bluuebunny/crossref_metadata_2025 huggingface dataset:
Apparent resistance to brodifacoum in
Authors: Sran Suman P. K. , Gartrell Brett G. , Fisher Penny , Armstrong Doug P.
Published: July 2022

Context Anticoagulants have been used in New Zealand for decades, but few data are available on the sustainability of these toxins for rodent control. It is important to regularly monitor for resistance in long-term brodifacoum-use areas and establish a database for future references. Aims This study aimed to estimate the effective dose (ED50) of brodifacoum for ship rats from an area of New Zealand with no history of brodifacoum use, in order to establish a blood-clotting response test for assessing resistance in rodent populations from other areas. Methods A ranging study was conducted whereby successive groups of ship rats were administered brodifacoum doses that were increased or decreased progressively, until an International Normalised Ratio (INR) of 3.6 was reached. Linear regression was used to model the relationship between dose and INR, and ED50 dose was estimated using the resulting model. Results None of the rats appeared susceptible to brodifacoum at previously reported LD50 exposures for this species. The ED50 of brodifacoum was estimated to be 2.88 mg/kg for males and 3.81 mg/kg for females. These values are 6–8 times greater than the previously published lethal dose values for ship rats in New Zealand. Conclusions Blood-clotting inhibition was detected in the rats only following high doses of brodifacoum, which may indicate resistance within the sampled population. Implications Relatively low susceptibility, or resistance, to brodifacoum in New Zealand ship rats may be mediated by spatial connections between areas with different histories and patterns of anticoagulant rodenticide use.
Peat subsidence in a tropical rubber plantation during a strong El Niño year
Authors: Wakhid Nur
Published: July 2022

El Niño usually induces peat fires because dry season was prolonged and rainfall was low. This event potentially increases soil CO2 emissions and peat subsidence on tropical peat due to low groundwater level. Despite this, El Niño impacts on peat soil subsidence is understudied in Indonesia. To fill the gap, we measured peat surface elevation to determine peat soil subsidence at monthly basis during dry season, from June to November, in the strong El Niño year of 2015 and the normal year of 2014. A rubber plantation cultivated on peat soil was selected as a representative area for this research. Subsidence (in cm) was determined by calculating the difference in ground elevation between June and November for 2014 and 2015. Measurement was done by inserting three steel pipes vertically until underlying mineral substrate. We found that peat soil subsidence in strong El Niño year was larger than that of normal year. This finding can be further exploited as the baseline information for peatland management under climate change and or in extreme weather.
Re-wetted peatland management through selection of native species in Sinarmas Forestry
Authors: Wahno I , Nugraheni M , Herdyantara B , Gafur A , Tjahjono B
Published: July 2022

Sinarmas Forestry R&D has initiated studies on development of native species in peatland since 2000. This paper describes progress of the research, especially in the last 5 years, which coincided with the implementation of the Government Regulation 71 of 2014 and in collaboration with Asia Pulp and Paper (APP), Forest Research and Development Agency of KLHK, Gadjah Mada University (UGM), Deltares and Euroconsult Mott MacDonald (EMM). The main objective was to identify alternative local species apart from Acacia crassicarpa as pulp and paper raw materials in peat areas with water table of < 40 cm (rewetted areas). Series of different trials have been established, including progeny and species trials. This paper focuses on the species trials. The trials were conducted in Siak Regency, Riau, in a randomized complete block design with 5 replicates and plot size of 6 x 6 trees. Based on the survival rate and growth data, 4 native trees, i.e. Geronggang (Cratoxylon arborescens), Gelam (Melaleuca leucadendra), Balangeran (Shorea balangeran), and Bush Merah (Lophostemon suaveolens) were great potentials as alternatives to A. crassicarpa. Propagation procedures of these species, including tissue culture techniques, are currently being explored.
The performance of grain yield and variability of ten high yielding varieties of rice at tidal swampland
Authors: Saleh M , Khairullah I
Published: July 2022

Rice is the main food crop for Indonesians; hence, increasing population leads to expanding demand for this commodity. This research was carried out over potential acid sulfate soils of tidal swamplands in Matang Danau village, Sambas regency, West Kalimantan during 2018 Dry Season. The aim of the research was to evaluate grain yields and the variability of ten rice varieties. The study employed completely randomized block design with three replications. Ten rice varieties, namely Inpara 1, Inpara 2, Inpara 3, Inpara 4, Inpara 6, Inpara 8, Inpara 9, Margasari, Inpari 32 and Cillosari (as control) were investigated. The results showed that all varieties performed good phenotypic acceptabilily (score 3), without symptoms of Fe toxicity. Yielded grain ranged from 2.44 to 5.39 tons/ha in dry milled grain. The highest yield was shown by Inpari 32 (5.33 t/ha) and Inpara 1 (5.39 t/ha), suggesting that these varieties suit acid sulfate soils as an alternative to existing Cilosari cultivar.
Does the exposure of water shortage in peat soil affect the nutrient uptake of seedlings between different oil palm varieties?
Authors: Farrasati Rana , Muhayat  , Ginting Eko N , Pradiko Iput , Winarna
Published: July 2022

Soil water content is an important property to indicate the quality of peat in supporting plant growth. Soil nutrient is affected by water content, and each plant has varied adaptation to encounter water stress. This study aimed to observe the effect of water stress to leaf nutrients, nutrient uptake dynamics, and biomass on oil palm seedlings with three different varieties (540, Langkat, Dumpy) and four different water stoppage periods (0, 14, 21, 28 days). Results showed that after 28 days, biomass, leaf nutrients, and plant nutrient uptake (N, P, K, Ca, Mg) from 3 varieties were not statistically different. However, different N, P, K, and Mg uptake only occurred if we compared watering period’s data. The highest water content and biomass correlation were shown in Langkat variety (r = -0.630). The pH increased longest water stoppage period (r = 0.116). Significant correlation was only found in Langkat and Dumpy’s N uptake (r = -0.431 - (- 0.420)), and P uptake of Langkat (r = -0.368). Sensitivity order of nutrient uptake in relation with low water content for 540 variety was N > Ca > Mg > P > K; Langkat variety was N > Ca > Mg > P > K, and Dumpy variety was N > Ca > P > Mg > K.
Understanding Material Selection Challenges in Geothermal Well and Systematic Qualification Approach
Authors: Tayactac R G , Manuel M C
Published: July 2022

Geothermal wells are usually operated under High Temperature High Pressure (HTHP) conditions where corrosion is the major threat to the well integrity. As a result, high operation cost and production time loss due to a short life span of steel casing reported in less than two years. This paper describes a study of the casing problems and failures observed in geothermal wells and a possible approach to optimize material selection and qualification of geothermal wellhead system materials.
Effect of Increasing Solar Radiation Reflected with Mirrors Perpendicularly on the Power Output of Photovoltaic System with Cooling
Authors: Kolamroudi Mohammad Karimzadeh , Ilkan Mustafa , Egelioglu Fuat , Safaei Babak
Published: July 2022

Solar energy is one of the most popular renewable energies in the world as solar energy can be easily accessed throughout most places of the world. However, converting solar energy into other sources of energy is not very cheap and numerous efficiency improvements methods are under investigation by researchers around the world. The current study proposes a low concentration photovoltaic system (LCPVS) with 4 mirrors and cooling. The aim of this project was to examine how using mirrors to concentrate solar radiation affects the amount of power generated by solar panels. The mirrors (ranging from 1 to 4) radiated the sun reflection onto the panel with a cooling system. The results obtained from the proposed project were compared to the results collected from the normal panel without concentration to measure the differences which revealed that the proposed system output power was almost three times more than conventional photovoltaic (PV) panel without concentration.
A Review – Earth-air Heat Exchanger: Applications, Advances and Challenges
Authors: Zeitoun Wael , Lin Jian , Siroux Monica
Published: July 2022

Due to global warming and energy security, renewable energy systems became a subject of interest in research. Earth-air heat exchanger is one of these systems that can decrease the primary energy consumption using shallow layers of the ground as a source or sink of heat. Different configurations and designs of EAHEs were under research to assess their performance and find the optimal designs. It is important to identify and classify these designs to further develop innovative research on this topic. This review sheds light on the different classifications of EAHEs and their applications.
Wave Conditions Variation Effects on Energy Recovery for a Dexa Wave Energy Converter
Authors: Jabrali Ahmed , Khatyr Rabha , Naciri Jaafar Khalid
Published: July 2022

The aim of this paper is to present the effects of wave amplitude and wave frequency variations on the energy recovered by a DEXA Wave, which is a wave energy converter (WEC) device. The two-body articulated floating WEC consists of two connected rigid bodies, the energy is recovered by taking advantage of the relative movement between the two parts set in motion differently by the wave. The results show that the value of the wave amplitude and wave period have an impact on the recovered energy by the WEC. The present work shown that for this type of WEC, an increase in the amplitude of the wave does not necessarily improve the energy recovered by the WEC also it is shown that the considered WEC could be typical for low wave amplitude areas.
Comparative Study of Biogas Production from Cassava Pulp in a Sequencing Batch Reactor and a Continuous Stirred Tank Reactor
Authors: Ruttithiwapanich T. , Waewsak C. , Laopitinan O. , Saengchan K. , Lueangwattanapong K. , Songkasiri W.
Published: July 2022

Thai cassava starch industry generates solid waste or pulp approximately of 9.5 Mt/y (with a moisture content of 70–80%). Biogas production technology has been introduced for several decades in Thailand. However, the implementation of biogas production using cassava pulp as a feedstock is still limited due to the complex lignocellulosic structure, which diminishes hydrolysis. This work investigated biogas production from cassava pulp in a 50-m3 pilot-scale sequencing batch reactor (SBR) and continuous stirred tank reactor (CSTR). Both reactors were fed with cassava pulp, under the organic loading rate (OLR) of 8 kg-COD/m3-d and the average hydraulic retention time (HRT) of 7 d. Under the batch operation, more than 60% of the starch content was utilized within the first three days. The SBR achieved methane production of 1.87 m3-CH4/ton-pulpfresh-d and acids production of 2.19 kg-TVA/ton-pulpfresh-d while the CSTR had methane production of 0.22 m3-CH4/ton-pulpfresh-d and acids production of 7.07 kg-TVA/ton-pulpfresh-d. The methane production was higher in the SBR because the settling process helped microorganisms remain in the system. In CSTR, acids rather than methane were produced due to the washout of methanogenic microorganisms. This work revealed that the SBR yielded higher biogas production, while the CSTR produced intermediate acids, which could be supplied to the biochemical industry.
Numerical Simulation of Thermal Process in a Phase Change Material Exposed to Solar Heating in a Tropical Region
Authors: Lotun S S , Lollchund M R , Gooroochurn M
Published: July 2022

The capacity for phase change material (PCM) to absorb and release latent heat has led to its applications in heating/cooling strategies in solar heating systems, air-conditioning system, electronics cooling and food preservation. The use of PCM in building construction through micro/macro-encapsulation to passively cool/heat a living space has attracted a lot of experimental and simulation research work, especially after the turmoil caused due to worldwide energy crises. In this paper, the thermal behaviour of a PCM exposed to solar heating in a tropical climate is studied numerically over a 24-hour period using the ANSYS fluent Software. A grid dependency test is initially devised to establish the most appropriate grid sizes and time steps to be used for the subsequent simulations with acceptable accuracy. PCM is setup to be in contact with one side of a concrete block. The other side of the concrete is exposed directly to a typical daily solar radiation profile of a tropical region. Results, in terms of temperature distribution and liquid fraction, show that a two-layer of a commercially available PCM is sufficient to flatten the temperature fluctuations arising from solar heating in the tropical regions.
Fertilizer Utilization Efficiency in China, 2001-2015
Authors: Huang Xiuquan , Wang Xi , Su Shaodan , Shen Yang , Chen Baoxin , Zhang Tao
Published: July 2022

This study employs the biennial-weight-modified Russell model to measure the efficiency of China’s fertilizer utilization during 2001-2015 while investigating the temporal and spatial characteristics. The empirical results showed that fertilizer utilization efficiency (FUE) in the eastern region was the highest, followed by the central region during the sample period. FUE in China and its three regions had only slight fluctuations without an obvious trend. But FUE varied greatly in some provinces. The provinces having higher FUEs mainly included Shanghai and Hainan, whereas those with lower FUEs mainly included Anhui, Shanxi, and Hubei. Therefore, the governments should pay attention to both the improvement of FUE and the inter-regional balance for the coordinated development of agricultural regions.
Comparing adoption determinants of solar home systems, LPG and electric cooking for holistic energy services in Sub-Saharan Africa
Authors: Kizilcec Vivien , Perros Tash , Bisaga Iwona , Parikh Priti
Published: July 2022

Globally, rates of electrification and clean cooking are low, particularly in Sub-Saharan Africa. Off-grid energy solutions have a vital role to play in accelerating clean energy access to address Sustainable Development Goal 7. For organisations aiming to provide both electricity and cooking services, there is a need for holistic studies on adoption determinants to aid market expansion. This paper presents a comprehensive literature review of the adoption determinants and barriers for liquefied petroleum gas (LPG), solar home systems (SHS) and electric cooking (e-cooking) in Sub-Saharan Africa. A total of 40 adoption determinants were identified across the 71 publications examined. Of these, 30 determinants were shared by at least two of the technologies, whilst six were specifically linked to LPG and four to SHS. Key determinants that cut across technologies included reliability of alternative technologies (such as grid supply), reliable energy supply through the technology in question, affordability, household size and location (urban/rural). The findings show that there is an overlap in the demographics that use these technologies, as urban households often use SHS as a backup to the electricity grid and their cooking needs can feasibly be met by LPG or e-cooking devices. There is a clear opportunity for e-cooking devices to be sold as appliances for SHS. E-cooking devices such as electric pressure cookers can be complementary to LPG due to their suitability for cooking different foods. Pay-as-you-go models, which have a proven track record with improving access to SHS and are beginning to also be applied to LPG, have the potential to provide a strong foundation for scaling up of LPG and e-cooking services.
Modelling and numerical simulation of magnetostrictive materials for reduction of friction
Authors: Silva José A , Ferreira Rita , Sobral Luís , Silva Filipe S , Carvalho Óscar , Catarino Susana O
Published: July 2022

This study aims to enhance the multifunctional properties in top piston rings by adding magnetostrictive materials to reduce friction between them and the cylinder lining. The magnetostrictive effect will create mechanical deformations in piston rings, with consequent friction reduction. The present study consisted of a finite element analysis (FEA), using COMSOL Multiphysics® software, where both the amplitude of deformation and the reduction of the contact forces were analysed. These variables are useful to predict the ability to introduce mechanical vibrations in piston rings that can lead to the reduction of friction. The results showed a reduction of the contact force below 4%, and deformation amplitudes in the sliding plane of 6.50 μm and 3.20 μm, approximately, in the axial and circumferential directions, respectively. Those results are promising, enhancing the potential of smart materials and magnetostrictive effects to create mechanical vibrations and reduce friction in piston ring structures.
BatchDTA: implicit batch alignment enhances deep learning-based drug–target affinity estimation
Authors: Luo Hongyu , Xiang Yingfei , Fang Xiaomin , Lin Wei , Wang Fan , Wu Hua , Wang Haifeng
Published: July 2022

Candidate compounds with high binding affinities toward a target protein are likely to be developed as drugs. Deep neural networks (DNNs) have attracted increasing attention for drug–target affinity (DTA) estimation owning to their efficiency. However, the negative impact of batch effects caused by measure metrics, system technologies and other assay information is seldom discussed when training a DNN model for DTA. Suffering from the data deviation caused by batch effects, the DNN models can only be trained on a small amount of ‘clean’ data. Thus, it is challenging for them to provide precise and consistent estimations. We design a batch-sensitive training framework, namely BatchDTA, to train the DNN models. BatchDTA implicitly aligns multiple batches toward the same protein through learning the orders of candidate compounds with respect to the batches, alleviating the impact of the batch effects on the DNN models. Extensive experiments demonstrate that BatchDTA facilitates four mainstream DNN models to enhance the ability and robustness on multiple DTA datasets (BindingDB, Davis and KIBA). The average concordance index of the DNN models achieves a relative improvement of 4.0%. The case study reveals that BatchDTA can successfully learn the ranking orders of the compounds from multiple batches. In addition, BatchDTA can also be applied to the fused data collected from multiple sources to achieve further improvement.
Evaluation of different computational methods for DNA methylation-based biological age
Authors: Di Lena Pietro , Sala Claudia , Nardini Christine
Published: July 2022

In recent years there has been a widespread interest in researching biomarkers of aging that could predict physiological vulnerability better than chronological age. Aging, in fact, is one of the most relevant risk factors for a wide range of maladies, and molecular surrogates of this phenotype could enable better patients stratification. Among the most promising of such biomarkers is DNA methylation-based biological age. Given the potential and variety of computational implementations (epigenetic clocks), we here present a systematic review of such clocks. Furthermore, we provide a large-scale performance comparison across different tissues and diseases in terms of age prediction accuracy and age acceleration, a measure of deviance from physiology. Our analysis offers both a state-of-the-art overview of the computational techniques developed so far and a heterogeneous picture of performances, which can be helpful in orienting future research.
Severing Clinical Ethics Consultation from the Ethical Commitments and Preferences of Clinical Ethics Consultants
Authors: Iltis Ana S
Published: July 2022

Recent work calls for excluding clinical ethics consultants’ religious ethical commitments from formulating recommendations about particular cases and communicating those recommendations. I demonstrate that three arguments that call for excluding religious ethical commitments from this work logically imply that consultants may not use their secular ethical commitments in their work. The call to sever clinical ethics consultation from the ethical commitments of clinical ethics consultants has implications for the scope of work consultants may do and for the competencies required for such work.
Haematological and biochemical reference intervals for wild green turtles (Chelonia mydas): a Bayesian approach for small sample sizes
Authors: Kophamel Sara , Rudd Donna , Ward Leigh C , Shum Edith , Ariel Ellen , Mendez Diana , Starling Jemma , Mellers Renee , Burchell Richard K , Munns Suzanne L
Published: July 2022

Animal health is directly linked to population viability, which may be impacted by anthropogenic disturbances and diseases. Reference intervals (RIs) for haematology and blood biochemistry are essential tools for the assessment of animal health. However, establishing and interpreting robust RIs for threatened species is often challenged by small sample sizes. Bayesian predictive modelling is well suited to sample size limitations, accounting for individual variation and interactions between influencing variables. We aimed to derive baseline RIs for green turtles (Chelonia mydas) across two foraging aggregations in North Queensland, Australia, using Bayesian generalized linear mixed-effects models (n = 97). The predicted RIs were contained within previously published values and had narrower credible intervals. Most analytes did not vary significantly with foraging ground (76%, 22/29), body mass (86%, 25/29) or curved carapace length (83%, 24/29). Length and body mass effects were found for eosinophils, heterophil:lymphocyte ratio, alkaline phosphatase, aspartate transaminase and urea. Significant differences between foraging grounds were found for albumin, cholesterol, potassium, total protein, triglycerides, uric acid and calcium:phosphorus ratio. We provide derived RIs for foraging green turtles, which will be helpful in future population health assessments and conservation efforts. Future RI studies on threatened species would benefit from adapting established veterinary and biomedical standards.
The effects of prehabilitation on body composition in patients undergoing multimodal therapy for esophageal cancer
Authors: Halliday Laura J , Boshier Piers R , Doganay Emre , Wynter-Blyth Venetia , Buckley John P , Moorthy Krishna
Published: July 2022

Prehabilitation aims to optimize a patient’s functional capacity in preparation for surgery. Esophageal cancer patients have a high incidence of sarcopenia and commonly undergo neoadjuvant therapy, which is associated with loss of muscle mass. This study examines the effects of prehabilitation on body composition during neoadjuvant therapy in esophageal cancer patients. In this cohort study, changes in body composition were compared between esophageal cancer patients who participated in prehabilitation during neoadjuvant therapy and controls who did not receive prehabilitation. Assessment of body composition was performed from CT images acquired at the time of diagnosis and after neoadjuvant therapy. Fifty-one prehabilitation patients and 28 control patients were identified. There was a significantly greater fall in skeletal muscle index (SMI) in the control group compared with the prehabilitation patients (Δ SMI mean difference = −2.2 cm2/m2, 95% CI –4.3 to −0.1, p=0.038). Within the prehabilitation cohort, there was a smaller decline in SMI in patients with ≥75% adherence to exercise in comparison to those with lower adherence (Δ SMI mean difference = −3.2, 95% CI –6.0 to −0.5, P = 0.023). A greater decrease in visceral adipose tissue (VAT) was seen with increasing volumes of exercise completed during prehabilitation (P = 0.046). Loss of VAT during neoadjuvant therapy was associated with a lower risk of post-operative complications (P = 0.017). By limiting the fall in SMI and promoting VAT loss, prehabilitation may have multiple beneficial effects in patients with esophageal cancer. Multi-center, randomized studies are needed to further explore these findings.
Greek Tragedy and Cathartic Violence in Leconte de Lisle’s Animal Poems
Authors: Shinabargar Scott
Published: July 2022

This article proposes a new understanding of Charles Marie René Leconte de Lisle’s famous animal poems. While recent studies have identified an innovative non-anthropocentric perspective in the texts – vivid snapshots of brute existence, without deeper meaning – we find that these animals function in a more complex manner. Locating them throughout his poetry, beyond the ‘portraits’ most readers are familiar with, we find that they are highly figurative participants in his extensive depictions of human history, lending a more visceral quality to this series of tragedies – recurring scenes that, with their sacrificial violence and devoured victims, indeed suggest an unexpected connection with this literary genre, in its earliest form. Equally unexpected, this connection appears most tenable not in those texts where humans share the stage (as in his adaptation of Aeschylus’s Oresteia), but where they are absent. Eliminating the figurative descriptions and impassioned dialogue of the historical and dramatic poems to focus on actual acts of predation, the poet allows the reader to experience these explosions of ‘purely animal’ violence as cathartic, tragic ritual.
Codesigning a Culture-Centered Age-Friendly Community for Māori Kaumātua: Cultural Principles and Practices
Authors: Simpson Mary Louisa , Oetzel John , Wilson Yvonne , Nock Sophie , Johnston Kirsten , Reddy Rangimahora
Published: July 2022

Objectives

This study examined a Māori (Indigenous people of Aotearoa New Zealand) age-friendly housing development. Two Māori community groups worked with multiple stakeholders to codesign a culture-centered, kaumātua (older adults) urban housing community. The purpose was to identify codesign and culture-centered principles in the development.

Methods

Kaupapa Māori (Māori-centered) and participatory research methodologies guided the culture-centered research design. Data collection included 27 interviews with 19 residents and 12 organizational stakeholders; three focus groups with residents’ families, service providers, and nonresident kaumātua (n = 16); and project documents. Data analysis used the framework method.

Results

Three codesign process themes emerged: (a) Kaumātua-centered vision; (b) realizing the vision; and (c) living the shared vision.

Discussion

Accounting for cultural practices in codesigning age-friendly and culture-centered housing for and with Indigenous older adults helps meet their cultural, social, health, and economic needs. The research offers a practical pathway to developing age-friendly housing environments for Māori kaumātua, their communities, wider society, and other Indigenous people.
“It’s You”: Caregiver and Clinician Perspectives on Lucidity in People Living With Dementia
Authors: Gilmore-Bykovskyi Andrea , Block Laura , Benson Clark , Fehland Jess , Botsch Meghan , Mueller Kimberly D , Werner Nicole , Shah Mindy J
Published: July 2022

Background and Objectives

Episodes of lucidity (ELs), or a transient return of abilities believed to be lost in people living with dementia, are a growing area of interest. These events hold important implications for care, caregiving, and our understanding of underlying etiologies. Research on ELs is largely limited to retrospective reports. The perspectives of professional and family caregivers on ELs and research approaches can inform efforts to define and study lucidity. The present study examined family caregiver and hospice clinician experiences with and perspectives on ELs in people living with dementia and observational approaches to studying these events.

Research Design and Methods

This exploratory, descriptive qualitative study employed semistructured interviews (N = 20 caregivers, N = 6 clinicians). Data were analyzed using Rapid Identification of Themes and subsequent duplicate review of interview data to enhance trustworthiness.

Results

Most participants readily recalled events they perceived as ELs, describing a transient return of abilities they felt was significant and/or meaningful. Defining features, interpretations, and the perceived impact of ELs varied, although ELs were commonly conceptualized as a manifestation of self. Caregivers described extensive efforts to detect patterns and supportive social conditions for ELs. Participants supported use of audiovisual observation to study ELs and provided recommendations for privacy, workflow, and caregiver engagement.

Discussion and Implications

Interpretations of ELs are heterogeneous, and recognition of these events may necessitate close familiarity with the person living with dementia. Participants endorse observational approaches and integration of caregivers in this research.
Catalytic promiscuity of O-methyltransferases from Corydalis yanhusuo leading to the structural diversity of benzylisoquinoline alkaloids
Authors: Bu Junling , Zhang Xiuhua , Li Qishuang , Ma Ying , Hu Zhimin , Yang Jian , Liu Xiuyu , Wang Ruishan , Jiao Xiang , Chen Tong , Lai Changjiangsheng , Cui Guanghong , Tang Jinfu , Kong Yu , Yang Lei , Lin Sheng , Chen Yun , Guo Juan , Huang Luqi
Published: July 2022

O-methyltransferases (OMTs) play essential roles in producing structural diversity and improving biological property of benzylisoquinoline alkaloids (BIAs) in plants. In this study, Corydalis yanhusuo, a plant used in traditional Chinese medicine due to the analgesic effects of its BIA active compounds, was employed to analyze the catalytic characteristics of OMTs in the formation of BIAs diversity. Seven genes encoding O-methyltransferases were cloned, and functionally characterized using seven potential BIA substrates. Specifically, an OMT (CyOMT2) with highly efficient catalytic activity of both 4’-and 6-O-methylations of 1-BIAs was found. CyOMT6 was found to perform two sequential methylations at both 9-and 2-positions of the essential intermediate of tetrahydroprotoberberines, (S)-scoulerine. Two OMTs (CyOMT5 and CyOMT7) with wide substrate promiscuity were found, with 2-position of tetrahydroprotoberberines as the preferential catalytic site for CyOMT5 (named scoulerine 2-O-methyltransferase), and 6-position of 1-BIAs as the preferential site for CyOMT7. In addition, through integrated phylogenetic, molecular docking analysis, and site directed mutation, it suggested that residues at sites of 172, 306, 313 and 314 in CyOMT5 are important for enzyme promiscuity related to O-methylations at 6- and 7-positions of isoquinoline. Cys at site 253 in CyOMT2 was proved to promote the methylation activity of 6-position and to expand substrate scopes. This work provides insight of O-methyltransferases in producing BIAs diversity in C. yanhusuo, and genetic elements for producing BIAs by metabolic engineering and synthetic biology.
The Common H202D Variant in GDF-15 Does Not Affect Its Bioactivity but Can Significantly Interfere with Measurement of Its Circulating Levels
Authors: Karusheva Yanislava , Ratcliff Matthew , Mörseburg Alexander , Barker Peter , Melvin Audrey , Sattar Naveed , Burling Keith , Backmark Anna , Roth Robert , Jermutus Lutz , Guiu-Jurado Esther , Blüher Matthias , Welsh Paul , Hyvönen Marko , O’Rahilly Stephen
Published: July 2022

Background

There is growing interest in the measurement of growth differentiation factor 15 (GDF-15) in a range of disorders associated with cachexia. We undertook studies to determine whether a common histidine (H) to aspartate (D) variant at position 202 in the pro-peptide (position 6 in the mature peptide) interfered with its detection by 3 of the most commonly used immunoassays.

Methods

Three synthetic GDF-15-forms (HH homo-, HD hetero-, and DD-homodimers) were measured after serial dilution using Roche Elecsys®, R&D QuantikineTM ELISA, and MSD R&D DuoSet® immunoassays. GDF-15 concentrations were measured by the Roche and the MSD R&D immunoassays in 173 genotyped participants (61 HH homozygotes, 59 HD heterozygotes, and 53 DD homozygotes). For the comparative statistical analyses of the GDF-15 concentrations, we used non-parametric tests, in particular Bland–Altman difference (bias) plots and Passing–Bablok regression. The bioactivity of the 2 different homodimers was compared in a cell-based assay in HEK293S-SRF-RET/GFRAL cells.

Results

The Roche assay detected H- and D-containing peptides similarly but the R&D reagents (Quantikine and DuoSet) consistently underreported GDF-15 concentrations in the presence of the D variant. DD dimers had recoveries of approximately 45% while HD dimers recoveries were 62% to 78%. In human serum samples, the GDF-15 concentrations reported by the R&D assay were a median of 4% lower for HH, a median of 36% lower for HD, and a median of 61% lower for DD compared to the Roche assay. The bioactivities of the HH and DD peptides were indistinguishable.

Conclusions

The D variant of GDF-15 substantially affects its measurement by a commonly used immunoassay, a finding that has clear implications for its interpretation in research and clinical settings.
Personalized Gamma Knife radiosurgery for cavernous sinus hemangiomas: A Chinese single-center retrospective study for 10 years of 187 patients
Authors: Yang Ruyi , Xv Ziqiang , Zhao Puxue , Li Junwu , An Quan , Huang Shan , Wang Xinjun
Published: July 2022

Background

The aim of this study is to retrospectively review the effectiveness and safety of personalized Gamma Knife radiosurgery (GKRS) for cavernous sinus hemangiomas (CSHs) and to summarize experience of personalized GKRS treatment for different volume of CSHs.

Methods

187 CSHs patients who received personalized GKRS treatment in our center from January 1, 2011 to December 31, 2020 were enrolled in this study and classified into small and medium CSHs (<20 ml), large CSHs (20–40 ml) and giant CSHs (≥40 ml) according to tumor volume. The personalized GKRS treatment strategy included single GKRS and staged GKRS. Tumor shrinkage rate, clinical symptoms response, and complications after GKRS were recorded during the follow-up period. Multivariate factors influencing clinical symptoms response were analyzed after personalized GKRS treatment.

Results

After a mean follow-up duration of 28 months (range 12–124 months), the tumor control rate was 100%, and the mean shrinkage rate of CSHs was 93.2% (61.3%–100%) in the last follow-up. Of the 115 patients with preexisting symptoms, 43 (37.5%) patients showed symptom disappearance, 17 (14.7%) patients demonstrated improvement, and 55 (47.8%) patients remained with no change. Previous surgical resection of CSHs (OR = 0.025, 95% CI 0.007–0.084, P = .000) was identified to be an independent risk factor for no symptom improvement after GKRS treatment.

Conclusions

Personalized GKRS is an effective and safe treatment for different volume of CSHs, which is capable of shrinking the tumor and improving symptoms with extremely low incidence of adverse effects and might be considered as the primary treatment strategy for CSHs.
Relationship Between Replay-Associated Ripples and Hippocampal N-Methyl-D-Aspartate Receptors: Preliminary Evidence From a PET-MEG Study in Schizophrenia
Authors: Nour Matthew M , Beck Katherine , Liu Yunzhe , Arumuham Atheeshaan , Veronese Mattia , Howes Oliver D , Dolan Raymond J
Published: July 2022

Background and Hypotheses

Hippocampal replay and associated high-frequency ripple oscillations are among the best-characterized phenomena in resting brain activity. Replay/ripples support memory consolidation and relational inference, and are regulated by N-methyl-D-aspartate receptors (NMDARs). Schizophrenia has been associated with both replay/ripple abnormalities and NMDAR hypofunction in both clinical samples and genetic mouse models, although the relationship between these 2 facets of hippocampal function has not been tested in humans.

Study Design

Here, we avail of a unique multimodal human neuroimaging data set to investigate the relationship between the availability of (intrachannel) NMDAR binding sites in hippocampus, and replay-associated ripple power, in 16 participants (7 nonclinical participants and 9 people with a diagnosis of schizophrenia, PScz). Each participant had both a [18F]GE-179 positron emission tomography (PET) scan (to measure NMDAR availability, VT) and a magnetoencephalography (MEG) scan (to measure offline neural replay and associated high-frequency ripple oscillations, using Temporally Delayed Linear Modeling).

Study Results

We show a positive relationship between hippocampal NMDAR availability and replay-associated ripple power. This linkage was evident across control participants (r(5) = .94, P = .002) and PScz (r(7) = .70, P = .04), with no group difference.

Conclusions

Our findings provide preliminary evidence for a relationship between hippocampal NMDAR availability and replay-associated ripple power in humans, and haverelevance for NMDAR hypofunction theories of schizophrenia.
Evaluation of psychometric properties of patient-reported outcome measures frequently used in narcolepsy randomized controlled trials: a systematic review
Authors: Schokman Aaron , Bin Yu Sun , Naehrig Diana , Cheung Janet M Y , Kairaitis Kristina , Glozier Nick
Published: July 2022

Study Objectives

To systematically determine subjective and objective outcome measures used to measure the efficacy of narcolepsy interventions in randomized controlled trials (RCTs) in adults and children and assess psychometric properties of patient-reported outcome measures (PROMs) used.

Methods

We searched bibliographical databases and clinical trial registries for narcolepsy RCTs and extracted objective and subjective outcome measures. If PROMs were used, we searched for psychometric studies conducted in a narcolepsy population using bibliographical databases and appraised using Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.

Results

In total, 80 different outcome measures were used across 100 RCTs. Epworth Sleepiness Scale (ESS) (n = 49) and Maintenance of Wakefulness Test (n = 47) were the most frequently used outcome measures. We found 19 validation studies of 10 PROMs in narcolepsy populations. There was limited evidence for validity or responsiveness of the ESS; yet sufficient reliability (pooled ICC: 0.81–0.87). Narcolepsy Severity Scale (NSS) had sufficient reliability (pooled ICC: 0.71–0.92) and both adult and pediatric versions had sufficient discriminant validity (treated/untreated). Content validity was only evaluated in pediatric populations for ESS-CHAD and NSS-P and rated inconclusive. Quality of evidence of the psychometric studies for all scales ranged from very low to low.

Conclusions

Although recognized by regulatory bodies and widely used as primary outcome measures in trials, there is surprisingly little evidence for the validity, reliability, and responsiveness of PROMs frequently used to assess treatment efficacy in narcolepsy. The field needs to establish patient-centered minimal clinically important differences for the PROMs used in these trials.
Supra-optimal leaf area index of a temperate lianaPueraria lobatafor competition withSolidago altissimaat the expense of canopy photosynthesis
Authors: Oikawa Shimpei
Published: July 2022

Leaf area index (LAI) measured for the actual plant canopy is higher than the LAI that maximizes canopy photosynthesis (referred to as optimal LAI) because each individual can increase its light interception by unilaterally producing more leaf area. The LAI of an invasive woody vine Pueraria lobata (kudzu) is one of the highest among plant species, sometimes attaining nearly 10 m2 m−2. The high LAI casts heavy shade over neighboring plants, making their survival difficult. Interesting to note is that the high LAI also increases self-shading, thereby decreasing its own photosynthesis processes. In the present study, the influences of the high LAI on light interception and canopy photosynthesis, as well as on the inter-specific competition was investigated on a roadside P. lobata vegetation in Japan. With the aid of a canopy photosynthesis model and a sensitivity analysis, it was revealed that the actual LAI was 2.2–3.0 times higher than the optimal LAI for maximizing canopy photosynthesis. In the following year, a field experiment was conducted where a nearly optimal LAI was maintained throughout the growth period by regularly clipping the leaves of P. lobata. Ultimately, the field results revealed that even with a nearly optimal LAI, P. lobata was outcompeted by a competing alien weed, Solidago altissima (tall goldenrod). These results indicate that the supra-optimal leaf area, rather than maximum canopy carbon gain, makes P. lobata the dominating species in light-competing environments.
A Novel Grading System of Destructive Lumbar Spondyloarthropathy Based on Evaluation of the Facet Joints
Authors: Hatano Masaki , Anno Masato , Miyoshi Kota , Isawa Kazuya , Hoshino Junichi , Sawa Naoki , Ubara Yoshifumi , Nakamura Masaki , Yamamoto Seizo , Kitajima Izuru
Published: July 2022

Study Design.

Retrospective cohort study.

Objective.

To develop and evaluate a new grading system for destructive lumbar spondyloarthropathy (DLSA) by assessing bony destruction of the facet joints; to evaluate interrater reliability; and to determine the association between anteroposterior (AP) dural sac diameter at the lumbar level and the new grading.

Summary of Background Data.

The characteristics of DLSA are unknown, hindering clinical care and research. Imaging to determine the cause of DLSA may positively contribute to patient outcome or well-being by providing prognostic information.

Patients and Methods.

In the magnetic resonance images (MRIs), we measured an axial midline AP dural sac diameter and evaluated bone destruction caused by amyloidosis at the level of the center of each lumbar disk of the lumbar spine. Two orthopedic surgeons independently evaluated each case at two-month intervals and assigned the grade by rating bone destruction at each lumbar level. Weighted κ and intraclass correlation coefficients for interrater reliability were calculated. In addition, the correlation between the AP diameter of the spinal dural sac at the lumbar level and the new MRI-based DLSA grade was examined.

Results.

The sample size of 82 patients was reached by examining records of 118 consecutive patients. The mean (SD) age of the included patients was 65 (7.2) years, and 36 (43.9%) were women. The grading of DLSA showed moderate to good interrater reliability at both assessments (κ, 0.59–0.78). Intraclass correlation coefficient showed substantial to excellent agreement (intraclass correlation coefficient, 0.63–0.86). The AP diameter of the spinal dural sac at the lumbar level showed a significant correlation with the new grading (P<0.001).

Conclusions.

The new MRI-based grading system for DLSA has good interrater reliability, although the strength of agreement varies somewhat. The new grading system correlates with AP dural sac diameter. Thus, this classification focused on facet erosion, which leads to functional incompetence may be helpful in surgical decision-making.
Evolution of Adult Cervical Deformity Surgery Clinical and Radiographic Outcomes Based on a Multicenter Prospective Study: Are Behaviors and Outcomes Changing With Experience?
Authors: Passias Peter G. , Krol Oscar , Moattari Kevin , Williamson Tyler K. , Lafage Virginie , Lafage Renaud , Kim Han Jo , Daniels Alan , Diebo Bassel , Protopsaltis Themistocles , Mundis Gregory , Kebaish Khaled , Soroceanu Alexandra , Scheer Justin , Hamilton D. Kojo. , Klineberg Eric , Schoenfeld Andrew J. , Vira Shaleen , Line Breton , Hart Robert , Burton Douglas C. , Schwab Frank A , Shaffrey Christopher , Bess Shay , Smith Justin S. , Ames Christopher P. ,   on behalf of the International Spine Study Group
Published: July 2022

Study Design.

Retrospective cohort study.

Objective.

Assess changes in outcomes and surgical approaches for adult cervical deformity surgery over time.

Summary of Background Data.

As the population ages and the prevalence of cervical deformity increases, corrective surgery has been increasingly seen as a viable treatment. Dramatic surgical advancements and expansion of knowledge on this procedure have transpired over the years, but the impact on cervical deformity surgery is unknown.

Materials and Methods.

Adult cervical deformity patients (18 yrs and above) with complete baseline and up to the two-year health-related quality of life and radiographic data were included. Descriptive analysis included demographics, radiographic, and surgical details. Patients were grouped into early (2013–2014) and late (2015–2017) by date of surgery. Univariate and multivariable regression analyses were used to assess differences in surgical, radiographic, and clinical outcomes over time.

Results.

A total of 119 cervical deformity patients met the inclusion criteria. Early group consisted of 72 patients, and late group consisted of 47. The late group had a higher Charlson Comorbidity Index (1.3 vs. 0.72), more cerebrovascular disease (6% vs. 0%, both P<0.05), and no difference in age, frailty, deformity, or cervical rigidity. Controlling for baseline deformity and age, late group underwent fewer three-column osteotomies [odds ratio (OR)=0.18, 95% confidence interval (CI): 0.06–0.76, P=0.014]. At the last follow-up, late group had less patients with: a moderate/high Ames horizontal modifier (71.7% vs. 88.2%), and overcorrection in pelvic tilt (4.3% vs. 18.1%, both P<0.05). Controlling for baseline deformity, age, levels fused, and three-column osteotomies, late group experienced fewer adverse events (OR=0.15, 95% CI: 0.28–0.8, P=0.03), and neurological complications (OR=0.1, 95% CI: 0.012–0.87, P=0.03).

Conclusion.

Despite a population with greater comorbidity and associated risk, outcomes remained consistent between early and later time periods, indicating general improvements in care. The later cohort demonstrated fewer three-column osteotomies, less suboptimal realignments, and concomitant reductions in adverse events and neurological complications. This may suggest a greater facility with less invasive techniques.