bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintain and Improve the Quality of Nutmeg Seeds (Myristica fragrans) through the on Farm to Postharvest Strategy on North Maluku
Authors: Sulistiono W , Assagaf M , Darniadi S , Wahab A 
Published: June 2022

Abstract
Nutmeg is a spice native to the North Maluku islands. The high and stable economic value of nutmeg has made this commodity a leading product for export, regional development and farmers' income. However, at the sales stage, not all of the nutmegs have high selling value. There are physical quality grades of seeds, namely A, B and C. The difference between the best grade A (whole seeds) and wrinkled B is IDR. 50,000; - 75,000; whereas grade C nutmeg is crushed (sticky nutmeg to the shell). In the optimal harvest conditions, 70-80% of the nutmegs are produced including grade A. Still, the large amount of nutmeg that goes to grade B (30-40%) makes farmers' income not optimal. Besides that, the quality of the aroma of nutmeg produced is in the form of essential oil content, low myristicin. To maintain the quality of nutmeg, technical efforts are needed in the field, on farm to postharvest. The technology for preparing superior seedlings from selected certified mother trees is the first step in developing nutmeg in order to obtain high quality and not sticky nutmeg. This step includes the production of generative and vegetative seedlings from the certified parent tree entries. The next step, the nutmeg harvest based on the ripeness of the fruit on the tree is about 80%, marked by the opening of the pulp. This step requires monitoring the condition of the fruit so that the harvest is simultaneous and on time to avoid falling fruit that has prolonged contact with the soil surface. The drying stage is carried out with a clean drying floor using sunlight or a drying machine. It is necessary to develop policies for integrated nutmeg commodity estate that carry out a production system with location-specific optimal technology, from garden optimization, harvesting techniques to drying.
Microscopic 3D printed optical tweezers for atomic quantum technology
Authors: Ruchka Pavel , Hammer Sina , Rockenhäuser Marian , Albrecht Ralf , Drozella Johannes , Thiele Simon , Giessen Harald , Langen Tim 
Published: June 2022

Abstract
Trapping of single ultracold atoms is an important tool for applications ranging from quantum computation and communication to sensing. However, most experimental setups, while very precise and versatile, can only be operated in specialized laboratory environments due to their large size, complexity and high cost. Here, we introduce a new trapping concept for ultracold atoms in optical tweezers based on micrometer-scale lenses that are 3D printed onto the tip of standard optical fibers. The unique properties of these lenses make them suitable for both trapping individual atoms and capturing their fluorescence with high efficiency. In an exploratory experiment, we have established the vacuum compatibility and robustness of the structures, and successfully formed a magneto-optical trap for ultracold atoms in their immediate vicinity. This makes them promising components for portable atomic quantum devices.
Graph-learning guided mechanistic insights into imipenem hydrolysis in GES carbapenemases
Authors: Song Zilin , Tao Peng 
Published: June 2022

Abstract
Pathogen resistance to carbapenem antibiotics compromises effective treatments of superbug infections. One major source of carbapenem resistance is the bacterial production of carbapenemases which effectively hydrolyze carbapenem drugs. In this computational study, the deacylation reaction of imipenem (IPM) by GES-5 carbapenemases (GES) is modeled to unravel the mechanistic factors that facilitate carbapenem resistance. Hybrid quantum mechanical/molecular mechanical (QM/MM) calculations are applied to sample the GES/IPM deacylation barriers on the minimum energy pathways (MEPs). In light of the recent emergence of graph-based deep-learning techniques, we construct graph representations of the GES/IPM active site. An edge-conditioned graph convolutional neural network (ECGCNN) is trained on the acyl-enzyme conformational graphs to learn the underlying correlations between the GES/IPM conformations and the deacylation barriers. A perturbative approach is proposed to interpret the latent representations from the graph-learning (GL) model and extract essential mechanistic understanding with atomistic detail. In general, our study combining QM/MM MEPs calculations and GL models explains mechanistic landscapes underlying the IPM resistance driven by GES carbapenemases. We also demonstrate that GL methods could effectively assist the post-analysis of QM/MM calculations whose data span high dimensionality and large sample-size.
Strategies to mitigate the on- and off-target toxicities of recombinant immunotoxins: an antibody engineering perspective
Authors: Li Mengyu , Mei Sen , Yang Yi , Shen Yuelei , Chen Lei 
Published: June 2022

Abstract
Targeted cancer therapies using immunotoxins have achieved remarkable efficacy in hematological malignancies. However, the clinical development of immunotoxins is also faced with many challenges like anti-drug antibodies and dose-limiting toxicity issues. Such a poor efficacy or safety ratio is also the major hurdle in the research and development of antibody-drug conjugates. From an antibody engineering perspective, various strategies were summarized or proposed to tackle the notorious on-target off-tumor toxicity issues, including passive strategy (XTENylation of immunotoxins) and active strategies (modulating the affinity and valency of the targeting moiety of immunotoxins, conditionally activating immunotoxins in the tumor microenvironments and reconstituting split toxin to reduce systemic toxicity, etc.). By modulating the functional characteristics of the targeting moiety and the toxic moiety of immunotoxins, selective tumor targeting can be augmented while sparing the healthy cells in normal tissues expressing the same target of interest. If successful, the improved therapeutic index will likely help to address the dose-limiting toxicities commonly observed in the clinical trials of various immunotoxins.
DURIAN: an integrative deconvolution and imputation method for robust signaling analysis of single-cell transcriptomics data
Authors: Karikomi Matthew , Zhou Peijie , Nie Qing 
Published: June 2022

Abstract
Single-cell RNA sequencing trades read-depth for dimensionality, often leading to loss of critical signaling gene information that is typically present in bulk data sets. We introduce DURIAN (Deconvolution and mUltitask-Regression-based ImputAtioN), an integrative method for recovery of gene expression in single-cell data. Through systematic benchmarking, we demonstrate the accuracy, robustness and empirical convergence of DURIAN using both synthetic and published data sets. We show that use of DURIAN improves single-cell clustering, low-dimensional embedding, and recovery of intercellular signaling networks. Our study resolves several inconsistent results of cell–cell communication analysis using single-cell or bulk data independently. The method has broad application in biomarker discovery and cell signaling analysis using single-cell transcriptomics data sets.
A Lipid Signature with Perturbed Triacylglycerol Co-Regulation, Identified from Targeted Lipidomics, Predicts Risk for Type 2 Diabetes and Mediates the Risk from Adiposity in Two Prospective Cohorts of Chinese Adults
Authors: Qiu Gaokun , Wang Hao , Yan Qi , Ma Hongxia , Niu Rundong , Lei Yanshou , Xiao Yang , Zhou Lue , Yang Handong , Xu Chengwei , Zhang Xiaomin , He Meian , Tang Huiru , Hu Zhibin , Pan An , Shen Hongbing , Wu Tangchun 
Published: June 2022

Abstract

Background
The roles of individual and co-regulated lipid molecular species in the development of type 2 diabetes (T2D) and mediation from metabolic risk factors remain unknown.

Methods
We conducted profiling of 166 plasma lipid species in 2 nested case-control studies within 2 independent cohorts of Chinese adults, the Dongfeng-Tongji and the Jiangsu non-communicable disease cohorts. After 4.61 (0.15) and 7.57 (1.13) years’ follow-up, 1039 and 520 eligible participants developed T2D in these 2 cohorts, respectively, and controls were 1:1 matched to cases by age and sex.

Results
We found 27 lipid species, including 10 novel ones, consistently associated with T2D risk in the 2 cohorts. Differential correlation network analysis revealed significant correlations of triacylglycerol (TAG) 50:3, containing at least one oleyl chain, with 6 TAGs, at least 3 of which contain the palmitoyl chain, all downregulated within cases relative to controls among the 27 lipids in both cohorts, while the networks also both identified the oleyl chain-containing TAG 50:3 as the central hub. We further found that 13 of the 27 lipids consistently mediated the association between adiposity indicators (body mass index, waist circumference, and waist-to-height ratio) and diabetes risk in both cohorts (all P &lt; 0.05; proportion mediated: 20.00%, 17.70%, and 17.71%, and 32.50%, 28.73%, and 33.86%, respectively).

Conclusions
Our findings suggested notable perturbed co-regulation, inferred from differential correlation networks, between oleyl chain- and palmitoyl chain-containing TAGs before diabetes onset, with the oleyl chain-containing TAG 50:3 at the center, and provided novel etiological insight regarding lipid dysregulation in the progression from adiposity to overt T2D.
Physical Activity in Adults With Crohn’s Disease: A Scoping Review
Authors: Neal Whitney N , Jones C Danielle , Pekmezi Dorothy , Motl Robert W 
Published: June 2022

AbstractBackgroundAs it becomes increasing clear that managing Crohn’s disease (CD) requires more than medical treatment alone, further research to identify second-line approaches for managing CD and its symptoms such as physical activity (PA) are necessary to address this public health concern.MethodsWe conducted a scoping review of descriptive, cross-sectional, and experimental studies to synthesize evidence regarding PA rates, determinants, health consequences, and interventions specifically in adults with CD. Adhering to the Preferred Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines, published literature was searched to identify articles that examined PA or exercise in adults with CD.ResultsTwenty-eight articles met inclusion criteria: 13 included a cross-sectional design, 4 a case–control design, 2 cohort designs, and 9 intervention designs. Adults with CD appear to be similar to somewhat less physically active than the general population, though self-report and objective rates of PA vary widely by geographical location. PA may be associated with the reduced risk of future active disease in adults with CD in clinical remission, as well as improve health-related quality of life, fatigue, cardiorespiratory fitness, and depression. Preliminary findings from interventional studies demonstrate that moderate-intensity PA is feasible, safe, and may have beneficial effects on disease activity.ConclusionsOverall, the benefits that can be accrued from regular PA are quite diverse; however, a substantially larger body of evidence is needed to provide firmer conclusions on the health benefits of PA that might underlie exercise-related changes in function and disease activity in adults with CD.
Diet and feeding behavior of a group of high-altitude rhesus macaques: high adaptation to food shortages and seasonal fluctuations
Authors: Zhang Kechu , Karim Fazal , Jin Zuxiang , Xiao Hongtao , Yao Yongfang , Ni Qingyong , Li Bajin , Pu-Cuo Wangjia , Huang Zhonghao , Xu Huailiang 
Published: June 2022

Abstract
Diet and feeding behavior data are crucial to a deep understanding of the behavioral response and adaptation of primates to a high-altitude environment. From August 2019 to June 2021, we collected data on the feeding behavior of a high-altitude rhesus macaque Macaca mulatta group from Yajiang County, Western Sichuan Plateau, which has an altitude of over 3,500 m. The results showed that feeding (33.0 ± 1.8%) and moving (28.3 ± 2.6%) were the dominant behavior of rhesus macaques. Macaques ate 193 food items, comprising 11 food categories from 90 species. Our study found that plant roots (30.9 ± 30.1%) and young leaves (28.0 ± 33.1%) were the main foods eaten by macaques. The preferred foods of rhesus macaques were young leaves, fruits, and seeds, and the consumption of these items was positively correlated with its food availability. When the availability of preferred foods was low, macaques took plant roots, barks, and fallen leaves as fallback foods. In particular, roots were a dominant food item in winter, and this way of feeding became a key survival strategy. Our results suggest that, facing the relative scarcity and strong seasonal fluctuations of food resources in high-altitude habitat, macaques adopt active foraging strategies, relying on a variety of food species and adjusting flexibly their food choices based on food availability, which may help to maximize the energy efficiency of high-altitude macaques.
Achievement of ESC/EAS LDL-C treatment goals after an acute coronary syndrome with statin and alirocumab
Authors: Landmesser Ulf , McGinniss Jennifer , Steg Ph Gabriel , Bhatt Deepak L , Bittner Vera A , Diaz Rafael , Dilic Mirza , Goodman Shaun G , Jukema J Wouter , Loy Megan , Pećin Ivan , Pordy Robert , Poulsen Steen H , Szarek Michael , White Harvey D , Schwartz Gregory G ,   for the ODYSSEY OUTCOMES Investigators
Published: June 2022

Abstract

Aims
European guidelines set low-density lipoprotein cholesterol (LDL-C) treatment goals &lt;1.4 mmol/L after acute coronary syndrome (ACS), and &lt;1.0 mmol/L for patients with recurrent cardiovascular events ≤2 years. Many ACS patients do not achieve these goals on statin alone. We examined actual goal achievement with alirocumab and projected achievement with ezetimibe, either added to optimized statin therapy.

Methods and results
The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18 924 patients with recent ACS and hyperlipidaemia despite high-intensity or maximum-tolerated statin therapy. This subanalysis comprised 17 589 patients with LDL-C ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment. High-intensity statin treatment was used in 88.8%. Median (interquartile range) baseline LDL-C was 2.3 (1.9−2.7) mmol/L. With alirocumab, 94.6% of patients achieved LDL-C &lt;1.4 mmol/L at ≥1 post-baseline measurement vs. 17.3% with placebo. Among 2236 patients with a previous cardiovascular event within 2 years (before the qualifying ACS), 85.2% vs. 3.5%, respectively, achieved LDL-C &lt;1.0 mmol/L. Among patients not treated with ezetimibe, we projected that its use would have achieved LDL-C &lt;1.4 and &lt;1.0 mmol/L in 10.6 and 0%, respectively, at baseline (assuming 18 ± 3% reduction of LDL-C).

Conclusion
Among patients with recent ACS and LDL-C ≥1.4 mmol/L despite optimized statin therapy, the addition of alirocumab allowed 94.6% to achieve the 2019 European guideline LDL-C goal &lt;1.4 mmol/L, and 85.2% of those with recurrent cardiovascular events to achieve &lt;1.0 mmol/L. In contrast, the addition of ezetimibe to optimized statin therapy was projected to achieve LDL-C &lt;1.4 mmol/L in only 10.6% of patients at baseline.
Self-reported daytime napping, daytime sleepiness, and other sleep phenotypes in the development of cardiometabolic diseases: a Mendelian randomization study
Authors: Jia Yiming , Guo Daoxia , Sun Lulu , Shi Mengyao , Zhang Kaixin , Yang Pinni , Zang Yuhan , Wang Yu , Liu Fanghua , Zhang Yonghong , Zhu Zhengbao 
Published: June 2022

AbstractAimsSleep disorders are associated with an increased risk of cardiometabolic diseases in observational studies, but the causality remains unclear. In this study, we leveraged two-sample Mendelian randomization (MR) analyses to assess the causal associations of self-reported daytime napping, daytime sleepiness, and other sleep phenotypes with cardiometabolic diseases including ischaemic stroke (IS), coronary artery disease (CAD), heart failure (HF), and Type 2 diabetes mellitus (T2DM).Methods and resultsWe selected genetic variants as instrumental variables for self-reported daytime napping, daytime sleepiness, morning person, insomnia, short sleep duration, and long sleep duration from European-descent genome-wide association studies (GWASs). Summary statistics for cardiometabolic diseases originated from four different GWASs with a total of 2 500 086 participants. We used the inverse-variance weighted method to explore the role of self-reported sleep phenotypes on the aetiology of cardiometabolic diseases in the main analyses, followed by several sensitivity analyses for robustness validation. Genetically predicted self-reported daytime napping [T2DM: OR, 1.56 (95% confidence interval, 1.21–2.02)], insomnia [IS: OR, 1.07 (1.04–1.11)]; CAD: OR, 1.13 (1.08–1.17); HF: OR, 1.10 (1.07–1.14); T2DM: OR, 1.16 (1.11–1.22); and short sleep duration [CAD: OR, 1.37 (1.21–1.55)] were causally associated with an elevated risk of cardiometabolic diseases. Moreover, genetically determined self-reported daytime sleepiness [CAD: OR, 2.05 (1.18–3.57); HF: OR, 1.82 (1.15–2.87)] and morning person [HF: 1.06 OR, (1.01–1.11)] had potential detrimental effect on cardiometabolic risks.ConclusionSelf-reported daytime napping, insomnia, and short sleep duration had causal roles in the development of cardiometabolic diseases, while self-reported daytime sleepiness and morning person was the potential risk factor for cardiometabolic diseases.
Evaluating Trade-Offs between Using Regional and Site-Specific Allometric Models to Predict Growing Stock Volume of Subtropical Atlantic Forests
Authors: Oliveira Laio Zimermann , Vibrans Alexander Christian 
Published: June 2022

Abstract
Choosing models to predict volume for individual trees is a relevant step in estimating growing stock volume. When large-area estimates are needed, models should ideally be constructed based on observations acquired across the population. However, due to multiple constraints, models are often constructed using samples collected at one or in a few sites. Therefore, this study aimed to evaluate trade-offs between using models based on a regional dataset (RD) and a model based on a local dataset (LD) and to assess the effects of such models on large-scale estimates of stem volume (V) per unit area. Regional and local V datasets and inventory data acquired throughout the subtropical Brazilian Atlantic Forest were employed. When used to predict V for trees of the RD (n = 1,192), the local model (LM), based on 419 tree observations, presented a mean systematic percentage error (MSPE) of +11%. In turn, when the regional model (RM) (n = 1,192) was used to predict V for trees of the LD (n = 419), it yielded an MSPE of –3%. The estimated mean V ha–1 using the LM was 9.4% greater than the estimated mean using the RM. Moreover, less precise estimates were attained using the LM.
Determination of mechanical properties of Zanthoxylum armatum using the discrete element method
Authors: Zhang Jian , Zhou Hong , Luo Fan , Wan Long , Li Chengsong , Wang Lihong 
Published: June 2022

Abstract
Using the discrete element method to investigate the behavior of particles is a crucial strategy in the research and development of novel equipment. Green pepper (Zanthoxylum armatum) is a globally renewable plant-derived medicinal and food homologous commodity with a wide range of uses and great demand, but the mechanical properties needed to develop its processing equipment are scarce. Thus, this case study aimed to systematically explore the necessary input parameters to model green pepper, and to provide new insights for the guidance of future industrial applications worldwide. On the basis of the experimental measured physical properties, the contact properties of green pepper on zinc-coated steel were first calibrated and then used to determine the contact properties between particles. The differences between the experimental and simulation results were analyzed for selection and verification of the contact properties accurately. Difference analysis confirmed that the coefficient of restitution, coefficient of static friction and coefficient of rolling friction for contact between the particle and zinc-coated steel have values of 0.392, 0.650, and 0.168, and those coefficients for particle-to-particle contact have values of 0.199, 0.710, and 0.184, respectively. Discoveries in this work may contribute to the research and development of production equipment for green pepper.
Temporal Analysis of Gene Expression and Isoform Switching in Brown Bears (Ursus arctos)
Authors: Perry Blair W , Armstrong Ellie E , Robbins Charles T , Jansen Heiko T , Kelley Joanna L 
Published: June 2022

AbstractHibernation in brown bears is an annual process involving multiple physiologically distinct seasons—hibernation, active, and hyperphagia. While recent studies have characterized broad patterns of differential gene regulation and isoform usage between hibernation and active seasons, patterns of gene and isoform expression during hyperphagia remain relatively poorly understood. The hyperphagia stage occurs between active and hibernation seasons and involves the accumulation of large fat reserves in preparation for hibernation. Here, we use time-series analyses of gene expression and isoform usage to interrogate transcriptomic regulation associated with all three seasons. We identify a large number of genes with significant differential isoform usage (DIU) across seasons and show that these patterns of isoform usage are largely tissue-specific. We also show that DIU and differential gene-level expression responses are generally non-overlapping, with only a small subset of multi-isoform genes showing evidence of both gene-level expression changes and changes in isoform usage across seasons. Additionally, we investigate nuanced regulation of candidate genes involved in the insulin signaling pathway and find evidence of hyperphagia-specific gene expression and isoform regulation that may enhance fat accumulation during hyperphagia. Our findings highlight the value of using temporal analyses of both gene- and isoform-level gene expression when interrogating complex physiological phenotypes and provide new insight into the mechanisms underlying seasonal changes in bear physiology.
Is shorter always better? The pros and cons of treating Gram-negative bloodstream infections with 7 days of antibiotics
Authors: Yahav Dafna , Paul Mical , Van Nieuwkoop Cees , Huttner Angela 
Published: June 2022

Abstract
Accumulating evidence from randomized controlled trials (RCTs) supports 7 days treatment for uncomplicated Gram-negative bacteraemia. However, some patient populations were not well represented in these RCTs, including critically ill patients, immunocompromised patients and those with MDR bacteria. In this debate document, we discuss the pros and cons for treating patients with Gram-negative bacteraemia with a 7 day antibiotic course. We surmise that the patients who were not well represented in the RCTs are probably those who have most to lose from the drawbacks of prolonged antibiotic courses, including adverse events, superinfections and resistance development. Treatment durations among these patients can be managed individually, with C-reactive protein or procalcitonin guidance or by clinical measures, and with care to discontinue antibiotics as soon as the patient recovers clinically from the infection.