bluuebunny/crossref_metadata_2025 huggingface dataset:
TrEKBQA:Traversing Knowledge Graph Embedding for Multi-hop Knowledge Base Question Answering
Authors: Shi Xiujin , Hu Jun , Sun Naiwen , Yu Shoujian
Published: January 2023

Recent research apply KG embedding to multi-hop Knowledge Base Question Answering(KBQA) to predict missing links, however, it is often affected by the skewed distribution of nodes in the knowledge graph, resulting in poor generalization of the model. Therefore, we propose a method TrEKBQA based on traversing the knowledge graph embedding space for multi-hop KBQA, which performs path traversal in the KG embedding space instead of KG itself for link prediction to complete the knowledge graph, thus improving the accuracy of multi-hop KBQA.TrEKBQA model complex relationships using correlations between individual links and longer paths connecting the same pair of entities to traverse the KG embedding space to mitigate the effects of biased distribution of nodes and improve the performance of link prediction. In the pre-processing process, TrEKBQA uses the PRN algorithm to extract subgraphs related to the problem entity to reduce the number of target entities. Through experiments on multiple benchmark datasets, we demonstrate the effectiveness of TrEKBQA on KBQA tasks.
Deformation Assessment of Deep Excavations Retaining Structure in Collapsible Loess Areas
Authors: Xu Jianzhuang , Sun Benli , Wu Ming , Yang Haifeng
Published: January 2023

In this study, the deformation characteristics of deep excavations retaining structure in loess areas are investigated statistically by analyzing filed measurements in three typical loess areas of Shaanxi, Shanxi, and Gansu. Generally, the study results showed that the maximum lateral displacement of the retaining structure ranges between 0.277‰H to 3.712‰H, with an average of 0.1029%H (H is the final excavation depth of excavations). The maximum lateral displacement is approximately located at 2/3 of the excavation depth. In addition, a quantitative analysis is carried out on the influencing factors for the lateral deformation of the retaining structure, such as the insertion ratio of retaining piles (walls), the length-wide ratio of the excavation plane, synthetical stiffness of the support system, heave-resistant safety factor, and the set depth of support in the first tunnel.
Research for the Influence of Ferris Wheel Deep Foundation Pit Excavation on Adjacent Existing Tunnel
Authors: Wu Xiaofeng , Zhang Di
Published: January 2023

The excavation of deep foundation pit could have a great impact on the adjacent existing structures. The proposed Ferris wheel is located in Jianghehui Block. The construction site is narrow and adjacent existing structures. In this paper, the finite element model was used to compare the influence of the underground separation wall protective measures on the deformation and internal force of adjacent existing tunnel. It was found that the foundation pit bottom presented a tendency of large deformation in the middle and small deformation on both sides. Based on the principle of soil-structure interaction, the optimization study of the underground separation wall was carried out, and it was found that the excessive thickness has little contribution to the reduction of lateral displacement.
Development of lower hybrid wave power feedback control and experiments on EAST
Authors: Wang Mao , Ma Wendong , Yang Yong , Li Miaohui , Wu Zege , Hu Huaichuan , Feng Jianqiang , Liu Liang , Zhao Lianmin , Zhang Jian , Zhu Liang , Cheng Min , Zhou Taian , Jia Hua , Xu Li , Ding Bojiang , Shan Jiafang , Liu Fukun
Published: January 2023

A new method of power feedback control for the lower hybrid wave (LHW) systems on the experimental advanced superconducting tokamak (EAST) is presented. Different methods are applied to control the power of two LHW systems with different frequency at 2.45 GHz and at 4.6 GHz, respectively. The old method is applied to control the 4.6 GHz LHW power through the exciter of klystrons, and the new one is used to control the 2.45 GHz LHW power through the high voltage power supply (HVPS) system. The new method has been applied in EAST and successfully assisted the development of relevant experiments such as loop voltage control, q profile control.
Transverse emittance measurement in 2D and 4D performed on a Low Energy Beam Transport line: benchmarking and data analysis
Authors: Osswald F. , Durand T. , Heine M. , Michaud J. , Poirier F. , Thomas J.C. , Traykov E.
Published: January 2023

2D and 4D transverse phase-space of a low-energy ion-beam is measured with two of the most common emittance scanners. The article covers the description of the installation, the setup, the settings, the experiment and the benchmark of the two emittance meters. We compare the results from three series of measurements and present the advantages and drawbacks of the two systems. Coupling between phase-space planes, correlations and mitigation of deleterious effects are discussed. The influence of background noise and aberrations of trace-space figures on emittance measurements and RMS calculations is highlighted, especially for low density beams and halos. A new data analysis method using noise reduction, filtering, and reconstruction of the emittance figure is described. Finally, some basic concepts of phase-space theory and application to beam transport are recalled.
Contribution of biomass burning to black carbon deposition on Andean glaciers: consequences for radiative forcing
Authors: Bonilla E X , Mickley L J , Beaudon E G , Thompson L G , Rodriguez W E , Encarnación R Cruz , Whicker C A , Flanner M G , Schmitt C G , Ginot P
Published: January 2023

Andean glaciers have melted rapidly since the 1960s. While some melting is likely due to anthropogenic climate change driven by increasing greenhouse gases, deposition of light-absorbing particles such as black carbon (BC) may also play a role. We hypothesize that BC from fires in the Amazon Basin and elsewhere may be deposited on Andean glaciers, reducing the surface albedo and inducing further melting. Here we investigate the role of BC deposition on albedo changes in the Andes for 2014–2019 by combining atmospheric chemistry modeling with observations of BC in snow or ice at four mountain sites in Peru (Quelccaya, Huascarán, Yanapaccha, and Shallap) and at one site in Bolivia (Illimani). We find that annual mean ice BC concentrations simulated by the chemical transport model GEOS-Chem for 2014–2019 are roughly consistent with those observed at the site with the longest record, Huascarán, with overestimates of 15%–40%. Smoke from fires account for 20%–70% of total wet and dry deposition fluxes, depending on the site. The rest of BC deposited comes from fossil fuel combustion. Using a snow albedo model, we find that the annual mean radiative forcing from the deposition of smoke BC alone on snow ranges from +0.1 to +3.2 W m−2 under clear-sky conditions, with corresponding average albedo reductions of 0.04%–1.1%. These ranges are dependent on site and snow grain size. This result implies a potentially significant climate impact of biomass burning in the Amazon on radiative forcing in the Andes.
High-accuracy identification of interferograms between two vortex beams via deep learning without adequate experimental data
Authors: Rui-Jia Lu , Zhi-Kun Su
Published: January 2023

The on-axis interference intensity patterns between a vortex beam and its conjugated beam can be used to measure the fractional topological charge of vortex beams. However, it is still challenging to efficiently recognize these intensity diagrams. On one hand, the difference of the patterns for adjacent modes with interval 0.1 is too subtle to be identified precisely. On the other hand, the interferograms are susceptible to undesirable experimental conditions such as the misalignment of the beams, the unequal arms of the interferometer and the deviation of splitting ratio of the beam splitters in the interferometer. Here, we propose a deep learning method to recognize these intensity diagrams with up to

97
%

accuracy. In particular, our method has reference values for deep learning model training when there is not adequate experimental data.
The crucial role of defect structure in understanding the electrical properties of spark plasma sintered antimony doped barium stannate
Authors: Vukašinović Jelena , Rapljenović Željko , Počuča-Nešić Milica , Ivek Tomislav , Branković Zorica , Branković Goran
Published: January 2023

The influence of structural defects in spark plasma sintered BaSn1-xSbxO3 (BSSO, x = 0.00 and 0.08) ceramic samples on their electrical properties was investigated in the temperature range of 300–4 K. X-ray photoelectron spectroscopy (XPS) revealed the presence of point defects, primarily oxygen vacancies (VO) and mixed oxidation states of tin (Sn2+/Sn4+) in both samples. As a result, the undoped BSSO sample exibited a non-standard semiconductor behavior, retaining its temperature-dependent resistivity. The electrical resistivity of the doped samples was two orders of magnitude lower than that of the undoped sample. The presence of structural defects such as VO, mixed oxidation states of the constituent elements, and significant amounts of O− species make the electrical resistivity of the doped sample constant in the temperature range of 300–70 K, indicating heavily-doped semiconductor behavior.
Investigation of paint removal by atmospheric pressure plasma jet
Authors: WANG Zhijun , CHEN Zhongwen , KANG Hao , YE Zongbiao
Published: January 2023

Acrylic polyurethane paint on the surface of 2A12 Al alloy was cleaned utilizing an atmospheric pressure plasma jet in this work. The dynamic evolution of the paint removal process during plasma treatment with time was explored through analysis of morphology and chemical states. The results showed that although the thickness of paint could be reduced effectively with an increase in cleaning time, the removal rate of paint gradually decreased with time. During the initial cleaning process range, its original smooth morphology of paint turned rugged quickly and was almost unchanged with further plasma treatment. Element and chemical state analysis showed that the content of C in the paint layer decreased obviously after plasma treatment. In contrast, the O content increased remarkably. The cleaning mechanism could be mainly attributed to the reaction between active O-containing species in air plasma and organic components in the paint. After removal of superficial organic matter, residue inorganic metal oxide substances aggregated on the base. The exposed metal oxides on the one hand elevated the superficial O content, but on the other hand hindered further plasma penetration, resulting in a gradual decrease in cleaning rate with cleaning time. Therefore, physical wiping was proposed to be incorporated with the plasma method and effective removal of paint was realized.
Complex systems in the spotlight: next steps after the 2021 Nobel Prize in Physics
Authors: Bianconi Ginestra , Arenas Alex , Biamonte Jacob , Carr Lincoln D , Kahng Byungnam , Kertesz Janos , Kurths Jürgen , Lü Linyuan , Masoller Cristina , Motter Adilson E , Perc Matjaž , Radicchi Filippo , Ramaswamy Ramakrishna , Rodrigues Francisco A , Sales-Pardo Marta , San Miguel Maxi , Thurner Stefan , Yasseri Taha
Published: January 2023

The 2021 Nobel Prize in Physics recognized the fundamental role of complex systems in the natural sciences. In order to celebrate this milestone, this editorial presents the point of view of the editorial board of JPhys Complexity on the achievements, challenges, and future prospects of the field. To distinguish the voice and the opinion of each editor, this editorial consists of a series of editor perspectives and reflections on few selected themes. A comprehensive and multi-faceted view of the field of complexity science emerges. We hope and trust that this open discussion will be of inspiration for future research on complex systems.
Pre-synaptic DC bias controls the plasticity and dynamics of three-terminal neuromorphic electrolyte-gated organic transistors
Authors: Rondelli Federico , Salvo Anna De , Sebastianella Gioacchino Calandra , Murgia Mauro , Fadiga Luciano , Biscarini Fabio , Lauro Michele Di
Published: January 2023

The role of pre-synaptic DC bias is investigated in three-terminal organic neuromorphic architectures based on electrolyte-gated organic transistors—EGOTs. By means of pre-synaptic offset it is possible to finely control the number of discrete conductance states in short-term plasticity experiments, to obtain, at will, both depressive and facilitating response in the same neuromorphic device and to set the ratio between two subsequent pulses in paired-pulse experiments. The charge dynamics leading to these important features are discussed in relationship with macroscopic device figures of merit such as conductivity and transconductance, establishing a novel key enabling parameter in devising the operation of neuromorphic organic electronics.
1365 PROACTIVE IT-ASSISTED CGA IN CARE HOMES IMPROVES ADHERENCE TO PREFERRED PLACE OF CARE AND DEATH, HOSPITALISATION AND MORTALITY RATES
Authors: Attwood D , Vafidis J , Boorer J , Ellis W , Earley M , Denovan J , Hart G , Williams M , Burdett N , Lemon M , Hope S V
Published: January 2023

Introduction

Primary care-based frailty identification and proactive comprehensive geriatric assessment (CGA) remains challenging. Our Devon-based Primary Care Network has developed and introduced an innovative, community-based IT-assisted CGA (i-CGA) process, which includes advance care planning (ACP). We wished to see if this process could improve effectiveness of ACP in residential care home (CH) residents.

Methods/Intervention

Interim analysis focused on adherence to ACP-documentation in severely frail residents, comparing groups:

Results

i-CGA group: 196 residents (16 mild/69 moderate/111 severe frailty); control group: 100(13 mild/31 moderate/56 severe). No significant baseline differences. 100% residents in the i-CGA group had documented resuscitation decisions, vs 72% (72/100) controls: in 97% of both groups (191/196,70/72) to ‘allow a natural death'. 85% (94/111) severely frail i-CGA residents preferred not to be hospitalised. 55% (52/94) died, 90% (47/52) in their CH. Compared to the preceding year, unplanned hospitalisation rates fell:0.86 to 0.68/person years alive. In severely frail control residents, unplanned hospitalisations increased: 0.87 to 2.05/person years alive. 29% (16/56) had no hospitalisation preferences documented. 16/16 died, 25% (4/16) in hospital. 40/56 had documented decisions, not all recent:38% (15/40) wished for admission. Significant group mortality difference was seen: 55% (62/111) severely frail i-CGA residents died compared to 77% (43/56) controls, p=0.0013.

Conclusions

Proactive primary care-led i-CGA in severely frail CH residents promotes up-to-date discussions regarding preferred place of care and death. Most prefer not to be hospitalised, despite traditionally high rates of unplanned admissions. Our i-CGA/ACP process improves adherence to preferences, reduces unplanned hospitalisations and mortality rates. Progressive i-CGA completion and annual/opportunistic reviews should confer progressive benefits.
A social theory-enhanced graph representation learning framework for multitask prediction of drug–drug interactions
Authors: Feng Yue-Hua , Zhang Shao-Wu , Feng Yi-Yang , Zhang Qing-Qing , Shi Ming-Hui , Shi Jian-Yu
Published: January 2023

Current machine learning-based methods have achieved inspiring predictions in the scenarios of mono-type and multi-type drug–drug interactions (DDIs), but they all ignore enhancive and depressive pharmacological changes triggered by DDIs. In addition, these pharmacological changes are asymmetric since the roles of two drugs in an interaction are different. More importantly, these pharmacological changes imply significant topological patterns among DDIs. To address the above issues, we first leverage Balance theory and Status theory in social networks to reveal the topological patterns among directed pharmacological DDIs, which are modeled as a signed and directed network. Then, we design a novel graph representation learning model named SGRL-DDI (social theory-enhanced graph representation learning for DDI) to realize the multitask prediction of DDIs. SGRL-DDI model can capture the task-joint information by integrating relation graph convolutional networks with Balance and Status patterns. Moreover, we utilize task-specific deep neural networks to perform two tasks, including the prediction of enhancive/depressive DDIs and the prediction of directed DDIs. Based on DDI entries collected from DrugBank, the superiority of our model is demonstrated by the comparison with other state-of-the-art methods. Furthermore, the ablation study verifies that Balance and Status patterns help characterize directed pharmacological DDIs, and that the joint of two tasks provides better DDI representations than individual tasks. Last, we demonstrate the practical effectiveness of our model by a version-dependent test, where 88.47 and 81.38% DDI out of newly added entries provided by the latest release of DrugBank are validated in two predicting tasks respectively.
GPDOCK: highly accurate docking strategy for metalloproteins based on geometric probability
Authors: Wang Kai
Published: January 2023

Accurately predicting the interaction modes for metalloproteins remains extremely challenging in structure-based drug design and mechanism analysis of enzymatic catalysis due to the complexity of metal coordination in metalloproteins. Here, we report a docking method for metalloproteins based on geometric probability (GPDOCK) with unprecedented accuracy. The docking tests of 10 common metal ions with 9360 metalloprotein–ligand complexes demonstrate that GPDOCK has an accuracy of 94.3% in predicting binding pose. What is more, it can accurately realize the docking of metalloproteins with ligand when one or two water molecules are engaged in the metal ion coordination. Since GPDOCK only depends on the three-dimensional structure of metalloprotein and ligand, structure-based machine learning model is employed for the scoring of binding poses, which significantly improves computational efficiency. The proposed docking strategy can be an effective and efficient tool for drug design and further study of binding mechanism of metalloproteins. The manual of GPDOCK and the code for the logistical regression model used to re-rank the docking results are available at https://github.com/wangkai-zhku/GPDOCK.git.
Reducing false positive rate of docking-based virtual screening by active learning
Authors: Wang Lei , Shi Shao-Hua , Li Hui , Zeng Xiang-Xiang , Liu Su-You , Liu Zhao-Qian , Deng Ya-Feng , Lu Ai-Ping , Hou Ting-Jun , Cao Dong-Sheng
Published: January 2023

Machine learning-based scoring functions (MLSFs) have become a very favorable alternative to classical scoring functions because of their potential superior screening performance. However, the information of negative data used to construct MLSFs was rarely reported in the literature, and meanwhile the putative inactive molecules recorded in existing databases usually have obvious bias from active molecules. Here we proposed an easy-to-use method named AMLSF that combines active learning using negative molecular selection strategies with MLSF, which can iteratively improve the quality of inactive sets and thus reduce the false positive rate of virtual screening. We chose energy auxiliary terms learning as the MLSF and validated our method on eight targets in the diverse subset of DUD-E. For each target, we screened the IterBioScreen database by AMLSF and compared the screening results with those of the four control models. The results illustrate that the number of active molecules in the top 1000 molecules identified by AMLSF was significantly higher than those identified by the control models. In addition, the free energy calculation results for the top 10 molecules screened out by the AMLSF, null model and control models based on DUD-E also proved that more active molecules can be identified, and the false positive rate can be reduced by AMLSF.
Prediction of anticancer peptides based on an ensemble model of deep learning and machine learning using ordinal positional encoding
Authors: Yuan Qitong , Chen Keyi , Yu Yimin , Le Nguyen Quoc Khanh , Chua Matthew Chin Heng
Published: January 2023

Anticancer peptides (ACPs) are the types of peptides that have been demonstrated to have anticancer activities. Using ACPs to prevent cancer could be a viable alternative to conventional cancer treatments because they are safer and display higher selectivity. Due to ACP identification being highly lab-limited, expensive and lengthy, a computational method is proposed to predict ACPs from sequence information in this study. The process includes the input of the peptide sequences, feature extraction in terms of ordinal encoding with positional information and handcrafted features, and finally feature selection. The whole model comprises of two modules, including deep learning and machine learning algorithms. The deep learning module contained two channels: bidirectional long short-term memory (BiLSTM) and convolutional neural network (CNN). Light Gradient Boosting Machine (LightGBM) was used in the machine learning module. Finally, this study voted the three models’ classification results for the three paths resulting in the model ensemble layer. This study provides insights into ACP prediction utilizing a novel method and presented a promising performance. It used a benchmark dataset for further exploration and improvement compared with previous studies. Our final model has an accuracy of 0.7895, sensitivity of 0.8153 and specificity of 0.7676, and it was increased by at least 2% compared with the state-of-the-art studies in all metrics. Hence, this paper presents a novel method that can potentially predict ACPs more effectively and efficiently. The work and source codes are made available to the community of researchers and developers at https://github.com/khanhlee/acp-ope/.
Median regularity and honest inference
Authors: Kuchibhotla Arun Kumar , Balakrishnan Sivaraman , Wasserman Larry
Published: January 2023

We introduce a new notion of regularity of an estimator called median regularity. We prove that uniformly valid honest inference for a functional is possible if and only if there exists a median regular estimator of that functional. To the best of our knowledge, such a notion of regularity that is necessary for uniformly valid inference is unavailable in the literature.
MAGP1 maintains tumorigenicity and angiogenesis of laryngeal cancer by activating Wnt/β-catenin/MMP7 pathway
Authors: Lv Fei , Li Xiaoqi , Wang Ying , Hao Liying
Published: January 2023

Microfibril-associated glycoprotein-1 (MAGP1), a crucial extracellular matrix protein, contributes to the initiation and progression of different cancers. However, the role of MAGP1 in laryngeal cancer is not clear. The purpose of this study was to investigate the clinical significance and biological function of MAGP1 in laryngeal cancer. MAGP1 was upregulated in public databases and laryngeal cancer tissues, and high MAGP1 expression led to a poor prognosis and was identified as an independent prognostic marker. Knocking-down MAGP1 inhibited laryngeal cancer cell growth and metastasis. According to gene set enrichment analysis, high MAGP1 expression revealed enrichment in Wnt/β-catenin signaling and knocking-down MAGP1 in laryngeal cancer cells also caused degradation, de-activation, re-location and loss of stability of β-catenin. Additionally, we observed MAGP1 in laryngeal cancer cells inhibits angiogenesis in an MMP7-dependent way. In conclusion, our study suggests a clinical role of MAGP1 in laryngeal cancer, signifying its potential as a therapeutic target in the future.
UPLC–MS/MS Method Development for Simultaneous Estimation of Diclofenac and Resveratrol-Loaded Liposomal Gel Formulation in Mice Skin Model: Application to Dermatokinetic Study
Authors: Alqahtani Safar M , Altharawi Ali , Alrobaian Majed , Almalki Waleed H , Alabbas Alhumaidi B , Ullah Shehla Nasar Mir Najib , Singh Tanuja , Thajudeen Kamal Younus , Khan Gyas , Rub Rehan A , Barkat Md Abul , Beg Sarwar , Rahman Mahfoozur
Published: January 2023

The current research work describes the development of a simple, fast, sensitive and efficient bioanalytical UPLC/MS–MS method for the simultaneous estimation of diclofenac and resveratrol in mice skin samples. Quetiapine was used as an internal standard (IS). Analytical separation was performed on ACQUITY UPLC C18 Column (2.1 × 100 mm; 1.7 μm) using ammonium acetate (5 mM) in water and methanol (B) with isocratic elution at ratio of (50, 50 v/v) and flow rate of 0.4 mL/min. The duration of separation was maintained for 3 min. Electrospray ionization mass spectrometry in a positive and negative ionization mode was used for detection. Selective ion mode monitoring was used for the quantification of m/z 296.025> 249.93 for diclofenac, m/z 229.09 > 143.03 for resveratrol and MRM/ES+ve mode applied in m/z 384.25> 253.189 for IS transitions from parent to daughter ion. The lower detection and quantification limits were accomplished, and precision (repeatability and intermediate precision) with a coefficient of variation below 10% produced satisfactory results. The developed bioanalytical method was found to be useful for its suitability for the dermatokinetic evaluation of treatments through rat skin. Improvement in AUC (1.58-fold for diclofenac and 1.60-fold for resveratrol) and t1/2 in the dermis (2.13 for diclofenac and 2.21-fold for resveratrol) followed by epidermis was observed for diclofenac and resveratrol-loaded liposomal gel formulation over the conventional gel. Overall, the developed method for the dermatokinetic studies of the above-mentioned dual drugs-loaded liposome gel was found to be reproducible and effective for bioanalytical.
Could Home Human Immunodeficiency Virus Self-Testing Ever Become a Game Changer?
Authors: Wood Brian R , Stekler Joanne D
Published: January 2023

Could home human immunodeficiency virus (HIV) self-testing make a major difference in identifying persons with undiagnosed HIV in the United States? We argue that approval of new self-test assays for home use would help but must be combined with extensive investment in community outreach and linkage to care to make an impact.
Commutability Assessment of Candidate Reference Materials for Lipoprotein(a) by Comparison of a MS-based Candidate Reference Measurement Procedure with Immunoassays
Authors: Dikaios Ioannis , Althaus Harald , Angles-Cano Eduardo , Ceglarek Uta , Coassin Stefan , Cobbaert Christa M , Delatour Vincent , Dieplinger Benjamin , Grimmler Matthias , Hoofnagle Andrew N , Kostner Gerhard M , Kronenberg Florian , Kuklenyik Zsusanna , Lyle Alicia N , Prinzing Urban , Ruhaak L Renee , Scharnagl Hubert , Vesper Hubert W , Deprez Liesbet
Published: January 2023

Background

Elevated concentrations of lipoprotein(a) [Lp(a)] are directly related to an increased risk of cardiovascular diseases, making it a relevant biomarker for clinical risk assessment. However, the lack of global standardization of current Lp(a) measurement procedures (MPs) leads to inconsistent patient care. The International Federation for Clinical Chemistry and Laboratory Medicine working group on quantitating apolipoproteins by mass spectrometry (MS) aims to develop a next-generation SI (International system of units)-traceable reference measurement system consisting of a MS-based, peptide-calibrated reference measurement procedure (RMP) and secondary serum-based reference materials (RMs) certified for their apolipoprotein(a) [apo(a)] content. To reach measurement standardization through this new measurement system, 2 essential requirements need to be fulfilled: a sufficient correlation among the MPs and appropriate commutability of future serum-based RMs.

Methods

The correlation among the candidate RMP (cRMP) and immunoassay-based MPs was assessed by measuring a panel of 39 clinical samples (CS). In addition, the commutability of 14 different candidate RMs was investigated.

Results

Results of the immunoassay-based MPs and the cRMPs demonstrated good linear correlations for the CS but some significant sample-specific differences were also observed. The results of the commutability study show that RMs based on unspiked human serum pools can be commutable with CS, whereas human pools spiked with recombinant apo(a) show different behavior compared to CS.

Conclusions

The results of this study show that unspiked human serum pools are the preferred candidate secondary RMs in the future SI-traceable Lp(a) Reference Measurement System.
Diagnosis of Familial Dysbetalipoproteinemia Based on the Lipid Abnormalities Driven by APOE2/E2 Genotype
Authors: Bea Ana M , Cenarro Ana , Marco-Bened Victoria , Laclaustra Martn , Martn Csar , Ibarretxe Daiana , Pint Xavier , Arrobas Teresa , Vials Clara , Civeira Fernando , Olmos Salvador
Published: January 2023

Background

Familial dysbetalipoproteinemia (FDBL) is a monogenic disease due to variants in APOE with a highly variable phenotype. Current diagnostic lipid-based methods have important limitations. The objective is twofold: to define characteristics of dysbetalipoproteinemia (DBL) based on the analysis of APOE in patients from a lipid unit and in a sample from the general population, and to propose a screening algorithm for FDBL.

Methods

Lipids and APOE genotype from consecutive unrelated subjects from Miguel Servet University Hospital (MSUH) (n 3603), subjects from the general population participants of the Aragon Workers Health Study (AWHS) (n 4981), and selected subjects from external lipid units (Ext) (n 390) were used to define DBL criteria and to train and validate a screening tool.

Results

Thirty-five subjects from MSUH, 21 subjects from AWHS, and 31 subjects from Ext were APOE2/2 homozygous. The combination of non high-density lipoprotein cholesterol (non-HDLc)/apoB 1.7 plus triglycerides/apoB 1.35, in mg/dL (non-HDLc [mmol/L]/apolipoprotein B (apoB) [g/L] 4.4 and triglycerides [mmol/L]/apoB [g/L] 3.5), provided the best diagnostic performance for the identification of subjects with hyperlipidemia and APOE2/2 genotype (sensitivity 100 in the 3 cohorts, and specificity 92.8 [MSUH], 80.9 [AWHS], and 77.6 [Ext]). This improves the performance of previous algorithms. Similar sensitivity and specificity were observed in APOE2/2 subjects receiving lipid-lowering drugs.

Conclusions

The combination of non-HDLc/apoB and triglycerides/apoB ratios is a valuable tool to diagnose DBL in patients with hyperlipidemia with or without lipid-lowering drugs. FDBL diagnosis requires DBL and the presence of a compatible APOE genotype. Most adult APOE2/2 subjects express DBL, making FDBL as common as familial hypercholesterolemia in the population.
Rescue Therapies for Steroid-refractory Acute Severe Ulcerative Colitis: A Review
Authors: Gisbert Javier P , García María José , Chaparro María
Published: January 2023

Background

One-third of patients with acute severe ulcerative colitis [ASUC] are steroid-refractory. We aimed to review the different options for the management of steroid-refractory ASUC, including not only the standard treatment [cyclosporine and infliximab], but also most recently developed agents [such as vedolizumab, ustekinumab, and tofacitinib].

Methods

We performed a bibliographical search to identify studies focusing on the treatment of steroid-refractory ASUC.

Results

Cyclosporine and infliximab currently represent the mainstays of salvage therapy and they are generally considered comparable. However, long-term persistence is higher in infliximab therapy, and many clinicians prefer to use infliximab given its ease of use. However, cost of cyclosporine is lower. Sequential rescue therapy after cyclosporine or infliximab failure [with infliximab and cyclosporine, respectively] could be considered in referral centres for highly selected cases. Tofacitinib, due to its rapid effect, represents an attractive rescue option mainly in biologic-experienced patients. The good safety profile of vedolizumab and ustekinumab makes them ideal candidates for use as maintenance therapy in combination with cyclosporine as induction therapy, especially for patients previously exposed to anti-TNFs or thiopurines.

Conclusions

Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also play a role. Tofacitinib, due to its rapid effect, is an attractive therapeutic rescue option. Vedolizumab and ustekinumab, as maintenance therapy in combination with the fast-acting cyclosporine as induction therapy, may represent a promising bridging strategy, especially in patients with previous failure to thiopurines and/or anti-TNF agents.
Vaccines in Children Exposed to Biological AgentsIn Uteroand/or During Breastfeeding: Are They Effective and Safe?
Authors: Gisbert Javier P , Chaparro María
Published: January 2023

Background

Biological agents cross the placenta, resulting in detectable blood levels in the neonate. Neonatal vaccinations are essential to prevent serious infections.

Aim

To review the effectiveness and safety of vaccines in children exposed to biological drugs in utero and/or those whose mothers received biological agents during lactation.

Methods

A systematic bibliographic search was performed.

Results

Infants exposed in utero to anti-tumour necrosis factor drugs [anti-TNFs], vedolizumab or ustekinumab mount adequate serological responses to vaccines. No relevant adverse events for non-live inactivated vaccines have been reported in newborns exposed in utero to biologics. Studies assessing the safety of live-attenuated vaccines administered to infants exposed to biologics in utero have not observed, in general, serious adverse events. However, although no severe complications have been reported with rotavirus live vaccination, several fatal disseminated tuberculosis infections after administration of the BCG live vaccine in infants exposed to anti-TNFs in utero have been reported. Infliximab, adalimumab, and probably also vedolizumab and ustekinumab treatments are considered compatible with breastfeeding, although minuscule amounts of these biologics have been detected in breast milk of treated nursing mothers. Based on the literature available, the benefits from breastfeeding while receiving infliximab [or any other anti-TNF] and at the same time adhering to national infant immunization programmes probably outweigh any hypothetical risk for the infant.

Conclusions

Vaccines appear to be effective in infants exposed to biologics in utero. Inactivated vaccines are probably safe, whereas live-attenuated vaccines should be avoided while the children have detectable levels of biological drugs. Vaccines [non-live and live] are probably safe in children breastfed by mothers treated with biologics.
Single-cell RNA sequencing reveals transcriptional changes of human choroidal and retinal pigment epithelium cells during fetal development, in healthy adult and intermediate age-related macular degeneration
Authors: Collin Joseph , Hasoon Megan S R , Zerti Darin , Hammadi Sarah , Dorgau Birthe , Clarke Lucy , Steel David , Hussain Rafiqul , Coxhead Jonathan , Lisgo Steven , Queen Rachel , Lako Majlinda
Published: January 2023

Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the developed world. Vision loss in the advanced stages of the disease is caused by atrophy of retinal photoreceptors, overlying retinal pigment epithelium (RPE) and choroidal endothelial cells. The molecular events that underline the development of these cell types from in utero to adult as well as the progression to intermediate and advanced stages AMD are not yet fully understood. We performed single-cell RNA-sequencing (RNA-Seq) of human fetal and adult RPE–choroidal tissues, profiling in detail all the cell types and elucidating cell type-specific proliferation, differentiation and immunomodulation events that occur up to midgestation. Our data demonstrate that progression from the fetal to adult state is characterized by an increase in expression of genes involved in the oxidative stress response and detoxification from heavy metals, suggesting a better defence against oxidative stress in the adult RPE–choroid tissue. Single-cell comparative transcriptional analysis between a patient with intermediate AMD and an unaffected subject revealed a reduction in the number of RPE cells and melanocytes in the macular region of the AMD patient. Together these findings may suggest a macular loss of RPE cells and melanocytes in the AMD patients, but given the complex processing of tissues required for single-cell RNA-Seq that is prone to technical artefacts, these findings need to be validated by additional techniques in a larger number of AMD patients and controls.
Management of testosterone around ovarian stimulation in transmasculine patients: challenging common practices to meet patient needs—2 case reports
Authors: Moravek Molly B , Dixon Marjorie , Pena Samantha M , Obedin-Maliver Juno
Published: January 2023

Approximately 50% of transmasculine people use testosterone for gender affirmation, yet very little is known about the effects of testosterone on future reproductive capacity. Moreover, there are no data to guide fertility specialists on how to manage testosterone leading up to or during ovarian stimulation. Most clinics require cessation of testosterone prior to ovarian stimulation in this setting of no data; however, the current literature does suggest a potential increase in dysphoria with cessation of testosterone and during stimulation. This divergence begs the question of whether clinicians may be doing more harm than good by enacting this requirement. Here, we present two cases of transmasculine individuals who were on testosterone prior to stimulation and maintained their testosterone dosage throughout stimulation as proof of concept, followed by a discussion of current clinical practice and providing some rationale to support continuation of testosterone throughout stimulation.
Almost All Alternating Groups are Invariably Generated by Two Elements of Prime Order
Authors: Teräväinen Joni
Published: January 2023

We show that for all $n\leq X$ apart from $O(X\exp (-c(\log X)^{1/2}(\log \log X)^{1/2}))$ exceptions, the alternating group $A_{n}$ is invariably generated by two elements of prime order. This answers (in a quantitative form) a question of Guralnick, Shareshian, and Woodroofe.
Unicellular LLT polynomials and twins of regular semisimple Hessenberg varieties
Authors: Masuda Mikiya , Sato Takashi
Published: January 2023

The solution of Shareshian–Wachs conjecture by Brosnan–Chow linked together the cohomology of regular semisimple Hessenberg varieties and graded chromatic symmetric functions on unit interval graphs. On the other hand, it is known that unicellular LLT polynomials have similar properties to graded chromatic symmetric functions. In this paper, we link together the unicellular LLT polynomials and twin of regular semisimple Hessenberg varieties introduced by Ayzenberg–Buchstaber. We prove the palindromicity of LLT polynomials from topological viewpoint. We also show that modules of a symmetric group generated by faces of a permutohedron are related to a shifted unicellular LLT polynomial and observe the $e$-positivity of shifted unicellular LLT polynomials, which is established by Alexandersson–Sulzgruber in general, for path graphs and complete graphs through the cohomology of the twins.
Artistic Exceptionalism and the Risks of Activist Art
Authors: Earley Christopher
Published: January 2023

Activist artists often face a difficult question: is striving to change the world undermined when pursued through difficult and experimental artistic means? Looking closely at Adrian Piper’s Four Intruders Plus Alarm Systems (1980), I consider why this is an important concern for activist art and assess three different responses in relation to Piper’s work. What I call the ‘conciliatory stance’ recommends that when activist artists encounter misunderstanding, they should downplay their experimental artistry in favor of fitting their work to their audience’s appreciative capacities. What I call the ‘steadfast stance’ recommends that activist artists have reason to use their privilege of artistic exceptionalism to challenge their audience’s expectations, even if this leads to misunderstanding. I claim that a middle position, which I call ‘liberal conciliation’, best balances the demands for actual change placed on activism and the experimental means that artists bring to activism.
Analysis of user interactions with a digital health wallet for enabling care continuity in the context of an ongoing pandemic
Authors: Wachira Charles , Ogallo William , Okwako Sharon , Remy Sekou Lionel , Bukania Zipporah , Njeru Mercy Karimi , Mwangi Moses , Mokua Sharon , Omwanda Wycliffe , Ressler Daniele , Walcott-Bryant Aisha
Published: January 2023

Background

The onset of COVID-19 and related policy responses made it difficult to study interactive health informatics solutions in clinical study settings. Instrumented log and event data from interactive systems capture temporal details that can be used to generate insights about care continuity during ongoing pandemics.

Objective

To investigate user interactions with a digital health wallet (DHW) system for addressing care continuity challenges in chronic disease management in the context of an ongoing pandemic.

Materials and methods

We analyzed user interaction log data generated by clinicians, nurses, and patients from the deployment of a DHW in a feasibility study conducted during the COVID-19 pandemic in Kenya. We used the Hamming distance from Information Theory to quantify deviations of usage patterns extracted from the events data from predetermined workflow sequences supported by the platform.

Results

Nurses interacted with all the user interface elements relevant to triage. Clinicians interacted with only 43% of elements relevant to consultation, while patients interacted with 67% of the relevant user interface elements. Nurses and clinicians deviated from the predetermined workflow sequences by 42% and 36%, respectively. Most deviations pertained to users going back to previous steps in their usage workflow.

Conclusions

User interaction log analysis is a valuable alternative method for generating and quantifying user experiences in the context of ongoing pandemics. However, researchers should mitigate the potential disruptions of the actual use of the studied technologies as well as use multiple approaches to investigate user experiences of health technology during pandemics.
Determination of Acephate, Dinotefuran, and Emamectin Benzoate in a Pesticide Formulation: A Single-Laboratory Validation
Authors: Patil Vilas K , Chandorkar Jayant G , Wagh Yogesh B , More Yogesh B , Narkhede Hemant P
Published: January 2023

Background

The advantage of simultaneous separation and quantification is the reduction of analysis time and consumption of solvents and reagents.

Objective

The objective of the present investigation was to optimize and validate a novel, rapid, and simple reverse-phase high-performance liquid chromatographic method for the simultaneous determination of acephate, dinotefuran, and emamectin benzoate in a pesticide formulation.

Method

The chromatographic separation and quantification were accomplished by using Kromasil CN column (250 mm × 4.6 mm; 5 μm) with a mobile phase consisting of acetonitrile and water [0.1% (v/v) triethylamine, pH 2.7 with 10% (v/v) orthophosphoric acid] in the ratio of 50:50 (v/v) with a flow rate of 1.0 mL/min and diode array detection at the wavelength of (215 nm and 245 nm).

Results

The HPLC method was able to separate and quantify all the actives in the formulation by isocratic elution within 10 min. The method was fully validated in accordance with the SANCO and Collaborative International Pesticide Analytical Council guidelines concerning system suitability, specificity, linearity, precision, accuracy, and robustness. All the analytical parameters are within the range of acceptable limits in the guidelines.

Conclusions

The validated method was successfully applied to a pesticide formulation.

Highlights

The novelty of the current research work lies in the development of the simple and rapid HPLC method for simultaneous determination of acephate, dinotefuran, and emamectin benzoate in wettable granular formulation.
Screening genes related to embryo implantation in Dazu black goats (Capra Hircus) by morphological and transcriptome analyses
Authors: Zhao Le , Yang Yongheng , Yang Haili , Luo Nanjian , Li Xingchun , Zheng Jikang , Yang Songjian , Zhao Yongju
Published: January 2023

Embryo implantation is a critical step in the establishment of pregnancy. However, the mechanisms of embryo implantation during early pregnancy in goats remain unclear due to the lack of published studies examining the genes involved in embryo implantation. As a popular goat breed in southwest China, Dazu black goats (DBGs) are highly adaptable and exhibit high fertility, making this breed a good model in which to study reproductive performance of goats. Here, morphological analysis showed that compared with the non-pregnant (NP) groups, the endometrial thickness of the goats in the P15 and P19 groups (15 and 19-day pregnant groups, respectively) were increased (P < 0.01). Proliferating Cell Nuclear Antigen (PCNA) staining showed that PCNA was expressed in the NP, P15, and P19 groups. Transcriptome analysis was then conducted to identify gene expression patterns in uterine tissue during DBG embryo implantation. By comparing uterine tissue at different stages of embryonic implantation, 48 in NP_vs._P15, 318 in NP_vs._P19, and 1439 in P15_vs._P19, differentially expressed mRNAs were identified. Gene Ontology (GO) enrichments of the differentially expressed genes were enriched in the extracellular region, extracellular space, transporter activity, extracellular region, immune system process, immune response, and defense response etc. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the biological metabolic pathways with which the differentially expressed genes are associated were explored. Through KEGG analysis, the DBGs were associated with oxidative phosphorylation, complement and coagulation cascades, arginine and proline metabolism, metabolic pathways, arachidonic acid metabolism, and ECM-receptor interaction. These candidate genes (CSF1, C1S, CST6, SLC24A4, HOXA10, HOXA11, MMP9, and ITGA11) and enriched signaling pathways could be valuable references for exploring the molecular mechanisms underlying goat embryo implantation.
Non-contingency in a paraconsistent setting
Authors: Kozhemiachenko Daniil , Vashentseva Liubov
Published: January 2023

We study an extension of first-degree entailment (FDE) by Dunn and Belnap with a non-contingency operator $\blacktriangle \phi $ which is construed as ‘$\phi $ has the same value in all accessible states’ or ‘all sources give the same information on the truth value of $\phi $’. We equip this logic dubbed $\textbf {K}^\blacktriangle _{\textbf {FDE}}$ with frame semantics and show how the bi-valued models can be interpreted as interconnected networks of Belnapian databases with the $\blacktriangle $ operator modelling search for inconsistencies in the provided information. We construct an analytic cut system for the logic and show its soundness and completeness. We prove that $\blacktriangle $ is not definable via the necessity modality $\Box $ of $\textbf {K}_{\textbf{FDE}}$. Furthermore, we prove that in contrast to the classical non-contingency logic, reflexive, $\textbf {S4}$ and $\textbf {S5}$ (among others) frames are definable.