bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Supporting and Constraining Factors of Physicians’ Acceptance of Telemedical Online Consultations: A Survey Study
Authors: Diel Sören , Doctor Eileen , Reith Riccardo , Buck Christoph , Eymann Torsten
Published: July 2023

As healthcare demands exceed outpatient physicians’ capacities, telemedicine holds far-reaching potential for both physicians and patients. It is crucial to holistically analyze physicians’ acceptance of telemedical applications, such as online consultation. This study seeks to identify supporting and constraining factors that influence outpatient physicians’ acceptance of telemedicine. We develop a model based on the unified theory of acceptance and use of technology (UTAUT). To empirically examine our research model, we conducted a survey among German physicians (n = 127) in 2018–2019. We used the partial least squares (PLS) modeling approach to test our model, including a mediation analysis. The results indicate that performance expectancy (β = .397, P < .001), effort expectancy (β = .134, P = .03), and social influence (β = .337, P < .001) strongly impact on the intention to conduct online consultations and explain 55% of its variance. Structural conditions regarding data security comprise a key antecedent, associating with performance expectancy (β = .193, P < .001) and effort expectancy (β = .295, P < .001). Regarding potential barriers to usage intentions, we find that IT anxiety predicts performance (β=–.342, P < .001) and effort expectancy (β=–.364, P < .001), while performance expectancy fully mediates (βdirect = .022, P = .71; βindirect=-.138, P < .001) the direct relationship between IT anxiety and the intention to use telemedical applications. This research provides explanations for physicians’ behavioral intention to use online consultation, underlining UTAUT’s applicability in healthcare contexts. Performance expectancy, effort expectancy, and social influence are the main drivers of the intention to use online consultations. Further, we identify IT anxiety and the importance of data security as significant antecedents that should be addressed by practitioners (e.g., in telemedical implementation projects) and by further research.
Multi-country collaborative citizen science projects to co-design cardiovascular disease prevention strategies and advocacy: findings from Ethiopia, Malawi, Rwanda, and South Africa
Authors: Okop Kufre J. , Lambert Estelle Victoria , Kedir Kiya , Getachew Hailemichael , Howe Rawleigh , Niyibizi Jean Berchmans , Bavuma Charlotte , Rulisa Stephen , Kasenda Stephen , Chipeta Effie , Bunn Christopher , Crampin Amelia C. , King Abby C. , Sell Kerstin , Puoane Thandi , Levitt Naomi S
Published: July 2023

Background
Cardiovascular diseases (CVD) are responsible for 17.9 million annual deaths globally, with a disproportionally high burden in sub-Saharan Africa (SSA). There is growing evidence of the use of citizen science and co-design approaches in developing interventions in different fields, but less so in the context of CVD prevention interventions in SSA. This paper reports on the outcomes of a multi-country collaborative project that employed a citizen science approach to explore, co-design, and implement CVD risk prevention and advocacy in SSA.
Methods
The study was implemented in rural and urban communities in Malawi, Ethiopia and Rwanda and urban South Africa, using citizen science and co-design approaches. Trained citizen scientists used a mobile app-based (EpiCollect) semi-structured survey questionnaire to collect data on CVD risk perceptions from participants purposively selected from two communities per country. Data collected per community included 100–150 photographs and 150–240 voice recordings on CVD risk perceptions, communication and health-seeking intentions. Thematic and comparative analysis were undertaken by citizen scientists and the results used to support citizen scientists-led advocacy workshops in each community.
Results
About 63% of 205 participants reported having a relative with CVD. The main perceived causes of CVD in all communities were substance use, food-related factors and litter, followed by physical inactivity, emotional factors, poverty, crime and violence. The perceived positive factors for cardiovascular health were nutrition, physical activity, green space, and clean/peaceful communities. Multi-level stakeholders (45–84 persons/country) including key decision-makers attended advocacy workshops, agreed on priority CVD prevention strategies, and supported successful implementation of CVD risk screening and referral to care interventions. The stakeholders in the health sector appreciated the citizen scientists’ work and indicated their support to utilise this approach in implementing national non-communicable disease prevention programmes. The citizen scientists were excited by the opportunity to lead research and advocacy. The collaborative engagement methods helped build capacity and relationships among citizen scientists, researchers, and stakeholders, leading to active and productive engagements that provided context-specific insights on CVD prevention.
Conclusion
Participatory citizen science can foster learning and co-designing of CVD risk prevention interventions and actionable advocacy strategies in different SSA settings.
Development of a highly efficient prime editor system in mice and rabbits
Authors: Qian Yuqiang , Wang Di , Niu Wenchao , Si Zheng , Wu Mao , Zhao Ding , Li Jinze , Gao Xun , Zhang Zhongtian , Lai Liangxue , li zhanjun
Published: July 2023

The recent prime editing (PE) technique is more precise and permits base-to-base conversion, replacement, and insertion and deletion in the genome. However, previous reports show that the efficiency of prime editing is insufficient for producing genome edited animals. In fact, prime-guide RNA (pegRNA) designs have been the drawback in achieving favorable editing efficiency. Here, we designed prime binding sites (PBS) with a melting temperature (Tm) of 42 ℃ leads to optimal performance in cells, and found the optimal Tm was affected by the culture temperature. In addition, the ePE3max system was developed by updating the PE architecture to PEmax and expressing engineered pegRNA (epegRNA) based on the original PE3 system. The updated ePE3max system can efficiently induce gene editing in mouse and rabbit embryos. Furthermore, we successfully generated Hoxd13 (c. 671 G > T) mutation in mice and Tyr (c. 572 del) mutation in rabbits by ePE3max. Collectively, the editing efficiency of modified ePE3max systems is superior to original PE3 system in producing genome editing animals, which can serve as an effective and versatile genome editing tool for precise genome modification in animal models.
A Metrics-Based Approach to Metadata Classification Applied in a Recommendation System
Authors: Santos Bruno Zolotareff dos , Vales Sandra Santos , Junior Jorge Rady Almeira
Published: July 2023

In this article we have presented a classification model for metadata extracted from tweets using collaborative filters, proposing a metadata recommendation system at the knowledge level. Due to the limited resources available for tagging in social media, the quality of metadata used for this practice often poses interpretation issues when selecting, resulting in a loss of engagement due to flaws in term formation or a lack of understanding of the shared metadata within the social network. In this study, we proposed a selection algorithm that filters and classifies metadata based on metrics that measure the collective intelligence aggregated in the metadata. We then index knowledge indexes that are readily identifiable visually. The proposed model involves two main steps for classifying and recommending metadata.
Multichannel Resonant Acoustic Rheometry System for Rapid and Efficient Quantification of Human Plasma Coagulation
Authors: Hendren Christina , Li Weiping , Stegemann Jan P. , Hall Timothy L. , Deng Cheri X.
Published: July 2023

Resonant Acoustic Rheometry (RAR), a newly developed ultrasound-based technique for non-contact characterization of soft viscoelastic materials, has shown promise for quantitative assessment of plasma coagulation by monitoring the entire dynamic process in real time. Here, we report the development of a multichannel RAR (mRAR) system for simultaneous monitoring of the coagulation of multiple small-volume plasma samples, a capability that is critical to efficiently provide improved assessment of coagulation. The mRAR system was constructed using an array of 4 custom-designed ultrasound transducers at 5.0 MHz and an electronic driving system that controlled the generation of synchronized ultrasound pulses for real time monitoring of multiple samples simultaneously. The mRAR system was tested using Coumadin-treated plasma samples with a range of International Normalized Ratio (INR) values, as well as normal pooled plasma samples. Tracking of dynamic changes in clotting of plasma samples triggered by either kaolin or tissue factor was performed for the entire duration of coagulation. The mRAR system captured distinct changes in the samples and identified parameters including clotting time, clotting speed, and the mechanical properties of the clots that were consistent with Coumadin dose and INR levels Data from this study demonstrate the feasibility of the mRAR system for the rapid, efficient, and accurate characterization of plasma coagulation.
Polaritonic and Excitonic Semiclassical Time Crystals based on TMDC strips in an external periodic potential
Authors: Martins Gabriel , Berman Oleg , Gumbs Godfrey
Published: July 2023

We investigated the dynamics of Bose-Einstein condensates (BECs) under an external periodic potential. We consider two such systems, the first being made of exciton-polaritons in a nanoribbon of transition metal dichalcogenides (TMDCs), such as MoSe2, embedded in a microcavity with a spatial curvature, which serves as the source of the external periodic potential. The second, made of bare excitons in a nanoribbon of twisted TMDC bilayer, which naturally creates a periodic Moiré potential that can be controlled by the twist angle. We proved that such systems behave as semiclassical Time Crystals (TCs). This was demonstrated by the fact that the calculated BEC spatial density profile shows a non-trivial long-range two-point correlator that oscillates in time. These BECs density profiles were calculated by solving the quantum Lindblad master equations for the density matrix within the mean-field approximation. We then go beyond the usual mean-field approach, by adding a stochastic term to the master equation, which corresponds to quantum corrections, and we show that the TC phase is still present.
Ethnic Diversity in Motion: Understanding the Relationship between Dynamic Ethnic Fractionalization and Economic Growth
Authors: Miladinovic Luka
Published: July 2023

The study explores the relationship between dynamic ethnic fractionalization and economic growth using a panel of 76 countries over four decades. This panel is the most extensive dataset on the topic to date. Results from the replication of previous approaches to the topic – both with time-invariant and dynamic ethnic diversity – underscore the importance of including the temporal component of ethnic diversity in an analysis of its effects on economic growth and challenge the prevalent assumption of constant ethnic diversity. In addition, we exploit the time variability of ethnic diversity by employing, for the first time, maximum likelihood dynamic panel data modeling – a rigorous methodological approach that enhances confidence in the conclusions. Our results show that ethnic diversity does not directly determine economic growth but rather influences other growth determinants, thereby impeding economic performance when the nation-state is the unit of observation. This sheds light on the contrasting conclusions observed in previous studies regarding the impact of ethnic diversity on economic performance.
JEL classification: O11; J15
Prognostic value of total, free and lipoprotein fraction-bound plasma mitotane levels in advanced adrenocortical carcinoma: a prospective study of the ENDOCAN-COMETE-Cancer network
Authors: Faron Matthieu , NAMAN Annabelle , Delahousse Julia , Hescot Segolene , Hadoux Julien , Castinetti Frederic , DRUI Delphine , Renoult-Pierre Peggy , Libe Rossella , Lamartina Livia , Leboulleux Sophie , Ghuzlan Abir Al , Lombes Marc , Paci Angelo , Baudin Eric
Published: July 2023

Purpose
Mitotane is the only approved treatment for metastatic adrenocortical carcinoma (ACC). Monitoring plasma levels is recommended, but its positive predictive value is insufficient.
Methods
This prospective study of the French ENDOCAN-COMETE network aimed to investigate the prognostic role of early plasma mitotane levels pharmacokinetics and free or bound to lipoprotein fraction dosages during six consecutive months. Lipoprotein fractions were isolated by ultracentrifugation, and mitotane level was determined by HPLC-UV. Total, free, and lipoprotein fraction bound plasma mitotane were monitored every two months for six months with a clinical and morphological assessment. The primary endpoint was overall survival (OS) since the initiation of mitotane.
Results
Twenty-one patients with metastatic ACC and at least two measurements of mitotane level during the MITOLIPO period were included. Median overall survival was 23 months. The median free mitotane level per patient was 12% (± 7%), and the majority (88%) was bound to lipoprotein fractions. Several pharmacokinetics measures of total mitotane were related to OS: the first level at one month (p: 0.047), the mean level (p: 0.082), and the area under the curve (AUC) (p: 0.089), with higher exposure associated to longer OS. Free mitotane (not bounded) and mitotane bounded to lipoprotein subfraction added no prognostic values. The relationship between the mitotane level and OS suggested a minimum "effective" threshold of 10-15mg/L or an area under the curve above 100mg/L/month with no individualized maximum value.
Conclusion
This prospective study did not identify any added prognostic value of free mitotane level over the total level. Early total mitotane level measurements (before 3–6 months) were related to OS with a higher and faster exposure related to more prolonged survival.
Conformational Dynamics of α-Synuclein: A Study of its Intramolecular Forces in the Presence of Selected Compounds
Authors: khatooni Zahed , Akhtari Keivan , Wilson Heather L.
Published: July 2023

Protein misfolding and aggregation play a role in amyloidogenic diseases through the self-assembly of intrinsically disordered proteins (IDPs) in type II diabetes (T2D), Alzheimer's (AD) and Parkinson's (PD) diseases. PD is the most common neurodegenerative disorder after AD, known for the loss of dopaminergic signaling, which causes motor and non-motor signs and symptoms. Lewy bodies and Lewy neurites are common pathological hallmarks of PD that are mainly composed of an aggregate of the disordered protein, α-synuclein (α-Syn). There have been many efforts to develop chemical-based compounds to prevent aggregation or facilitate disruption of the fibrils. These have been tested in wet labs, but most fail to generate a robust impact. Further, the atomistic roles and interactions of such compounds have yet to be revealed. The conformational diversity and detailed interactions among homo-oligomer chains of α-Syn are also unknown; identifying these might help uncover a practical approach to developing a potent therapy. In this study, we use an in-silico investigation to address the conformational diversity of α-Syn oligomers. The roles of several point mutations in protein aggregation in PD are known; we take this further by evaluating the interactional energies and contributions of all residues in stability and chain–chain interactions. We dock three chemical derivatives of known compounds with high-score drug-likeness to evaluate the roles of our ligands in the conformational dynamicity of the oligomers, with emphasis on intramolecular forces. Preventing fibril formations is a heated topic in this area. Free energy evaluation of the modeled inter- and intramolecular interactions through MD simulation shows strong binding between α-Syn compounds. However, we find that they do not disrupt or even weaken the interactions, and in some cases, they contributed to boosting interactions between oligomer chains.
Differentially expressed male infertility-associated genes in sperm as prospective diagnostic biomarkers
Authors: Ebrahimi Amir , Ghavi Davood , Mirzaei Zohreh , Barati Tahereh , Mansoori Sima
Published: July 2023

Background
Genetic defects in sperm are responsible for a great percentage of male infertility. The association between numerous genes and spermatogenesis has been observed. Dysregulation of these genes greatly influence sperm morphology, motility and viability. Therefore, analyzing gene expression aberrancies is a must in male infertility. Microarray analysis is practically used for several aspects in male infertility including detection of differentially expressed genes (DEGs), selection of finest sperm for assisted reproductive therapy (ART) and identification of potential infertility biomarkers.
Methods
We conducted a meta-analysis using microarray datasets from NCBI.GEO. We have included datasets containing sperm tissues from both healthy and infertile males. Seven datasets qualified for inclusion in this study. These data were then transformed into a single set of meta-data. For these genes, expression and diagnostic analyses were conducted. In addition, enrichment analysis revealed the role and function of these genes in cellular processes.
Results
Six genes, including S100Z, SLC2A2, IMPG1, HOXD12, RAPGEFL1, and DMBX1, were identified as being significantly down-regulated in infertile men's sperm. Notably, the expression of these genes was highly correlated in sterile sperm. In addition, an analysis of the receiver operating curve indicated that these genes may serve as useful biomarkers for infertility diagnosis. The role of these genes in transporting glucose, vitamins and fructose as the sperm's primary fuel source, was suggested by pathway analysis.
Conclusion
Overall, our results suggest genes with expression abnormalities that may mediate the underlying mechanisms of infertility and also offer promising diagnostic values.
EDKSANet: An Efficient Dual-Kernel Split Attention Neural Network for the classification of Tibetan medicinal materials
Authors: Qi Jindong , Wangdui Bianba , Jiang Jun , Yang Jie , Zhou Yanxia
Published: July 2023

Tibetan medicine has received wide acclaim for its unique diagnosis and treatment methods. The identification of Tibetan medicinal materials, which are a vital component of Tibetan medicine, is a key research area in this field. However, traditional deep learning-based visual neural networks face significant challenges in efficiently and accurately identifying Tibetan medicinal materials, due to their large number, complex morphology, and the scarcity of public visual datasets. To address this issue, we constructed a computer vision dataset with 300 Tibetan medicinal materials and proposed a lightweight and efficient cross-dimensional attention mechanism, the Dual-Kernel Split Attention (DKSA) module, which can adaptively share parameters of the kernel in both spatial and channel dimensions. We then replaced the 3×3 convolutional kernel in the bottleneck blocks of ResNet with the DKSA module, obtaining an EDKSA block that can be embedded into various backbone architectures to enhance the model?s performance. Based on the EDKSA blocks, we developed a novel lightweight backbone architecture, EDKSANet, and demonstrated its competitive performance in image classification, object detection, and instance segmentation on the ImageNet and MS COCO public datasets. Moreover, EDKSANet achieved excellent classification performance on the Tibetan medicinal materials dataset, with an accuracy of up to 96.85%.
Novel Residual Hybrid Machine Learning for Solar Activity Prediction in Smart Cities
Authors: Abdulkadir Rabiu Aliyu , Hasan Mohammad Kamrul , Islam Shayla , ReddyGadekallu Thippa , Pandey Bishwajeet , Safie Nurhizam , Syväjärvi Mikael
Published: July 2023

Predicting global solar activity is crucial for smart cities, especially space activities, communication industries, and climate change monitoring. The recently developed models to predict solar activity based on stand-alone artificial intelligence, based on machine and deep learning models, and hybrid models are promising. Yet they may not be effective at capturing simpler linear patterns in the data and often fail to provide reliable predictions due to the computationally expensive and complex. This article proposed a novel residual hybrid machine learning method integrating linear regression machine learning, and deep learning neural networks for solving predictive accuracy in individual machine learning models that reduces complexity. The residual hybrid model leverages the capacities of the support vector machine (SVM) and long short-term memory neural network (LSTM) for hybrid SVM-LSTM model. The performance of the model is evaluated using the correlation coefficient, determination coefficient, root-mean-squared error (RMSE) and mean-absolute error. The simulation results indicated that compared to the SVM-LSTM, the training and testing RMSE of the LSTM is reduced by 76.62% and 71.18%, respectively. It also decreases the training and testing RMSE of the SVM by 77.06% and 71.81%, respectively. The proposed model can be implemented as reliable solution for accurately predicting solar activities in smart cities.
The efficacy of c-di-AMP as an immunopotentiator for inactivated PRV vaccine
Authors: Hou Liting , Zhang Chenxin , Yu Xiaoming , Du Luping , Cheng Haiwei , Chen Jin , Zheng Qisheng , Hou Jibo
Published: July 2023

Pseudorabies is an acute infectious disease caused by pseudorabies virus which bring huge losses to the swine industry. Compared to live vaccine, the inactivated Pseudorabies virus (PRV)vaccine is generally safe, but it could not elicit strong immunity protection as live vaccine. Improve the efficacy of the inactivated vaccines with immunopotentiator is a research hotspot. Viability-associated pathogen-related molecular patterns(vita-PAMPs) are a type of PAMPs that only exist in active microorganisms. Once entering the body, vita-PAMPs could quickly and efficiently initiate the immune response, and then produce a high level and lasting immune efficacy similar to live vaccine immunity. C-di-AMP is a type of vita-PAMPs which recognized by antigen presenting cell (APC), they can mobilize a high degree of inflammation and activate the adaptive immune response. Hence, we evaluate the effect of c-di-AMP on the efficacy of the pseudorabies inactivated vaccine using a murine model. The immunological enhancement characteristics of c-di-AMP were evaluated for PRV inactivated vaccine in mice. In this study, we measured the level of early inflammatory factors and the recruitment of antigen presenting cells in draining lymph nodes, the activation of follicular helper T cells (Tfh) and the formation of germinal center (GC) by flow cytometry analysis. We also tested the level of serum antibody and the duration of it. The result showed that PRV inactivated vaccine adding c-di-AMP promote the secretion of TNF-α, IL-1β, and IFN-β, recruitment of DCs, Mo and MPh at 7days post-immunization(dpi), and enhance murine antibody levels of PRV by promoting Tfh activated, which directly controls the magnitude of the GC B cell response. These results indicate that c-di-AMP can enhance the immunogenicity of PRV inactivated vaccines, thus providing a novel strategy for improving its efficacy.
Regeneration and Valorization of Spent Bleaching Earth in Edible Oil Refining Industry
Authors: Benkhoud Ikhlas , MANSOUR Lassaad BEN
Published: July 2023

The spent bleaching earth (SBE) from the edible oil refining industry was successfully regenerated through an extraction process using different organic solvents for removal of residual oil, followed by through heat treatment. The total percentage of extracted oil (PEO) for the solvents used showed the following order: PEO (Hexane) > PEO(Acetone) >PEO(Xylene) >PEO(MEK)>PEO (MIBK). The experimental results showed that regeneration by extraction process is insufficient to regenerate SBE, thus requiring also a high temperature treatment. In the current study, the effects of factors, such as liquid to solid ratio [1:1-5:1], temperature [20-40°C], and stirring time [30-60min] on the efficiency of extracted oil were investigated by maceration method. In order to determine the optimal condition, the Experience Planning Methodology (EPM) was adopted. To enhance the oil bleaching efficiency the regenerated SBE by solvent extraction was also treated at different temperatures (300°C – 500°C).
Tool condition monitoring for cavity milling based on bispectrum analysis and Bayesian optimized SVM
Authors: Li Yuhang , Wang Guofeng , Hu Mantang , Ma Kaile
Published: July 2023

Tool wear status seriously affects the dimensional accuracy and surface quality of the machined parts. Therefore, tool condition monitoring (TCM) is essential in the milling process of aerospace structural parts due to the use of difficult-to-cut materials and complex cutting trajectories. The Higher order spectrum (HOS) was first employed to analyze the vibration signals, and then bispectral features extracted from de-noised signals were used to characterize the tool wear status. The improved Pearson’s correlation coefficient was used for feature selection to reduce the influence of periodic components on feature selection process. Furthermore, a novel objective function was proposed to guide the hyperparameters optimization process of support vector machine based on Bayesian optimization algorithm, in which the effect of imbalanced data on the recognition rates was considered. To demonstrate the effectiveness of the proposed method, a structural part milling experiment was performed on a vertical machining center and vibration signals of spindle were collected. Based on this, an online TCM model was established. The present study suggests that the proposed TCM system is accurate and robust.
Experimental study on the transporting and crushing effect of gas on coal powder during the develop stage of coal and gas outburst in roadway
Authors: Cao Jie , Hu Qianting , Dai Linchao , Yang Xuelin
Published: July 2023

In recent years, coal and gas outburst (CGO) disasters are still occurring and difficult to prevent, seriously endangering the safe production in coal mine. It is well known that the transporting and crushing of outburst coal is the major pathway of energy dissipation of CGO process. However, a consensus regarding how gas involves in outburst and affects energy dissipation is still lacking. Quantitative study on the gas effect on migration and fragmentation characteristics of outburst coal in restricted roadway space can improve the energy model. In this study, an improved visual CGO dynamic effect simulation experiment system was utilized to conduct CGO simulation experiments at different gas pressure conditions. The results showed that the ejected coal has experienced various flow patterns in the roadway. In the initial stage, the motion of ejected coal was dominated by stratified flow. However, with the increase of gas pressure, the initial acceleration increases, and the outburst coal mainly move forward rapidly in the form of plug flow. The average velocity at 0.3, 0.5, and 0.8 MPa gas pressure condition were 6.75, 22.22, and 35.81 m/s, respectively. Gas also has a crushing effect on outburst coal bodies. With gas pressure increasing, the number of coal powder particles of the same mass increased significantly, the range of the particle size distribution of decreaed, and the median particle size decreased. In addition, the outburst intensity gradually increases with gas pressure, and the total energy involved in the outburst work also increases. However, the energy dissipation pathways are different. At 0.3 MPa, the energy dissipation is dominated by crushing energy, which is about six times the ejection energy. When the gas pressure increased to 0.8 MPa, the proportion of the ejection energy gradually increases to about twice that of the crushing energy. Under the experimental conditions, 2.71–13.43% of the adsorbed gas involves in the outburst (AGIO) through rapid desorption, and the proportion increases with gas pressure increasing. This paper improves the energy model of CGO, which is applicable to risk assessment and prevention of outburst disasters.
State-dependent Modulation of Low-threshold-current-regulated Dendritic Ca 2+ Response in Thalamic Reticular Neurons with Extracellular Electric Fields
Authors: Fan Yaqin , Wei Xile , Lu Meili , Wang Jiang , Yi Guosheng
Published: July 2023

Deep brain stimulation (DBS) in thalamic reticular nucleus (TRN) neuron provides a novel treatment for drug-resistant epilepsy via the induced electrical field (EFs). However, the mechanisms underlying EF effects remain unclear. This paper investigated how EFs regulate low-threshold dendritic Ca2+ (dCa) response and thus contribute to the input-output relationship of TRN cell. Our results showed that EFs modulate firing modes differently in a neuronal state-dependent manner. At the depolarized state, EFs only regulate the spike timing of a somatic stimulus-evoked single action potential (AP) with less contribution in the regulation of dCa response but could induce the transition between a dendritic stimulus-evoked single AP and a tonic burst of APs via the moderate regulation of dCa response. At the hyperpolarized state, EFs have significant effects on the dCa response, which modulate the large dCa response-dependent burst discharge and even cause a transition from this type of burst discharge to a single AP with less dCa response. Moreover, EF effects on stimulation threshold of somatic spiking prominently depend on EF-regulated dCa responses and the onset time differences between the stimulus and EF give rise to the distinct effect in the EF regulation of dCa responses. Finally, the larger neuronal axial resistance tends to result in the dendritic stimulus-evoked dCa response independent of somatic state. Interestingly, in this case, the EF application could reproduce the similar somatic state-dependent dCa response to dendritic stimulus which occurs in the case of lower axial resistance. These results suggest that the influence of EF on neuronal activities depends on neuronal intrinsic properties, which provides insight into understanding how DBS in TRN neuron modulates epilepsy from the point of view of biophysics.
The rescue potentials of OPC-41061, OPC-31260 and OPC-21268 on mutant AVPR2s that cause nephrogenic diabetes insipidus
Authors: SAHIN Dilara , Tuncdemir Beril Erdem , Ozer Emel Saglar , MERGEN Hatice
Published: July 2023

Purpose
Nephrogenic Diabetes insipidus (NDI) is a rare disease which is characterized by polyuria and polydipsia. AVPR2 mutations can cause NDI. Mutants may not function properly since the mutations can affect their folding process and make them be trapped in the Endoplasmic reticulum (ER). Recent studies showed that pharmacological chaperones (PCs) may rescue mutant AVPR2s and they can be functional again. OPC-41061, OPC-31260 and OPC-21268 are these kind of PCs and they can specifically bind to the mutant AVPR2s and rescue them from ER via helping their folding process. In this study, the effects of OPC-41061, OPC-31260 and OPC-21268 on AVPR2 mutants (R68W, ΔR67-G69/G107W, V162A and T273M) were analyzed.
Methods
We performed cell surface and total ELISA, and cAMP accumulation assay for mutant AVPR2s after the treatment with 3 different PCs.
Results
It was observed that OPC-41061 improved cell surface expressions of all mutants except V162A and ΔR67-G69/G107W, and cell surface expressions of R68W and ΔR67-G69 were increased with all three PCs. Then mutants were stimulated with their agonists to measure cAMP accumulation in the cell as a functional analysis. As a result, we found that R68W and ΔR67-G69 (except T273M) were rescued and could be functional after the treatment with OPC-41061 and OPC-31260.
Conclusion
Showing specific rescue potential of these kind of PCs has an importance on the development of new treatment strategies on NDI. Determining the responses of mutant proteins to various chaperones is extremely important for current treatment approaches and identifying the new PCs.
Effectiveness and Safety of Anticoagulants Among Patients with Venous Thromboembolism and Active Cancer Who Also Had Prior Bleed or Prior Renal Disease
Authors: Cohen Alexander , Noxon Virginia , Dhamane Amol D , Shah Shrushti , Hines Dionne M , Alfred Tamuno , Chaves Jose , Luo Xuemei
Published: July 2023

PURPOSE: Patients with active cancer and venous thromboembolism (VTE) have elevated risk of major bleeding (MB) and recurrent VTE (rVTE). The risk is even higher within those with a prior bleeding event or renal disease. There is a need to understand the risk of MB and rVTE of commonly used anticoagulants among these high-risk patients.
METHODS: VTE patients with active cancer and treated with apixaban, warfarin or low molecular weight heparin (LMWH) within 30-days of VTE were identified from 5 claims databases in the United States. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Post-IPTW population was stratified by prior bleed or renal disease status. Cox proportional hazards models were used to evaluate interactions of treatment with prior bleed or renal disease and risk of rVTE and MB,withp-value <0.1 as significant.
RESULTS: 30,586 VTE cancer patients met all study criteria: 35.0% had prior bleed and 29.0% had renal disease. Use of apixaban, warfarin or LMWH was similar regardless of prior bleed and renal disease status. Patients with prior bleed or renal disease had a higher incidence of MB vs those without the condition respectively. Generally, no significant interactions were observed between treatment of apixaban, warfarin or LMWH with prior bleed or with renal disease on rVTE and MB (p for interaction >0.1).
CONCLUSION: Incidence of MB was higher among those with prior bleed or renal disease. Effects of treatment with apixaban, warfarin, or LMWH were generally consistent regardless of prior bleed or renal disease status.
Total network controllability analysis discovers explainable drugs for Covid-19 treatment
Authors: Wei Xinru , Pan Chunyu , Zhang Xizhe , Zhang Weixiong
Published: July 2023

Background
The active pursuit of network medicine for drug repurposing, particularly for combating Covid-19, has stimulated interest in the concept of structural control capability in cellular networks. We sought to extend this theory, focusing on the defense rather than control of the cell against viral infections. Accordingly, we extended structural controllability to total structural controllability and introduced the concept of control hubs. Perturbing any control hub may render the cell uncontrollable by exogenous stimuli like viral infections, so control hubs are ideal drug targets.
Results
We developed an efficient algorithm to identify all control hubs, applying it to the largest homogeneous network of human protein interactions, including interactions between human and SARS-CoV-2 proteins. Our method recognized 65 druggable control hubs with enriched antiviral functions. Utilizing these hubs, we categorized potential drugs into four groups: antiviral and anti-inflammatory agents, drugs acting on the central nervous system, dietary supplements, and compounds enhancing immunity. An exemplification of our approach's effectiveness, Fostamatinib, a drug initially developed for chronic immune thrombocytopenia, is now in clinical trials for treating Covid-19. Preclinical trial data demonstrated that Fostamatinib could reduce mortality rates, ICU stay length, and disease severity in Covid-19 patients.
Conclusions
Our findings confirm the efficacy of our novel strategy that leverages control hubs as drug targets. This approach provides insights into the molecular mechanisms of potential therapeutics for Covid-19, making it a valuable tool for interpretable drug discovery.
Description and genomic characterization of Cohnella amylolytica sp. nov., isolated from Hot Springs in Yunnan province, south-west China
Authors: Xiang Ming-Xian , Miao Cui-Ping , Wang Juan , Li Yi-Qing , Yin Min , Tang Shu-Kun
Published: July 2023

A bacterial strain, Gram staining positive, strictly aerobic, rod-shaped, motile bacterium with flagellum and endospore-forming, designated strain YIM B05605T, was isolated from soil sampled in Hamazui hot springs, Tengchong City, Yunnan province, China. Optimum growth for the strain occurred at pH 7.0 and 45 °C. The predominant menaquinone of strain YIM B05605T was MK-7. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PME), unidentified glycolipid (GL), three unknown aminophospholipids (APLs) and unidentified polarlipid (PL) were part of the polar lipid profle. The major fatty acids were anteiso-C15:0 and iso-C16:0. The DNA G+C content of the type strain was 58.76 mol%. Genome-based phylogenetic analysis confirmed that strain YIM B05605T formed a distinct phylogenetic cluster within the genus Cohnella. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values of strain YIM B05605T with the most related species C. fontinalis YT-1101T were 73.42 % and 15.7 %. Based on phylogenomic and phylogenetic analyses coupled with phenotypic and chemotaxonomic characterizations, strain YIM B05605T could be classified as a novel species of the genus Cohnella, for which the name Cohnella amylolytica sp. nov., is proposed. The type strain is YIM B05605T (= CGMCC 1.60052 T= KCTC 43462 T= NBRC 115921 T).
Indirect estimation of distance of a star from apparent magnitude.
Authors: Adhikary Abisa Sinha , Chattopadhyay Tanuka , Chattopadhyay Asis Kumar
Published: July 2023

Space observatory Gaia has prepared a large catalog of 1 billion astronomical objects which consists primarily of stars but also planets, comets, asteroids and quasars among others whose parallaxes are measured instead of distances (r). Bailer-Jones (Bailer-Jones [1]) established that distance estimation from parallaxes is not trivial once the fractional parallax error is larger than about 20%, which will be the case for about 80% of stars in the Gaia catalog. In the present model the distance estimates are developed through a Bayesian model using apparent magnitudes which are distant dependent intrinsic properties of stars. The proposed model is based on apparent magnitude limited distribution (viz. φ(m)) constructed with the combination of the probability density function (pdf) of an absolute magnitude limited distribution Φ(M) along with a prior. The former one is constructed from real data set of Gaia Catalogue of apparent magnitudes, corrected for extinction and parallaxes of a huge number of stars. The posterior distribution of the estimated distances thus found has variances and bias under control even for a lager fractional error (viz. more than 80 % compared to the previous work ) and hence for a larger distance.
Airborne dust particles originated from sand and gravel quarries: Mineralogical, geochemical, and size distribution constraints on their potential health impacts
Authors: Menhaje-Bena Rabeah , Modabberi Soroush , Bakand Shahnaz , Kazemian Hossein , Khansari Mahmoud Ghazi , Koohi Mohammad Kazem
Published: July 2023

Dust particles derived from sand and gravel mining have been considered as one of the possible sources of suspended particles in Tehran, the capital city of Iran. In this research, the size, morphological, and geochemical characteristics of the airborne particles originated from open mines were investigated. Twenty-two samples from different heights (3 to 21m) were collected from a sand and gravel quarry in Shahriar as the representative of the numerous quarries in western Tehran. The selected samples were further analyzed using X-ray powder diffraction (XRD) and Scanning Electron Microscopy with Energy Dispersive X-Ray Spectroscopy (SEM-EDS). The main mineralogy of airborne dust was dominated by quartz, followed by albite and calcite. The size distribution of deposited particles at different heights ranged from 0.05 µm to 100 µm and about 80% of them were respirable (< 10 µm) and available for transfer through the atmosphere. Si/Al ratios fall mainly into a range between 4 and 10. About 80% of the total particles are below 10 µm. Most nanoparticles were settled into agglomerated forms.
The impacts of patient mistreatment on healthcare workers’ role behaviors: a study in Chinese Fangcang shelter hospitals
Authors: Yan Wei , Bao Na , Zheng Shuangjiang , Wang Huan , Yue Dongmei , Chen Li
Published: July 2023

Background: Fangcang shelter hospitals have played an important role in the battle against the COVID-19 epidemic in China. Verbal and physical attacks on patients are prone to occur in such hospitals. This study explored the impacts of patient mistreatment on healthcare workers’ role behaviors (service performance and patient-oriented organizational citizenship behavior).
Methods: We examined the influence of patient mistreatment on service performance and patient-oriented organizational citizenship behavior, as well as the mediating effect of emotional exhaustion and the moderating effect of displaced aggression by patients, using hierarchical linear regression and conditional process analysis.
Results: Patient mistreatment was positively associated with emotional exhaustion among healthcare workers, while emotional exhaustion was negatively associated with service performance and patient-oriented organizational citizenship behavior. Mediation analysis revealed that emotional exhaustion mediated the association between patient mistreatment and both types of role behaviors. Moderated mediation analysis found that the mediation effect was weaker when the displaced aggression by patients was high.
Conclusions: The findings clarified the relationship between patient mistreatment, emotional exhaustion, service performance, and patient-oriented organizational citizenship behavior. Additional assistance should be provided to healthcare workers dealing with patient mistreatment. Displaced aggression by patients attenuates the positive effects of patient mistreatment on the emotional exhaustion of healthcare workers. Our findings reveal the mechanism and boundary conditions of patient mistreatment affecting healthcare workers' service performance and patient-oriented organizational citizenship behavior.
Ethanol tolerance in engineered strains of Clostridium thermocellum
Authors: Olson Daniel G. , Maloney Marybeth , Lanahan Anthony , Cervenka Nicholas , Xia Ying , Pech-Canul Angel , Hon Shuen , Tian Liang , Ziegler Samantha J. , Bomble Yannick , Lynd Lee R.
Published: July 2023

Clostridium thermocellum is a natively cellulolytic bacterium that is promising candidate for cellulosic biofuel production, but the ethanol titers produced thus far are too low for commercial application. In several strains of C. thermocellum engineered for increased ethanol yield, ethanol titer seems to be limited by ethanol tolerance. Previous work to improve ethanol tolerance has focused on the WT organism. In this work, we focused on understanding ethanol tolerance in several engineered strains of C. thermocellum. We observed a tradeoff between ethanol tolerance and production. Adaptation for increased ethanol tolerance decreases ethanol production. Second, we observed a consistent genetic response to ethanol stress involving mutations at the AdhE locus. These mutations typically reduced NADH-linked ADH activity. About half of the ethanol tolerance phenotype could be attributed to the elimination of NADH-linked activity based on a targeted deletion of adhE. Finally, we observed that rich growth medium increases ethanol tolerance, but this effect is eliminated in an adhE deletion strain. Together, these suggest that ethanol inhibits growth and metabolism via a redox-imbalance mechanism. The improved understanding of mechanisms of ethanol tolerance described here lays a foundation for developing strains of C. thermocellum with improved ethanol production.
Epigenetic reprogramming of Nannochloropsis oceanica in response to CO 2 fluctuated environment
Authors: Liu Danmei , Wei Li
Published: July 2023

Low CO2 could induce carbon concentrating mechanism (CCM) in majority of microalgae and CCM are regulated at RNA level are well known, however, epigenetic modifications and their potential regulation of the transcription of masked genes at the genome level in response to CO2 fluctuation remain unclear. Here we examine histone modifications and gene expression during CCM induction using ChIP-seq and mRNA-seq. Epigenetic regulation in response to CO2 fluctuation and epigenome-association with phenotypic plasticity of CCM are firstly uncovered in marine microalga Nannochloropsis oceanica IMET1. The result showed that lysine butyrylation (Kbu) and histone H3K9m2 modifications were present in N. oceanica IMET1. Moreover, Kbu positively regulated gene expression. In response to CO2 fluctuation, there were 5,438 and 1,106 genes regulated by Kbu and H3K9m2, respectively. Differential modifications were enriched in carbon fixation, photorespiration, photosynthesis, and lipid metabolism etc. For low carbon adaption, we observed that massively genome-wide epigenetic reprogramming would occur after N. oceanica cells shifted from high CO2 to low CO2. Gained or lost histone methylations were closely associated with activating or repressing gene expressions. Particularly, we firstly noted that the transcription of the key low CO2 responsive carbonic anhydrase (CA5), a key component involved in CCM stress signaling, was potentially regulated by bivalent Kbu-H3K9m2 modifications in microalgae. This study provides novel insights into epigenetic regulation in Nannochloropsis, which will lay foundation on genetic improvement of CCM at epigenetic level.
GWAS combined with transcriptome and metabolome to excavate key candidate genes for rice anaerobic germination
Authors: Li Dandan , Liu Kai , Zhao Chuanchao , Liang Siyi , Yang Jing , Peng Ziai , Xia Aoyun , Yang Meng , Luo Lixin , Huang Cuihong , Wang Jiafeng , Huang Ming , Xiao Wuming , Wang Hui , Su Ling , Guo Tao
Published: July 2023

In this study, a total of 317 SNP loci were detected based on dynamic genome-wide association study (GWAS) of the length (CL), surface area (CSA), volume (CV) and diameter (CD) of the coleoptile growing in 2d, 3d and 4d under anaerobic conditions in 591 natural rice populations. Integrated dynamic widely targeted metabolomic technology combined with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) and data analysis, we found that xanthine, L-alanine and GABA may be key biomarkers that are sensitive and respond strongly to hypoxic stress perception. By combining targeted metabolomics and transcriptomics for WGCNA, we found that OsAlaAT1, OsGAD4, OsAAH and Os09g0424600 are the key structural genes that best characterize the metabolic processes of L-alanine, GABA and xanthine. Among them, OsAlaAT1 (Os10g0390500), located in Chr10-12877840, which is within the GWAS location range of CVAN3d, is considered to be a more reliable candidate gene. Through phenotype observation of OsAlaAT1 transgenic plants and qRT‒PCR analysis, it was found that the coleoptile length (CL) and relative expression level of the ko-alaat1 mutant were significantly decreased compared with the control (ZH11). GUS staining showed that OsAlaAT1 was strongly expressed in the coleoptile, embryo and radicle during seed germination under anaerobic conditions. Overall, in addition to providing new insight into the metabolic regulation of L-alanine, GABA and xanthine during hypoxic germination of rice, the outcome of our study establishes a foundation for anaerobic germination (AG) improvement in rice.