bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal Structure Beneath the Tarim Craton and Its Tectonic Implications
Authors: Xu Xi , Xiong Shengqing , Tanaka Akiko , Zheng Qiang , Kuang Xingtao , Zhu Xiaoying , Zhou Daoqing , Zheng Qifang , Wan Jianhua , Yu Xuezhong , Wang Baodi
Published: August 2021

The lateral distribution of the magnetic layer beneath the Tarim Craton and its environs was estimated from spectral analysis using the newest high-resolution aeromagnetic dataset of mainland China, which is enlarged by EMAG2. As a proxy, the Curie point depth (CPD) provides a comprehensive view of a crust-scale thermal regime, accounted for the depth at which magnetite becomes paramagnetic, and the correspondence of the CPD with the tectonic regime indicates that the CPD is useful for delineating the regional crustal thermal structure. Furthermore, lateral variations in CPD provide useful insights into the lithospheric thermal state of the Tarim Craton and its surrounding areas and can be related to ancient and active tectonics, such as geothermal activity, seismicity, and mineral-petroleum generation. In the Tarim interior, the NW domain covering the Bachu Uplift and its surrounding areas corresponds to the minimum magnetic CPD signature geometry of this area, which is most likely linked to the Permian Tarim plume-lithosphere interaction. In contrast, the other domains are characterized by large CPD values (up to 50 km), which are floored by a Precambrian basement without the Permian magmatism modification. Moreover, the estimated CPD values are consistent with surface heat flow measurements with an inverse correlation, which can assist in identifying the potential area for mineral deposits and hydrocarbon fields. Earthquakes are mostly concentrated in the gradient and transition zones of the Curie surface, suggesting that these abrupt variation domains in the crustal thermal structure act as a secondary mechanism for earthquake generation.
Intelligent Interpretation of the Geometric Properties of Rock Mass Discontinuities Based on an Unmanned Aerial Vehicle
Authors: Chen Na , Du Chang-jie , Ding Xiang
Published: August 2021

The geometric properties of rock mass discontinuities are essential for the evaluation of the safety of rock masses. Numerous studies have recently been performed on the extraction of discontinuity information. However, most methods are characterized by poor data collection and processing efficiency. This paper presents a UAV-based methodology for the accurate and complete acquisition of rock surface data, as well as the automatic extraction of discontinuity information. Moreover, a program called Random Sample Consensus (RANSAC) Discontinuity Detection (RDD) is developed to extract discontinuity information based on the proposed method. The conclusions of this research are as follows. 1) RANSAC Discontinuity Detection (RDD) can identify the feature point set of discontinuities from a raw point cloud, and can calculate the discontinuity orientation. 2) The boundary of a discontinuity can be precisely depicted using the improved Graham scan algorithm. 3) The orientations of marked discontinuities extracted by RDD are compared with those extracted by the three-point method in CloudCompare. The differences in the orientations extracted by the two methods are found to be less than 3° for flat discontinuities and only about 4.87° for rough discontinuities, which are within a reasonable error range in practical engineering applications. Therefore, the feasibility of the proposed method is verified.
Dragonfly Conservation in the Increasingly Stressed African Mediterranean-Type Ecosystems
Authors: Khelifa Rassim , Deacon Charl , Mahdjoub Hayat , Suhling Frank , Simaika John P. , Samways Michael J.
Published: August 2021

Freshwater habitats worldwide are experiencing many threats from environmental and anthropogenic sources, affecting biodiversity and ecosystem functioning. In Africa, particularly in Mediterranean climate zones, rapid human population growth is predicted to have great impact on natural habitats besides naturally occurring events such as unpredictable drought frequency and severity. Here, we analyze the potential correlation between odonate assemblage conservation priority (measured with the Dragonfly Biotic Index: DBI) and the magnitude of climate change and human perturbation in African regions with a dominant Mediterranean climate, namely Northern (NAR: Morocco, Algeria and Tunisia) and Southern African region (SAR: South Africa). Using a compilation of studies assessing odonate assemblages in lotic and lentic habitats of both regions (295 sites in NAR and 151 sites in SAR), we estimated DBI, temporal change in average annual temperature (T), annual precipitation (P), and human footprint index (HFI) in each site, then we tested whether sites with different levels of DBI were associated with different magnitudes of climatic and anthropogenic change. We estimated past (between 1980–1999 and 2000–2018) and future changes (between 1980–1999 and 2081–2100) in T and P based on three CMIP6 scenarios representing low (SSP126), moderate (SSP245), and high emission (SSP585), as well as the change in HFI from 1993 to 2009. We found that assemblages with higher DBI (i.e. higher conservation priority) encountered lower increase in T and slightly greater decrease in P than assemblages with lower DBI (i.e. lower conservation priority) in NAR during 1980–2018, but are projected to experience higher increase in T and lower decrease in P in future projections for 2081–2100. In SAR, the increase in T was mostly similar across assemblages but the decline in P was higher for assemblages with higher DBI during 1980–2018 and 2081–2100, suggesting that assemblages of higher conservation priority in SAR are threatened by drought. While HFI showed an overall increase in NAR but not in SAR, its temporal change showed only minor differences across assemblages with different DBI levels. We discuss the importance of management plans to mitigate the effects of climatic and anthropogenic threats, so improving conservation of odonate assemblages in these regions.
Unraveling City-Specific Microbial Signatures and Identifying Sample Origins for the Data From CAMDA 2020 Metagenomic Geolocation Challenge
Authors: Zhang Runzhi , Ellis Dorothy , Walker Alejandro R. , Datta Susmita
Published: August 2021

The composition of microbial communities has been known to be location-specific. Investigating the microbial composition across different cities enables us to unravel city-specific microbial signatures and further predict the origin of unknown samples. As part of the CAMDA 2020 Metagenomic Geolocation Challenge, MetaSUB provided the whole genome shotgun (WGS) metagenomics data from samples across 28 cities along with non-microbial city data for 23 of these cities. In our solution to this challenge, we implemented feature selection, normalization, clustering and three methods of machine learning to classify the cities based on their microbial compositions. Of the three methods, multilayer perceptron obtained the best performance with an error rate of 19.60% based on whether the correct city received the highest or second highest number of votes for the test data contained in the main dataset. We then trained the model to predict the origins of samples from the mystery dataset by including these samples with the additional group label of “mystery.” The mystery dataset compromised of samples collected from a subset of the cities in the main dataset as well as samples collected from new cities. For samples from cities that belonged to the main dataset, error rates ranged from 18.18 to 72.7%. For samples from new cities that did not belong to the main dataset, 57.7% of the test samples could be correctly labeled as “mystery” samples. Furthermore, we also predicted some of the non-microbial features for the mystery samples from the cities that did not belong to main dataset to draw inferences and narrow the range of the possible sample origins using a multi-output multilayer perceptron algorithm.
Case Report: Whole Exome Sequencing Revealed Two Novel Mutations of PIEZO1 Implicated in Nonimmune Hydrops Fetalis
Authors: Chen Yuan , Jiang Ying , Chen Bangwu , Qian Yeqing , Liu Jiao , Yang Mengmeng , Zhao Baihui , Luo Qiong
Published: August 2021

Nonimmune hydrops fetalis (NIHF) is a serious and complex fetal condition. Prenatal diagnosis of hydrops fetalis is not difficult by ultrasound. However, determining the underlying etiology of NIHF remains a challenge which is essential to address for prenatal counseling. We extracted DNA from a proband prenatally diagnosed unexplained NIHF. Trio-whole exome sequencing (WES) was performed to filter candidate causative variants. Two gene mutations were identified as a compound heterozygous state in the proband. Both variants located on the PIEZO1 gene: c.3895C > T, a missense mutation in exon 27 paternally inherited; c.4030_4032del, a maternally inherited in-frame deletion in exon 28. Both variants were first reported to be related to NIHF. PIEZO1 gene mutations, leading to an autosomal recessive congenital lymphatic dysplasia, which can present as NIHF and partial or complete resolution postnatally. In conclusion, WES can aid in the elucidation of the genetic cause of NIHF and has a positive effect on the assessment of prognosis.
Genetic Diversity Analysis of Surface-Related Antigen (SRA) in Plasmodium falciparum Imported From Africa to China
Authors: Yang Bo , Liu Hong , Xu Qin-Wen , Sun Yi-Fan , Xu Sui , Zhang Hao , Tang Jian-Xia , Zhu Guo-Ding , Liu Yao-Bao , Cao Jun , Cheng Yang
Published: August 2021

Plasmodium falciparum surface-related antigen (SRA) is located on the surfaces of gametocyte and merozoite and has the structural and functional characteristics of potential targets for multistage vaccine development. However, little information is available regarding the genetic polymorphism of pfsra. To determine the extent of genetic variation about P. falciparum by characterizing the sra sequence, 74 P. falciparum samples were collected from migrant workers who returned to China from 12 countries of Africa between 2015 and 2019. The full length of the sra gene was amplified and sequenced. The average pairwise nucleotide diversities (π) of P. falciparum sra gene was 0.00132, and the haplotype diversity (Hd) was 0.770. The average number of nucleotide differences (k) for pfsra was 3.049. The ratio of non-synonymous (dN) to synonymous (dS) substitutions across sites (dN/dS) was 1.365. Amino acid substitutions of P. falciparum SRA could be categorized into 35 unique amino acid variants. Neutrality tests showed that the polymorphism of PfSRA was maintained by positive diversifying selection, which indicated its role as a potential target of protective immune responses and a vaccine candidate. Overall, the ability of the N-terminal of PfSRA antibodies to evoke inhibition of merozoite invasion of erythrocytes and conserved amino acid at low genetic diversity suggest that the N-terminal of PfSRA could be evaluated as a vaccine candidate against P. falciparum infection.
Improving de novo Molecule Generation by Embedding LSTM and Attention Mechanism in CycleGAN
Authors: Wang Feng , Feng Xiaochen , Guo Xiao , Xu Lei , Xie Liangxu , Chang Shan
Published: August 2021

The application of deep learning in the field of drug discovery brings the development and expansion of molecular generative models along with new challenges in this field. One of challenges in de novo molecular generation is how to produce new reasonable molecules with desired pharmacological, physical, and chemical properties. To improve the similarity between the generated molecule and the starting molecule, we propose a new molecule generation model by embedding Long Short-Term Memory (LSTM) and Attention mechanism in CycleGAN architecture, LA-CycleGAN. The network layer of the generator in CycleGAN is fused head and tail to improve the similarity of the generated structure. The embedded LSTM and Attention mechanism can overcome long-term dependency problems in treating the normally used SMILES input. From our quantitative evaluation, we present that LA-CycleGAN expands the chemical space of the molecules and improves the ability of structure conversion. The generated molecules are highly similar to the starting compound structures while obtaining expected molecular properties during cycle generative adversarial network learning, which comprehensively improves the performance of the generative model.
Immunoporosis: Role of Innate Immune Cells in Osteoporosis
Authors: Saxena Yogesh , Routh Sanjeev , Mukhopadhaya Arunika
Published: August 2021

Osteoporosis or porous bone disorder is the result of an imbalance in an otherwise highly balanced physiological process known as ‘bone remodeling’. The immune system is intricately involved in bone physiology as well as pathologies. Inflammatory diseases are often correlated with osteoporosis. Inflammatory mediators such as reactive oxygen species (ROS), and pro-inflammatory cytokines and chemokines directly or indirectly act on the bone cells and play a role in the pathogenesis of osteoporosis. Recently, Srivastava et al. (Srivastava RK, Dar HY, Mishra PK. Immunoporosis: Immunology of Osteoporosis-Role of T Cells. Frontiers in immunology. 2018;9:657) have coined the term “immunoporosis” to emphasize the role of immune cells in the pathology of osteoporosis. Accumulated pieces of evidence suggest both innate and adaptive immune cells contribute to osteoporosis. However, innate cells are the major effectors of inflammation. They sense various triggers to inflammation such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), cellular stress, etc., thus producing pro-inflammatory mediators that play a critical role in the pathogenesis of osteoporosis. In this review, we have discussed the role of the innate immune cells in great detail and divided these cells into different sections in a systemic manner. In the beginning, we talked about cells of the myeloid lineage, including macrophages, monocytes, and dendritic cells. This group of cells explicitly influences the skeletal system by the action of production of pro-inflammatory cytokines and can transdifferentiate into osteoclast. Other cells of the myeloid lineage, such as neutrophils, eosinophils, and mast cells, largely impact osteoporosis via the production of pro-inflammatory cytokines. Further, we talked about the cells of the lymphoid lineage, including natural killer cells and innate lymphoid cells, which share innate-like properties and play a role in osteoporosis. In addition to various innate immune cells, we also discussed the impact of classical pro-inflammatory cytokines on osteoporosis. We also highlighted the studies regarding the impact of physiological and metabolic changes in the body, which results in chronic inflammatory conditions such as ageing, ultimately triggering osteoporosis.
Inflammasome Signaling: A Novel Paradigm of Hub Platform in Innate Immunity for Cancer Immunology and Immunotherapy
Authors: Li Ying , Lv Jiao , Shi Weikai , Feng Jia , Liu Mingxi , Gan Shenao , Wu Hongjin , Fan Weiwei , Shi Ming
Published: August 2021

Inflammasomes are fundamental innate immune mechanisms that promote inflammation and induce an inflammatory form of programmed cell death, pyroptosis. Pyroptotic inflammasome has been reported to be closely associated with tumorigenesis and prognosis of multiple cancers. Emerging studies show that the inflammasome assembly into a higher-order supramolecular complex has been utilized to evaluate the status of the innate immune response. The inflammasomes are now regarded as cellular signaling hubs of the innate immunity that drive the production of inflammatory cytokines and consequent recruitment of immune cells to the tumor sites. Herein, we provided an overview of molecular characteristics and biological properties of canonical and non-canonical inflammasome signaling in cancer immunology and immunotherapy. We also focus on the mechanism of regulating pyroptotic inflammasome in tumor cells, as well as the potential roles of inflammasome-mediated pyroptotic cell death in cancers, to explore the potential diagnostic and therapeutic markers contributing to the prevention and treatment of cancers.
Structural Study of the Hydration of Lipid Membranes Upon Interaction With Mesoporous Supports Prepared by Standard Methods and/or X‐Ray Irradiation
Authors: Marmiroli Benedetta , Sartori Barbara , Kyvik Adriana R. , Ratera Imma , Amenitsch Heinz
Published: August 2021

Mesoporous materials feature ordered tailored structures with uniform pore sizes and highly accessible surface areas, making them an ideal host for functional organic molecules or nanoparticles for analytical and sensing applications. Moreover, as their porosity could be employed to deliver fluids, they could be suitable materials for nanofluidic devices. As a first step in this direction, we present a study of the hydration of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) model lipid membranes on solid mesoporous support. POPC was selected as it changes the structure upon hydration at room temperature. Mesoporous films were prepared using two different templating agents, Pluronic P123 (PEO–PPO–PEO triblock copolymer where PEO is polyethylene oxide and PPO is polypropylene oxide) and Brij 58 (C16H33(EO)20OH where EO is ethylene oxide), both following the conventional route and by X-ray irradiation via deep X-ray lithography technique and subsequent development. The same samples were additionally functionalized with a self-assembly monolayer (SAM) of (3-aminopropyl)triethoxysilane. For every film, the contact angle was measured. A time resolved structural study was conducted using in situ grazing incidence small-angle X-ray scattering while increasing the external humidity (RH), from 15 to 75% in a specially designed chamber. The measurements evidenced that the lipid membrane hydration on mesoporous films occurs at a lower humidity value with respect to POPC deposited on silicon substrates, demonstrating the possibility of using porosity to convey water from below. A different level of hydration was reached by using the mesoporous thin film prepared with conventional methods or the irradiated ones, or by functionalizing the film using the SAM strategy, meaning that the hydration can be partially selectively tuned. Therefore, mesoporous films can be employed as “interactive” sample holders with specimens deposited on them. Moreover, thanks to the possibility of patterning the films using deep X-ray lithography, devices for biological studies of increasing complexity by selectively functionalizing the mesopores with biofunctional SAMs could be designed and fabricated.
Intrinsic Complex Vacancy-Induced d0 Magnetism in Ca2Nb2O7 PLD Film
Authors: Wu Linjie , Zhang Yongjia , Nie Zhongquan , Cao Ensi
Published: August 2021

Introducing magnetism into the ferroelectric Ca2Nb2O7 with high Curie temperature can make it a potential multiferroic material at room temperature. Stoichiometric Ca2Nb2O7, nonstoichiometric Ca1.9Nb2O7-δ and Ca2Nb1.9O7-δ single phase films were deposited on STO (110) substrate by pulsed laser deposition under appropriate conditions. The films were characterized by XRD, FE-SEM, Element mapping and XPS. Both stoichiometric Ca2Nb2O7 and Ca1.9Nb2O7-δ films were diamagnetic in the magnetic measurement and ab initio calculations, while the Ca2Nb1.9O7-δ film with the complex vacancy of VNb+O exhibited ferromagnetic behavior at room temperature, with the saturated magnetization of 3.6 emu/cm3. Calculations on the Ca2Nb2O7 (010) surface indicate that the VNb+O can induce spin polarization on the residual O atoms around the Nb vacancies, and the system was most stable when the Nb and O vacancies were the 4th nearest-neighbored, with FM coupling energetically more stable than the AFM coupling. Our work verified experimentally and theoretically the feasibility of introducing ferromagnetism into Ca2Nb2O7 film by the intrinsic complex vacancy of VNb+O.
A Pilot Study of Blood Pressure Monitoring After Cardiac Surgery Using a Wearable, Non-invasive Sensor
Authors: Kachel Erez , Constantini Keren , Nachman Dean , Carasso Shemy , Littman Romi , Eisenkraft Arik , Gepner Yftach
Published: August 2021

Background: Continuous blood pressure (BP) measurement in intensive care units is based on arterial line (AL) transducers, sometimes associated with clinical complications. Our objective was to evaluate continuous BP measurements obtained from a non-invasive, wireless photoplethysmography (PPG)-based device using two distinct configurations (wristwatch and chest-patch monitors) compared to an AL.

Methods: In this prospective evaluation study, comparison of the PPG-based devices to the AL was conducted in 10 patients immediately following cardiac surgery. Pulse rate (PR), systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were recorded using both the AL and the PPG-based devices simultaneously for an average of 432 ± 290 min starting immediately after cardiac surgery. Bland-Altman plots and Pearson's correlations were used to assess the accuracy and degree of agreement between techniques.

Results: A total of ~4,000 data points were included in the final analysis. AL measurements for PR, SBP, DBP and MAP were significantly (p < 0.001) and strongly correlated with both the wristwatch (r = 0.99, r = 0.94, r = 0.93 and r = 0.96, respectively) and the chest-patch (r = 0.99, r = 0.95, r = 0.93 and r = 0.95, respectively) monitors. Both configurations showed a marginal bias of <1 mmHg for BP measurements and <1 beat/min for PR [95% limits of agreement −3,3 beat/min; BP measurements: (−6)–(−10), 6–10 mmHg] compared to AL measurements.

Conclusion: The PPG-based devices offer a high level of accuracy for cardiac-related parameters compared to an AL in post-cardiac surgery patients. Such devices could provide advanced monitoring capabilities in a variety of clinical settings, including immediate post-operative and intensive care unit settings.

Clinical Trial Registration:www.clinicaltrials.gov, NCT03603860.
Investigating the Added Value of the EQ-5D-5L With Two Bolt-On Items in Patients With Hemophilia
Authors: Xu Richard Huan , Dong Dong , Luo Nan , Yang Renchi , Liu Junshuai , Zhang Shuyang
Published: August 2021

Objective: This study examined the impact of adding two condition-specific bolt-on items to the EQ-5D-5L and assessed their psychometric properties in patients with hemophilia.

Methods: The data were obtained from a nationwide cross-sectional online survey of patients with hemophilia in China. Self-reported and proxy-reported data were analyzed separately. Ceiling effect, informativity, and discriminatory power of the EQ-5D-5L with two bolt-on items, dignity (DG), and bleeding (BL), were examined. Spearman's rank correlation (rho) was used to assess the associations of the EQ-5D-5L and two bolt-on items with the Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) and SF-12. Multiple regression analysis was performed to evaluate the explained variance of the EQ-5D-5L and bolt-on items in predicting EQ-VAS scores.

Results: A total of 895 patients and 222 caregivers completed the questionnaire. The ceiling effect decreased from 1.9 to 0.6% and 5.9 to 0.9% when using the EQ-5D-5L and the EQ-5D-5L with two bolt-on items among participants with both self- and proxy-completed questionnaires. Both DG and BL were strongly correlated with Haem-A-QoL sum score [rho: DG = 0.64 (patient) vs. 0.66(proxy); BL = 0.49 (patient) vs. 0.31 (proxy)], SF-12 mental component [rho: DG = −0.36 (patient) vs. −0.41 (proxy); BL = −0.53 (patient) vs. −0.57(proxy)], and SF-12 physical component [rho: DG = −0.61 (patient) vs. −0.61 (proxy); BL = −0.35 (patient) vs. −0.39 (proxy)]. Known-group comparisons confirmed that the two bolt-on items had satisfactory discriminatory power. Multiple regression analysis indicated that adding two bolt-on items significantly increased the ability to predict EQ-VAS scores. The adjusted R2 increased by 8.2 and 8.8% for reports completed by the patients or patients' proxy respondents, respectively.

Conclusion: Adding the DG and BL bolt-on items can increase performance on the EQ-5D-5L in patients with hemophilia. A future valuation study will be carried out.
Effectiveness of a Peer-Led Pain Management Program in Relieving Chronic Pain and Enhancing Pain Self-Efficacy Among Older Adults: A Clustered Randomized Controlled Trial
Authors: Tse Mimi M. Y. , Ng Shamay S. M. , Lee Paul H. , Bai Xue , Lo Raymond , Tang Shuk Kwan , Chan Ka Long , Li Yajie
Published: August 2021

Chronic pain is common in nursing home residents, who may have difficulty seeking out pain management strategies. Peer support model show promise as a strategy for managing chronic conditions. This was a clustered randomized controlled trial. A peer-led pain management program was provided for the experimental group. Pain situation, depression, quality of life, non-drug strategies used, and pain knowledge were measured. A total of 262 participants joined the study (146 were allocated as experimental group and 116 as control group). Before our intervention, the mean pain score reported was as high as 6.36 on a 10-point Likert Scale. The high intensity of their pain very much interfered with the daily activities of the participants. Pain interference was high and the participants had poor coping as indicated by the low pain self-efficacy. Depression and a low quality of life score was found. Upon completion of our PAP, there was a significant increase in pain self-efficacy, pain interference as well as quality of life for the participants in the experimental group and not in the control group, and this improvement sustained in 3-month follow up. The present study used a peer support models and proven to be effective in managing pain and pain related situations for nursing home residents with chronic pain. The peer volunteers involved in the pain management program taught relevant pain knowledge and pain management strategies to help our participants.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03823495, NCT03823495.
Risk Factors for Maternal and Fetal Mortality in Acute Fatty Liver of Pregnancy and New Predictive Models
Authors: Meng Zhaoli , Fang Wei , Meng Mei , Zhang Jicheng , Wang Qizhi , Qie Guoqiang , Chen Man , Wang Chunting
Published: August 2021

Acute fatty liver of pregnancy (AFLP) is a rare but potentially life-threatening hepatic disorder that leads to considerable maternal and fetal mortality. To explore the risk factors for maternal and fetal mortality in AFLP and develop new predictive models, through this retrospective study, we analyzed the demographic characteristics, clinical symptoms, and laboratory findings of 106 patients with AFLP who were admitted to Shandong Provincial Hospital. Risk factors for maternal and fetal mortality were analyzed by univariate and multivariate logistic regression analysis. The new models based on the multivariate logistic regression analysis and the model for end-stage liver disease (MELD) were tested in AFLP. The receiver operating characteristic curve (ROC) was applied to compare the predictive efficiency, sensitivity, and specificity of the two models. Prenatal nausea (p = 0.037), prolonged prothrombin time (p = 0.003), and elevated serum creatinine (p = 0.003) were independent risk factors for maternal mortality. The ROC curve showed that the area under the curve (AUC) of the MELD was 0.948, with a sensitivity of 100% and a specificity of 83.3%. The AUC of the new model for maternal mortality was 0.926, with a sensitivity of 90% and a specificity of 94.8%. Hepatic encephalopathy (p = 0.016) and thrombocytopenia (p = 0.001) were independent risk factors for fetal mortality. Using the ROC curve, the AUC of the MELD was 0.694, yielding a sensitivity of 68.8% and a specificity of 64.4%. The AUC of the new model for fetal mortality was 0.893, yielding a sensitivity of 100% and a specificity of 73.3%. Both the new predictive model for maternal mortality and the MELD showed good predictive efficacy for maternal mortality in patients with AFLP (AUC = 0.926 and 0.948, respectively), and the new predictive model for fetal mortality was superior to the MELD in predicting fetal mortality (AUC = 0.893 and 0.694, respectively). The two new predictive models were more readily available, less expensive, and easier to implement clinically, especially in low-income countries.
Spatiotemporal Assembly of Bacterial and Fungal Communities of Seed-Seedling-Adult in Rice
Authors: Kim Hyun , Lee Yong-Hwan
Published: August 2021

Seeds harbor not only genetic information about plants but also microbial communities affecting plants’ vigor. Knowledge on the movement and formation of seed microbial communities during plant development remains insufficient. Here, we address this knowledge gap by investigating endophytic bacterial and fungal communities of seeds, seedlings, and adult rice plants. We found that seed coats act as microbial niches for seed bacterial and fungal communities. The presence or absence of the seed coat affected taxonomic composition and diversity of bacterial and fungal communities associated with seeds and seedlings. Ordination analysis showed that niche differentiation between above- and belowground compartments leads to compositional differences in endophytic bacterial and fungal communities originating from seeds. Longitudinal tracking of the composition of microbial communities from field-grown rice revealed that bacterial and fungal communities originating from seeds persist in the leaf, stem, and root endospheres throughout the life cycle. Our study provides ecological insights into the assembly of the initial endophytic microbial communities of plants from seeds.
In vitro Effect of Harmine Alkaloid and Its N-Methyl Derivatives Against Toxoplasma gondii
Authors: Alomar Maria L. , Yañuk Juan G. , Angel Sergio O. , Gonzalez M. Micaela , Cabrerizo Franco M.
Published: August 2021

Toxoplasmosis is one of the most prevalent and neglected zoonotic global diseases caused by Toxoplasma gondii. The current pharmacological treatments show clinical limitations, and therefore, the search for new drugs is an urgent need in order to eradicate this infection. Due to their intrinsic biological activities, β-carboline (βC) alkaloids might represent a good alternative that deserves further investigations. In this context, the in vitro anti-T. gondii activity of three βCs, harmine (1), 2-methyl-harminium (2), and 9-methyl-harmine (3), was evaluated herein. Briefly, the three alkaloids exerted direct effects on the parasite invasion and/or replication capability. Replication rates of intracellular treated tachyzoites were also affected in a dose-dependent manner, at noncytotoxic concentrations for host cells. Additionally, cell cycle analysis revealed that both methyl-derivatives 2 and 3 induce parasite arrest in S/M phases. Compound 3 showed the highest irreversible parasite growth inhibition, with a half maximal inhibitory concentration (IC50) value of 1.8 ± 0.2 μM and a selectivity index (SI) of 17.2 at 4 days post infection. Due to high replication rates, tachyzoites are frequently subjected to DNA double-strand breaks (DSBs). This highly toxic lesion triggers a series of DNA damage response reactions, starting with a kinase cascade that phosphorylates a large number of substrates, including the histone H2A.X to lead the early DSB marker γH2A.X. Western blot studies showed that basal expression of γH2A.X was reduced in the presence of 3. Interestingly, the typical increase in γH2A.X levels produced by camptothecin (CPT), a drug that generates DSB, was not observed when CPT was co-administered with 3. These findings suggest that 3 might disrupt Toxoplasma DNA damage response.
The Ageing Brain: Investigating the Role of Age in Changes to the Human Cerebral Microvasculature With an in silico Model
Authors: Graff Barnaby J. , Payne Stephen J. , El-Bouri Wahbi K.
Published: August 2021

Ageing causes extensive structural changes to the human cerebral microvasculature, which have a significant effect on capillary bed perfusion and oxygen transport. Current models of brain capillary networks in the literature focus on healthy adult brains and do not capture the effects of ageing, which is critical when studying neurodegenerative diseases. This study builds upon a statistically accurate model of the human cerebral microvasculature based on ex-vivo morphological data. This model is adapted for “healthy” ageing using in-vivo measurements from mice at three distinct age groups—young, middle-aged, and old. From this new model, blood and molecular exchange parameters are calculated such as permeability and surface-area-to-volume ratio, and compared across the three age groups. The ability to alter the model vessel-by-vessel is used to create a continuous gradient of ageing. It was found that surface-area-to-volume ratio reduced in old age by 6% and permeability by 24% from middle-age to old age, and variability within the networks also increased with age. The ageing gradient indicated a threshold in the ageing process around 75 years old, after which small changes have an amplified effect on blood flow properties. This gradient enables comparison of studies measuring cerebral properties at discrete points in time. The response of middle aged and old aged capillary beds to micro-emboli showed a lower robustness of the old age capillary bed to vessel occlusion. As the brain ages, there is thus increased vulnerability of the microvasculature—with a “tipping point” beyond which further remodeling of the microvasculature has exaggerated effects on the brain. When developing in-silico models of the brain, age is a very important consideration to accurately assess risk factors for cognitive decline and isolate early biomarkers of microvascular health.
Alemtuzumab in a Large Real-Life Cohort: Interim Baseline Data of the TREAT-MS Study
Authors: Ziemssen Tjalf , Hoffmann Frank , Richter Stephan , Engelmann Ulrich , White Robin
Published: August 2021

The non-interventional long-Term study foR obsErvAtion of Treatment with alemtuzumab in active relapsing–remitting MS (TREAT-MS) study collects the so far largest real-life cohort regarding utilization, long-term effectiveness, and safety of alemtuzumab, a humanized monoclonal antibody directed against the cell surface glycoprotein CD52, in adult patients with active relapsing–remitting multiple sclerosis (RRMS). An interim analysis of baseline parameters at inclusion of a non-interventional real-world study about alemtuzumab in Germany including previous multiple sclerosis (MS) medication utilization, MS activity, severity, and duration, as well as comorbidities was performed. Of the 883 patients, 71.6% were women. Mean age was 35.7 ± 9.2 years, time since first MS symptoms (=disease duration) is 8.0 ± 6.8 years, and Expanded Disability Status Scale (EDSS) is 2.7 ± 1.8 points (range, 0.0–7.5 points). The number of relapses in the 12 and 24 months prior to inclusion were 1.6 ± 1.2 and 2.2 ± 1.8, respectively. Of the patients, 14.4% were treatment naive, while for the majority, a wide spectrum of MS disease-modifying treatments (DMTs) and treatment sequences were documented. Overall, interferon beta (IFN-beta) was reported most frequently (52.4%), followed by fingolimod (35.2%), natalizumab (34.9%), and glatiramer acetate (28.9%). Patients with longer disease duration and higher EDSS had a higher number of previous DMTs. Compared to the pivotal phase 2/3 studies, RRMS patients starting alemtuzumab treatment had a longer disease duration in real-world conditions. There was variety of different treatment sequences before the final switch to alemtuzumab. In the future, linking these treatment sequences or other baseline characteristics with effectiveness and safety outcomes might be useful to support treatment decisions. Registered at Paul-Ehrlich-Institut under NIS 281.
Hyperattenuated Lesions on Immediate Non-contrast CT After Endovascular Therapy Predict Intracranial Hemorrhage in Patients With Acute Ischemic Stroke: A Retrospective Propensity Matched Study
Authors: Han Nannan , Zhang Gejuan , Li Yige , Ma Haojun , Ge Hanming , Zhang Xiao , Zhao Yong , Li Shilin , Zhang Leshi , Gao Yanjun , Shi Wenzhen , Yan Peng , Li Wu , Chang Mingze , Tian Ye
Published: August 2021

Background and Purpose: This study aimed to analyze the association between hyperattenuated lesions (HALs) and postoperative intracranial hemorrhage (IH) and predict perioperative IH through quantitative analysis of HALs in acute ischemic stroke (AIS) with anterior large vessel occlusion (LVO) after endovascular therapy (ET).

Materials and Methods: This retrospective, propensity-matched study enrolled AIS who received ET from a single-center registry study between August 2017 and May 2020. The enrolled patients were divided into two groups: IH and non-IH, by follow-up postoperative CT. The occurrences of HALs on immediate CT after ET were also recorded. The association between IH and HALs after propensity score matching (PSM) was determined by binary logistic regression models. The receiver operating characteristic (ROC) curve was used to determine the predictive value of the highest CT Hounsfield units (HU) value on immediate CT.

Results: Initially, 1,418 patients who underwent digital subtraction angiography were reviewed and 114 AIS patients with immediate postoperative CT and follow-up CT after ET were enrolled. Forty-nine out of the 114 patients developed IH after therapy. After PSM analysis, patients with IH were more likely to have HALs on immediate CT (Odds Ratio, OR 11.9, P = 0.002, and 95% CI: 2.485–57.284). For 80 patients with HALs, ROC analysis of the highest CT value in the HALs territory showed that the cut-off value was 97 HU, the sensitivity was 70.21%, and the specificity was 81.82%.

Conclusions: Patients with HALs after ET are more likely to have perioperative IH. The highest CT value in the HALs area might be used to predict IH.
Advance Care Planning and Care Coordination for People With Parkinson's Disease and Their Family Caregivers—Study Protocol for a Multicentre, Randomized Controlled Trial
Authors: Meinders Marjan J. , Gentile Giovanni , Schrag Anette E. , Konitsiotis Spiros , Eggers Carsten , Taba Pille , Lorenzl Stefan , Odin Per , Rosqvist Kristina , Chaudhuri K. Ray , Antonini Angelo , Bloem Bastiaan R. , Groot Marieke M.
Published: August 2021

Background: Parkinson's disease (PD) is a progressive neurodegenerative disease with motor- and non-motor symptoms. When the disease progresses, symptom burden increases. Consequently, additional care demands develop, the complexity of treatment increases, and the patient's quality of life is progressively threatened. To address these challenges, there is growing awareness of the potential benefits of palliative care for people with PD. This includes communication about end-of-life issues, such as Advance Care Planning (ACP), which helps to elicit patient's needs and preferences on issues related to future treatment and care. In this study, we will assess the impact and feasibility of a nurse-led palliative care intervention for people with PD across diverse European care settings.

Methods: The intervention will be evaluated in a multicentre, open-label randomized controlled trial, with a parallel group design in seven European countries (Austria, Estonia, Germany, Greece, Italy, Sweden and United Kingdom). The “PD_Pal intervention” comprises (1) several consultations with a trained nurse who will perform ACP conversations and support care coordination and (2) use of a patient-directed “Parkinson Support Plan-workbook”. The primary endpoint is defined as the percentage of participants with documented ACP-decisions assessed at 6 months after baseline (t1). Secondary endpoints include patients' and family caregivers' quality of life, perceived care coordination, patients' symptom burden, and cost-effectiveness. In parallel, we will perform a process evaluation, to understand the feasibility of the intervention. Assessments are scheduled at baseline (t0), 6 months (t1), and 12 months (t2). Statistical analysis will be performed by means of Mantel–Haenszel methods and multilevel logistic regression models, correcting for multiple testing.

Discussion: This study will contribute to the current knowledge gap on the application of palliative care interventions for people with Parkinson's disease aimed at ameliorating quality of life and managing end-of-life perspectives. Studying the impact and feasibility of the intervention in seven European countries, each with their own cultural and organisational characteristics, will allow us to create a broad perspective on palliative care interventions for people with Parkinson's disease across settings.

Clinical Trial Registration:www.trialregister.nl, NL8180.
The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment: The Nor-COAST Study
Authors: Aam Stina , Gynnild Mari Nordbø , Munthe-Kaas Ragnhild , Saltvedt Ingvild , Lydersen Stian , Knapskog Anne-Brita , Ihle-Hansen Hege , Ellekjær Hanne , Eldholm Rannveig Sakshaug , Fure Brynjar
Published: August 2021

Introduction: Post-stroke cognitive impairment (PSCI) is common, but evidence on the impact of vascular risk factors is lacking. We explored the association between pre-stroke vascular risk factors and PSCI and studied the course of PSCI.

Materials and Methods: Vascular risk factors were collected at baseline in stroke survivors (n = 635). Cognitive assessments of attention, executive function, memory, language, and the Montreal Cognitive Assessment (MoCA) were performed at 3 and/or 18 months post-stroke. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). PSCI was measured with global z; MoCA z-score; and z-score of the four assessed cognitive domains. Mixed-effect linear regression was applied with global z, MoCA z-score, and z-scores of the cognitive domains as dependent variables. Independent variables were the vascular risk factors (hypertension, hypercholesterolemia, smoking, diabetes mellitus, atrial fibrillation, coronary heart disease, previous stroke), time, and the interaction between these. The analyses were adjusted for age, education, and sex. There were between 5 and 25% missing data for the variables for PSCI.

Results: Mean age was 71.6 years (SD 11.7); 42% were females; and the mean NIHSS score at admittance was 3.8 (SD 4.8). Regardless of vascular risk factors, global z, MoCA, and all the assessed cognitive domains were impaired at 3 and 18 months, with MoCA being the most severely impaired. Atrial fibrillation (AF) was associated with poorer language at 18 months and coronary heart disease (CHD) with poorer MoCA at 18 months (LR = 12.80, p = 0.002, and LR = 8.32, p = 0.004, respectively). Previous stroke was associated with poorer global z and attention at 3 and 18 months (LR = 15.46, p < 0.001, and LR = 16.20, p < 0.001). In patients without AF, attention improved from 3 to 18 months, and in patients without CHD, executive function improved from 3 to 18 months (LR = 10.42, p < 0.001, and LR = 9.33, p = 0.009, respectively).

Discussion: Our findings indicate that a focal stroke lesion might be related to pathophysiological processes leading to global cognitive impairment. The poorer prognosis of PSCI in patients with vascular risk factors emphasizes the need for further research on complex vascular risk factor interventions to prevent PSCI.
Serum Anti-oligodendrocyte Autoantibodies in Patients With Multiple Sclerosis Detected by a Tissue-Based Immunofluorescence Assay
Authors: Miyachi Yukino , Fujii Takayuki , Yamasaki Ryo , Tsuchimoto Daisuke , Iinuma Kyoko , Sakoda Ayako , Fukumoto Shoko , Matsushita Takuya , Masaki Katsuhisa , Isobe Noriko , Nakabeppu Yusaku , Kira Jun-ichi
Published: August 2021

Multiple sclerosis (MS), the most prevalent inflammatory disease of the central nervous system (CNS), is characterized by damaged to myelin sheaths and oligodendrocytes. Because MS patients have variable clinical courses and disease severities, it is important to identify biomarkers that predict disease activity and severity. In this study, we assessed the frequencies of serum autoantibodies against mature oligodendrocytes in MS patients using a tissue-based immunofluorescence assay (IFA) to determine whether anti-oligodendrocyte antibodies are associated with the clinical features of MS patients and whether they might be a biomarker to assess CNS tissue damage in MS patients. We assessed the binding of serum autoantibodies to mouse oligodendrocytes expressing Nogo-A, a reliable mature oligodendrocyte marker, by IFA with mouse brain and sera from 147 MS patients, comprising 103 relapsing–remitting MS (RRMS), 22 secondary progressive MS (SPMS), and 22 primary progressive MS (PPMS) patients, 38 neuromyelitis optica spectrum disorder (NMOSD) patients, 23 other inflammatory neurological disorder (OIND) patients, and 39 healthy controls (HCs). Western blotting (WB) was performed using extracted mouse cerebellum proteins and IgG from anti-oligodendrocyte antibody-positive MS patients. Tissue-based IFA showed that anti-oligodendrocyte antibodies were positive in 3/22 (13.6%) PPMS and 1/22 (4.5%) SPMS patients but not in RRMS, NMOSD, and OIND patients or HCs. WB demonstrated the target CNS proteins recognized by serum anti-oligodendrocyte antibodies were approximately 110 kDa and/or 150 kDa. Compared with anti-oligodendrocyte antibody-negative MS patients, MS patients with anti-oligodendrocyte antibodies were significantly older at the time of serum sampling, scored significantly higher on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and had a higher frequency of mental disturbance. Although the clinical significance of anti-oligodendrocyte antibodies is still unclear because of their low frequency, anti-oligodendrocyte autoantibodies are potential biomarkers for monitoring the disease pathology and progression in MS.