bluuebunny/crossref_metadata_2025 huggingface dataset:
Desafíos teóricos y metodológicos en torno al documento de archivo como objeto digital en la red
Authors: Isoglio Antonela , Vigna Diego Germán
Published: May 2021

La noción de documento de archivo presenta un rol central en la teoría y la metodología archivísticas. La difusión de las tecnologías de la información digital en las entidades productoras de documentos y los archivos implicó una serie de cambios, entre los que se encuentra la consideración acerca de la naturaleza del objeto de estudio e intervención. Sin embargo, las transformaciones más radicales se comenzaron a observar en las prácticas de archivo de objetos digitales en internet. Este artículo de revisión tiene el objetivo de analizar las premisas teóricas y metodológicas del concepto de documento de archivo, y contrastarlas con las peculiaridades que fueron surgiendo en torno a las prácticas archivísticas de objetos digitales en internet. El trabajo se estructura en tres partes. Mientras que la primera presenta los presupuestos teóricos y metodológicos de dicho concepto dentro del paradigma dominante, la segunda los pone en relación con las propiedades emergentes de la práctica de archivo de objetos digitales en internet. Finalmente, la tercera parte aporta una reflexión acerca de los desafíos teóricos y metodológicos que se abren en el contexto actual, proponiendo algunas líneas de indagación para nuevas aproximaciones.
SBMOpenMM: A Builder of Structure-Based Models for OpenMM
Authors: Floor Martin , Li Kengjie , Estévez-Gay Miquel , Agulló Luis , Muñoz Pau Marc , Hwang Jenn-Kang , Osuna Sílvia , Villà-Freixa Jordi
Published: May 2021

Here we introduce SBMOpenMM, a python library to build Structure-Based Models (SBMs), that uses the OpenMM framework to create and run SBM simulations. The code is flexible, user-friendly, and profits from high customizability and GPU performance provided by the OpenMM platform. We demonstrate its use in the evaluation of the two-step folding process of FoxP1 transcription factor protein. Our results indicate that the newly developed SBM can be successfully applied to elucidating the underlying mechanisms of biomolecular processes.
Capturing the Transient Microstructure of a Physically Assembled Gel Subjected to Temperature and Large Deformation
Authors: Badani Prado Rosa Maria , Mishra Satish , Burghardt Wesley R. , Kundu Santanu
Published: May 2021

The microstructure of physically assembled gels depends on mechanical loading and environmental stimuli such as temperature. Here, we report the real-time change in the structure of physically assembled triblock copolymer gels that consist of 10 wt% and 20 wt% of poly(styrene)-poly(isoprene)-poly(styrene) [PS-PI-PS] triblock copolymer in mineral oil (i) during the gelation process with decreasing temperature, (ii) subjected to large oscillatory deformation, and (iii) during the stress-relaxation process after the application of a step-strain. The presence of loosely bounded PS-aggregates at temperatures higher than the rheometrically determined gelation temperature (Tgel) captures the progressive gelation process spanning over a broad temperature range. However, the microstructure fully develops at temperatures suciently lower than Tgel, and the storage modulus (G0 ) also reaches a plateau at those temperatures. The microstructure orients in the stretching direction with the applied strain. In an oscillation strain cycle, such oriented structure has been observed at low-strain. But, at large-strain, the oriented structure splits, and only a fraction of midblock participates in load-bearing. This has been attributed to the endblock pullout from the aggregates, likely caused by the strain localization in the samples. Both microstructure recovery and time-dependent moduli during the stress-relaxation process after the application of a step-strain can be captured using a stretched-exponential model. However, the microstructure recovery time has been found to be two orders of magnitude slower than the stress-relaxation time at room temperature, indicating a complex nature of relaxation process involving midblock relaxation, endblock pullout and reassociation process. Due to their viscoelastic nature, these gels' mechanical responses are sensitive to strain, temperature, and rate of deformation. Therefore, insights into the microstructural information as a function of these parameters will assist these gels' real-life applications and design new gels with improved properties
The Brazilian Compound Library (BraCoLi) Database: A Brazilian Repository of Chemical and Biological Information for Drug Design
Authors: Veríssimo Gabriel Corrêa , dos Santos Junior Valtair Severino , Almeida Ingrid Ariela do Rosário de , Ruas Marina Sant'Anna Mitraud , Coutinho Lukas Galuppo , Oliveira Renata Barbosa de , Maltarollo Vinicius
Published: May 2021

The Brazilian Compound Library (BraCoLi) is a novel virtual library of manually curated compounds developed by Brazilian research groups to support further computer-aided drug design works. Herein, the first version of the database is described comprising 1,176 compounds. Also, the chemical diversity and drug-like profile of BraCoLi were defined to analyze its chemical space. A significant amount of the compounds fitted Lipinski and Veber’s rules, alongside other drug-likeness properties. Principal component analysis showed that BraCoLi is similar to other databases (FDA-approved drugs and NuBBEDB) regarding structural and physicochemical patterns. Finally, a scaffold analysis showed that BraCoLi presents several privileged chemical skeletons with great diversity.
Ti(OiPr)4-Enabled Dual Photoredox and Nickel-Catalyzed Arylation and Alkenylation of Cyclopropanols
Authors: Varabyeva Nastassia A. , Barysevich Maryia V. , Aniskevich Yauhen , Hurski Alaksiej
Published: May 2021

In this article, we report an application of cyclopropanols as coupling partners in the dual photoredox/nickel catalyzed reaction with aryl and vinyl bromides. We found that this cross-coupling proceeds smoothly in the presence of Ti(OiPr)4 as an additive to provide β-aryl or γ,δ-unsaturated ketones.
Influence of crude extract of Hawthorn crataegus oxyacantha on some physiological aspects in mature male Rats exposed to hydrogen peroxide over load.
Authors: Al-Abdaly Anwar I. Obeed
Published: May 2021

This study was carried out to investigate the protective effects of 70% ethanolic alcohol extract of hawthorn (crataegus oxycantha) on some physiological functions of male rats exposed to 1% H2O2. Fifteen mature male Newzeland rats were randomly divided into three groups:- control group (C) ,two groups treated with 1% H2O2 alone (G1) or 1%H2O2 with crude extract of hawthorn(G2) orally daily for 30 days .Blood samples were taken at zero time and 30 days of the experiment .The present study declared an alteration in the lipid profile of the treated group (G2) at the end of treatment (30 days) manifested by asignificant reduction (p<0.05) in serumTC,TAG,LDL-C, VLDL-C concentrations. And elevation (p<0.05) in serum, HDL-C, as compared to the treated group (G1). Antioxidant status also exhibited significant (p<0.05) changes characterized by an elevation of serum GSH in group (G2). Histological study revealed that oral treatment with 1% H2O2 caused congestion of blood vessels of the heart with infiltration of inflammatory cells and odema between muscle fibers. It is concluded that treatment with hawthorn showed no clear pathological lesions.
Evaluation of Antibacterial Activity of Aqueous Extracts of Pomegranate Peels, Green Tea Leaves and Bay Leaves against Vibrio cholera
Authors: Al-Dhaher Zainab A.
Published: May 2021

The antibacterial activity of aqueous extracts of Pomegranate peels, Green tea leaves, Bay leaves were evaluated in this study. Agar diffusion technique was applied. The three extracts were found to have inhibitory effect against Vibrio cholera and the mean of the diameter of inhibition zones ranges from (11-23 mm) for pomegranate peels, (9-20 mm) for Green tea leaves and (718mm) for Bay leaves extracts and statistically analyzed. There were significant differences between pomegranate peels, tea leaves and bay leaves extracts at each concentration used in this study. The pomegranate peels were found to have greater effects against Vibrio cholera followed by tea leaves, Bay leaves. Minimum bactericidal concentration (MBC) was also determined and it was shown that 10mg/ml was the MBC for pomegranate peels, 10-15mg/ml the MBC for tea leaves and 20-25mg/ml the MBC for Bay leaves.
Drónok a Közel-Keleten
Authors: Ember István , Szilágyi-Kiss Hajnalka
Published: May 2021

A Közel-Kelet egy olyan konfliktuszóna, amelyet folyamatosan szükséges vizsgálni. Mivel a vallási és etnikai  kérdések jelentős forrásai a térségben folyó katonai,  félkatonai és terroristaszervezetek műveleteinek, nem  várható jelentős csillapodás azokban. A drónok mint  napjaink pilóta nélküli repülőeszközei egyre nagyobb  szerepet töltenek be ezekben a konfliktusokban, ezért  fontos összegezni azok felhasználási lehetőségeit.  Mindezek mellett elengedhetetlen, hogy az egyre fejlődő technikai eszközökkel lépést tartva keressünk modern  megoldásokat a katonáknak, akik a hadszíntéren  tevékenykednek. Jelen esetben a tűzszerész-szakfeladatok  támogatásához azonosítjuk be azokat a technikai  elvárásokat, amelyekkel egy ilyen repülőeszköznek  rendelkeznie szükséges.
Advanced DNA Detection via Multispectral Plasmonic Metasurfaces
Authors: Di Meo Valentina , Moccia Massimo , Sanità Gennaro , Crescitelli Alessio , Lamberti Annalisa , Galdi Vincenzo , Rendina Ivo , Esposito Emanuela
Published: May 2021

We propose and demonstrate a sensing platform based on plasmonic metasurfaces for the detection of very low concentrations of deoxyribo-nucleic acid (DNA) fragments. The platform relies on surface-enhanced infrared absorption spectroscopy, implemented via a multispectral metasurface. Specifically, different regions (“pixels”) are engineered so as to separately cover the medium-infrared range of the electromagnetic spectrum extending from the functional-groups to the fingerprint region of a single analyte. In conjunction with a suitable bio-functionalization, this enables univocal and label-free recognition of specific molecules. For experimental validation, we fabricate a large-area gold metasurface on a silicon chip, and functionalize it with a recognition layer of peptide nucleic acid (PNA). Our experimental results indicate the possibility to detect complementary DNA fragments in concentrations as low as 50 fM, i.e., well below the value attained by standard methods, with additional advantages in terms of processing time, versatility and ease of implementation/operation.
Stress Induced Hyperglycemia in the Context of Acute Coronary Syndrome: Definitions, Interventions, and Underlying Mechanisms
Authors: Li Mingmin , Chen Guo , Feng Yingqing , He Xuyu
Published: May 2021

Elevation of glucose level in response to acute coronary syndrome (ACS) has been recognized as stress induced hyperglycemia (SIH). Plenty of clinical studies have documented that SIH occurs very common in patients hospitalized with ACS, even in those without previously known diabetes mellitus. The association between elevated blood glucose levels with adverse outcome in the ACS setting is well-established. Yet, the precise definition of SIH in the context of ACS remains controversial, bringing confusions about clinical management strategy. Several randomized trials aimed to evaluate the effect of insulin-based therapy on outcomes of ACS patients failed to demonstrate a consistent benefit of intensive glucose control. Mechanisms underlying detrimental effects of SIH on patients with ACS are undetermined, oxidative stress might play an important role in the upstream pathways leading to subsequent harmful effects on cardiovascular system. This review aims to discuss various definitions of SIH and their values in predicting adverse outcome in the context of ACS, as well as the effect of intensive glucose control on clinical outcome. Finally, a glimpse of the underlying mechanisms is briefly discussed.
Indirect Effects of Microplastic-Contaminated Soils on Adjacent Soil Layers: Vertical Changes in Soil Physical Structure and Water Flow
Authors: Kim Shin Woong , Liang Yun , Zhao Tingting , Rillig Matthias C.
Published: May 2021

Previous microplastic research under laboratory conditions has focused on microplastics that are homogeneously mixed into test media, in order to maximize test reproducibility and uniform bio-accessibility. Here we specifically focused on testing the idea that microplastics in soil could affect adjacent soil layers not containing microplastic themselves. We included two different microplastics (low-density polyethylene films and polyacrylonitrile fibers) and carried out a soil column test consisting of three different vertical layers (0–3 cm, top, control soil; 3–6 cm, middle, microplastic-containing soil; 6–9 cm, bottom, control soil). Our study shows that microplastic-containing soil layers can act as an anthropogenic barrier in the soil column, interrupting the vertical water flow. These changes directly affected the water content of adjacent layers, and changes in the proportion of soil aggregate sizes occurred for each depth of the soil columns. We also observed that these physical changes trigger changes in soil respiration, but do not translate to effects on enzyme activities. These results imply that the soil environment in non-contaminated parts of the soil can be altered by microplastic contamination in adjacent layers, as might occur for example during ploughing on agricultural fields. More generally, our results highlight the need to further examine effects of microplastic in experiments that do not treat this kind of pollution as uniformly distributed.
Enhancing Coral Survival on Deployment Devices With Microrefugia
Authors: Randall Carly J. , Giuliano Christine , Heyward Andrew J. , Negri Andrew P.
Published: May 2021

Surviving after settlement through the first year of life is a recognised bottleneck in up-scaling reef coral restoration. Incorporating spatial refugia in settlement devices has the potential to alleviate some hazards experienced by young recruits, such as predation and accidental grazing, and can increase the likelihood of survival to size-escape thresholds. Yet optimising the design of microrefugia is challenging due to the complexity of physical and biological processes that occur at fine spatial scales around a recruit. Here, we investigated the effects of microhabitat features on the survival ofAcropora tenuisspat in a year-long experimental field deployment of two types of artificial settlement devices—grooved-tiles and lattice-grids—onto three replicate racks on a shallow, central mid-shelf reef of the Great Barrier Reef. Spat survival across device types averaged between 2 and 39% and about half of all devices had at least one surviving coral after a year. While the larvae settled across all micro-habitats available on the devices, there was strong post-settlement selection for corals on the lower edges, lower surfaces, and in the grooves, with 100% mortality of recruits on upper surfaces, nearly all within the first 6 months of deployment. The device type that conferred the highest average survival (39%) was a tile with wide grooves (4 mm) cut all the way through, which significantly improved survival success over flat and comparatively featureless control tiles (13%). We hypothesise that the wide grooves provided protection from accidental grazing while also minimising sediment accumulation and allowing higher levels of light and water flow to reach the recruits than featureless control devices. We conclude that incorporating design features into deployment devices such as wide slits has the potential to substantially increase post-deployment survival success of restored corals.
Unbiased Characterization of the Microbiome and Virome of Questing Ticks
Authors: Chandra Shona , Harvey Erin , Emery David , Holmes Edward C. , Šlapeta Jan
Published: May 2021

Due to their vector capacity, ticks are ectoparasites of medical and veterinary significance. Modern sequencing tools have facilitated tick-associated microbiota studies, but these have largely focused on bacterial pathogens and symbionts. By combining 16S rRNA gene sequencing with total RNA-sequencing methods, we aimed to determine the complete microbiome and virome of questing, female Ixodes holocyclus recovered from coastal, north-eastern New South Wales (NSW), Australia. We present, for the first time, a robust and unbiased method for the identification of novel microbes in ticks that enabled us to identify bacteria, viruses, fungi and eukaryotic pathogens. The dominant bacterial endosymbionts were Candidatus Midichloria sp. Ixholo1 and Candidatus Midichloria sp. Ixholo2. Candidatus Neoehrlichia australis and Candidatus Neoehrlichia arcana were also recovered, confirming that these bacteria encompass I. holocyclus’ core microbiota. In addition, seven virus species were detected—four previously identified in I. holocyclus and three novel species. Notably, one of the four previously identified virus species has pathogenic potential based on its phylogenetic relationship to other tick-associated pathogens. No known pathogenic eukaryotes or fungi were identified. This study has revealed the microbiome and virome of female I. holocyclus from the environment in north-eastern NSW. We propose that future tick microbiome and virome studies utilize equivalent methods to provide an improved representation of the microbial diversity in ticks globally.
Bacterial Biofilm Inhibition: A Focused Review on Recent Therapeutic Strategies for Combating the Biofilm Mediated Infections
Authors: Srinivasan Ramanathan , Santhakumari Sivasubramanian , Poonguzhali Pandurangan , Geetha Mani , Dyavaiah Madhu , Xiangmin Lin
Published: May 2021

Biofilm formation is a major concern in various sectors and cause severe problems to public health, medicine, and industry. Bacterial biofilm formation is a major persistent threat, as it increases morbidity and mortality, thereby imposing heavy economic pressure on the healthcare sector. Bacterial biofilms also strengthen biofouling, affecting shipping functions, and the offshore industries in their natural environment. Besides, they accomplish harsh roles in the corrosion of pipelines in industries. At biofilm state, bacterial pathogens are significantly resistant to external attack like antibiotics, chemicals, disinfectants, etc. Within a cell, they are insensitive to drugs and host immune responses. The development of intact biofilms is very critical for the spreading and persistence of bacterial infections in the host. Further, bacteria form biofilms on every probable substratum, and their infections have been found in plants, livestock, and humans. The advent of novel strategies for treating and preventing biofilm formation has gained a great deal of attention. To prevent the development of resistant mutants, a feasible technique that may target adhesive properties without affecting the bacterial vitality is needed. This stimulated research is a rapidly growing field for applicable control measures to prevent biofilm formation. Therefore, this review discusses the current understanding of antibiotic resistance mechanisms in bacterial biofilm and intensely emphasized the novel therapeutic strategies for combating biofilm mediated infections. The forthcoming experimental studies will focus on these recent therapeutic strategies that may lead to the development of effective biofilm inhibitors than conventional treatments.
Decreased Functional Connectivity in the Reward Network and Its Relationship With Negative Emotional Experience After Total Sleep Deprivation
Authors: Zhang Ying , Dai Cimin , Shao Yongcong , Peng Jiaxi , Yang Yan , Hou Yanhong
Published: May 2021

Sleep deprivation (SD) induces a negative emotional experience due to a prolonged time spent awake. However, few studies have focused on the mechanism underlying communication within brain networks or alterations during this emotional deterioration. We propose that negative reward judgment is important in poor emotional processing after SD, which will be reflected in functional connectivity in the reward network. We sought to analyze alterations in functional connectivity within the reward network and cerebral cortex. Furthermore, we analyzed changes in functional connectivity correlation with negative emotional experience after SD. Twenty-six healthy volunteers participated in this study. Two resting-state fMRI scans were obtained from the participants, once during resting wakefulness, and once after 36 h of total SD. The bilateral nucleus accumbens (NAc) was selected as a seed region for region of interest (ROI)-to-ROI functional connectivity analysis. Correlation analyses between functional connectivity alterations within the reward network and negative emotional experience were also performed. We found that SD decreased functional connectivity between the left NAc and anterior cingulate cortex (ACC) compared with resting wakefulness. There was a decreased functional connectivity with the ACC and right inferior frontal gyrus (IFG) after SD in the right NAc. Furthermore, decreased functional connectivity between the right NAc and right IFG, and NAc and ACC was negatively correlated with emotional experience scores. Sleep deprivation decreased functional connectivity within the reward network. This may be associated with the enhanced negative emotional experience that was found after total sleep deprivation.
Identification of TH Variants in Chinese Dopa-Responsive Dystonia Patients and Long-Term Outcomes
Authors: Li Xin-yao , Yang Ying-mai , Li Li-bo , Zhang Meng-yu , Huang Yang-yu , Wang Jie , Wang Lin , Wan Xin-hua
Published: May 2021

Background: Dopa-responsive dystonia (DRD) is a movement disorder that is highly clinically and genetically heterogeneous. Our study summarizes clinical characteristics and long-term outcomes in patients with dopa-responsive dystonia with the aim of obtaining further knowledge on this disorder.

Methods: Patients who met DRD genetic diagnostic criteria through whole-exome sequencing and took levodopa for over 3 years were included in our study. Detailed information was collected on these patients, including family history, age at onset, age and dosage at starting levodopa, current medication and dosage, levodopa duration, diurnal fluctuation, and other clinical features. The Burke–Fahn–Marsden Dystonia Rating Scale-Motor (BFMDRS-M) score was used to evaluate patients' dystonia and variation after levodopa. According to the long-term outcomes, patients were further graded as good (dystonia improved by more than 50% after levodopa, and no further motor symptoms appeared) and poor (dystonia improved by <50% after levodopa, or new motor symptoms appeared).

Results: A total of 20 DRD patients were included (11 with GCH1 variants, 9 with TH variants). During long-term levodopa treatment, three patients with TH variants (3/20, 15%) developed motor symptoms, including body jerks and paroxysmal symptoms, and responded well to increasing levodopa doses. The patient with homozygous mutation c.1481C>T/p. Thr494Met harbored more serious symptoms and poor response to levodopa and showed decreased cardiac uptake in MIBG.

Conclusions: Most DRD patients showed satisfactory treatment outcomes after long-term levodopa, whereas few patients with TH variants presented motor symptoms, which is considered to be related to dopamine insufficiency. For patients with motor symptoms after long-term levodopa, increasing the dose slowly might be helpful to relieve symptoms.
Patterns of Health Service Use Among Young People With Cerebral Palsy in England
Authors: Ryan Jennifer M. , Lavelle Grace , Theis Nicola , Kilbride Cherry , Noorkoiv Marika
Published: May 2021

Background: Although the provision of healthcare for people with cerebral palsy (CP) is typically focussed on childhood, many people with CP require access to services periodically throughout their life. Few studies have examined patterns of health service use among young people with CP in England. Understanding patterns of use may inform future service development.

Objective: To describe patterns of visits to rehabilitation and medical professionals among ambulatory young people with CP living in England, and identify factors associated with service use.

Methods: Sixty-two young people with CP aged 10–19 years [mean (SD) age 13.7 (2.5) years] in Gross Motor Function Classification System (GMFCS) levels I-III reported visits to a range of health professionals, hospital admissions and visits to the emergency department over a median duration of 34 weeks (min–max: 12–34 weeks). Negative binomial models were used to examine factors associated with number of visits.

Results: Physiotherapists were the most commonly used professional, with 67.7% of participants visiting a physiotherapist at least once, followed by dentists (66.1%), general practitioners (48.4%), occupational therapists (40.3%) and orthopaedic surgeons (40.3%). Physiotherapists were also the most frequently visited professional with a total of 473 visits (13.3 visits per person-year). Speech and language therapists (5.0 visits per person-year), occupational therapists (4.5 visits per person-year) and nurses (4.3 per person-year) were the next most frequently visited professionals. Age, GMFCS level, and speech impairment were associated with rate of visits to a physiotherapist.

Conclusions: The proportion of young people who visited medical and rehabilitation professionals during the study period varied considerably depending on the profession. Generally, the proportion of young people using services was low. In the context of limited resources, data on service use in combination with data on unmet need, may support the reorganisation of services to maximise benefits to young people with CP.
Peripheral Precocious Puberty of Ovarian Origin in a Series of 18 Girls: Exome Study Finds Variants in Genes Responsible for Hypogonadotropic Hypogonadism
Authors: Brauner Raja , Bignon-Topalovic Joelle , Bashamboo Anu , McElreavey Ken
Published: May 2021

Background: Peripheral precocious puberty of ovarian origin is a very rare condition compared to central form. It may be associated with an isolated ovarian cyst (OC). The causes of OC in otherwise healthy prepubertal girls is currently unknown.

Methods: Exome sequencing was performed on a cohort of 18 unrelated girls presenting with prenatal and/or prepubertal OC at pelvic ultrasonography. The presenting symptom was prenatal OC in 5, breast development in 7 (with vaginal bleeding in 3) and isolated vaginal bleeding in 6. All had OC ≥ 10 mm. The girls had no other anomalies. Four patients had a familial history of ovarian anomalies and/or infertility.

Results: In 9 girls (50%), candidate or known pathogenic variants were identified in genes associated with syndromic and non-syndromic forms of hypogonadotropic hypogonadism including PNPLA6, SEMA3A, TACR3, PROK2, KDM6A, KMT2D, OFD1, GNRH1, GNRHR, GLI3, INSR, CHD7, CDON, RNF216, PROKR2, GLI3, LEPR. Basal plasma concentrations of gonadotropins were undetectable and did not increase after gonadotropin-releasing hormone test in 3 of them whilst 5 had prepubertal values. The plasma estradiol concentrations were prepubertal in 6 girls, high (576 pmol/L) in one and not evaluated in 2 of them.

Conclusions: In the first study reporting exome sequencing in prepubertal OC, half of the patients with OC carry either previously reported pathogenic variants or potentially pathogenic variants in genes known to be associated with isolated or syndromic forms of congenital hypogonadotropic hypogonadism. Functional studies and studies of other cohorts are recommended to establish the causality of these variants.
How to Value Orphan Drugs? A Review of European Value Assessment Frameworks
Authors: Blonda Alessandra , Denier Yvonne , Huys Isabelle , Simoens Steven
Published: May 2021

Background: Decision-makers have implemented a variety of value assessment frameworks (VAFs) for orphan drugs in European jurisdictions, which has contributed to variations in access for rare disease patients. This review provides an overview of the strengths and limitations of VAFs for the reimbursement of orphan drugs in Europe, and may serve as a guide for decision-makers.

Methods: A narrative literature review was conducted using the databases Pubmed, Scopus and Web of Science. Only publications in English were included. Publications known to the authors were added, as well as conference or research papers, or information published on the website of reimbursement and health technology assessment (HTA) agencies. Additionally, publications were included through snowballing or focused searches.

Results: Although a VAF that applies a standard economic evaluation treats both orphan drugs and non-orphan drugs equally, its focus on cost-effectiveness discards the impact of disease rarity on data uncertainty, which influences an accurate estimation of an orphan drug’s health benefit in terms of quality-adjusted life-years (QALYs). A VAF that weighs QALYs or applies a variable incremental cost-effectiveness (ICER) threshold, allows the inclusion of value factors beyond the QALY, although their methodologies are flawed. Multi-criteria decision analysis (MCDA) incorporates a flexible set of value factors and involves multiple stakeholders’ perspectives. Nevertheless, its successful implementation relies on decision-makers’ openness toward transparency and a pragmatic approach, while allowing the flexibility for continuous improvement.

Conclusion: The frameworks listed above each have multiple strengths and weaknesses. We advocate that decision-makers apply the concept of accountability for reasonableness (A4R) to justify their choice for a specific VAF for orphan drugs and to strive for maximum transparency concerning the decision-making process. Also, in order to manage uncertainty and feasibility of funding, decision-makers may consider using managed-entry agreements rather than implementing a separate VAF for orphan drugs.
Studying the Impact of Different Field Environmental Conditions on Seed Quality of Quinoa: The Case of Three Different Years Changing Seed Nutritional Traits in Southern Europe
Authors: Granado-Rodríguez Sara , Aparicio Nieves , Matías Javier , Pérez-Romero Luis Felipe , Maestro Isaac , Gracés Irene , Pedroche Justo Javier , Haros Claudia Monika , Fernandez-Garcia Nieves , Navarro del Hierro Joaquín , Martin Diana , Bolaños Luis , Reguera María
Published: May 2021

Chenopodium quinoa Willd (quinoa) has acquired an increased agronomical and nutritional relevance due to the capacity of adaptation to different environments and the exceptional nutritional properties of their seeds. These include high mineral and protein contents, a balanced amino acid composition, an elevated antioxidant capacity related to the high phenol content, and the absence of gluten. Although it is known that these properties can be determined by the environment, limited efforts have been made to determine the exact changes occurring at a nutritional level under changing environmental conditions in this crop. To shed light on this, this study aimed at characterizing variations in nutritional-related parameters associated with the year of cultivation and different genotypes. Various nutritional and physiological traits were analyzed in seeds of different quinoa cultivars grown in the field during three consecutive years. We found differences among cultivars for most of the nutritional parameters analyzed. It was observed that the year of cultivation was a determinant factor in every parameter studied, being 2018 the year with lower yields, germination rates, and antioxidant capacity, but higher seed weights and seed protein contents. Overall, this work will greatly contribute to increase our knowledge of the impact of the environment and genotype on the nutritional properties of quinoa seeds, especially in areas that share climatic conditions to Southern Europe.
Priming Soybean cv. Primus Leads to Successful Systemic Defense Against the Root-Lesion Nematode, Pratylenchus penetrans
Authors: Adss Shimaa , Liu Benye , Beerhues Ludger , Hahn Volker , Heuer Holger , Elhady Ahmed
Published: May 2021

Root lesion nematodes, Pratylenchus penetrans, are major pests of legumes with little options for their control. We aimed to prime soybean cv. Primus seedlings to improve basic defense against these nematodes by root application of N-3-oxo-tetradecanoyl-L-homoserine lactone (oxo-C14-HSL). The invasion of soybean roots by P. penetrans was significantly reduced in plants that were pre-treated with the oxo-C14-HSL producing rhizobacterium Ensifer meliloti strain ExpR+, compared to non-inoculated plants or plants inoculated with the nearly isogenic strain E. meliloti AttM with plasmid-mediated oxo-C14-HSL degradation. The nematodes were more clustered in the root tissues of plants treated with the AttM strain or the control compared to roots treated with the ExpR+ strain. In split-root systems primed on one side with strain ExpR+, root invasion was reduced on the opposite side compared to non-primed plants indicating a systemic plant response to oxo-C14-HSL. No additional local effect was detected, when inoculating nematodes on the ExpR+ primed side. Removal of oxo-C14-HSL after root exposure resulted in reduced root invasion compared to non-primed plants when the nematodes were added 3, 7, or 15 days later. Thus, probably the plant memorized the priming stimulus. Similarly, the plants were primed by compounds released from the surface of the nematodes. HPLC analysis of the root extracts of oxo-C14-HSL treated and untreated plants revealed that priming resulted in enhanced phytoalexin synthesis upon P. penetrans challenge. Without root invading nematodes, the phytoalexin concentrations of primed and non-primed plants did not significantly differ, indicating that priming did not lead to a persistently increased stress level of the plants. Upon nematode invasion, the phytoalexins coumestrol, genistein, and glyceollin increased in concentration in the roots compared to control plants without nematodes. Glyceollin synthesis was significantly more triggered by nematodes in primed plants compared to non-primed plants. The results indicated that the priming of soybean plants led to a more rapid and strong defense induction upon root invasion of nematodes.
The Rlm13 Gene, a New Player of Brassica napus–Leptosphaeria maculans Interaction Maps on Chromosome C03 in Canola
Authors: Raman Harsh , Raman Rosy , Qiu Yu , Zhang Yuanyuan , Batley Jacqueline , Liu Shengyi
Published: May 2021

Canola exhibits an extensive genetic variation for resistance to blackleg disease, caused by the fungal pathogen Leptosphaeria maculans. Despite the identification of several Avr effectors and R (race-specific) genes, specific interactions between Avr-R genes are not yet fully understood in the Brassica napus–L. maculans pathosystem. In this study, we investigated the genetic basis of resistance in an F2:3 population derived from Australian canola varieties CB-Telfer (Rlm4)/ATR-Cobbler (Rlm4) using a single-spore isolate of L. maculans, PHW1223. A genetic linkage map of the CB-Telfer/ATR-Cobbler population was constructed using 7,932 genotyping-by-sequencing-based DArTseq markers and subsequently utilized for linkage and haplotype analyses. Genetic linkage between DArTseq markers and resistance to PHW1223 isolate was also validated using the B. napus 60K Illumina Infinium array. Our results revealed that a major locus for resistance, designated as Rlm13, maps on chromosome C03. To date, no R gene for resistance to blackleg has been reported on the C subgenome in B. napus. Twenty-four candidate R genes were predicted to reside within the quantitative trait locus (QTL) region. We further resequenced both the parental lines of the mapping population (CB-Telfer and ATR-Cobbler, > 80 × coverage) and identified several structural sequence variants in the form of single-nucleotide polymorphisms (SNPs), insertions/deletions (InDels), and presence/absence variations (PAVs) near Rlm13. Comparative mapping revealed that Rlm13 is located within the homoeologous A03/C03 region in ancestral karyotype block “R” of Brassicaceae. Our results provide a “target” for further understanding the Avr–Rlm13 gene interaction as well as a valuable tool for increasing resistance to blackleg in canola germplasm.
Modelling the Distribution of the Red Macroalgae Asparagopsis to Support Sustainable Aquaculture Development
Authors: O’Mahony James , de la Torre Cerro Rubén , Holloway Paul
Published: May 2021

Fermentative digestion by ruminant livestock is one of the main ways enteric methane enters the atmosphere, although recent studies have identified that including red macroalgae as a feed ingredient can drastically reduce methane produced by cattle. Here, we utilize ecological modelling to identify suitable sites for establishing aquaculture development to support sustainable agriculture and Sustainable Development Goals 1 and 2. We used species distributions models (SDMs) parameterized using an ensemble of multiple statistical and machine learning methods, accounting for novel methodological and ecological artefacts that arise from using such approaches on non-native and cultivated species. We predicted the current distribution of two Asparagopsis species to high accuracy around the coast of Ireland. The environmental drivers of each species differed depending on where the response data was sourced from (i.e., native vs. non-native), suggesting that the length of time A. armata has been present in Ireland may mean it has undergone a niche shift. Subsequently, researchers looking to adopt SDMs to support aquaculture development need to acknowledge emerging conceptual issues, and here we provide the code needed to implement such research, which should support efforts to effectively choose suitable sites for aquaculture development that account for the unique methodological steps identified in this research.
Locusts and People: Integrating the Social Sciences in Sustainable Locust Management
Authors: Therville Clara , Anderies John M. , Lecoq Michel , Cease Arianne
Published: May 2021

Locust outbreaks have impacted agricultural societies for millennia, they persist today, and humans aim to manage them using preventative strategies. While locusts have been a focus for natural sciences for more than a century, social sciences remain largely underrepresented. Yet, organizational, economic, and cultural variables substantially impact these management strategies. The social sciences are one important means through which researchers and practitioners can better understand these issues. This paper examines the scope and purpose of different subfields of social science and explores how they can be applied to different issues faced by entomologists and practitioners to implement sustainable locust research and management. In particular, we discuss how environmental governance studies resonate with two major challenges faced by locust managers: implementing a preventative strategy over a large spatial scale and managing an intermittent outbreak dynamic characterized by periods of recession and absence of the threat. We contend that the social sciences can help facilitate locust management policies, actions and outcomes that are more legitimate, salient, robust, and effective.
Dispensing a Synthetic Green Leaf Volatile to Two Plant Species in a Common Garden Differentially Alters Physiological Responses and Herbivory
Authors: Freundlich Grace E. , Shields Maria , Frost Christopher J.
Published: May 2021

Herbivore-induced plant volatile (HIPV)-mediated eavesdropping by plants is a well-documented, inducible phenomenon that has practical agronomic applications for enhancing plant defense and pest management. However, as with any inducible phenomenon, responding to volatile cues may incur physiological and ecological costs that limit plant productivity. In a common garden experiment, we tested the hypothesis that exposure to a single HIPV would decrease herbivore damage at the cost of reduced plant growth and reproduction. Lima bean (Phaseolus lunatus) and pepper (Capsicum annuum) plants were exposed to a persistent, low dose (~10 ng/h) of the green leaf volatile cis-3-hexenyl acetate (z3HAC), which is a HIPV and damage-associated volatile. z3HAC-treated pepper plants were shorter, had less aboveground and belowground biomass, and produced fewer flowers and fruits relative to controls, while z3HAC-treated lima bean plants were taller and produced more leaves and flowers than did controls. Natural herbivory was reduced in z3HAC-exposed lima bean plants, but not in pepper. Cyanogenic potential, a putative direct defense mechanism in lima bean, was lower in young z3HAC-exposed leaves, suggesting a growth–defense tradeoff from z3HAC exposure alone. Plant species-specific responses to an identical volatile cue have important implications for agronomic costs and benefits of volatile-mediated interplant communication under field conditions.
Common Bean Yield and Zinc Use Efficiency in Association with Diazotrophic Bacteria Co-Inoculations
Authors: Jalal Arshad , Galindo Fernando Shintate , Boleta Eduardo Henrique Marcandalli , Oliveira Carlos Eduardo da Silva , Reis André Rodrigues dos , Nogueira Thiago Assis Rodrigues , Moretti Neto Mário João , Mortinho Emariane Satin , Fernandes Guilherme Carlos , Teixeira Filho Marcelo Carvalho Minhoto
Published: May 2021

Enrichment of staple food with zinc (Zn) along with solubilizing bacteria is a sustainable and practical approach to overcome Zn malnutrition in human beings by improving plant nutrition, nutrient use efficiency, and productivity. Common bean (Phaseolus vulgaris L.) is one of a staple food of global population and has a prospective role in agronomic Zn biofortification. In this context, we evaluated the effect of diazotrophic bacterial co-inoculations (No inoculation, Rhizobium tropici, R. tropici + Azospirillum brasilense, R. tropici + Bacillus subtilis, R. tropici + Pseudomonas fluorescens, R. tropici + A. brasilense + B. subtilis, and R. tropici + A. brasilense + P. fluorescens) in association with soil Zn application (without and with 8 kg Zn ha−1) on Zn nutrition, growth, yield, and Zn use efficiencies in common bean in the 2019 and 2020 crop seasons. Soil Zn application in combination with R. tropici + B. subtilis improved Zn accumulation in shoot and grains with greater shoot dry matter, grain yield, and estimated Zn intake. Zinc use efficiency, recovery, and utilization were also increased with co-inoculation of R. tropici + B. subtilis, whereas agro-physiological efficiency was increased with triple co-inoculation of R. tropici + A. brasilense + P. fluorescens. Therefore, co-inoculation of R. tropici + B. subtilis in association with Zn application is recommended for biofortification and higher Zn use efficiencies in common bean in the tropical savannah of Brazil.
Effects of Defatted Rice Bran Inclusion Level on Nutrient Digestibility and Growth Performance of Different Body Weight Pigs
Authors: Huang Bingbing , Shi Huangwei , Wang Li , Wang Lu , Lyu Zhiqian , Hu Qile , Zang Jianjun , Li Defa , Lai Changhua
Published: May 2021

This study was conducted to determine the effects of low-protein diet prepared with different levels of defatted rice bran (DFRB) and weight stages on growth performance and nutrient digestibility of growing–finishing pigs. The animal experiment included three stages. A total of 240 growing pigs with an initial body weight of 28.06 ± 8.56 kg for stage 1 were allocated to five diets including one control group and four DFRB diets supplemented with 2.5%, 5%, 7.5% and 10% DFRB, respectively. The 192 crossbred pigs with initial body weights of 55.03 ± 7.31 kg and 74.55 ± 9.10 kg were selected for stage 2 and stage 3, respectively. Pigs were allocated to four diets including one control group and three DFRB diets supplemented with 10%, 15% and 20% DFRB, respectively. The results showed that with the increase in DFEB intake, the gain: feed was linearly increased (p < 0.05), and the average daily feed intake tended to linearly decrease (p = 0.06) in stage 1. Except for the apparent total tract digestibility (ATTD) of acid detergent fiber (ADF) in stage 3, levels of DFRB had significant effects on the ATTD of gross energy (GE), dry matter (DM), ash, neutral detergent fiber (NDF) and ADF in three weight stages. In stage 1, with the increase in levels of DFRB, the ATTD of NDF and hemicellulose were firstly increased and then decreased (p < 0.01). In stage 2, with the increasing levels of DFRB, the ATTD of DM, ash and cellulose were firstly increased and then decreased (p < 0.01). In stage 3, the ATTD of GE, DM, ash, NDF and hemicellulose decreased linearly with the increase in levels of DFRB (p < 0.01). Collectively, DFRB could be used as a replacement for corns and soybean meal, and weight stage is important to consider when adjusting the additive proportion.
Antibiotic-Resistant Bacteria in Clams—A Study on Mussels in the River Rhine
Authors: Zacharias Nicole , Löckener Iris , Essert Sarah M. , Sib Esther , Bierbaum Gabriele , Kistemann Thomas , Schreiber Christiane
Published: May 2021

Bacterial infections have been treated effectively by antibiotics since the discovery of penicillin in 1928. A worldwide increase in the use of antibiotics led to the emergence of antibiotic resistant strains in almost all bacterial pathogens, which complicates the treatment of infectious diseases. Antibiotic-resistant bacteria play an important role in increasing the risk associated with the usage of surface waters (e.g., irrigation, recreation) and the spread of the resistance genes. Many studies show that important pathogenic antibiotic-resistant bacteria can enter the environment by the discharge of sewage treatment plants and combined sewage overflow events. Mussels have successfully been used as bio-indicators of heavy metals, chemicals and parasites; they may also be efficient bio-indicators for viruses and bacteria. In this study an influence of the discharge of a sewage treatment plant could be shown in regard to the presence of E. coli in higher concentrations in the mussels downstream the treatment plant. Antibiotic-resistant bacteria, resistant against one or two classes of antibiotics and relevance for human health could be detected in the mussels at different sampling sites of the river Rhine. No multidrug-resistant bacteria could be isolated from the mussels, although they were found in samples of the surrounding water body.
Ubisol-Q10, a Nanomicellar and Water-Dispersible Formulation of Coenzyme-Q10 as a Potential Treatment for Alzheimer’s and Parkinson’s Disease
Authors: Wear Darcy , Vegh Caleb , Sandhu Jagdeep K. , Sikorska Marianna , Cohen Jerome , Pandey Siyaram
Published: May 2021

The world continues a desperate search for therapies that could bring hope and relief to millions suffering from progressive neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD). With oxidative stress thought to be a core stressor, interests have long been focused on applying redox therapies including coenzyme-Q10. Therapeutic use has failed to show efficacy in human clinical trials due to poor bioavailability of this lipophilic compound. A nanomicellar, water-dispersible formulation of coenzyme-Q10, Ubisol-Q10, has been developed by combining coenzyme-Q10 with an amphiphilic, self-emulsifying molecule of polyoxyethanyl α-tocopheryl sebacate (derivatized vitamin E). This discovery made possible, for the first time, a proper assessment of the true therapeutic value of coenzyme-Q10. Micromolar concentrations of Ubisol-Q10 show unprecedented neuroprotection against neurotoxin exposure in in vitro and in vivo models of neurodegeneration and was extremely effective when delivered either prior to, at the time of, and most significantly, post-neurotoxin exposure. These findings indicate a possible way forward for clinical development due to effective doses well within Federal Drug Administration guidelines. Ubisol-Q10 is a potent mobilizer of astroglia, antioxidant, senescence preventer, autophagy activator, anti-inflammatory, and mitochondrial stabilizer. Here we summarize the work with oil-soluble coenzyme-Q10, its limitations, and focus mainly on efficacy of water-soluble coenzyme-Q10 in neurodegeneration.