bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of biofilms developed from alginate extracted from Padina sp. incorporated with calcium chloride (CaCl2)
Authors: Hanry E L , Redzwan N F M , Badeges N F A K , Surugau N
Published: August 2022

Seaweed has been used in many industries, whether directly or its extract. Padina sp. is one of the understudied species of brown seaweed. Brown seaweed have alginate embedded in their cell wall which is a type of hydrocolloids and can be used in many industries and applications including development of biofilms. The main objective of this current study is to develop biofilms using alginate extracted from Padina sp. and incorporated with calcium chloride at different concentrations. Prior to that, the functional groups of Padina sp. and alginate extract were determined. Then, functional groups, surface morphology, mechanical properties, swelling ability and biodegradability of the biofilms were studied using standard methods. The results showed that there were no significant changes in their FTIR spectra with increasing CaCl2 content. Surface morphology showed improvement in bonding while mechanical properties showed the best tensile strength of 9.43mm and 8.61mm elongation-at-break (EAB) after addition of 0.12g CaCl2. As for their swelling and biodegradability, the samples were completely dissolved after one hour and degraded after 24 hours. This shows that the biofilms with CaCl2 indeed improve the quality of alginate-based biofilms which can further be studied to improve other aspects such as water sorption kinetic and thermal stability.
Geochemical Distribution of Heavy Metals in Peat Soil Profile and Estimation of Water Table Patterns in Peatland at Klias Peninsular, Sabah.
Authors: Zamri S N M , Saleh H , Musta B
Published: August 2022

The geochemical distribution of heavy metals in peat soil profile and estimation of water table patterns of peatland in oil palm plantation were carried out in the Klias Peninsular West Coast of Sabah. The geological setting of the Klias Peninsular mainly consists of the Crocker Formation and Quaternary Alluvium which in mainly composed of peat soil. The peat soil from 10 sites were collected for the geochemical analysis. The geophysical surveys were performed to measure the water table, which influenced the concentration of trace metals. The geochemical analysis of the peat soil at 0-6m depth shows an acidic pH value (3.0-4.0), moisture content (90%-1000%) and organic matter content (30-99) %. The texture of the peat soil profile varies from peat at the top of profile to silty clay at the bottom of the peat profile. The result of geochemical analysis shows that the element of Fe has the highest concentration (37.54-2049.18)mg/kg and followed by Zn(5.13-270.06)mg/kg, Mn(0.1-253.56)mg/kg, Pb(0.71-157.46)mg/kg, Cr(0.05-152.62)mg/kg, Ni(0.1-64.48) mg/kg and Cu(1.81-61.39)mg/kg. The water table ranging from (0.25m-0.3m) induced the oxidation of Fe. The concentration of Fe2+ tends to absorb other elements such as Zn and Mn. Whereas, the organic matter at pH value (5-5.5) enhanced the absorption of elements Pb, Cr, Ni and Cu in the peat soil profile.
Study of Composition and Surface Morphology of Seaweed as Biosorbent: A Review
Authors: Mingu N , Aziz S A , Stidi E Y , Majid M H A , Idris J , Sarjadi M S
Published: August 2022

Heavy metal contamination is harmful to living creatures and deteriorate environment. Adsorption of heavy metal by biomass as adsorbent been the best alternative for heavy metal removal. Despite abundance of biomass as biosorbent, approach on adsorption by seaweed been studied because of its prominence benefits such as accessibility, minimal cost and ease of use. Some metal can be accumulated by seaweed without causing any hazardous by product. Thus, sorption of heavy metal by seaweed as biosorbent is studied. In this article, relationship between adsorption of heavy metal ions with composition and surface morphology of seaweeds are reviewed. Tables used to summarise the difference of composition and morphology of seaweed after treated with metal.
Climate impact emergence and flood peak synchronization projections in the Ganges, Brahmaputra and Meghna basins under CMIP5 and CMIP6 scenarios
Authors: Gädeke Anne , Wortmann Michel , Menz Christoph , Islam AKM Saiful , Masood Muhammad , Krysanova Valentina , Lange Stefan , Hattermann Fred Fokko
Published: August 2022

The densely populated delta of the three river systems of the Ganges, Brahmaputra and Meghna is highly prone to floods. Potential climate change-related increases in flood intensity are therefore of major societal concern as more than 40 million people live in flood-prone areas in downstream Bangladesh. Here we report on new flood projections using a hydrological model forced by bias-adjusted ensembles of the latest-generation global climate models of CMIP6 (SSP5-8.5/SSP1-2.6) in comparison to CMIP5 (RCP8.5/RCP2.6). Results suggest increases in peak flow magnitude of 36% (16%) on average under SSP5-8.5 (SSP1-2.6), compared to 60% (17%) under RCP8.5 (RCP2.6) by 2070–2099 relative to 1971–2000. Under RCP8.5/SSP5-8.5 (2070–2099), the largest increase in flood risk is projected for the Ganges watershed, where higher flood peaks become the ‘new norm’ as early as mid-2030 implying a relatively short time window for adaptation. In the Brahmaputra and Meghna rivers, the climate impact signal on peak flow emerges after 2070 (CMIP5 and CMIP6 projections). Flood peak synchronization, when annual peak flow occurs simultaneously at (at least) two rivers leading to large flooding events within Bangladesh, show a consistent increase under both projections. While the variability across the ensemble remains high, the increases in flood magnitude are robust in the study basins. Our findings emphasize the need of stringent climate mitigation policies to reduce the climate change impact on peak flows (as presented using SSP1-2.6/RCP2.6) and to subsequently minimize adverse socioeconomic impacts and adaptation costs. Considering Bangladesh’s high overall vulnerability to climate change and its downstream location, synergies between climate change adaptation and mitigation and transboundary cooperation will need to be strengthened to improve overall climate resilience and achieve sustainable development.
Recognition of asphalt road hazards based on high-density gray point clouds
Authors: Tang Chao , Xia Mengxuan , Fan Tingli , Wang Li , Yu Haibin , Xu Yiqun , Hou Haiqian , Wang Xiaojing
Published: August 2022

Road hazards can lead to dangerous accidents and endanger the safety of pedestrians. Frequent and thorough road inspection is required to maintain road safety. This paper proposes an improved U-Net model that combines gray-scale images and depth images and uses a data statistics method based on a road depth map to eliminate hazard-free data automatically and reduce the computational complexity involved in hazard detection. Experiments showed that the proposed model, based on the improved U-Net-based pavement hazard recognition and extraction algorithm, could smoothly and efficiently extract pavement cracks and deformation hazards in complex scenes with noise interference and produce results with strong robustness. Comprehensive indicators such as global recognition accuracy rate A (Accuracy), precision rate P (Precision), recall rate R (Recall), evaluation index F1 (F -Measure), and Mean Intersection over Union (MIoU) were used to assess the effectiveness of the proposed model in comparison with existing hazard detection models; the proposed model greatly outperformed the models in all the indicators. The proposed model can provide a significant reference for subsequent pavement repair work and be used to improve road safety.
The context of American elections and political parties
Authors: Maisel L. Sandy
Published: August 2022

“The Context of American Elections and Political Parties” explains the framework under which elections are run in the United States. This is laid out in the Constitution, which outlines the basic tenets of democracy in America. The most important aspects of that framework are the separation of powers, with a single executive separate from and elected separately from the legislature, and the federal system with residual powers left to the states. The Electoral College system, unique to the United States, is a result of the initial decisions made at the time of the framing of the Constitution.
A brief history of American political parties
Authors: Maisel L. Sandy
Published: August 2022

“A Brief History of American Political Parties” traces the development of US politics from the initial emergence of parties as the Founders differed on policies they believed served the nation’s interests. The modern Democratic Party has transformed from its early manifestation as the Democratic-Republican Party, while the Republican Party was formed as a result of the division over slavery and eclipsed earlier parties, including the National Republicans and Whigs, as the major alternative to the Democrats. Despite party changes, the election process remains the same; it is still about organizing, understanding the rules and the voters, and knowing how to appeal to the voters most efficiently under the rules.
Party organizations:
Authors: Maisel L. Sandy
Published: August 2022

“Party organizations: What Do They Look Like? What Do They Do?” examines each of those questions and reveals that political party organizations in the United States reflect the nation’s federal system. The party is organized at each electoral level. The main purpose of the party is to assist their candidates to get into office. The party organization does not define party policy nor do its leaders exercise much authority over those elected under the party label. This is a situation that has changed markedly over the past century as changes have taken place in the electoral process.
Who are Republicans? Who are Democrats? Who are the “others”?
Authors: Maisel L. Sandy
Published: August 2022

“Who Are Republicans? Who Are Democrats? Who Are the ‘Others’?” looks at party affiliation and the different relationships citizens have with political parties. Most American citizens have no formal affiliation with a political party, but hold a strong impression of what the two major parties stand for. Many who consider themselves independent will vote for either Democrats or Republicans. Candidates run with the support of party organizations, and once elected, they identify with a party label but exercise a great deal of independence, while the electorate frequently switches support from one party to another.
Anarchism: A Very Short Introduction
Authors: Prichard Alex
Published: August 2022

This short book provides a new point of departure for our understanding of anarchism. It questions standard understandings of anarchy and anarchism as an ideology of chaos and disorder, and sheds new light on anarchism as a lived set of prefigurative practices, with a rich historical legacy. The book explores anarchist approaches to public health provision, education, work, law and order, and world politics, including topics of war and violence, federalism, and climate change. By locating the emergence of anarchist ideas in a global history of colonialism and imperialism, it links anarchism into struggles for freedom across the world, and argues that anarchism still holds value for thinking about new models of freedom and democracy today.
The globalization of anarchism
Authors: Prichard Alex
Published: August 2022

Why did anarchism became a global movement so quickly? To answer this question we need to see how anarchism emerged in the context of the first wave of globalization, around the middle of the 19th century. Anarchism was carried worldwide on the winds of colonization and industrialization, and appealed to peasants and landless workers, expropriated during the enclosures of the 19th century, and then took root in the emerging industrial unions worldwide. Anarchism also infused anti-colonial movements and struggles worldwide by the turn of the 20th century. Anarchism (and its synonyms, libertarian communism and anarcho-syndicalism) was the most prominent revolutionary ideology prior to the Second World War.
Anarchism and world politics
Authors: Prichard Alex
Published: August 2022

This last chapter explores three challenges to anarchist thought: violence, climate change, and global governance. What do anarchists have to say about these issues? The history of anarchist terrorism and anarchist pacifism is explored in the context of the discovery of dynamite and the emergence of nation states. The discussion then turns to how anarchists have understood climate change and emerged as the most vocal and active wing of the environmental movement over the past 30 years. Finally, the anarchist approach to federalism and global governance offers a constitutional framework for linking up myriad experiments in prefigurative lifestyles and communities, a global anarchy underpinned by a new theory of freedom.
Calculation
Authors: Swade Doron
Published: August 2022

This chapter describes the history of physical aids used for calculation, from pebbles (calculi) to the desktop mechanical calculators of the early 20th century. It deals with the variety of manual instruments, devices, and mechanisms used to augment human capacity to count and calculate. It traces pre-electronic development from the techniques of antiquity (knotted cords, the abacus), through instruments and scaled devices with graduated markings, including slide rules. It concludes with the mechanical calculators of the office appliance industry of the 1920s and 1930s. It uses a 17th-century quadrant by William Leybourn to identify the defining features of scaled devices and to examine the sense in which such devices can be said to compute. It identifies three features that assist in structuring pre-electronic histories of such devices and aids: the way number is physicalized (representation), the ways in which representations are manipulated (mechanization), and the extent to which human agency is embodied in the machine (automation). It describes the distinction between analogue and digital devices, and explains the concepts of precision, noise immunity, and algorithm. It describes the 17th-century mechanical calculators of Schickard, Pascal, and Leibniz, and a revisionist account of Leibniz’s role is considered. The arithmometer of Thomas de Colmar is presented as a turning point. It briefly describes the industry, based on pinwheel desktop calculators in the 19th century, rivalries, and competition for markets. The overlaps in product life of various device classes are illustrated diagrammatically.
Automatic computation
Authors: Swade Doron
Published: August 2022

This chapter describes automatic computation in the pre-electronic era, i.e. up to the late 1930s. It traces the main systems devised using mechanical and electromechanical technologies to perform numerical computation. Analogue and digital computers are described. It introduces automatic digital computation through the 19th-century mechanical calculating engines of Charles Babbage. It explores his aspirations for machine computation and his collaboration with Ada Lovelace. It offers correctives to received perceptions. It describes the principles and use of analogue computers for calculation and for solving equations, including Kelvin’s tide predictor, Phillips’ economics computer, and Bush’s electrically driven differential analysers. It traces the revival of automatic digital computation through initiatives in Germany and the US: Zuse’s mechanical and electromechanical machines in Berlin, the machines of Stibitz at Bell Labs using electromechanical relays, and Aiken’s hybrid machine, the Harvard Mark. I. It demonstrates examples of two repeated themes: the challenges of emerging new technologies and the stimulus of war. It discusses the ambitions for the machines and the uses to which they were put. Each is located in the overall developmental arcs of industry, use, and public perception. It recounts the misunderstood origin story of the word ‘bug’.
The computer boom
Authors: Swade Doron
Published: August 2022

This chapter traces the emergence of the computer from the workshop into the workplace. It describes the role of the corporate mainframe from the early 1950s to the late 1970s and IBM’s dominance. It starts with IBM’s response to the threat, to its office automation interests, posed by UNIVAC and a new generation of electronic computers. It describes the impetus given to innovation by the Cold War through the Whirlwind project and the SAGE air defence system for the US military. It describes innovative technologies including magnetic-core memory, interactive screen display, reliability protocols and techniques, double-sided printed circuit boards, real-time operating software, duplex standby, digital communication over standard telephone lines, time sharing, and software/programming disciplines. The account shows how SAGE gave IBM a head start in computing, networking, and communications, and how the migration of expertise into the private sector fuelled commercial spin-offs. It describes two sectors transformed by the new technologies: automated banking (ERMA) and the introduction of the credit card, and airline reservation (SABRE). It describes the shakeout in the computer industry in the 1960s in which IBM saw off its competitors (the ‘seven dwarves’) to secure its dominance following the radical introduction of the System/360.
The future of history
Authors: Swade Doron
Published: August 2022

This chapter considers current trends and what they indicate about the future directions and computer history. The collapse of familiar object categories defined by use is discussed. Decentering the computer is identified as a feature of more recent accounts, i.e. the diffusion of computers into our physical environments and the way in which networks and, for example, the Internet of Things (IoT) challenges traditional ideas of computer as localized object. The problems posed by software and the imbalance caused by difficulties integrating its histories into established narratives are discussed. It argues that existing narratives inadequately serve new activities that have outgrown their narrative scope—gaming, entertainment, sport, media, graphics, and communications platforms. The need for a new narrative is seen as an increasingly pressing challenge to history.
Difference and culture
Authors: Belsey Catherine
Published: August 2022

This chapter builds upon Chapter 1’s discussion of difference by exploring the implications of Saussure’s account of language for our understanding of culture. If Saussure is right about the non-referential character of language, there are no ideas or values motivating it from outside or beyond culture itself. Culture consists of the meanings its subjects produce and reproduce. Even in the process of analysing it, we are simply taking up another position in culture, inhabiting a space culture itself provides, or can be induced to provide. Outlining the significance of Roland Barthes’s Mythologies and Barthes’s debt to Marxism, the chapter explains how semiology invites us to ask what interests are served by the naturalization of particular convictions and values. It also engages with Louis Althusser’s account of ideology, Claude Lévi-Strauss’s structural anthropology, and the radical challenge to structuralism posed by poststructuralism.
Opioid Use Disorder Among Ohio’s Medicaid Population: Prevalence Estimates From 19 Counties Using a Multiplier Method
Authors: Doogan Nathan J , Mack Aimee , Wang Jianing , Crane Dushka , Jackson Rebecca , Applegate Mary , Villani Jennifer , Chandler Redonna , Barocas Joshua A
Published: August 2022

The decades-long overdose epidemic in the United States is driven by opioid misuse. Overdoses commonly, although not exclusively, occur in individuals with opioid use disorder (OUD). To allocate adequate resources and develop appropriately scaled public health responses, accurate estimation of the prevalence of OUD is needed. Indirect methods (e.g., a multiplier method) of estimating prevalence of problematic substance-use behavior circumvent some limitations of household surveys and use of administrative data. We used a multiplier method to estimate OUD prevalence among the adult Medicaid population (ages 18–64 years) in 19 Ohio counties that are highly affected by overdose. We used Medicaid claims data and the US National Vital Statistics System overdose death data, which were linked at the person level. A statistical model leveraged opioid-related death rate information from a group with known OUD to estimate prevalence among a group with unknown OUD status given recorded opioid-related deaths in that group. We estimated that 13.6% of the total study population had OUD in 2019. Men (16.7%) had a higher prevalence of OUD than women (11.4%), and persons aged 35–54 had the highest prevalence (16.7%). Our approach to prevalence estimation has important implications for OUD surveillance and treatment in the United States.
Intradermal Botulinum Toxin A Injection for Scalp Sebum Secretion Regulation: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Prospective Study in Chinese Subjects
Authors: Li Yiming , Chen Xia , Luo Xiaoou , Li Li , Lin Yan
Published: August 2022

Background

Although botulinum toxin type A (BTX-A) injection has been proved to reduce topical sebum secretion, the impact of intradermal BTX-A injection on scalp sebum production has never been reported.

Objectives

The purpose of this study was to investigate the efficacy and safety of intradermal BTX-A treatment vs intradermal normal saline (NS) injection for scalp sebum secretion regulation.

Methods

This multicenter, randomized, double-blinded, prospective study recruited patients complaining of oily scalp and/or hair. The patients were randomly allocated to receive either 1 session of intradermal BTX-A or NS injection. The baseline and posttreatment scalp sebum secretion at 24, 48, 72, and 96 hours postshampooing was measured with a Sebumeter SM815 (Cutometer Dual MPA 580, Courage & Khazaka, Cologne, Germany) at 1, 3, 4, and 6 months after treatment. The patients’ comments, satisfaction, and adverse events were evaluated and compared.

Results

In total, 25 patients in the BTX-A group and 24 patients in the NS group completed the follow-up. For the treated region, compared with NS, intradermal BTX-A treatment (50-65 U) significantly reduced scalp sebum secretion at 24, 48, and 72 hours postshampooing at the 1- and 3-month follow-up visits (P < 0.05). No significant difference between the 2 groups was observed at 4 and 6 months after the treatment. The patients’ satisfaction ratings were significantly higher for the BTX-A treatment (P = 0.000). No serious adverse events occurred.

Conclusions

Compared with NS, 1 session of intradermal BTX-A injection (50-65 U) effectively and safely reduced scalp sebum secretion and greasiness perception in the treated region at 24 and 48 hours postshampooing for 3 months.

Level of Evidence: 4
A merged molecular representation deep learning method for blood–brain barrier permeability prediction
Authors: Tang Qiang , Nie Fulei , Zhao Qi , Chen Wei
Published: August 2022

The ability of a compound to permeate across the blood–brain barrier (BBB) is a significant factor for central nervous system drug development. Thus, for speeding up the drug discovery process, it is crucial to perform high-throughput screenings to predict the BBB permeability of the candidate compounds. Although experimental methods are capable of determining BBB permeability, they are still cost-ineffective and time-consuming. To complement the shortcomings of existing methods, we present a deep learning–based multi-model framework model, called Deep-B3, to predict the BBB permeability of candidate compounds. In Deep-B3, the samples are encoded in three kinds of features, namely molecular descriptors and fingerprints, molecular graph and simplified molecular input line entry system (SMILES) text notation. The pre-trained models were built to extract latent features from the molecular graph and SMILES. These features depicted the compounds in terms of tabular data, image and text, respectively. The validation results yielded from the independent dataset demonstrated that the performance of Deep-B3 is superior to that of the state-of-the-art models. Hence, Deep-B3 holds the potential to become a useful tool for drug development. A freely available online web-server for Deep-B3 was established at http://cbcb.cdutcm.edu.cn/deepb3/, and the source code and dataset of Deep-B3 are available at https://github.com/GreatChenLab/Deep-B3.
Large-scale comparison of machine learning algorithms for target prediction of natural products
Authors: Liang Lu , Liu Ye , Kang Bo , Wang Ru , Sun Meng-Yu , Wu Qi , Meng Xiang-Fei , Lin Jian-Ping
Published: August 2022

Natural products (NPs) and their derivatives are important resources for drug discovery. There are many in silico target prediction methods that have been reported, however, very few of them distinguish NPs from synthetic molecules. Considering the fact that NPs and synthetic molecules are very different in many characteristics, it is necessary to build specific target prediction models of NPs. Therefore, we collected the activity data of NPs and their derivatives from the public databases and constructed four datasets, including the NP dataset, the NPs and its first-class derivatives dataset, the NPs and all its derivatives and the ChEMBL26 compounds dataset. Conditions, including activity thresholds and input features, were explored to access the performance of eight machine learning methods of target prediction of NPs, including support vector machines (SVM), extreme gradient boosting, random forests, K-nearest neighbor, naive Bayes, feedforward neural networks (FNN), convolutional neural networks and recurrent neural networks. As a result, the NPs and all their derivatives datasets were selected to build the best NP-specific models. Furthermore, the consensus models, as well as the voting models, were additionally applied to improve the prediction performance. More evaluations were made on the external validation set and the results demonstrated that (1) the NP-specific model performed better on the target prediction of NPs than the traditional models training on the whole compounds of ChEMBL26. (2) The consensus model of FNN + SVM possessed the best overall performance, and the voting model can significantly improve recall and specificity.
STArS (STrain-Amplicon-Seq), a targeted nanopore sequencing workflow for SARS-CoV-2 diagnostics and genotyping
Authors: Maestri Simone , Grosso Valentina , Alfano Massimiliano , Lavezzari Denise , Piubelli Chiara , Bisoffi Zeno , Rossato Marzia , Delledonne Massimo
Published: August 2022

Diagnostic tests based on reverse transcription–quantitative polymerase chain reaction (RT–qPCR) are the gold standard approach to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from clinical specimens. However, unless specifically optimized, this method is usually unable to recognize the specific viral strain responsible of coronavirus disease 2019, a crucial information that is proving increasingly important in relation to virus spread and treatment effectiveness. Even if some RT–qPCR commercial assays are currently being developed for the detection of viral strains, they focus only on single/few genetic variants that may not be sufficient to uniquely identify a specific strain. Therefore, genome sequencing approaches remain the most comprehensive solution for virus genotyping and to recognize viral strains, but their application is much less widespread due to higher costs. Starting from the well-established ARTIC protocol coupled to nanopore sequencing, in this work, we developed STArS (STrain-Amplicon-Seq), a cost/time-effective sequencing-based workflow for both SARS-CoV-2 diagnostics and genotyping. A set of 10 amplicons was initially selected from the ARTIC tiling panel, to cover: (i) all the main biologically relevant genetic variants located on the Spike gene; (ii) a minimal set of variants to uniquely identify the currently circulating strains; (iii) genomic sites usually amplified by RT–qPCR method to identify SARS-CoV-2 presence. PCR-amplified clinical samples (both positive and negative for SARS-CoV-2 presence) were pooled together with a serially diluted exogenous amplicon at known concentration and sequenced on a MinION device. Thanks to a scoring rule, STArS had the capability to accurately classify positive samples in agreement with RT–qPCR results, both at the qualitative and quantitative level. Moreover, the method allowed to effectively genotype strain-specific variants and thus also return the phylogenetic classification of SARS-CoV-2-postive samples. Thanks to the reduced turnaround time and costs, the proposed approach represents a step towards simplifying the clinical application of sequencing for viral genotyping, hopefully aiding in combatting the global pandemic.
In Alzheimer-prone brain regions, metabolism and risk-gene expression are strongly correlated
Authors: Ye Fengdan , Funk Quentin , Rockers Elijah , Shulman Joshua M , Masdeu Joseph C , Pascual Belen ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2022

Neuroimaging in the preclinical phase of Alzheimer’s disease provides information crucial to early intervention, particularly in people with a high genetic risk. Metabolic network modularity, recently applied to the study of dementia, is increased in Alzheimer’s disease patients compared with controls, but network modularity in cognitively unimpaired elderly with various risks of developing Alzheimer’s disease needs to be determined. Based on their 5-year cognitive progression, we stratified 117 cognitively normal participants (78.3 ± 4.0 years of age, 52 women) into three age-matched groups, each with a different level of risk for Alzheimer’s disease. From their fluorodeoxyglucose PET we constructed metabolic networks, evaluated their modular structures using the Louvain algorithm, and compared them between risk groups. As the risk for Alzheimer’s disease increased, the metabolic connections among brain regions weakened and became more modular, indicating network fragmentation and functional impairment of the brain. We then set out to determine the correlation between regional brain metabolism, particularly in the modules derived from the previous analysis, and the regional expression of Alzheimer-risk genes in the brain, obtained from the Allen Human Brain Atlas. In all risk groups of this elderly population, the regional brain expression of most Alzheimer-risk genes showed a strong correlation with brain metabolism, particularly in the module that corresponded to regions of the brain that are affected earliest and most severely in Alzheimer’s disease. Among the genes, APOE and CD33 showed the strongest negative correlation and SORL1 showed the strongest positive correlation with brain metabolism. The Pearson correlation coefficients remained significant when contrasted against a null-hypothesis distribution of correlation coefficients across the whole transcriptome of 20 736 genes (SORL1: P = 0.0130; CD33, P = 0.0136; APOE: P = 0.0093). The strong regional correlation between Alzheimer-related gene expression in the brain and brain metabolism in older adults highlights the role of brain metabolism in the genesis of dementia.
Effects of severe anthropogenic disturbance on the heart rate and body temperature in free-living greylag geese (Anser anser)
Authors: Wascher Claudia A F , Arnold Walter , Kotrschal Kurt
Published: August 2022

Anthropogenic disturbances are a major concern for the welfare and conservation of wildlife. We recorded heart rate and body temperature of 20 free-living greylag geese in response to a major regularly re-occurring anthropogenic disturbance—New Year’s Eve fireworks. Heart rate and body temperature were significantly higher in the first and second hour of the new year, compared with the same hour on the 31st of December, the average during December and the average during January. Heart rate and body temperature was not significantly affected by sex or age. From 0200 to 0300 onwards, 1st of January heart rates did not significantly differ from the other periods; however, body temperatures were significantly increased until 0300–0400. From 0400 to 0500, heart rate was not affected by any of the investigated factors, whereas body temperature was significantly increased on the 1st of January compared with the 31st of December and the December average but not compared with the January average. To conclude, our results show that New Year’s Eve fireworks cause a substantial physiological response, indicative of a stress response in greylag geese, which is costly in terms of energy expenditure.
Natriuretic peptide pathways in heart failure: further therapeutic possibilities
Authors: Sangaralingham S Jeson , Kuhn Michaela , Cannone Valentina , Chen Horng H , Burnett John C
Published: August 2022

The discovery of the heart as an endocrine organ resulted in a remarkable recognition of the natriuretic peptide system (NPS). Specifically, research has established the production of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) from the heart, which exert pleiotropic cardiovascular, endocrine, renal, and metabolic actions via the particulate guanylyl cyclase A receptor (GC-A) and the second messenger, cGMP. C-type natriuretic peptide (CNP) is produced in the endothelium and kidney and mediates important protective auto/paracrine actions via GC-B and cGMP. These actions, in part, participate in the efficacy of sacubitril/valsartan in heart failure (HF) due to the augmentation of the NPS. Here, we will review important insights into the biology of the NPS, the role of precision medicine, and focus on the phenotypes of human genetic variants of ANP and BNP in the general population and the relevance to HF. We will also provide an update of the existence of NP deficiency states, including in HF, which provide the rationale for further therapeutics for the NPS. Finally, we will review the field of peptide engineering and the development of novel designer NPs for the treatment of HF. Notably, the recent discovery of a first-in-class small molecule GC-A enhancer, which is orally deliverable, will be highlighted. These innovative designer NPs and small molecule possess enhanced and novel properties for the treatment of HF and cardiovascular diseases.
Do syntactic trees enhance Bidirectional Encoder Representations from Transformers (BERT) models for chemical–drug relation extraction?
Authors: Tang Anfu , Deléger Louise , Bossy Robert , Zweigenbaum Pierre , Nédellec Claire
Published: August 2022

Collecting relations between chemicals and drugs is crucial in biomedical research. The pre-trained transformer model, e.g. Bidirectional Encoder Representations from Transformers (BERT), is shown to have limitations on biomedical texts; more specifically, the lack of annotated data makes relation extraction (RE) from biomedical texts very challenging. In this paper, we hypothesize that enriching a pre-trained transformer model with syntactic information may help improve its performance on chemical–drug RE tasks. For this purpose, we propose three syntax-enhanced models based on the domain-specific BioBERT model: Chunking-Enhanced-BioBERT and Constituency-Tree-BioBERT in which constituency information is integrated and a Multi-Task-Learning framework Multi-Task-Syntactic (MTS)-BioBERT in which syntactic information is injected implicitly by adding syntax-related tasks as training objectives. Besides, we test an existing model Late-Fusion which is enhanced by syntactic dependency information and build ensemble systems combining syntax-enhanced models and non-syntax-enhanced models. Experiments are conducted on the BioCreative VII DrugProt corpus, a manually annotated corpus for the development and evaluation of RE systems. Our results reveal that syntax-enhanced models in general degrade the performance of BioBERT in the scenario of biomedical RE but improve the performance when the subject–object distance of candidate semantic relation is long. We also explore the impact of quality of dependency parses. [Our code is available at: https://github.com/Maple177/syntax-enhanced-RE/tree/drugprot (for only MTS-BioBERT); https://github.com/Maple177/drugprot-relation-extraction (for the rest of experiments)]

Database URL https://github.com/Maple177/drugprot-relation-extraction
Statistical primer: an introduction to the application of linear mixed-effects models in cardiothoracic surgery outcomes research—a case study using homograft pulmonary valve replacement data
Authors: Wang Xu , Andrinopoulou Eleni-Rosalina , Veen Kevin M , Bogers Ad J J C , Takkenberg Johanna J M
Published: August 2022

OBJECTIVES

The emergence of big cardio-thoracic surgery datasets that include not only short-term and long-term discrete outcomes but also repeated measurements over time offers the opportunity to apply more advanced modelling of outcomes. This article presents a detailed introduction to developing and interpreting linear mixed-effects models for repeated measurements in the setting of cardiothoracic surgery outcomes research.

METHODS

A retrospective dataset containing serial echocardiographic measurements in patients undergoing surgical pulmonary valve replacement from 1986 to 2017 in Erasmus MC was used to illustrate the steps of developing a linear mixed-effects model for clinician researchers.

RESULTS

Essential aspects of constructing the model are illustrated with the dataset including theories of linear mixed-effects models, missing values, collinearity, interaction, nonlinearity, model specification, results interpretation and assumptions evaluation. A comparison between linear regression models and linear mixed-effects models is done to elaborate on the strengths of linear mixed-effects models. An R script is provided for the implementation of the linear mixed-effects model.

CONCLUSIONS

Linear mixed-effects models can provide evolutional details of repeated measurements and give more valid estimates compared to linear regression models in the setting of cardio-thoracic surgery outcomes research.
An orally administered drug prevents selection for antibiotic-resistant bacteria in the gut during daptomycin therapy
Authors: Morley Valerie J , Sim Derek G , Penkevich Aline , Woods Robert J , Read Andrew F
Published: August 2022

Background and objectives

Previously, we showed proof-of-concept in a mouse model that oral administration of cholestyramine prevented enrichment of daptomycin-resistant Enterococcus faecium in the gastrointestinal (GI) tract during daptomycin therapy. Cholestyramine binds daptomycin in the gut, which removes daptomycin selection pressure and so prevents the enrichment of resistant clones. Here, we investigated two open questions related to this approach: (i) can cholestyramine prevent the enrichment of diverse daptomycin mutations emerging de novo in the gut? and (ii) how does the timing of cholestyramine administration impact its ability to suppress resistance?

Methodology

Mice with GI E. faecium were treated with daptomycin with or without cholestyramine, and E. faecium was cultured from feces to measure changes in daptomycin susceptibility. A subset of clones was sequenced to investigate the genomic basis of daptomycin resistance.

Results

Cholestyramine prevented the enrichment of diverse resistance mutations that emerged de novo in daptomycin-treated mice. Whole-genome sequencing revealed that resistance emerged through multiple genetic pathways, with most candidate resistance mutations observed in the clsA gene. In addition, we observed that cholestyramine was most effective when administration started prior to the first dose of daptomycin. However, beginning cholestyramine after the first daptomycin dose reduced the frequency of resistant E. faecium compared to not using cholestyramine at all.

Conclusions and implications

Cholestyramine prevented the enrichment of diverse daptomycin-resistance mutations in intestinal E. faecium populations during daptomycin treatment, and it is a promising tool for managing the transmission of daptomycin-resistant E. faecium.
TcMYC2 regulates Pyrethrin biosynthesis in Tanacetum cinerariifolium
Authors: Zeng Tuo , Li Jia-Wen , Xu Zhi-Zhuo , Zhou Li , Li Jin-Jin , Yu Qin , Luo Jin , Chan Zhu-Long , Jongsma Maarten A , Hu Hao , Wang Cai-Yun
Published: August 2022

Pyrethrins constitute a class of terpene derivatives with high insecticidal activity and are mainly synthesized in the capitula of the horticulturally important plant, Tanacetum cinerariifolium. Treatment of T. cinerariifolium with methyl jasmonate (MeJA) in the field induces pyrethrin biosynthesis, but the mechanism linking MeJA with pyrethrin biosynthesis remains unclear. In this study, we explored the transcription factors involved in regulating MeJA-induced pyrethrin biosynthesis. A single spray application of MeJA to T. cinerariifolium leaves rapidly upregulated the expression of most known pyrethrin biosynthesis genes and subsequently increased the total pyrethrin content in the leaf. A continuous 2-week MeJA treatment resulted in enhanced pyrethrin content and increased trichome density. TcMYC2, a key gene in jasmonate signaling, was screened at the transcriptome after MeJA treatment. TcMYC2 positively regulated expression of the pyrethrin biosynthesis genes TcCHS, TcAOC, and TcGLIP by directly binding to E-box/G-box motifs in the promoters. The stable overexpression of TcMYC2 in T. cinerariifolium hairy roots significantly increased the expression of TcAOC and TcGLIP. Further transient overexpression and viral-induced gene-silencing experiments demonstrated that TcMYC2 positively promoted pyrethrin biosynthesis. Collectively, the results reveal a novel molecular mechanism for MeJA-induced pyrethrin biosynthesis in T. cinerariifolium involving TcMYC2.
Multi-omics analyses reveal MdMYB10 hypermethylation being responsible for a bud sport of apple fruit color
Authors: Liu Yu , Gao Xiu-hua , Tong Lu , Liu Mei-zi , Zhou Xiao-kang , Tahir Muhammad Mobeen , Xing Li-bo , Ma Juan-juan , An Na , Zhao Cai-ping , Yao Jia-Long , Zhang Dong
Published: August 2022

Apple bud sports offer a rich resource for clonal selection of numerous elite cultivars. The accumulation of somatic mutations as plants develop may potentially impact the emergence of bud sports. Previous studies focused on somatic mutation in the essential genes associated with bud sports. However, the rate and function of genome-wide somatic mutations that accumulate when a bud sport arises remain unclear. In this study, we identified a branch from a 10-year-old tree of the apple cultivar ‘Oregon Spur II’ as a bud sport. The mutant branch showed reduced red coloration on fruit skin. Using this plant material, we assembled a high-quality haplotype reference genome consisting of 649.61 Mb sequences with a contig N50 value of 2.04 Mb. We then estimated the somatic mutation rate of the apple tree to be 4.56 × 10 −8 per base per year, and further identified 253 somatic single-nucleotide polymorphisms (SNPs), including five non-synonymous SNPs, between the original type and mutant samples. Transcriptome analyses showed that 69 differentially expressed genes between the original type and mutant fruit skin were highly correlated with anthocyanin content. DNA methylation in the promoter of five anthocyanin-associated genes was increased in the mutant compared with the original type as determined using DNA methylation profiling. Among the genetic and epigenetic factors that directly and indirectly influence anthocyanin content in the mutant apple fruit skin, the hypermethylated promoter of MdMYB10 is important. This study indicated that numerous somatic mutations accumulated at the emergence of a bud sport from a genome-wide perspective, some of which contribute to the low coloration of the bud sport.
The BBX gene CmBBX22 negatively regulates drought stress tolerance in chrysanthemum
Authors: Liu Yanan , Cheng Hua , Cheng Peilei , Wang Chunmeng , Li Jiayu , Liu Ye , Song Aiping , Chen Sumei , Chen Fadi , Wang Likai , Jiang Jiafu
Published: August 2022

BBX transcription factors play vital roles in plant growth, development, and stress responses. Although BBX proteins have been studied in great detail in the model plant Arabidopsis, their roles in crop plants such as chrysanthemum are still largely uninvestigated. Here, we cloned CmBBX22 and further determined the function of CmBBX22 in response to drought treatment. Subcellular localization and transactivation assay analyses revealed that CmBBX22 was localized in the nucleus and possessed transactivation activity. Overexpression of CmBBX22 in chrysanthemum was found to reduce plant drought tolerance, whereas expression of the chimeric repressor CmBBX22-SRDX was found to promote a higher drought tolerance than that shown by wild-type plants, indicating that CmBBX22 negatively regulates drought tolerance in chrysanthemum. Transcriptome analysis and physiological measurements indicated the potential involvement of the CmBBX22-mediated ABA response, stomatal conductance, and antioxidant responses in the negative regulation of drought tolerance in chrysanthemum. Based on the findings of this study, we were thus able to establish the mechanisms whereby the transcriptional activator CmBBX22 negatively regulates drought tolerance in chrysanthemum via the regulation of the abscisic acid response, stomatal conductance, and antioxidant responses.
Comparative transcriptome and metabolome analysis reveal key regulatory defense networks and genes involved in enhanced salt tolerance of Actinidia (kiwifruit)
Authors: Abid Muhammad , Gu Shichao , Zhang Yong-Jie , Sun Shihang , Li Zhi , Bai Dan-Feng , Sun Leiming , Qi Xiu-Juan , Zhong Yun-Peng , Fang Jin-Bao
Published: August 2022

The Actinidia (kiwifruit) is an emerging fruit plant that is severely affected by salt stress in northern China. Plants have evolved several signaling network mechanisms to cope with the detrimental effects of salt stress. To date, no reported work is available on metabolic and molecular mechanisms involved in kiwifruit salt tolerance. Therefore, the present study aims to decipher intricate adaptive responses of two contrasting salt tolerance kiwifruit species Actinidia valvata [ZMH (an important genotype), hereafter referred to as R] and Actinidia deliciosa [‘Hayward’ (an important green-fleshed cultivar), hereafter referred to as H] under 0.4% (w/w) salt stress for time courses of 0, 12, 24, and 72 hours (hereafter refered to as h) by combined transcriptome and metabolome analysis. Data revealed that kiwifruit displayed specific enrichment of differentially expressed genes (DEGs) under salt stress. Interestingly, roots of R plants showed a differential expression pattern for up-regulated genes. The KEGG pathway analysis revealed the enrichment of DEGs related to plant hormone signal transduction, glycine metabolism, serine and threonine metabolism, glutathione metabolism, and pyruvate metabolism in the roots of R under salt stress. The WGCNA resulted in the identification of five candidate genes related to glycine betaine (GB), pyruvate, total soluble sugars (TSS), and glutathione biosynthesis in kiwifruit. An integrated study of transcriptome and metabolome identified several genes encoding metabolites involved in pyruvate metabolism. Furthermore, several genes encoding transcription factors were mainly induced in R under salt stress. Functional validation results for overexpression of a candidate gene betaine aldehyde dehydrogenase (AvBADH, R_transcript_80484) from R showed significantly improved salt tolerance in Arabidopsis thaliana (hereafter referred to as At) and Actinidia chinensis [‘Hongyang’ (an important red-fleshed cultivar), hereafter referred to as Ac] transgenic plants than in WT plants. All in all, salt stress tolerance in kiwifruit roots is an intricate regulatory mechanism that consists of several genes encoding specific metabolites.