bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating traditional and complementary medicines: Where do we go from here?
Authors: Lin Lydia Wenxin , Ananthakrishnan Aparna , Teerawattananon Yot 
Published: March 2021

Abstract
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.
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

AbstractDrainage 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

AbstractAs 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

AbstractA 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

AbstractEolian 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

Abstract
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

Abstract
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

AbstractThis 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

AbstractAnkylosing 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

AbstractOsteoarthritis 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

AbstractAnti-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

Abstract
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

AbstractA 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

Abstractc-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

AbstractPaper, 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.