bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Diastereoselective Synthesis of Tetrahydroquinoline Derivatives via [4 + 2] Annulation of Ortho-Tosylaminophenyl-Substituted Para-Quinone Methides and Cyanoalkenes
Authors: Dong Taiwei , Wei Peifeng , Li Min , Gao Feng , Qin Yuan
Published: November 2021

As a privileged structural motif, tetrahydroquinoline skeletons widely exist in biologically active natural products and pharmaceuticals. In this protocol, a highly diastereoselective [4 + 2] annulation of ortho-tosylaminophenyl-substituted p-QMs and cyanoalkenes to construct tetrahydroquinoline derivatives has been successfully achieved. This strategy proceeds efficiently under mild condition, offering straightforward route to a variety of 4-aryl-substituted tetrahydroquinolines with high yields, excellent diastereoselectivities, broad functional group tolerance as well as gram-scale capacity. Moreover, a one-pot reaction sequence utilizing in situ generated p-QMs under the similar condition to build tetrahydroquinoline framework is smoothly conducted with good reaction performance as well as step and atom economy.
A Human Osteocyte Cell Line Model for Studying Staphylococcus aureus Persistence in Osteomyelitis
Authors: Gunn Nicholas J. , Zelmer Anja R. , Kidd Stephen P. , Solomon Lucian B. , Roscioli Eugene , Yang Dongqing , Atkins Gerald J.
Published: November 2021

Infectious osteomyelitis associated with periprosthetic joint infections is often recalcitrant to treatment and has a high rate of recurrence. In the case of Staphylococcus aureus, the most common pathogen in all forms of osteomyelitis, this may be attributed in part to residual intracellular infection of host cells, yet this is not generally considered in the treatment strategy. Osteocytes represent a unique cell type in this context due to their abundance, their formation of a syncytium throughout the bone that could facilitate bacterial spread and their relative inaccessibility to professional immune cells. As such, there is potential value in studying the host-pathogen interactions in the context of this cell type in a replicable and scalable in vitro model. Here, we examined the utility of the human osteosarcoma cell line SaOS2 differentiated to an osteocyte-like stage (SaOS2-OY) as an intracellular infection model for S. aureus. We demonstrate that S. aureus is capable of generating stable intracellular infections in SaOS2-OY cells but not in undifferentiated, osteoblast-like SaOS2 cells (SaOS2-OB). In SaOS2-OY cells, S. aureus transitioned towards a quasi-dormant small colony variant (SCV) growth phenotype over a 15-day post-infection period. The infected cells exhibited changes in the expression of key immunomodulatory mediators that are consistent with the infection response of primary osteocytes. Thus, SaOS2-OY is an appropriate cell line model that may be predictive of the interactions between S. aureus and human osteocytes, and this will be useful for studying mechanisms of persistence and for testing the efficacy of potential antimicrobial strategies.
Lesion-Specific Peri-Coronary Fat Attenuation Index Is Associated With Functional Myocardial Ischemia Defined by Abnormal Fractional Flow Reserve
Authors: Ma Shaowei , Chen Xujiao , Ma Yue , Liu Hui , Zhang Jiayin , Xu Lei , Wang Yining , Liu Ting , Wang Kunhua , Yang Jinzhu , Hou Yang
Published: November 2021

Background: The association between abnormal invasive fractional flow reserve (FFR) and the fat attenuation index (FAI) of lesion-specific peri-coronary adipose tissue (PCAT) is unclear.

Method: Data of patients who underwent coronary computed tomography angiography (CTA) and subsequent invasive coronary angiography (ICA) and FFR measurement within 1 week were retrospectively included. Lesion-specific FAI (FAIlesion), lesion-free FAI (FAInormal), epicardial adipose tissue (EAT) volume and attenuation was collected, along with stenosis severity and plaque characteristics. Lesions with FFR <0.8 were considered functionally significant. The association between FFR and each parameter was analyzed by logistic regression or receiver operating characteristic curve.

Result: A total of 227 patients from seven centers were included. EAT volume or attenuation, traditional risk factors, and FAInormal (with vs. without ischemia: −82 ± 11 HU vs. −81 ± 11 HU, p = 0.65) were not significantly different in patients with or without abnormal FFR. In contrast, lesions causing functional ischemia presented more severe stenosis, greater plaque volume, and higher FAIlesion (with vs. without ischemia: −71 ± 8 HU vs. −76 ± 9 HU, p < 0.01). Additionally, the CTA-assessed stenosis severity (OR 1.06, 95%CI 1.04–1.08, p < 0.01) and FAIlesion (OR 1.08, 95%CI 1.04–1.12, p < 0.01) were determined to be independent factors that could predict ischemia. The combination model of these two CTA parameters exhibited a diagnostic value similar to the invasive coronary angiography (ICA)-assessed stenosis severity (AUC: 0.820 vs. 0.839, p = 0.39).

Conclusion: It was FAIlesion, not general EAT parameters, that was independently associated with abnormal FFR and the diagnostic performance of CTA-assessed stenosis severity for functional ischemia was significantly improved in combination with FAIlesion.
Optimizing Cognitive Assessment Outcome Measures for Alzheimer's Disease by Matching Wordlist Memory Test Features to Scoring Methodology
Authors: Bock Jason R. , Russell Julie , Hara Junko , Fortier Dennis
Published: November 2021

Cognitive assessment with wordlist memory tests is a cost-effective and non-invasive method of identifying cognitive changes due to Alzheimer's disease and measuring clinical outcomes. However, with a rising need for more precise and granular measures of cognitive changes, especially in earlier or preclinical stages of Alzheimer's disease, traditional scoring methods have failed to provide adequate accuracy and information. Well-validated and widely adopted wordlist memory tests vary in many ways, including list length, number of learning trials, order of word presentation across trials, and inclusion of semantic categories, and these differences meaningfully impact cognition. While many simple scoring methods fail to account for the information that these features provide, extensive effort has been made to develop scoring methodologies, including the use of latent models that enable capture of this information for preclinical differentiation and prediction of cognitive changes. In this perspective article, we discuss prominent wordlist memory tests in use, their features, how different scoring methods fail or successfully capture the information these features provide, and recommendations for emerging cognitive models that optimally account for wordlist memory test features. Matching the use of such scoring methods to wordlist memory tests with appropriate features is key to obtaining precise measurement of subtle cognitive changes.
On the Origin of ULF Magnetic Waves Before the Taiwan Chi-Chi 1999 Earthquake
Authors: Anagnostopoulos Georgios
Published: November 2021

The ultra low frequency (ULF) electromagnetic (EM) wave activity usually recorded on Earth’s ground has been found to depend on various types of space weather. In addition ULF waves observed before an earthquake have been hypothesized to be a result of geotectonic processes. In this study we elaborate for the first time the origin of sub-ULF (<1 msec) magnetic field waves before an earthquake (Chi-Chi/Taiwan, 20.9.1999) by comparing simultaneously obtained measurements in the interplanetary space (ACE satellite) and on the Earth’s ground (Taiwan). The most striking result of our data analysis, during a period of 7 weeks, is that the detection of four groups of sub-ULF waves in Taiwan coincide in time with the quasi-periodic detection of two solar wind streams by the satellite ACE with approximately the solar rotation period (∼28 days). The high speed solar wind streams (HSSs) in the interplanetary space were accompanied by sub-ULF Alfvén wave activity, quasi-periodic southward IMF and solar wind density perturbations, which are known as triggering agents of magnetic storm activity. The four HSSs were followed by long lasting decreases in the magnetic field in Taiwan. The whole data set examined in this study strongly suggest that the subULF magnetic field waves observed in Taiwan before the Chi-Chi 1999 earthquake is a normal consequence of the incident of HSSs to the magnetosphere. We provide some observational evidence that the sub-ULF electromagnetic radiation on the Earth was most probably a partner to (not a result of) geotectonic processes preparing the Taiwan 1999 earthquake.
Impact of Professional and Scientific Societies’ Student Chapters on the Development of Underrepresented Undergraduate Students
Authors: Barnes Lily , Grajales Joshua , Velasquez Baez Jocelyn , Hidalgo Daniel , Padilla-Benavides Teresita
Published: November 2021

Undergraduate students from historically underrepresented groups (URG) in institutions of higher education with a focus on science, technology, engineering, and math (STEM) careers often lack the support, resources, and community necessary to succeed in their desired fields. Through mentoring, webinars, seminars, and various research presentation opportunities, national societies and “locally-based” institutional student chapters provide atmospheres in which URG undergraduates can develop the skills required for academic and professional careers in STEM. In addition, national societies and student chapters contribute to outreach activities aimed towards the public in order to foster interest in STEM, as well as to primary and secondary school students to help them develop competency in skills and areas that lead to successful STEM careers. While many of these societies have operated for decades, the onset of the COVID-19 pandemic proved to be an unexpected roadblock, creating difficulties in terms of maintaining community dynamics and overcoming limits on in-person meetings. Though the conditions were challenging, they allowed for new perspectives on problem-solving in the face of adversity. The pandemic promoted the development of creative ways by which institutions and national societies could continue to educate students virtually. In this review, we discuss the role of national societies and student chapters in providing URG students with resources and skills to succeed in STEM fields while incorporating them into a community of like-minded peers with similar experiences.
Effect of Smoking on Coronary Artery Plaques in Type 2 Diabetes Mellitus: Evaluation With Coronary Computed Tomography Angiography
Authors: Jiang Yu , Pang Tong , Shi Rui , Qian Wen-lei , Yan Wei-feng , Li Yuan , Yang Zhi-gang
Published: November 2021

Background

The effect of smoking on coronary artery plaques examined by coronary computed tomography angiography (CCTA) in type 2 diabetes mellitus (DM) patients is not fully understood. This study explored the effect of smoking on coronary artery plaques by comparing the characteristics of plaques between diabetes patients with and without a smoking history and among those with different smoking durations.

Materials and Methods

In total, 1058 DM patients found to have coronary plaques on CCTA were categorized into the smoker (n=448) and nonsmoker groups (n=610). Smokers were stratified by smoking duration [≤20 years (n=115), 20~40 years (n=233) and >40 years (n=100)]. The plaque types, luminal stenosis [obstructive (<50%) or nonobstructive (≥50%) stenosis], segment involvement score (SIS), and segment stenosis score (SSS) of the CCTA data were compared among groups.

Results

Compared to nonsmokers, smokers demonstrated increased odds ratios (ORs) of any noncalcified plaques (OR=1.423; P=0.014), obstructive plaques (OR=1.884; P<0.001), multivessel disease (OR=1.491; P=0.020), SIS≥4 (OR=1.662; P<0.001), and SSS≥7 (OR=1.562; P=0.001). Compared to diabetes patients with a smoking duration ≤20 years, those with a smoking duration of 20~40 years and >40 years had higher OR of any mixed plaques (OR=2.623 and 3.052, respectively; Ps<0.001), obstructive plaques (OR=2.004 and 2.098; P=0.003 and 0.008, respectively), multivessel disease (OR=3.171 and 3.784; P<0.001 and P=0.001, respectively), and SSS≥7 (OR=1.605 and 1.950; P=0.044 and 0.020, respectively). Diabetes with a smoking duration >40 years had a higher OR of SIS≥4 (OR=1.916, P=0.034).

Conclusion

Smoking is independently associated with the presence of noncalcified, obstructive, and more extensive coronary artery plaques in diabetes patients, and a longer smoking duration is significantly associated with a higher risk of mixed, obstructive, and more extensive plaques.
Extranodal Extension Is an Independent Prognostic Factor in Papillary Thyroid Cancer: A Propensity Score Matching Analysis
Authors: Zhou Tian-han , Lin Bei , Wu Fan , Lu Kai-ning , Mao Lin-lin , Zhao Ling-qian , Jiang Ke-cheng , Zhang Yu , Zheng Wei-Jun , Luo Ding-cun
Published: November 2021

Purpose

To investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC).

Methods

Seven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan–Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC.

Results

Thirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS.

Conclusions

Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.
Soil Physico-Chemical Properties Change Across an Urbanity Gradient in Berlin
Authors: Whitehead James , Hempel Stefan , Hiller Anne , von der Lippe Moritz , Rillig Matthias C.
Published: November 2021

In this study the impacts of urbanity on physical soil properties were explored by measuring water stable aggregates, combined particle size, infiltration rate and hydrophobicity across an urban gradient. The use of a gradient allowed for the relative importance of different environmental drivers to be assessed. We sampled 54 sites across Berlin and used a pre-existing database of environmental variables to extract three main axes of variation relating to urbanity, soil nutrient content, and heavy metal content. These axes, along with site age, were used to explore the drivers of changes in physical properties across an urban landscape. The percentage of water stable aggregates was found to decrease with urbanity, whilst infiltration rate was found to increase. Hydrophobicity did not appear to be influenced by urbanity but interacted with both infiltration rate and water stable aggregates. Combined particle sizes in the soil were found to increase with urbanity. Our findings provide evidence for urbanity being an important driver of variation in physico-chemical soil properties, which has implications for the provision of ecosystem services by these soils.
Sex Role Reversal and High Frequency of Social Polyandry in the Pheasant-Tailed Jacana (Hydrophasianus chirurgus)
Authors: Fresneau Nolwenn , Lee Ya-Fu , Lee Wen-Chen , Kosztolányi András , Székely Tamás , Liker András
Published: November 2021

In a few species, males invest more than females in parental care while the females invest in mating competition and producing multiple broods for several mates. Species in the family Jacanidae are commonly used for studying this type of breeding system (called sex-role reversal), and previous studies found discrepancies and variation between species in the expected characteristics of reversed sex roles. Yet, a better understanding of sex role differences in breeding behavior in such species is crucial for disentangling possible evolutionary mechanisms leading to this peculiar breeding system. Sex-role reversal in the pheasant-tailed jacana Hydrophasianus chirurgus has been documented long time ago. Since the very early observation of this species, however, there was no attempt to provide a comprehensive and quantitative description of their breeding. This study aims to fill these knowledge gaps by investigating the sex role differences in the breeding behavior of pheasant-tailed jacanas, by observing and monitoring a breeding population in Taiwan. We focused on three main characteristics of sex-role reversal: (1) competition between females for access to males, such as agonistic and courtship behaviors, (2) polyandrous mating, and (3) male-only care. As expected, we found that females provide most of the territory defense toward conspecifics. Males also participated in agonistic behaviors, although less frequently than females. Furthermore, contrary to what was expected, we found that males spent more time than females on courtship behavior. Polyandrous females performed mating and laying sequentially with different mates but maintained the pair bonds simultaneously with multiple males. For the first time for the species, we could estimate that the average number of mates per female (i.e., degree of polyandry) was 2.4 and that at least 81.8% of the females in the population were polyandrous. Finally, our observations corroborated that brood care is predominantly provided by males, nevertheless females were also participating to some degree in brood attendance but never in direct care (i.e., brooding). This study highlights that some aspects of polyandrous breeding might deviate from stereotyped view on sex-role reversal, and stress the importance of further within species and comparative studies in order to fully understand the mechanisms leading to sex-role reversal.
A Decade Long Slowdown in Road Crashes and Inherent Consequences Predicted for South Africa
Authors: Machetele Dimakatso , Yessoufou Kowiyou
Published: November 2021

Globally, there are 1.35 million road fatalities every year, which are estimated to cost governments approximately US$ 518 billion, making road fatalities the eighth leading cause of death across all age groups and the leading cause of death of children and young adults. In South Africa, despite tremendous governmental efforts to curb the soaring trajectory of road crashes, the annual number of road fatalities has increased by 26% in recent years. By fitting a structural equation model (SEM) and a GARCH Model (Generalized Auto-Regressive Conditional Heteroskedasticity) to analyze and predict future trend of road crashes (number of road crashes, number of casualties, number of fatal crashes and number of persons killed) in South Africa, we propose and test a complex metamodel that integrates multiple causality relationships. We show an increasing trend of road crashes over time, a trend that is predictable by number of vehicles in the country, the population of the country and the total distance travelled by vehicles. We further show that death rate linked to road crashes is on average 23.14 deaths per 100,000 persons. Finally, in the next decade, the number of road crashes is predicted to be roughly constant at 617,253 crashes but can reach 1,896,667 crashes in the worst-case scenario. The number of casualties was also predicted to be roughly constant at 93,531 over time, although this number may reach 661,531 in the worst-case scenario. However, although the number of fatal crashes may decrease in the next decade, it is forecasted to reach 11,241 within the next 10 years with the worse scenario estimated at 19,034 within the same period. At the same time, the number of persons killed in fatal crashes is also predicted to be roughly constant at 14,739 but may also reach 172,784 in the worse scenario. Overall, the present study reveals perhaps the positive effects of government initiatives to curb road crashes and their consequences; we call for more stronger actions for a drastic reduction in road accident events in South Africa.
Composition and Dynamics of H1N1 and H7N9 Influenza A Virus Quasispecies in a Co-infected Patient Analyzed by Single Molecule Sequencing Technology
Authors: Lin Peng , Jin Tao , Yu Xinfen , Liang Lifeng , Liu Guang , Jovic Dragomirka , Sun Zhou , Yu Zhe , Pan Jingcao , Fan Guangyi
Published: November 2021

A human co-infected with H1N1 and H7N9 subtypes influenza A virus (IAV) causes a complex infectious disease. The identification of molecular-level variations in composition and dynamics of IAV quasispecies will help to understand the pathogenesis and provide guidance for precision medicine treatment. In this study, using single-molecule real-time sequencing (SMRT) technology, we successfully acquired full-length IAV genomic sequences and quantified their genotypes abundance in serial samples from an 81-year-old male co-infected with H1N1 and H7N9 subtypes IAV. A total of 26 high diversity nucleotide loci was detected, in which the A-G base transversion was the most abundant substitution type (67 and 64%, in H1N1 and H7N9, respectively). Seven significant amino acid variations were detected, such as NA:H275Y and HA: R222K in H1N1 as well as PB2:E627K and NA: K432E in H7N9, which are related to viral drug-resistance or mammalian adaptation. Furtherly, we retrieved 25 H1N1 and 22 H7N9 genomic segment haplotypes from the eight samples based on combining high-diversity nucleotide loci, which provided a more concise overview of viral quasispecies composition and dynamics. Our approach promotes the popularization of viral quasispecies analysis in a complex infectious disease, which will boost the understanding of viral infections, pathogenesis, evolution, and precision medicine.
Inflammatory Cytokines Shape an Altered Immune Response During Myeloid Malignancies
Authors: Camacho Virginia , Kuznetsova Valeriya , Welner Robert S.
Published: November 2021

The immune microenvironment is a critical driver and regulator of leukemic progression and hematological disease. Recent investigations have demonstrated that multiple immune components play a central role in regulating hematopoiesis, and dysfunction at the immune cell level significantly contributes to neoplastic disease. Immune cells are acutely sensitive to remodeling by leukemic inflammatory cytokine exposure. Importantly, immune cells are the principal cytokine producers in the hematopoietic system, representing an untapped frontier for clinical interventions. Due to a proinflammatory cytokine environment, dysregulation of immune cell states is a hallmark of hematological disease and neoplasia. Malignant immune adaptations have profound effects on leukemic blast proliferation, disease propagation, and drug-resistance. Conversely, targeting the immune landscape to restore hematopoietic function and limit leukemic expansion may have significant therapeutic value. Despite the fundamental role of the immune microenvironment during the initiation, progression, and treatment response of hematological disease, a detailed examination of how leukemic cytokines alter immune cells to permit, promote, or inhibit leukemia growth is lacking. Here we outline an immune-based model of leukemic transformation and highlight how the profound effect of immune alterations on the trajectory of malignancy. The focus of this review is to summarize current knowledge about the impacts of pro- and anti-inflammatory cytokines on immune cells subsets, their modes of action, and immunotherapeutic approaches with the potential to improve clinical outcomes for patients suffering from hematological myeloid malignancies.
Designing Coastal Adaptation Strategies to Tackle Sea Level Rise
Authors: Bongarts Lebbe Théophile , Rey-Valette Hélène , Chaumillon Éric , Camus Guigone , Almar Rafael , Cazenave Anny , Claudet Joachim , Rocle Nicolas , Meur-Férec Catherine , Viard Frédérique , Mercier Denis , Dupuy Christine , Ménard Frédéric , Rossel Bernardo Aliaga , Mullineaux Lauren , Sicre Marie-Alexandrine , Zivian Anna , Gaill Françoise , Euzen Agathe
Published: November 2021

Faced with sea level rise and the intensification of extreme events, human populations living on the coasts are developing responses to address local situations. A synthesis of the literature on responses to coastal adaptation allows us to highlight different adaptation strategies. Here, we analyze these strategies according to the complexity of their implementation, both institutionally and technically. First, we distinguish two opposing paradigms – fighting against rising sea levels or adapting to new climatic conditions; and second, we observe the level of integrated management of the strategies. This typology allows a distinction between four archetypes with the most commonly associated governance modalities for each. We then underline the need for hybrid approaches and adaptation trajectories over time to take into account local socio-cultural, geographical, and climatic conditions as well as to integrate stakeholders in the design and implementation of responses. We show that dynamic and participatory policies can foster collective learning processes and enable the evolution of social values and behaviors. Finally, adaptation policies rely on knowledge and participatory engagement, multi-scalar governance, policy monitoring, and territorial solidarity. These conditions are especially relevant for densely populated areas that will be confronted with sea level rise, thus for coastal cities in particular.
Different Early Responses of Laminariales to an Endophytic Infection Provide Insights About Kelp Host Specificity
Authors: Xing Qikun , Bernard Miriam , Rousvoal Sylvie , Corre Erwan , Markov Gabriel V. , Peters Akira F. , Leblanc Catherine
Published: November 2021

The filamentous algal endophyte Laminarionema elsbetiae is highly prevalent in European populations of the brown alga Saccharina latissima, but has also been found occasionally in the other kelp species Laminaria digitata. The presence of L. elsbetiae coincides with morphological changes in the hosts such as twisted stipes and deformed blades, however, little is known about the molecular bases of these algal host-endophyte interactions. Using a co-cultivation experiment, we showed that physiological and gene regulation responses, and later endophyte prevalences are different between the main and the occasional host. The contact with the endophyte L. elsbetiae induced a stronger and faster transcriptomic regulation in the occasional host L. digitata after 24 h, from which growth rate was later affected. During the first two days of co-cultivation, only 21 differentially expressed genes (DEGs) were common in both kelps, indicating a crucial difference between the molecular responses of the two hosts. By functional annotation, we identified DEGs related to host-endophyte recognition, defense response and cell wall modification. Our results suggest that expression pattern differences between the two kelps related to the recognition of the endophyte and later defense reactions could explain the variability of observed physiological responses and host-endophyte specificity in kelp natural populations.
An Efficient Track-Scale Model for Laser Powder Bed Fusion Additive Manufacturing: Part 2—Mechanical Model
Authors: Tangestani Reza , Sabiston Trevor , Chakraborty Apratim , Yuan Lang , Krutz Nicholas , Martin Étienne
Published: November 2021

This is the second of two manuscripts that presents a computationally efficient full-field deterministic model for laser powder bed fusion (LPBF). The Hybrid Line (HL) thermal model developed in part I is extended to predict the in-process residual stresses due to laser processing of a nickel-based superalloy, RENÉ 65. The computational efficiency and accuracy of the HL thermo-mechanical model is first compared to the exponential decaying heat input model on a single-track simulation. LPBF thin-wall builds with three different laser powers and four printing patterns are evaluated in this study and compared with part-scale simulations. The simulations show good agreements with the experimental X-Ray diffraction measured residual stresses. Compared to the laser power, the scanning pattern is demonstrated to have significant effects on residual stresses. Laser scan patterns utilizing short laser paths generate lower tensile stress along the longitudinal direction of the part and higher compressive stress along the build direction.
Research on Microstructure, Mechanical Properties and Electromagnetic Shielding Properties of Mg-6Zn-3Sn-0.5Cu Alloy
Authors: Liu Yan Hui , Ma Ming Long , Li Xing Gang , Li Yong Jun , Shi Guo Liang , Yuan Jia Wei , Zhang Kui
Published: November 2021

In this paper, the microstructure, electromagnetic shielding properties and mechanical properties of Mg-6Zn-3Sn-0.5Cu alloys are studied. As indicated from the results, the phases in the as-cast alloy comprise α-Mg, MgZnCu, Mg2Sn and Mg2Zn3 phases. After homogenization, Mg2Sn and Mg2Zn3 phases are decomposed, but the MgZnCu phase remains. During extrusion, complete dynamic recrystallization (DRX) occurs, and the spherical Mg2Sn phase precipitates dynamically. Due to considerable rod-like β′1 phases precipitate by complying with the [0001] Mg direction, the mechanical properties of aged alloys are remarkably enhanced. The peak-aged alloy achieves the tensile strength of 366 MPa, the yield strength of 358 MPa and the elongation of 7%. With the increase in the size of the β′1 phase, the mechanical properties of the over-aged alloy are reduced. Since the phases precipitate, the electrical conductivity of the alloy is enhanced, and the internal reflective interface increases, so the aged alloys exhibit improved electromagnetic shielding performance. The electromagnetic shielding efficiency of the peak-aged alloy exceeds 105 dB in the range of 30–1500 MHz, showing the best match between mechanical and electromagnetic shielding properties.
Development and Validation of a Simple-to-Use Nomogram for Predicting In-Hospital Mortality in Patients With Acute Heart Failure Undergoing Continuous Renal Replacement Therapy
Authors: Gao Luyao , Bian Yuan , Cao Shengchuan , Sang Wentao , Zhang Qun , Yuan Qiuhuan , Xu Feng , Chen Yuguo
Published: November 2021

Background: Patients with acute heart failure (AHF) who require continuous renal replacement therapy (CRRT) have a high risk of in-hospital mortality. It is clinically important to screen high-risk patients using a model or scoring system. This study aimed to develop and validate a simple-to-use nomogram consisting of independent prognostic variables for the prediction of in-hospital mortality in patients with AHF undergoing CRRT.

Methods: We collected clinical data for 121 patients with a diagnosis of AHF who underwent CRRT in an AHF unit between September 2011 and August 2020 and from 105 patients in the medical information mart for intensive care III (MIMIC-III) database. The nomogram model was created using a visual processing logistic regression model and verified using the standard method.

Results: Patient age, days after admission, lactic acid level, blood glucose concentration, and diastolic blood pressure were the significant prognostic factors in the logistic regression analyses and were included in our model (named D-GLAD) as predictors. The resulting model containing the above-mentioned five factors had good discrimination ability in both the training group (C-index, 0.829) and the validation group (C-index, 0.740). The calibration and clinical effectiveness showed the nomogram to be accurate for the prediction of in-hospital mortality in both the training and validation cohort when compared with other models. The in-hospital mortality rates in the low-risk, moderate-risk, and high-risk groups were 14.46, 40.74, and 71.91%, respectively.

Conclusion: The nomogram allowed the optimal prediction of in-hospital mortality in adults with AHF undergoing CRRT. Using this simple-to-use model, the in-hospital mortality risk can be determined for an individual patient and could be useful for the early identification of high-risk patients. An online version of the D-GLAD model can be accessed at https://ahfcrrt-d-glad.shinyapps.io/DynNomapp/.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT0751838.
A Clinically-Compatible Workflow for Computer-Aided Assessment of Brain Disease Activity in Multiple Sclerosis Patients
Authors: Combès Benoit , Kerbrat Anne , Pasquier Guillaume , Commowick Olivier , Le Bon Brandon , Galassi Francesca , L'Hostis Philippe , El Graoui Nora , Chouteau Raphael , Cordonnier Emmanuel , Edan Gilles , Ferré Jean-Christophe
Published: November 2021

Over the last 10 years, the number of approved disease modifying drugs acting on the focal inflammatory process in Multiple Sclerosis (MS) has increased from 3 to 10. This wide choice offers the opportunity of a personalized medicine with the objective of no clinical and radiological activity for each patient. This new paradigm requires the optimization of the detection of new FLAIR lesions on longitudinal MRI. In this paper, we describe a complete workflow—that we developed, implemented, deployed, and evaluated—to facilitate the monitoring of new FLAIR lesions on longitudinal MRI of MS patients. This workflow has been designed to be usable by both hospital and private neurologists and radiologists in France. It consists of three main components: (i) a software component that allows for automated and secured anonymization and transfer of MRI data from the clinical Picture Archive and Communication System (PACS) to a processing server (and vice-versa); (ii) a fully automated segmentation core that enables detection of focal longitudinal changes in patients from T1-weighted, T2-weighted and FLAIR brain MRI scans, and (iii) a dedicated web viewer that provides an intuitive visualization of new lesions to radiologists and neurologists. We first present these different components. Then, we evaluate the workflow on 54 pairs of longitudinal MRI scans that were analyzed by 3 experts (1 neuroradiologist, 1 radiologist, and 1 neurologist) with and without the proposed workflow. We show that our workflow provided a valuable aid to clinicians in detecting new MS lesions both in terms of accuracy (mean number of detected lesions per patient and per expert 1.8 without the workflow vs. 2.3 with the workflow, p = 5.10−4) and of time dedicated by the experts (mean time difference 2′45″, p = 10−4). This increase in the number of detected lesions has implications in the classification of MS patients as stable or active, even for the most experienced neuroradiologist (mean sensitivity was 0.74 without the workflow and 0.90 with the workflow, p-value for no difference = 0.003). It therefore has potential consequences on the therapeutic management of MS patients.
Novel Targets in a High-Altitude Pulmonary Hypertension Rat Model Based on RNA-seq and Proteomics
Authors: Xu Xiang , Li Hanlu , Wei Qingxia , Li Xin , Shen Yanying , Guo Ge , Chen Yibing , He Kunlun , Liu Chunlei
Published: November 2021

High-altitude pulmonary hypertension (HAPH) is a complication arising from an inability to acclimatize to high altitude and is associated with high morbidity and mortality. We aimed to analyze the effects of macitentan, selexipag, riociguat, and reoxygenation on HAPH, and to screen possible targets of these treatments for future drug screening. Rats were subjected to hypobaric hypoxia for 35 days to induce HAPH, and treated with vehicle or selexipag, macitentan, riociguat, or with reoxygenation, from days 21 to 35. Selexipag, macitentan, and reoxygenation prevented an increase in mean pulmonary artery pressure and hypoxia-induced right ventricular hypertrophy, compared to the vehicle. Riociguat had little effect. RNA-seq and proteomics revealed strong correlations between responses to the three drugs, which had almost identical effects. GO-enrichment revealed that the differentially expressed genes included those involved in metabolic regulation, transcription, and translation. Various molecular pathways were annotated. Selexipag, macitentan, and reoxygenation ameliorated HAPH. Serpina1, Cryz, and Cmc1 were identified, via multi-omics screening, as key genes involved in HAPH. These findings provide new insights into the targeted drug mechanisms in HAPH.
Characterization of Co-infection With Fowl Adenovirus Serotype 4 and 8a
Authors: Liu Jingyi , Shi Xinjin , Lv Lu , Wang Kai , Yang Zhiwei , Li Yunzhang , Chen Hongjun
Published: November 2021

Fowl adenoviruses (FAdVs), which are distributed worldwide, have caused considerable economic losses to poultry farms. Co-infection with FAdVs and other avian pathogens has been reported previously. However, the pathogenicity of different serotypes of FAdVs causing co-infection remains unclear. Herein, strain HN from FAdV species C serotype 4 (FAdV-4) and strain AH720 from species E serotype 8a (FAdV-8a) were used to assess the pathogenicity of their co-infection in specific-pathogen-free (SPF) chickens. Compared with chickens infected with FAdV-4 alone, those co-infected with FAdV-4 and FAdV-8a showed similar clinical symptoms, mortality rates and degree of tissue lesions, and notably decreased viral loads of HN. Conversely, the viral loads of AH720 increased markedly in the co-infection group compared with that in chickens infected with AH720 strain alone. Increased viral loads of AH720 in the liver were suspected to contribute to the pathogenicity of chickens co-infected with the HN and AH720 strains. This was further investigated by histopathology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining analyses. Collectively, these data indicated that co-infection with FAdV-4 and FAdV-8a suppresses the replication and proliferation of FAdV-4 but enhances the replication and proliferation of FAdV-8a in chicken liver. This study will provide valuable information for the further investigation of the interactions between FAdV-4 and FAdV-8a during co-infection.
Cardioprotective Properties of Ginkgo Biloba Extract 80 via the Activation of AKT/GSK3β/β-Catenin Signaling Pathway
Authors: Zheng XiangWei , Gao Qi , Liang Shuang , Zhu GuoQin , Wang DanDan , Feng Yi
Published: November 2021

Elderly people are more likely to experience myocardial infarction (MI) than young people, with worse post-MI mortality and prognosis. Ginkgo biloba extract 50 (GBE50) is an oral GBE product that matches the German product, EGb761, which has been used to treat acute myocardial infarction (AMI). The extraction purity of GBE50 was improved to form a new formulation, Ginkgo biloba extract 80 (GBE80). This study investigates the effect of GBE80 on aged acute myocardial infarction rats. GBE80 injection is a novel formulation that was prepared by mixing Ginkgo flavonoids and lactones in a 4:1 weight ratio, with a Ginkgo content of more than 80%. Cell Counting Kit-8 was used to determine the biological safety and protective effect of GBE80 on cardiomyocytes against oxidative damage. An aged AMI rat model was developed and used to determine the myocardial infarction weight ratio using triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was applied to detect cell apoptosis in myocardial tissue. Western blotting and immunohistochemistry were used to measure the protein levels of members of the AKT/GSK3β/β-catenin pathway in vitro and in vivo, respectively. We found that GBE80 in vitro suppressed H2O2-induced cytotoxicity by promoting AKT/GSK3β/β-catenin signaling, while it did not show cytotoxicity to normal cardiomyocytes in the 0–500 μg/ml dose range. After 7 days of administration to aged AMI rats, GBE80 markedly reduced the weight ratio of the infarction and inhibited cell apoptosis in myocardial tissue. Furthermore, the AKT/GSK3β/β-catenin signaling pathway was activated by GBE80. These results suggest that GBE80 injection effectively inhibited AMI-induced myocardial damage and in vitro H2O2-induced cardiomyocyte cytotoxicity by activating the AKT/GSK3β/β-catenin signaling pathway.
Challenges to the Vestibular System in Space: How the Brain Responds and Adapts to Microgravity
Authors: Carriot Jérome , Mackrous Isabelle , Cullen Kathleen E.
Published: November 2021

In the next century, flying civilians to space or humans to Mars will no longer be a subject of science fiction. The altered gravitational environment experienced during space flight, as well as that experienced following landing, results in impaired perceptual and motor performance—particularly in the first days of the new environmental challenge. Notably, the absence of gravity unloads the vestibular otolith organs such that they are no longer stimulated as they would be on earth. Understanding how the brain responds initially and then adapts to altered sensory input has important implications for understanding the inherent abilities as well as limitations of human performance. Space-based experiments have shown that altered gravity causes structural and functional changes at multiple stages of vestibular processing, spanning from the hair cells of its sensory organs to the Purkinje cells of the vestibular cerebellum. Furthermore, ground-based experiments have established the adaptive capacity of vestibular pathways and neural mechanism that likely underlie this adaptation. We review these studies and suggest that the brain likely uses two key strategies to adapt to changes in gravity: (i) the updating of a cerebellum-based internal model of the sensory consequences of gravity; and (ii) the re-weighting of extra-vestibular information as the vestibular system becomes less (i.e., entering microgravity) and then again more reliable (i.e., return to earth).
Restricted Kinematics in Children With Autism in the Execution of Complex Oscillatory Arm Movements
Authors: Zhao Zhong , Zhang Xiaobin , Tang Haiming , Hu Xinyao , Qu Xingda , Lu Jianping , Peng Qiongling
Published: November 2021

Restricted and repetitive behavior is a core symptom of autism spectrum disorder (ASD) characterized by features of restrictedness, repetition, rigidity, and invariance. Few studies have investigated how restrictedness is manifested in motor behavior. This study aimed to address this question by instructing participants to perform the utmost complex movement. Twenty children with ASD and 23 children with typical development (TD) performed one-dimensional, left-right arm oscillations by demonstrating varying amplitudes and frequencies. The entropy of amplitude and velocity was calculated as an index of kinematic complexity. Results showed that the velocity entropy, but not the amplitude entropy, was significantly lower in ASD than in TD (p < 0.01), suggesting restricted kinematics. Further analysis demonstrated that a significantly higher proportion of the velocity values was allocated at a low-speed level in the children with ASD (p < 0.01). A qualitative comparison of the complex movement with movement at preferred frequency suggested that the children with ASD might be less likely to shift away from the preferred movement. However, our study can be improved in terms of recruiting a larger sample of participants, measuring the level of motivation, and collecting both complex and preferred movements of the same participant.
A Review of the Potential of Virtual Walking Techniques for Gait Rehabilitation
Authors: Janeh Omar , Steinicke Frank
Published: November 2021

Virtual reality (VR) technology has emerged as a promising tool for studying and rehabilitating gait disturbances in different cohorts of patients (such as Parkinson's disease, post-stroke, or other neurological disorders) as it allows patients to be engaged in an immersive and artificial environment, which can be designed to address the particular needs of each individual. This review demonstrates the state of the art in applications of virtual walking techniques and related technologies for gait therapy and rehabilitation of people with movement disorders makes recommendations for future research and discusses the use of VR in the clinic. However, the potential for using these techniques in gait rehabilitation is to provide a more personalized approach by simulate the experience of natural walking, while patients with neurological disorders are maintained localized in the real world. The goal of our work is to investigate how the human nervous system controls movement in health and neurodegenerative disease.
Numerosity Perception in Peripheral Vision
Authors: Li Min Susan , Abbatecola Clement , Petro Lucy S. , Muckli Lars
Published: November 2021

Peripheral vision has different functional priorities for mammals than foveal vision. One of its roles is to monitor the environment while central vision is focused on the current task. Becoming distracted too easily would be counterproductive in this perspective, so the brain should react to behaviourally relevant changes. Gist processing is good for this purpose, and it is therefore not surprising that evidence from both functional brain imaging and behavioural research suggests a tendency to generalize and blend information in the periphery. This may be caused by the balance of perceptual influence in the periphery between bottom-up (i.e., sensory information) and top-down (i.e., prior or contextual information) processing channels. Here, we investigated this interaction behaviourally using a peripheral numerosity discrimination task with top-down and bottom-up manipulations. Participants compared numerosity between the left and right peripheries of a screen. Each periphery was divided into a centre and a surrounding area, only one of which was a task relevant target region. Our top-down task modulation was the instruction which area to attend – centre or surround. We varied the signal strength by altering the stimuli durations i.e., the amount of information presented/processed (as a combined bottom-up and recurrent top-down feedback factor). We found that numerosity perceived in target regions was affected by contextual information in neighbouring (but irrelevant) areas. This effect appeared as soon as stimulus duration allowed the task to be reliably performed and persisted even at the longest duration (1 s). We compared the pattern of results with an ideal-observer model and found a qualitative difference in the way centre and surround areas interacted perceptually in the periphery. When participants reported on the central area, the irrelevant surround would affect the response as a weighted combination – consistent with the idea of a receptive field focused in the target area to which irrelevant surround stimulation leaks in. When participants report on surround, we can best describe the response with a model in which occasionally the attention switches from task relevant surround to task irrelevant centre – consistent with a selection model of two competing streams of information. Overall our results show that the influence of spatial context in the periphery is mandatory but task dependent.