bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implications of antibiotics use during the COVID-19 pandemic: present and future
Authors: Miranda Carla , Silva Vanessa , Capita Rosa , Alonso-Calleja Carlos , Igrejas Gilberto , Poeta Patrícia 
Published: July 2020

Abstract
COVID-19 is caused by the SARS-CoV-2 virus, which has infected more than 4 million people with 278 892 deaths worldwide as of 11 May 2020. This disease, which can manifest as a severe respiratory infection, has been declared as a public health emergency of international concern and is being treated with a variety of antivirals, antibiotics and antifungals. This article highlights the administration of antimicrobials in COVID-19 patients worldwide, during the 2019–20 pandemic. It is imperative to be aware of the unreported amounts of antibiotics that have been administered worldwide in just a few months and a marked increase in antimicrobial resistance should therefore be expected. Due to the lack of data about antimicrobial use during this pandemic, the global impact on the emergence of new antimicrobial resistance is as yet unknown. This issue must be at the forefront of public health policymaking and planning in order that we are prepared for the potentially severe consequences for human and animal health and the environment.
Clinical concept normalization with a hybrid natural language processing system combining multilevel matching and machine learning ranking
Authors: Chen Long , Fu Wenbo , Gu Yu , Sun Zhiyong , Li Haodan , Li Enyu , Jiang Li , Gao Yuan , Huang Yang 
Published: July 2020

AbstractObjectiveNormalizing clinical mentions to concepts in standardized medical terminologies, in general, is challenging due to the complexity and variety of the terms in narrative medical records. In this article, we introduce our work on a clinical natural language processing (NLP) system to automatically normalize clinical mentions to concept unique identifier in the Unified Medical Language System. This work was part of the 2019 n2c2 (National NLP Clinical Challenges) Shared-Task and Workshop on Clinical Concept Normalization.Materials and MethodsWe developed a hybrid clinical NLP system that combines a generic multilevel matching framework, customizable matching components, and machine learning ranking systems. We explored 2 machine leaning ranking systems based on either ensemble of various similarity features extracted from pretrained encoders or a Siamese attention network, targeting at efficient and fast semantic searching/ranking. Besides, we also evaluated the performance of a general-purpose clinical NLP system based on Unstructured Information Management Architecture.ResultsThe systems were evaluated as part of the 2019 n2c2 challenge, and our original best system in the challenge obtained an accuracy of 0.8101, ranked fifth in the challenge. The improved system with newly designed machine learning ranking based on Siamese attention network improved the accuracy to 0.8209.ConclusionsWe demonstrate the successful practice of combining multilevel matching and machine learning ranking for clinical concept normalization. Our results indicate the capability and interpretability of our proposed approach, as well as the limitation, suggesting the opportunities of achieving better performance by combining general clinical NLP systems.
Remote symptom monitoring integrated into electronic health records: A systematic review
Authors: Gandrup Julie , Ali Syed Mustafa , McBeth John , van der Veer Sabine N , Dixon William G 
Published: July 2020

Abstract

Objective
People with long-term conditions require serial clinical assessments. Digital patient-reported symptoms collected between visits can inform these, especially if integrated into electronic health records (EHRs) and clinical workflows. This systematic review identified and summarized EHR-integrated systems to remotely collect patient-reported symptoms and examined their anticipated and realized benefits in long-term conditions.

Materials and Methods
We searched Medline, Web of Science, and Embase. Inclusion criteria were symptom reporting systems in adults with long-term conditions; data integrated into the EHR; data collection outside of clinic; data used in clinical care. We synthesized data thematically. Benefits were assessed against a list of outcome indicators. We critically appraised studies using the Mixed Methods Appraisal Tool.

Results
We included 12 studies representing 10 systems. Seven were in oncology. Systems were technically and functionally heterogeneous, with the majority being fully integrated (data viewable in the EHR). Half of the systems enabled regular symptom tracking between visits. We identified 3 symptom report-guided clinical workflows: Consultation-only (data used during consultation, n = 5), alert-based (real-time alerts for providers, n = 4) and patient-initiated visits (n = 1). Few author-described anticipated benefits, primarily to improve communication and resultant health outcomes, were realized based on the study results, and were only supported by evidence from early-stage qualitative studies. Studies were primarily feasibility and pilot studies of acceptable quality.

Discussion and Conclusions
EHR-integrated remote symptom monitoring is possible, but there are few published efforts to inform development of these systems. Currently there is limited evidence that this improves care and outcomes, warranting future robust, quantitative studies of efficacy and effectiveness.
The effects of the forage-to-concentrate ratio on the conversion of digestible energy to metabolizable energy in growing beef steers
Authors: Fuller Amanda L , Wickersham Tryon A , Sawyer Jason E , Freetly Harvey C , Brown-Brandl Tami M , Hales Kristin E 
Published: July 2020

Abstract
Metabolizable energy (ME) is calculated from digestible energy (DE) using a constant conversion factor of 0.82. Methane and urine energy losses vary across diets and dry matter intake (DMI), suggesting that a static conversion factor fails to describe the biology. To quantify the effects of the forage-to-concentrate ratio (F:C) on the efficiency of conversion of DE to ME, 10 Angus steers were used in a 5 × 5 replicated Latin square. Dry-rolled corn was included in experimental diets at 0%, 22.5%, 45.0%, 67.5%, and 83.8% on a dry matter (DM) basis, resulting in a high F:C (HF:C), intermediate F:C (IF:C), equal F:C (EF:C), low F:C (LF:C), and a very low F:C (VLF:C), respectively. Each experimental period consisted of a 23-d diet adaption followed by 5 d of total fecal and urine collections and a 24-h gas exchange collection. Contrasts were used to test the linear and quadratic effects of the F:C. There was a tendency (P = 0.06) for DMI to increase linearly as F:C decreased. As a result, gross energy intake (GEI) increased linearly (P = 0.04) as F:C decreased. Fecal energy loss expressed as Mcal/d (P = 0.02) or as a proportion of GEI (P &lt; 0.01) decreased as F:C decreased, such that DE (Mcal/d and Mcal/kg) increased linearly (P &lt; 0.01) as F:C decreased. As a proportion of GEI, urine energy decreased linearly (P = 0.03) as F:C decreased. Methane energy loss as a proportion of GEI responded quadratically (P &lt; 0.01), increasing from HF:C to IF:C then decreasing thereafter. The efficiency of DE to ME conversion increased quadratically (P &lt; 0.01) as F:C decreased, ranging from 0.86 to 0.92. Heat production (Mcal) increased linearly (P &lt; 0.04) as F:C decreased but was not different as a proportion of GEI (P ≥ 0.22). As a proportion of GEI, retained energy responded quadratically (P = 0.03), decreasing from HF:C to IF:C and increasing thereafter. DM, organic matter, and neutral detergent fiber digestibility increased linearly (P &lt; 0.01) and starch digestibility decreased linearly (P &lt; 0.01) as the F:C decreased. Total N retained tended to increase linearly as the proportion of concentrate increased in the diet (P = 0.09). In conclusion, the efficiency of conversion of DE to ME increased with decreasing F:C due to decreasing methane and urine energy loss. The relationship between DE and ME is not static, especially when differing F:C.
P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency
Authors: Rachadech Wanitcha , Kato Yusuke , Abou El-Magd Rabab M , Shishido Yuji , Kim Soo Hyeon , Sogabe Hirofumi , Maita Nobuo , Yorita Kazuko , Fukui Kiyoshi 
Published: July 2020

AbstractHuman D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at Position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7–0.9 µM) compared with wild-type (1.2–2.0 µM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. This study provides new insights into the structure–function relationship of human DAO.
Prevalence and associated factors of perceived cancer-related stigma in Japanese cancer survivors
Authors: Fujisawa Daisuke , Umezawa Shino , Fujimori Maiko , Miyashita Mitsunori 
Published: July 2020

Abstract
This study aimed to examine the prevalence and associated factors of perceived cancer-related stigma among Japanese cancer survivors. In this web-based survey involving 628 Japanese cancer survivors, perceived cancer-related stigma, quality of life (Quality of Life-Cancer Survivors Instrument), psychological distress (K6) and perceived social support (multidimensional scale of perceived social support) were evaluated. Perceived cancer-related stigma was endorsed by 61.2% of the participants. Perceived cancer-related stigma was significantly associated with quality of life (R = 0.35–0.37), psychological distress (R = 0.35) and perceived social support (R = 0.10). Logistic regression analysis demonstrated that cancer survivors at younger ages (odds ratio = 0.96), with low income (odds ratio = 2.49), with poorer performance status (odds ratio = 2.33), and with breast, urinary or gynecological cancers (odds ratio = 4.27, 4.01, 4.01, respectively) were at higher risk for perceived cancer-related stigma.
International transfers of health data between the EU and USA: a sector-specific approach for the USA to ensure an ‘adequate’ level of protection
Authors: Bradford Laura , Aboy Mateo , Liddell Kathleen 
Published: July 2020

Abstract
International health research increasingly depends on collaboration and combination using medical data to advance treatment and drug discovery. The European Union (EU), through its General Data Protection Regulation, has tightened the rules for sharing data across borders to protect individual privacy. These new rules threaten cooperation between the EU and the USA, the two largest public funders of biomedical research. This article analyzes the primary pathway for sharing research data with the USA, the US–EU Privacy Shield††, and argues that the Shield is ill-suited to support complex health studies. Its legitimacy is in question under both EU and US law, and its terms are too restrictive for the variety of exchanges underlying research, treatment, and care. As an alternative, we propose that the USA seek an additional sector-based adequacy determination based on the existing US health privacy law, the Health Insurance Portability and Accountability Act. A sector-specific approach to adequacy for health would avoid many of the most contentious issues that divide the USA and EU on data protection. It could also serve as a model for other third-party jurisdictions and facilitate international harmonization of health research practices.
MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment
Authors: Wang Bing , Lim Chuan-Bian , Yan Jiawei , Li Lizhen , Wang Jufang , Little John B , Yuan Zhi-Min 
Published: July 2020

Abstract
A role of tumor-suppressive activity of p53 in the tumor microenvironment (TME) has been implicated but remains fairly understudied. To address this knowledge gap, we leveraged our MdmxS314A mice as recipients to investigate how implanted tumor cells incapacitate host p53 creating a conducive TME for tumor progression. We found that tumor cell-associated stress induced p53 downregulation in peritumor cells via an MDMX-Ser314 phosphorylation-dependent manner. As a result, an immunosuppressive TME was developed, as reflected by diminished immune cell infiltration into tumors and compromised macrophage M1 polarization. Remarkably, ablation of MDMX-Ser314 phosphorylation attenuated p53 decline in peritumor cells, which was associated with mitigation of immunosuppression and significant tumor growth delay. Our data collectively uncover a novel role of p53 in regulating the tumor immune microenvironment, suggesting that p53 restoration in the TME can be exploited as a potential strategy of anticancer therapy.
Contesting Roles: Rising Powers as “Net Providers of Security”
Authors: Fung Courtney J , Lam Shing-hon 
Published: July 2020

AbstractWhat is a “net provider of security,” or a “global security provider”? How are such roles adopted by rising powers? We define a net provider of security as a social role, when an actor provides novel, niche, and functionally differentiated security duties, supporting burden-sharing in providing public goods. The nascent literature on these US-vectored roles characterizes role adoption as largely successful. However, rising powers contest the US-designated net provider of security role. Rising powers have stated or latent foreign policy goals to shape international order in their strategic vision, reflecting ideational capacity to reconceptualize their role in global politics, or a material capacity to reposition their rank. Building upon insights from role theory, we illustrate that rising powers exploit temporal and rhetorical ambiguities and leverage their material and ideational resources to execute role differentiation through three micro-processes of role resistance—role acknowledgment, role task rejection, and role task substitution—used to promote an idiosyncratic role, casting the US-vectored role as non-functional, non-representational, and untenable. We examine crucial cases of rising powers, India and China, to develop our theoretical contribution. Our findings speak to the literatures on the logic of identity management, rhetoric in international politics, the taxonomy of contemporary ad hoc security arrangements, and the epistemological project of globalizing international relations.
Overexpression of the chloroplastic 2-oxoglutarate/malate transporter disturbs carbon and nitrogen homeostasis in rice
Authors: Zamani-Nour Shirin , Lin Hsiang-Chun , Walker Berkley J , Mettler-Altmann Tabea , Khoshravesh Roxana , Karki Shanta , Bagunu Efren , Sage Tammy L , Quick W Paul , Weber Andreas P M 
Published: July 2020

Abstract
The chloroplastic 2-oxaloacetate (OAA)/malate transporter (OMT1 or DiT1) takes part in the malate valve that protects chloroplasts from excessive redox poise through export of malate and import of OAA. Together with the glutamate/malate transporter (DCT1 or DiT2), it connects carbon with nitrogen assimilation, by providing 2-oxoglutarate for the GS/GOGAT (glutamine synthetase/glutamate synthase) reaction and exporting glutamate to the cytoplasm. OMT1 further plays a prominent role in C4 photosynthesis: OAA resulting from phosphoenolpyruvate carboxylation is imported into the chloroplast, reduced to malate by plastidic NADP-malate dehydrogenase, and then exported for transport to bundle sheath cells. Both transport steps are catalyzed by OMT1, at the rate of net carbon assimilation. To engineer C4 photosynthesis into C3 crops, OMT1 must be expressed in high amounts on top of core C4 metabolic enzymes. We report here high-level expression of ZmOMT1 from maize in rice (Oryza sativa ssp. indica IR64). Increased activity of the transporter in transgenic rice was confirmed by reconstitution of transporter activity into proteoliposomes. Unexpectedly, overexpression of ZmOMT1 in rice negatively affected growth, CO2 assimilation rate, total free amino acid content, tricarboxylic acid cycle metabolites, as well as sucrose and starch contents. Accumulation of high amounts of aspartate and the impaired growth phenotype of OMT1 rice lines could be suppressed by simultaneous overexpression of ZmDiT2. Implications for engineering C4 rice are discussed.
Developmentally controlled changes during Arabidopsis leaf development indicate causes for loss of stress tolerance with age
Authors: Kanojia Aakansha , Gupta Saurabh , Benina Maria , Fernie Alisdair R , Mueller-Roeber Bernd , Gechev Tsanko , Dijkwel Paul P 
Published: July 2020

AbstractLeaf senescence is the final stage of leaf development and is induced by the gradual occurrence of age-related changes (ARCs). The process of leaf senescence has been well described, but the cellular events leading to this process are still poorly understood. By analysis of progressively ageing, but not yet senescing, Arabidopsis thaliana rosette leaves, we aimed to better understand processes occurring prior to the onset of senescence. Using gene expression analysis, we found that as leaves mature, genes responding to oxidative stress and genes involved in stress hormone biosynthesis and signalling were up-regulated. A decrease in primary metabolites that provide protection against oxidative stress was a possible explanation for the increased stress signature. The gene expression and metabolomics changes occurred concomitantly to a decrease in drought, salinity, and dark stress tolerance of individual leaves. Importantly, stress-related genes showed elevated expression in the early ageing mutant old5 and decreased expression in the delayed ageing mutant ore9. We propose that the decreased stress tolerance with age results from the occurrence of senescence-inducing ARCs that is integrated into the leaf developmental programme, and that this ensures a timely and certain death.
The zinc finger transcription factor ATF1 regulates aluminum tolerance in barley
Authors: Wu Liyuan , Guo Yiyi , Cai Shengguan , Kuang Liuhui , Shen Qiufang , Wu Dezhi , Zhang Guoping 
Published: July 2020

Abstract
Aluminum (Al) toxicity is a major abiotic stress that restricts crop production in acid soils. Plants have evolved internal and external mechanisms of tolerance, and among them it is well known that AtSTOP1 and OsART1 are key transcription factors involved in tolerance through regulation of multiple downstream genes. Here, we identified the closest homolog of these two proteins in barley, namely HvATF1, Al-tolerance Transcription Factor 1, and determined its potential function in Al stress. HvATF1 is expressed in the nucleus, and functions in transcriptional activation. The transcription of HvATF1 was found to be constitutive in different tissues, and was little affected by Al stress. Knockdown of HvATF1 by RNAi resulted in increased Al sensitivity. Transcriptomics analysis identified 64 differently expressed genes in the RNAi lines compared to the wild-type, and these were considered as candidate downstream genes regulated by HvATF1. This study provides insights into the different molecular mechanisms of Al tolerance in barley and other plants.
Plasma Cell Proliferation Is Reduced in Myeloma-Induced Hypercalcemia and in Co-Culture with Normal Healthy BM-MSCs
Authors: Vazifeh Shiran Nader , Abroun Saeid 
Published: July 2020

AbstractObjectiveIn multiple myeloma (MM), stimulation of osteoclasts and bone marrow (BM) lesions lead to hypercalcemia, renal failure, and anemia. Co-culture of the myeloma cells in both hypocalcemia and hypercalcemia concentrations with bone marrow-mesenchymal stem cells were evaluated.Materials and MethodsViability and survival of myeloma cells were assessed by microculture tetrazolium test and flow cytometric assays. Mesenchymal stem cells (MSCs) were extracted from normal and myeloma patients and were co-cultured with myeloma cells.ResultsMyeloma cells showed less survival in both hypocalcaemia and hypercalcemia conditions (P &lt;.01). The paracrine and juxtacrine conditions of demineralized bone matrix-induced hypercalcemia increased the proliferation and survival of the cells (P &lt;.05). Unlike myeloma MSCs, normal MSCs reduced the survival of and induced apoptosis in myeloma cells (P &lt;.1).ConclusionNormal healthy-MSCs do not protect myeloma cells, but inhibit them. However, increasing the ratio of myeloma cells to MSCs reduces their inhibitory effects of MSCs and leads to their myelomatous transformation.
Neolog: Reforming Judaism in a Hungarian Milieu
Authors: Lupovitch Howard 
Published: July 2020

Abstract
This article explores the mentality of Neolog Judaism and how its early proponents fashioned a centrist, non-ideological alternative to both Orthodoxy and German-Jewish style Reform Judaism, an alternative that emphasized Judaism’s inherent compatibility with and adaptability to the demands of citizenship. Early proponents of this Neolog mentality, such as Aron Chorin and Leopold Löw, argued that adapting Jewish practice within the framework and systemic rules of Jewish law, precedent, and custom would not undermine a commitment to traditional Judaism in any way, as Orthodox jeremiads predicted; nor would it require the sort of re-definition of Judaism that Reform Jews advocated. Four aspects of Neolog mentality, in particular, laid the foundation for this outlook: a belief that Judaism has always been inherently malleable and diverse; a willingness to see leniency as no less authentic an option than stringency (in contrast to the “humra culture” that has defined Orthodox Judaism for the last two centuries); a preference for unity over schism (contra the secession of Orthodox communities in Germany and Hungary); and the use of halachic precedent and argumentation as a mandatory part of the rationale for innovation.