewish women before the law in medieval England. It contends that, far from enjoying a level of ‘legal sexual equality’ not available to Christian women, Anglo-Jewish women at the Exchequer of the Jews in fact shared many of their experiences of (secular) law and justice with their Christian counterparts. This contention is possible in part because of the greater interest, over the last decade, in pre-modern European women's litigation and the realisation that Christian women of all classes were able to navigate their way around judicial systems in ways that confounded any theoretical legal disadvantages they may have faced. The article variously examines the number of Jewish women litigating at the Exchequer of the Jews, their roles in court and representation in the records, and the types of litigation in which they took part. It demonstrates that if we are ever to seek a holistic view of the operation of legal jurisdictions in medieval England, our knowledge must include the experiences of Anglo-Jewish women.
“People Crushed by Law Have No Hopes but from Power”: Free Speech and Protest in the 1940s
Authors: Fisk Catherine L.
Published: March 2021

In a trio of cases handed down on the same day in 1950, the Supreme Court denied constitutional free speech protection to civil rights picketing and labor picketing. The civil rights case, Hughes v. Superior Court, has often been portrayed as an early test case about affirmative action, but it originated in repression of an alliance of radical labor and civil rights activists exasperated by the legislature's repeated failure to enact fair employment law. Seeking a people's law like the labor general strikers and sit-downers of the 1930s and the civil rights sit-inners of the 1960s, they insisted that the true meaning of free speech was the right to speak truth to power. Courts and Congress forced the labor movement to abandon direct action even as it became the defining feature of the civil rights movement. The free speech rights consciousness they invoked challenged the prevailing conservative conception of rights and law. Direct action was a form of legal argument, a subaltern law of solidarity. It was not, as civil rights protest is often portrayed, a form of civil disobedience. What happened during and after the case reveals how the subaltern law and formal law labor and civil rights began to diverge, along with the legal histories of the movements.
CME-Labor 63: Eisenstoffwechsel-Diagnostik
Authors: von Eckardstein Arnold
Published: March 2021

Zusammenfassung. Eisenmangel ist häufig und beeinflusst den Verlauf vieler chronischer Erkrankungen. Die Diagnose einer absoluten und manifesten Eisenmangelanämie kann leicht durch Messung der Hämoglobin- und Serumferritinspiegel gestellt werden. Bei entzündlichen Erkrankungen kann die Diagnose durch zusätzliche Laborparameter wie dem löslichen Transferrin-Rezeptor erleichtert werden. Bei mehreren chronischen Erkrankungen wie Herz- oder Niereninsuffizienz gelten je nach Krankheit und Stadium unterschiedliche und höhere Schwellenwerte für Serumferritin, manchmal auch unter zusätzlicher Berücksichtigung der Transferrinsättigung. Die Transferrinsättigung ist zudem wichtig für die Diagnostik der Hämochromatose. Bei Patientinnen und Patienten mit Transferrinsättigung >45 % erfordert die Diagnose in der Regel den Nachweis der Homozygotie für die C282Y-Mutation im HFE-Gen.
CME: Kranke und ihre Berufe in der Allgemeinarztpraxis
Authors: Stadtmüller Klaus Ernst
Published: March 2021

Zusammenfassung. Mehr Gesundheitsstörungen als erwartet, die zu einem Arztbesuch führen, haben ursächlich mit Belastungen am Arbeitsplatz zu tun. Auch wenn die meisten dieser arbeitsbedingten Erkrankungen nicht zur Anerkennung als Berufskrankheit qualifizieren, kann die Hausärztin/der Hausarzt wichtige Weichen für Heilbehandlung und Prävention stellen. Für eine effiziente Beratung seiner Patientinnen und Patienten muss sie/er jedoch ein Konzept der Regulation von Arbeitssicherheit und Gesundheitsschutz haben und wissen, welche Sozialversicherung welche Rolle bei der Prävention spielt.
Drainage Canals in Southeast Asian Peatlands Increase Carbon Emissions
Authors: Dadap Nathan C. , Hoyt Alison M. , Cobb Alexander R. , Oner Doruk , Kozinski Mateusz , Fua Pascal V. , Rao Krishna , Harvey Charles F. , Konings Alexandra G.
Published: March 2021

Drainage canals associated with logging and agriculture dry out organic soils in tropical peatlands, thereby threatening the viability of long‐term carbon stores due to increased emissions from decomposition, fire, and fluvial transport. In Southeast Asian peatlands, which have experienced decades of land use change, the exact extent and spatial distribution of drainage canals are unknown. This has prevented regional‐scale investigation of the relationships between drainage, land use, and carbon emissions. Here, we create the first regional map of drainage canals using high resolution satellite imagery and a convolutional neural network. We find that drainage is widespread—occurring in at least 65% of peatlands and across all land use types. Although previous estimates of peatland carbon emissions have relied on land use as a proxy for drainage, our maps show substantial variation in drainage density within land use types. Subsidence rates are 3.2 times larger in intensively drained areas than in non‐drained areas, highlighting the central role of drainage in mediating peat subsidence. Accounting for drainage canals was found to improve a subsidence prediction model by 30%, suggesting that canals contain information about subsidence not captured by land use alone. Thus, our data set can be used to improve subsidence and associated carbon emissions predictions in peatlands, and to target areas for hydrologic restoration.
Spatial Characteristics of Coronavirus Disease 2019 and Their Possible Relationship With Environmental and Meteorological Factors in Hubei Province, China
Authors: Huang Xiaochi , Zhou Han , Yang Xiaofeng , Zhou Wen , Huang Jiejun , Yuan Yanbin
Published: March 2021

As of July 27, 2020, COVID‐19 has caused 640,000 deaths worldwide and has had a major impact on people's productivity and lives. Analyzing the spatial distribution characteristics of COVID‐19 cases and their relationships with meteorological and environmental factors might help enrich our knowledge of virus transmission and formulate reasonable epidemic prevention strategies. Taking the cumulative confirmed cases in Hubei province from January 23, 2020, to April 8, 2020, as an example, this study analyzed the spatial evolution characteristics of confirmed COVID‐19 cases in Hubei province using exploratory spatial data analysis and explored the spatial relationship between the main environmental and meteorological factors and confirmed COVID‐19 cases using a geographically weighted regression (GWR) model. Results show that there was no obvious spatial clustering of confirmed COVID‐19 cases in Hubei province, while the decline and end of the newly confirmed cases revealed relatively obvious negative spatial correlations. Due to the lockdown in Hubei province, the main air quality indexes (e.g., AQI and PM2.5) decreased significantly and environmental quality was better than historical contemporaneous levels. Meanwhile, the results of the GWR model suggest that the impacts of environmental and meteorological factors on the development of COVID‐19 were not significant. These findings indicate that measures such as social distancing and isolation played the primary role in controlling the development of the COVID‐19 epidemic.
Equatorial Waves, Diurnal Tides and Small‐Scale Thermal Variability in the Tropical Lower Stratosphere From COSMIC‐2 Radio Occultation
Authors: Randel William J. , Wu Fei , Podglajen Aurélien
Published: March 2021

A new constellation of radio occultation satellites called COSMIC‐2 (Constellation Observing System for Meteorology, Ionosphere, and Climate‐2) is providing unprecedented dense measurements of the tropical atmosphere, with on average more than 4,000 high quality observations per day over 40°N–S. We use these data to evaluate large‐ and small‐scale thermal variability in the tropical lower stratosphere during October 2019 – April 2020. Space‐time spectral analysis of 6‐hourly gridded COSMIC‐2 data reveals a rich spectrum of traveling planetary‐scale waves, including Kelvin waves, mixed Rossby‐gravity waves and inertia gravity waves, in addition to propagating diurnal tides. These coherent modes show enhanced amplitudes from the tropical tropopause through the lower stratosphere (∼17–25 km). Characteristics of small‐scale temperature variances, calculated as deviations from the gridded fields, reveal systematic spatial patterns including time average maxima over Africa and South America overlying frequent deep convection. Small‐scale variances also exhibit transient maxima in the equatorial lower stratosphere tied to local variations in static stability, associated with large‐scale Kelvin waves. The new COSMIC‐2 observations provide novel details on the rich spectrum of large‐ and small‐scale waves near and above the tropical tropopause.
Climatically Modulated Dust Inputs from New Zealand to the Southwest Pacific Sector of the Southern Ocean Over the Last 410 kyr
Authors: Wu Yi , Roberts Andrew P. , Grant Katharine M. , Heslop David , Pillans Brad J. , Zhao Xiang , Rohling Eelco J. , Ronge Thomas A. , Ma Mingming , Hesse Paul P. , Palmer Alan S.
Published: March 2021

Eolian mineral dust is an active agent in the global climate system. It affects planetary albedo and can influence marine biological productivity and ocean‐atmosphere carbon dynamics. This makes the understanding of the global dust cycle crucial for constraining the dust/climate relationship, which requires long‐term dust emission records for all major dust sources. Despite their importance, the sources of atmospheric dust deposited in the Southern Ocean remain poorly constrained. Eolian dust in the Pacific sector of the Southern Ocean is generally assumed to originate from Australia, with minor contributions from New Zealand. Here, we present a high‐resolution elemental record of terrestrial inputs for the past ∼410 kyr from marine sediment core PS75/100‐4 recovered from east of South Island, New Zealand. Sediment grain size is slightly finer than that of loess deposits from South Island, New Zealand, and is coarser than that of marine sediments in the Tasman Sea to the west of New Zealand, which indicates that the dust originated mainly from New Zealand and not only from Australia. Core PS75/100‐4 records lithogenic mass accumulation rates ranging from ∼0.01 to 0.69 g/cm2/kyr (∼0.20 g/cm2/kyr average), with variations over a factor of ∼3–4 over glacial versus interglacial timescales for the past 410 kyr. Our geochemical data correlate well with the Southern Ocean and Antarctic eolian dust records and suggest a westerly wind‐supplied dust signal from New Zealand. Our findings, therefore, suggest that New Zealand should be considered an important long‐term regional dust source in global dust cycle models.
Nutrient complexity triggers transitions between solitary and colonial growth in bacterial populations
Authors: D’Souza Glen G , Povolo Vanessa R , Keegstra Johannes M , Stocker Roman , Ackermann Martin
Published: March 2021

Microbial populations often experience fluctuations in nutrient complexity in their natural environment such as between high molecular weight polysaccharides and simple monosaccharides. However, it is unclear if cells can adopt growth behaviors that allow individuals to optimally respond to differences in nutrient complexity. Here, we directly control nutrient complexity and use quantitative single-cell analysis to study the growth dynamics of individuals within populations of the aquatic bacterium Caulobacter crescentus. We show that cells form clonal microcolonies when growing on the polysaccharide xylan, which is abundant in nature and degraded using extracellular cell-linked enzymes; and disperse to solitary growth modes when the corresponding monosaccharide xylose becomes available or nutrients are exhausted. We find that the cellular density required to achieve maximal growth rates is four-fold higher on xylan than on xylose, indicating that aggregating is advantageous on polysaccharides. When collectives on xylan are transitioned to xylose, cells start dispersing, indicating that colony formation is no longer beneficial and solitary behaviors might serve to reduce intercellular competition. Our study demonstrates that cells can dynamically tune their behaviors when nutrient complexity fluctuates, elucidates the quantitative advantages of distinct growth behaviors for individual cells and indicates why collective growth modes are prevalent in microbial populations.
Regulation of olfactomedin 4 by Porphyromonas gingivalis in a community context
Authors: Fitzsimonds Zackary R , Liu Chengcheng , Stocke Kendall S , Yakoumatos Lan , Shumway Brian , Miller Daniel P , Artyomov Maxim N , Bagaitkar Juhi , Lamont Richard J
Published: March 2021

At mucosal barriers, the virulence of microbial communities reflects the outcome of both dysbiotic and eubiotic interactions with the host, with commensal species mitigating or potentiating the action of pathogens. We examined epithelial responses to the oral pathogen Porphyromonas gingivalis as a monoinfection and in association with a community partner, Streptococcus gordonii. RNA-Seq of oral epithelial cells showed that the Notch signaling pathway, including the downstream effector olfactomedin 4 (OLFM4), was differentially regulated by P. gingivalis alone; however, regulation was overridden by S. gordonii. OLFM4 was required for epithelial cell migratory, proliferative and inflammatory responses to P. gingivalis. Activation of Notch signaling was induced through increased expression of the Notch1 receptor and the Jagged1 (Jag1) agonist. In addition, Jag1 was released in response to P. gingivalis, leading to paracrine activation. Following Jag1-Notch1 engagement, the Notch1 extracellular domain was cleaved by P. gingivalis gingipain proteases. Antagonism by S. gordonii involved inhibition of gingipain activity by secreted hydrogen peroxide. The results establish a novel mechanism by which P. gingivalis modulates epithelial cell function which is dependent on community context. These interrelationships have relevance for innate inflammatory responses and epithelial cell fate decisions in oral health and disease.
Psychiatric symptoms and behavioral adjustment during the COVID-19 pandemic: evidence from two population-representative cohorts
Authors: Hou Wai Kai , Lee Tatia Mei-chun , Liang Li , Li Tsz Wai , Liu Huinan , Tong Horace , Ben-Ezra Menachem , Goodwin Robin
Published: March 2021

This study examined prevalences of anxiety and depression and their correlations with daily routines among Hong Kong Chinese during the COVID-19 pandemic. Random digit dialing recruited two population-representative samples of 6029 residents during a period of low infection and limited intervention (survey 1:n = 4021) and high incidence and intensive measures (survey 2:n = 2008). Prevalence of anxiety for survey 1 and survey 2 were 14.9% and 14% and depression were 19.6% and 15.3%, respectively. Increased odds of anxiety and depression were associated with disrupted routines and lower socioeconomic status in both surveys, whereas depression was inversely related to the novel preventive routine of avoiding going to crowded places in survey 1. The prevalences of anxiety and depression were higher than preceding public health/social crises. A heavier burden of psychiatric conditions was evidenced amongst people experiencing disrupted daily routines across different phases of the pandemic and without novel preventive routines in the early phase.
Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification
Authors: Yu Tao , Zhang Jianguo , Zhu Wei , Wang Xiao , Bai Yun , Feng Bin , Zhuang Qianyu , Han Chang , Wang Shengru , Hu Qimiao , An Senbo , Wan Mei , Dong Shiwu , Xu Jianzhong , Weng Xisheng , Cao Xu
Published: March 2021

Ankylosing spondylitis (AS) is chronic inflammatory arthritis with a progressive fusion of axial joints. Anti-inflammatory treatments such as anti-TNF-α antibody therapy suppress inflammation but do not effectively halt the progression of spine fusion in AS patients. Here we report that the autoimmune inflammation of AS generates a microenvironment that promotes chondrogenesis in spine ligaments as the process of spine fusion. Chondrocyte differentiation was observed in the ligaments of patients with early-stage AS, and cartilage formation was followed by calcification. Moreover, a large number of giant osteoclasts were found in the inflammatory environment of ligaments and on bony surfaces of calcified cartilage. Resorption activity by these giant osteoclasts generated marrow with high levels of active TGF-β, which induced new bone formation in the ligaments. Notably, no Osterix+ osteoprogenitors were found in osteoclast resorption areas, indicating uncoupled bone resorption and formation. Even at the late and maturation stages, the uncoupled osteoclast resorption in bony interspinous ligament activates TGF-β to induce the progression of ossification in AS patients. Osteoclast resorption of calcified cartilage-initiated ossification in the progression of AS is a similar pathologic process of acquired heterotopic ossification (HO). Our finding of cartilage formation in the ligaments of AS patients revealed that the pathogenesis of spinal fusion is a process of HO and explained why anti-inflammatory treatments do not slow ankylosing once there is new bone formation in spinal soft tissues. Thus, inhibition of HO formation, such as osteoclast activity, cartilage formation, or TGF-β activity could be a potential therapy for AS.
Subchondral bone microenvironment in osteoarthritis and pain
Authors: Hu Yan , Chen Xiao , Wang Sicheng , Jing Yingying , Su Jiacan
Published: March 2021

Osteoarthritis comprises several joint disorders characterized by articular cartilage degeneration and persistent pain, causing disability and economic burden. The incidence of osteoarthritis is rapidly increasing worldwide due to aging and obesity trends. Basic and clinical research on osteoarthritis has been carried out for decades, but many questions remain unanswered. The exact role of subchondral bone during the initiation and progression osteoarthritis remains unclear. Accumulating evidence shows that subchondral bone lesions, including bone marrow edema and angiogenesis, develop earlier than cartilage degeneration. Clinical interventions targeting subchondral bone have shown therapeutic potential, while others targeting cartilage have yielded disappointing results. Abnormal subchondral bone remodeling, angiogenesis and sensory nerve innervation contribute directly or indirectly to cartilage destruction and pain. This review is about bone-cartilage crosstalk, the subchondral microenvironment and the critical role of both in osteoarthritis progression. It also provides an update on the pathogenesis of and interventions for osteoarthritis and future research targeting subchondral bone.
LSD1 silencing contributes to enhanced efficacy of anti-CD47/PD-L1 immunotherapy in cervical cancer
Authors: Xu Shengjie , Wang Xiaoyun , Yang Yongbing , Li Yanli , Wu Sufang
Published: March 2021

Anti-CD47/PD-L1 immunotherapies aiming to enhance antitumor immunity are being intensively investigated and show promising results in cancer therapy; however, not all patients treated with these new drugs respond. Thus, developing new immunotherapy agents or combination treatments to enhance the efficacy of immunotherapy is an urgent challenge. Here, we found that LSD1 knockdown directly downregulated the expression of CD47 and PD-L1 through upregulating H3K4me2 levels in the CD47 and CD274 promoter regions. In addition, the LSD1/wild-type p53/miR-34a signaling axis was also involved in the regulation of CD47/PD-L1 expression by targeting the 3′ untranslated regions (3′UTRs) of CD47/PD-L1. Further, the results showed that an LSD1 inhibitor (ORY-1001) combined with anti-CD47/PD-L1 monoclonal antibodies inhibited tumor growth in an established subcutaneous xenograft model more effectively than a single blockade strategy. Collectively, these findings indicate that LSD1 inhibition enhances the therapeutic efficacy of PD-L1/CD47 blockade by reducing CD47 and PD-L1 expression in cervical cancer.
Automated feature-based grading and progression analysis of diabetic retinopathy
Authors: Al-Turk Lutfiah , Wawrzynski James , Wang Su , Krause Paul , Saleh George M. , Alsawadi Hend , Alshamrani Abdulrahman Zaid , Peto Tunde , Bastawrous Andrew , Li Jingren , Tang Hongying Lilian
Published: March 2021

Background

In diabetic retinopathy (DR) screening programmes feature-based grading guidelines are used by human graders. However, recent deep learning approaches have focused on end to end learning, based on labelled data at the whole image level. Most predictions from such software offer a direct grading output without information about the retinal features responsible for the grade. In this work, we demonstrate a feature based retinal image analysis system, which aims to support flexible grading and monitor progression.

Methods

The system was evaluated against images that had been graded according to two different grading systems; The International Clinical Diabetic Retinopathy and Diabetic Macular Oedema Severity Scale and the UK’s National Screening Committee guidelines.

Results

External evaluation on large datasets collected from three nations (Kenya, Saudi Arabia and China) was carried out. On a DR referable level, sensitivity did not vary significantly between different DR grading schemes (91.2–94.2.0%) and there were excellent specificity values above 93% in all image sets. More importantly, no cases of severe non-proliferative DR, proliferative DR or DMO were missed.

Conclusions

We demonstrate the potential of an AI feature-based DR grading system that is not constrained to any specific grading scheme.
Interactions between gut microbiota and metabolites modulate cytokine network imbalances in women with unexplained miscarriage
Authors: Liu Yongjie , Chen Hainan , Feng Liping , Zhang Jun
Published: March 2021

A dysregulation of cytokine networks has been suggested to be involved in the pathogenesis of unexplained pregnancy loss. Gut microbiota affects host immune response and induces an imbalance in cytokine levels. However, how gut microbial dysbiosis disturbs cellular immune function in miscarriage remains inconclusive. Here we report that IL-2, IL-17A, IL-17F, TNF-α, and IFN-γ are significantly increased in serum of miscarriage patients. Fecal microbiome analyses indicate that microbial diversity and the relative abundances of Prevotella_1, Prevotellaceae_UCG_003 and Selenomonas_1 are significantly reduced in the cases. Correlation analyses indicate that some microbe-associated metabolites are positively associated with changes in levels of Th1/Th17 cytokines in the miscarriage group. Moreover, we identify that imidazolepropionic acid and 1,4-methylimidazoleacetic acid are associated with subsequent recurrent miscarriage. Our study highlights the network among gut microbiota, fecal metabolites and Th1/Th17-mediated immune response in miscarriage patients and explores the potential predictive values of two fecal metabolites for recurrent miscarriages.
OMO-1 reduces progression and enhances cisplatin efficacy in a 4T1-based non-c-MET addicted intraductal mouse model for triple-negative breast cancer
Authors: Steenbrugge Jonas , Vander Elst Niels , Demeyere Kristel , De Wever Olivier , Sanders Niek N. , Van Den Broeck Wim , Ciamporcero Eric , Perera Timothy , Meyer Evelyne
Published: March 2021

c-MET is considered a driver of cancer progression, impacting tumor growth and tumor-supporting stroma. Here, we investigated the therapeutic efficacy of OMO-1, a potent and selective c-MET inhibitor, in an immunocompetent intraductal mouse model for triple-negative breast cancer (TNBC). OMO-1 reduced non-c-MET addicted 4T1 tumor progression dose dependently as monotherapeutic and provided additional disease reduction in combination with cisplatin. At the stromal level, OMO-1 significantly reduced neutrophil infiltration in 4T1 tumors, promoted immune activation, and enhanced cisplatin-mediated reduction of tumor-associated macrophages. OMO-1 treatment also reduced 4T1 tumor hypoxia and increased expression of pericyte markers, indicative for vascular maturation. Corroborating this finding, cisplatin delivery to the 4T1 primary tumor was enhanced upon OMO-1 treatment, increasing cisplatin DNA-adduct levels and tumor cell death. Although verification in additional cell lines is warranted, our findings provide initial evidence that TNBC patients may benefit from OMO-1 treatment, even in cases of non-c-MET addicted tumors.
Facile fabrication of paper-based flexible thermoelectric generator
Authors: Dong Zuoyuan , Liu Hua , Yang Xin , Fan Jichen , Bi Hengchang , Wang Chaolun , Zhang Yonghua , Luo Chen , Chen Xinqian , Wu Xing
Published: March 2021

Paper, as a foldable, pollution-free, and low-cost material, has become a suitable support substrate for producing flexible thermoelectric (TE) generators to realize waste heat recycling and the application of human-powered electronic devices. We propose a facile fabrication method to modify cellulose paper with inorganic TE powders via vacuum filtration, making a modified paper that possesses good thermoelectric properties. By connecting the modified paper to copper foils, flexible paper-based TE generators (PTGs) are fabricated. The obtained PTG with three units of P–N modules can generate an output voltage of ∼41.2 mV at a temperature difference of 50 K. Based on this modified paper, a thermal sensor that responds to heat sources, such as fingers, is proposed with a rapid response time of 0.25 s. This work offers a promising strategy for the simple fabrication of PTGs, paving the way for achieving the commercial application of self-powered wearable electronics.