bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Immune Cells in the Tumor Microenvironment of HCC: New Opportunities and Challenges
Authors: Hao Xiaopei , Sun Guangshun , Zhang Yao , Kong Xiangyi , Rong Dawei , Song Jinhua , Tang Weiwei , Wang Xuehao
Published: November 2021

Immune associated cells in the microenvironment have a significant impact on the development and progression of hepatocellular carcinoma (HCC) and have received more and more attention. Different types of immune-associated cells play different roles, including promoting/inhibiting HCC and several different types that are controversial. It is well known that immune escape of HCC has become a difficult problem in tumor therapy. Therefore, in recent years, a large number of studies have focused on the immune microenvironment of HCC, explored many mechanisms worth identifying tumor immunosuppression, and developed a variety of immunotherapy methods as targets, laying the foundation for the final victory in the fight against HCC. This paper reviews recent studies on the immune microenvironment of HCC that are more reliable and important, and provides a more comprehensive view of the investigation of the immune microenvironment of HCC and the development of more immunotherapeutic approaches based on the relevant summaries of different immune cells.
Perspectives on Pyrochlores, Defect Fluorites, and Related Compounds: Building Blocks for Chemical Diversity and Functionality
Authors: Lumpkin Gregory R. , Aughterson Robert D.
Published: November 2021

In this article we provide some perspectives on a range of pyrochlore and defect fluorite type compounds with nominal A2B2O7, A2BO5, ABC2O7, and other stoichiometries. Typically, the phase transformations and stability fields in these systems are mapped as a function of the ionic radii of the A and B-site cations, e.g., the A/B cation radius ratio (rA/rB). This provides a useful guide to compatible structures and compositions for the development of advanced materials. Pyrochlore commonly transforms to a defect fluorite structure at high temperature in many systems; however, it is not uncommon to observe defect fluorite as the initial metastable phase at low temperature. The patterns of order-disorder observed in these materials are primarily due to the energetics of layer stacking, the defect formation and migration energies of cations and anions, or modulations of the parent cubic structure in 3 + n dimensional space. The first lead to predominantly non-cubic derivatives of the parent defect fluorite structure (e.g., zirconolite polytypes), the second control the order-disorder processes, and the latter lead to a variety of subtle additional scattering features within the cubic parent structure. Although the energetics of cation disorder and anion-vacancy disorder have become more accessible via atomistic approaches (e.g., MD and DFT), we continue to find interesting physical-chemical problems in these materials. For example, although there are significant differences in composition (Tb/Zr ratio and O content) between Tb2Zr2O7 and Tb2ZrO5, both of which are defect fluorites, we note that the modulations found in these two compounds by electron scattering are virtually identical with regard to the direction and magnitude of displacement from the normal Bragg diffracted beams. This suggests that neither the A/B cation ratio nor the oxygen stoichiometry have a significant effect on the modulations. The general observations on the systems of compounds noted in this paper rest primarily in the context of industrial materials for nuclear waste disposal, potential applications in inert matrix fuel designs, and other important technological applications such as ionic conductivity, electrical conductivity, and magnetism. Scientific advances in these areas have been underpinned by recent advances in ion irradiation, synchrotron X-ray, neutron scattering, and modelling and simulation capabilities. Furthermore, there has been some renewed interest in natural samples, e.g., Th-U zirconolite and pyrochlore as analogues for potential host phases in nuclear waste forms. In particular, the natural pyrochlores have provided additional details with regard to radiation damage ingrowth, percolation transitions, and the relationships between accumulated dose and physical properties including hardness, elastic modulus. Specific details of the thermal annealing of these samples have also been elucidated in considerable detail.
Acute Hemodynamic Responses to Enhanced External Counterpulsation in Patients With Coronary Artery Disease
Authors: Zhang Yahui , Chen Ziqi , Mai Zhouming , Zhou Wenjuan , Wang Hui , Zhang Xiaodong , Wei Wenbin , Du Jianhang , Wu Guifu
Published: November 2021

Purpose: Enhanced external counterpulsation is a non-invasive treatment that increases coronary flow in patients with coronary artery disease (CAD). However, the acute responses of vascular and blood flow characteristics in the conduit arteries during and immediately after enhanced external counterpulsation (EECP) need to be verified.

Methods: Forty-two patients with CAD and 21 healthy controls were recruited into this study to receive 45 min-EECP. Both common carotid arteries (CCAs), namely, the left carotid (LC) and right carotid (RC), the right brachial (RB), and right femoral (RF) artery were imaged using a Color Doppler ultrasound. The peak systolic velocity (PSV), end-diastolic velocity (EDV), mean inner diameter (ID), resistance index (RI), and mean flow rate (FR) were measured and calculated before, during, and after the 45 min-EECP treatment.

Results: During EECP, in the CCAs, the EDV was significantly decreased, while the RI was markedly increased in the two groups (both P < 0.01). However, immediately after EECP, the RI in the RC was significantly lower than that at the baseline in the patients with CAD (P = 0.039). The FR of the LC was markedly increased during EECP only in the CAD patients (P = 0.004). The PSV of the patients with CAD was also significantly reduced during EECP (P = 0.015) and immediately after EECP (P = 0.005) compared with the baseline. Moreover, the ID of the LC, RB, and RF was significantly higher immediately after EECP than that at the baseline (all P < 0.05) in the patients with CAD. In addition, they were also higher than that in the control groups (all P < 0.05). Furthermore, by the subgroup analysis, there were significant differences in the FR, PSV, and RI between females and males during and immediately after EECP (all P < 0.05).

Conclusions: Enhanced external counterpulsation creates different responses of vascular and blood flow characteristics in carotid and peripheral arteries, with more significant effects in both the carotid arteries. Additionally, the beneficial effects in ID, blood flow velocity, RI, and FR after 45 min-EECP were shown only in the patients with CAD. More importantly, acute improvement of EECP in the FR of the brachial artery was showed in males, while the FR and RI of the carotid arteries changed in females.
Association of Systemic Immune-Inflammation Index With Short-Term Mortality of Congestive Heart Failure: A Retrospective Cohort Study
Authors: Tang Yiyang , Zeng Xiaofang , Feng Yilu , Chen Qin , Liu Zhenghui , Luo Hui , Zha Lihuang , Yu Zaixin
Published: November 2021

Purpose: The present study aimed to clarify the potential predictive significance of Systemic immune-inflammation index (SII) in assessing the poor prognosis of critically ill patients with congestive heart failure (CHF).

Methods: Detailed clinical data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III database after gaining access and building the local platform. The 30- and 90-day and hospital all-cause mortalities of the patient was the primary outcome, and the readmission rate and the occurrence of major cardiovascular adverse events (MACEs) were the secondary outcomes. the Cox proportional hazard model and Logistic regression analysis were selected to reveal the relationship between SII level and the research outcome. Further, the propensity score matching (PSM) analysis was performed to improve the reliability of results by reducing the imbalance across groups.

Results: There were a total of 4,606 subjects who passed the screening process and entered the subsequent analysis. Multivariate regression analysis showed that after adjusting for possible confounders, including age, heart rate, and albumin, etc., the high level of SII was independently associated with 30- and 90-day and hospital mortalities (tertile 3 vs. tertile 1: HR, 95% CIs: 1.23, 1.04-1.45; 1.21, 1.06-1.39; 1.26, 1.05-1.50) and the incidence of MACEs (tertile 3 vs. tertile 1: OR, 95% CI: 1.39, 1.12-1.73) in critically ill patients with CHF, but no significant correlation was found between SII and the readmission rate. Consistently, patients with high SII level still presented a significantly higher short-term mortality than patients with low SII in the PSM subset.

Conclusion: In critically ill patients with CHF, high level of SII could effectively predict high 30- and 90-day and hospital mortalities, as well as the high risk of occurrence of MACEs.
Myocardial Viability, Functional Status, and Collaterals of Patients With Chronically Occluded Coronary Arteries
Authors: Yang Xueyao , Tian Jinfan , Zhang Lijun , Dong Wei , Mi Hongzhi , Li Jianan , Li Jiahui , Han Ye , Zuo Huijuan , An Jing , He Yi , Song Xiantao
Published: November 2021

Objective: Viability and functional assessments are recommended for indication and intervention for chronic coronary total occlusion (CTO). We aimed to evaluate myocardial viability and left ventricular (LV) functional status by using cardiovascular magnetic resonance (CMR) and to investigate the relationship between them and collaterals in patients with CTO.

Materials and Methods: We enrolled 194 patients with one CTO artery as detected by coronary angiography. Patients were scheduled for CMR within 1 week after coronary angiography.

Results: A total of 128 CTO territories (66%) showed scar based on late gadolinium enhancement (LGE) imaging. There were 1,112 segments in CTO territory, while only 198 segments (18%) subtended by the CTO artery showed transmural scar (i.e., >50% extent on LGE). Patients with viable myocardium had higher LV ejection fraction (LVEF) (56.7 ± 13.5% vs. 48.3 ± 15.4%, p < 0.001) than those with transmural scar. Angiographically, well-developed collaterals were found in 164 patients (85%). There was no significant correlation between collaterals and the presence of myocardial scar (p = 0.680) or between collaterals and LVEF (p = 0.191). Nevertheless, more segments with transmural scar were observed in patients with poorly-developed collaterals than in those with well-developed collaterals (25 vs. 17%, p = 0.010).

Conclusion: Myocardial infarction detected by CMR is widespread among patients with CTO, yet only a bit of transmural myocardial scar was observed within CTO territory. Limited number of segments with transmural scar is associated with preserved LV function. Well-developed collaterals are not related to the prevalence of myocardial scar or systolic functioning, but could be related to reduce number of non-viable segments subtended by the CTO artery.
Exosomes in Cardiovascular Diseases: Pathological Potential of Nano-Messenger
Authors: Jadli Anshul S. , Parasor Ananya , Gomes Karina P. , Shandilya Ruchita , Patel Vaibhav B.
Published: November 2021

Cardiovascular diseases (CVDs) represent a major global health problem, due to their continued high incidences and mortality. The last few decades have witnessed new advances in clinical research which led to increased survival and recovery in CVD patients. Nevertheless, elusive and multifactorial pathophysiological mechanisms of CVD development perplexed researchers in identifying efficacious therapeutic interventions. Search for novel and effective strategies for diagnosis, prevention, and intervention for CVD has shifted research focus on extracellular vesicles (EVs) in recent years. By transporting molecular cargo from donor to recipient cells, EVs modulate gene expression and influence the phenotype of recipient cells, thus EVs prove to be an imperative component of intercellular signaling. Elucidation of the role of EVs in intercellular communications under physiological conditions implied the enormous potential of EVs in monitoring and treatment of CVD. The EVs secreted from the myriad of cells in the cardiovascular system such as cardiomyocytes, cardiac fibroblasts, cardiac progenitor cells, endothelial cells, inflammatory cells may facilitate the communication in physiological and pathological conditions. Understanding EVs-mediated cellular communication may delineate the mechanism of origin and progression of cardiovascular diseases. The current review summarizes exosome-mediated paracrine signaling leading to cardiovascular disease. The mechanistic role of exosomes in cardiovascular disease will provide novel avenues in designing diagnosis and therapeutic interventions.
The Outcomes of Total Anomalous Pulmonary Venous Connection in Neonates−10-Year Experience at a Single Center
Authors: Ji Erchao , Qiu Hailong , Liu Xiaobing , Xie Wen , Liufu Rong , Liu Tao , Chen Jimei , Wen Shusheng , Li Xiaohua , Cen Jianzheng , Zhuang Jian
Published: November 2021

Background: Recent developments in surgical techniques and hospital care have led to improved outcomes following repair of total anomalous pulmonary venous connection (TAPVC). However, surgical repair of neonatal TAPVC remains associated with a high risk of postoperative mortality and pulmonary venous obstruction (PVO). We conducted this retrospective study to identify risk factors associated with surgical outcomes in the neonatal population.

Methods: A retrospective review was conducted for all 127 neonates who underwent operations for isolated TAPVC from January 2009 to January 2019.

Results: Preoperative PVO occurred in 33 (26.0%) of the 127 patients. Fifty patients (39.4%) required tracheal intubation before the operation. Twenty-three patients (18.1%) underwent emergency surgery. There were 11 (8.7%) early deaths. Significant risk factors were prolonged cardiopulmonary bypass (CPB) time (p = 0.013) and increased postoperative central venous pressure (CVP, p = 0.036). There were 5 (4.3%) late deaths within 1 year of repair. The risk factors for overall death were preoperative acidosis (p = 0.001), prolonged CPB time (p < 0.001) and increased postoperative CVP (p = 0.007). In particular, mortality was significantly higher (p = 0.007) with a postoperative CVP > 8 mmHg. With an increase in use of sutureless techniques (p = 0.001) and decrease in deep hypothermic circulatory arrest (p = 0.009) over the past 5 years, postoperative mortality greatly decreased (21.2%: 6.7%, p = 0.016). Postoperative PVO occurred in 15 patients (11.8%). Risk factors were mixed TAPVC (p = 0.037), preoperative acidosis (p = 0.001) and prolonged CPB time (p = 0.006).

Conclusion: Although postoperative mortality of neonatal TAPVC has dropped to 6.7% over the past 5 years, it is still relatively high. Risk factors for postoperative death include preoperative acidosis, prolonged CPB time and increased postoperative CVP. Mortality was significantly higher for neonates with an average CVP > 8 mmHg 24 h after surgery.
Local and Distributed Machine Learning for Inter-hospital Data Utilization: An Application for TAVI Outcome Prediction
Authors: Lopes Ricardo R. , Mamprin Marco , Zelis Jo M. , Tonino Pim A. L. , van Mourik Martijn S. , Vis Marije M. , Zinger Svitlana , de Mol Bas A. J. M. , de With Peter H. N. , Marquering Henk A.
Published: November 2021

Background: Machine learning models have been developed for numerous medical prognostic purposes. These models are commonly developed using data from single centers or regional registries. Including data from multiple centers improves robustness and accuracy of prognostic models. However, data sharing between multiple centers is complex, mainly because of regulations and patient privacy issues.

Objective: We aim to overcome data sharing impediments by using distributed ML and local learning followed by model integration. We applied these techniques to develop 1-year TAVI mortality estimation models with data from two centers without sharing any data.

Methods: A distributed ML technique and local learning followed by model integration was used to develop models to predict 1-year mortality after TAVI. We included two populations with 1,160 (Center A) and 631 (Center B) patients. Five traditional ML algorithms were implemented. The results were compared to models created individually on each center.

Results: The combined learning techniques outperformed the mono-center models. For center A, the combined local XGBoost achieved an AUC of 0.67 (compared to a mono-center AUC of 0.65) and, for center B, a distributed neural network achieved an AUC of 0.68 (compared to a mono-center AUC of 0.64).

Conclusion: This study shows that distributed ML and combined local models techniques, can overcome data sharing limitations and result in more accurate models for TAVI mortality estimation. We have shown improved prognostic accuracy for both centers and can also be used as an alternative to overcome the problem of limited amounts of data when creating prognostic models.
Impact of October Snow Cover in Central Siberia on the Following Spring Extreme Precipitation Frequency in Southern China
Authors: Zhang Mengqi , Sun Jianqi
Published: November 2021

Spring extreme precipitation poses great challenges to agricultural production and economic development in southern China. From the perspective of prediction, the relationship between spring extreme precipitation frequency (SEPF) in southern China and preceding autumn snow cover over Eurasia is investigated. The results indicate that the southern China SEPF is significantly correlated with October snow cover in central Siberia. Corresponding to reduced October snow cover, the vertical propagation of planetary waves is suppressed, which leads to a strengthened stratospheric polar vortex from October to following December. The signal of the anomalous stratospheric polar vortex propagates downward to the surface, contributing to a positive North Atlantic Oscillation (NAO)-like pattern in December. The southwesterlies in the northern Eurasia-eastern Arctic associated with the positive NAO induce sea ice loss in the Barents–Kara seas in January–February, which then tends to enhance the vertical propagation of planetary waves by constructively interfering with the climatological wavenumber-1 component. Therefore, the stratosphere polar vortex is significantly weakened in spring, which further contributes to a negative Arctic Oscillation (AO)-like pattern in the troposphere. The negative spring AO is related to an anomalous cyclone in East Asia, which induces upward motion and moisture convergence in southern China, consequently providing favorable dynamic and moisture conditions for extreme precipitation in the region. The snow cover signal in central Siberia in the preceding October provides a potential source for the prediction of spring extreme precipitation variability in southern China with two seasons in advance.
Perceived Social Resources Affect Help-Seeking and Academic Outcomes in the Initial Phase of Undergraduate Studies
Authors: Schlusche Christian , Schnaubert Lenka , Bodemer Daniel
Published: November 2021

First-year students are challenged cognitively and socially by the need to integrate into a new environment. This article investigates the role of peer students as a social resource for academic help-seeking to overcome knowledge-related difficulties. Receiving useful help may require close and regular contacts (social embeddedness) as well as awareness about peer’s knowledge (group awareness). Hence, effects of social embeddedness and group awareness on academic success (i.e., achievement, satisfaction, and dropout intention) are expected to be mediated by academic help-seeking. First-semester students in science (n = 49) and engineering (n = 80) have been surveyed. Both study programs differ in occasions to form small groups, which may influence student’s aggregation of social resources. Both social embeddedness (engineering only) and group awareness (both groups) predict successful academic help-seeking. Moreover, the effect of group awareness on student satisfaction and dropout intention is partially mediated by successful academic help-seeking (engineering only). Both social variables can contribute to help-seeking behavior and student’s academic success. The results provide evidence to advice researchers and practitioners to improve academic help-seeking among students.
Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells In Vitro
Authors: Zhao Xingyi , Ji Minpeng , Wen Xin , Chen Dan , Huang Fu , Guan Xiaoju , Tian Jing , Xie Jiajia , Shao Jingjing , Wang Jiexia , Huang Luoqi , Lin Han , Ye Leping , Chen Haolin
Published: November 2021

Background

Midazolam is a neurological drug with diverse functions, including sedation, hypnosis, decreased anxiety, anterograde amnesia, brain-mediated muscle relaxation, and anticonvulsant activity. Since it is frequently used in children and adolescents for extended periods of time, there is a risk that it may affect their pubertal development. Here, we report a potential effect of the drug on the development of Leydig cells (LCs), the testosterone (T)-producing cells in the testis.

Methods

Stem LCs (SLCs), isolated from adult rat testes by a magnetic-activated cell sorting technique, were induced to differentiate into LCs in vitro for 3 weeks. Midazolam (0.1–30 μM) was added to the culture medium, and the effects on LC development were assayed.

Results

Midazolam has dose-dependent effects on SLC differentiation. At low concentrations (0.1–5 μM), the drug can mildly increase SLC differentiation (increased T production), while at higher concentrations (15–30 μM), it inhibits LC development (decreased T production). T increases at lower levels may be due to upregulations of scavenger receptor class b Member 1 (SCARB1) and cytochrome P450 17A1 (CYP17A1), while T reductions at higher levels of midazolam could be due to changes in multiple steroidogenic proteins. The uneven changes in steroidogenic pathway proteins, especially reductions in CYP17A1 at high midazolam levels, also result in an accumulation of progesterone. In addition to changes in T, increases in progesterone could have additional impacts on male reproduction. The loss in steroidogenic proteins at high midazolam levels may be mediated in part by the inactivation of protein kinase B/cAMP response element-binding protein (AKT/CREB) signaling pathway.

Conclusion

Midazolam has the potential to affect adult Leydig cell (ALC) development at concentrations comparable with the blood serum levels in human patients. Further studies are needed to test the effects on human cells.
Hyperuricemia and the Risk of Heart Failure: Pathophysiology and Therapeutic Implications
Authors: Si Ke , Wei Chijing , Xu Lili , Zhou Yue , Lv Wenshan , Dong Bingzi , Wang Zhongchao , Huang Yajing , Wang Yangang , Chen Ying
Published: November 2021

The association between hyperuricemia and cardiovascular disease (CVD) has been reported and studied in the past two decades. Xanthine oxidase (XO) induced uric acid (UA) serves as a risk factor and has the independent prognostic and functional impact of heart failure (HF), but whether it plays a positive role in the pathogenesis of HF has remained unclear. Growing evidence suggest the up-regulated XO avtivity and increased production of free oxygen radical (ROS) correspondingly are the core pathogenesis of HF with hyperuricemia, which results in a whole cluster of pathophysiologic cardiovascular effects such as oxidative stress, endothelial dysfunction, vascular inflammation, left ventricular (LV) dysfunction as well as insulin resistance (IR). The use of XO inhibition represents a promising therapeutic choice in patients with HF due to its dual effect of lowering serum UA levels as well as reducing ROS production. This review will discuss the pathophysiologic mechanisms of hyperuricemia with HF, the targeted therapeutic interventions of UA lowering therapies (ULT) with XO inhibition and mechanism underlying beneficial effects of ULT. In addition, the review also summarizes current evidence on the role of ULT in HF and compares CV risk between allopurinol and febuxostat for practical and clinical purposes. Guidelines and implementation of CV risk management in daily practice will be discussed as well.
Experimental Study on Sweep Characteristics of Gas Gravity Drainage in the Interlayer Oil Reservoir
Authors: Yu Hongwei , Wang Lu , Zhou Daiyu , Wang Fuyong , Li Shi , Li Jun , Chen Xinglong , Cao An , Han Haishui
Published: November 2021

Stable gas gravity drainage is considered an effective method to enhance oil recovery, especially suitable for deep buried, large dip angle, and thick oil reservoirs. The influence of reservoir heterogeneity on controlling the gas–oil interface and sweep characteristics of injected gas is particularly important to design reservoir development schemes. In this study, according to the interlayer characteristics of Donghe carboniferous oil reservoirs in the Tarim Basin, NW China, 2D visual physical models are established, in which the matrix permeability is 68.1 mD and average pore throat radius is 60 nm. Then, hydrocarbon gas gravity drainage simulation experiments are carried out systematically, and a high-speed camera is used to record the process of gas–oil flow and interface movement. In this experiment, the miscible zone of crude oil and hydrocarbon gas is observed for the first time. The interlayer has an obvious shielding influence, which can destroy the stability of the gas–oil interface and miscible zone, change the movement direction of the gas–oil interface, and reduce the final oil recovery after gravity drainage. The remaining oil mainly is distributed near the interlayers. The higher displacement pressure leads to increased stability of the gas–oil displacement front and later gas breakthrough, which leads to higher oil recovery. The lower gas injection rate contributes to a slower front velocity and wider miscible zone, which could delay gas breakthrough. For the immiscible gas gravity drainage, there is a critical gas injection rate, with which the oil recovery factor is the highest.
Vertical Structure of a Snowfall Event Based on Observations From the Aircraft and Mountain Station in Beijing
Authors: Huang Yu , Zhao Delong , Du Yuanmou , Chen Yichen , Zhang Lei , Li Xia , Jing Yingying
Published: November 2021

An aircraft platform, ground-based disdrometer, cloud radar, radiometer, and automatic station were combined to study a snowfall case (16:30–21:00 observed by ground cloud radar) on the Yangqing Mountains in Beijing. Comparing the variation of ice habit and number concentration at aircraft altitude (2.9–3.2 km) and ground, we discussed the ice growth mechanisms in the Beijing Mountains. Results indicated that the snowfall was steady but not strong with reflectivity less than 20dBZ, and cloud top altitude less than 4.5 km. The number concentrations for both liquid and ice crystals at aircraft altitude and ground were very similar, both dominated by small particles at diameters of 0.1–1.2 mm, and the proportion of mean number concentrations at small diameters both in the aircraft and on the ground was large, peaking at 44 L−1 mm−1 and 8826 L−1 mm−1 respectively, and decreased rapidly as the diameter increased. There was no mixed phase in clouds with little liquid water. Particles were relatively regular, and were transparent with dendritic and disk-hexagonal shapes. The ice crystals and snowflakes were mainly grown by the deposition and aggregation, rarely by the riming process, and no secondary ice formation was observed.
Naïve and Experienced Honeybee Foragers Learn Normally Configured Flowers More Easily Than Non-configured or Highly Contrasted Flowers
Authors: Howard Scarlett R. , Dyer Adrian G. , Garcia Jair E. , Giurfa Martin , Reser David H. , Rosa Marcello G. P. , Avarguès-Weber Aurore
Published: November 2021

Angiosperms have evolved to attract and/or deter specific pollinators. Flowers provide signals and cues such as scent, colour, size, pattern, and shape, which allow certain pollinators to more easily find and visit the same type of flower. Over evolutionary time, bees and angiosperms have co-evolved resulting in flowers being more attractive to bee vision and preferences, and allowing bees to recognise specific flower traits to make decisions on where to forage. Here we tested whether bees are instinctively tuned to process flower shape by training both flower-experienced and flower-naïve honeybee foragers to discriminate between pictures of two different flower species when images were either normally configured flowers or flowers which were scrambled in terms of spatial configuration. We also tested whether increasing picture contrast, to make flower features more salient, would improve or impair performance. We used four flower conditions: (i) normally configured greyscale flower pictures, (ii) scrambled flower configurations, (iii) high contrast normally configured flowers, and (iv) asymmetrically scrambled flowers. While all flower pictures contained very similar spatial information, both experienced and naïve bees were better able to learn to discriminate between normally configured flowers than between any of the modified versions. Our results suggest that a specialisation in flower recognition in bees is due to a combination of hard-wired neural circuitry and experience-dependent factors.
Managing Uncertainty in Scots Pine Range-Wide Adaptation Under Climate Change
Authors: Hallingbäck Henrik R. , Burton Vanessa , Vizcaíno-Palomar Natalia , Trotter Felix , Liziniewicz Mateusz , Marchi Maurizio , Berlin Mats , Ray Duncan , Benito Garzón Marta
Published: November 2021

Forests provide important ecosystem services and renewable materials. Yet, under a future climate, optimal conditions will likely shift outside the current range for some tree species. This will challenge the persistence of populations to rely on inherent plasticity and genetic diversity to acclimate or adapt to future uncertain conditions. An opportunity to study such processes is offered by Scots pine (Pinus sylvestris L.), a forest tree with a large distribution range including populations locally adapted to a wide variety of environments, which hinders a range-wide assessment of the species to climate change. Here we evaluate tree height growth uncertainty of Scots pine marginal populations in Spain and the Nordic countries linked to their genetic adaptation promoted by different climatic drivers. Our aims are to: (i) review the main climatic drivers of Scots pine adaptation across its range; (ii) undertake provenance-based modeling and prediction of tree height under current and future climate scenarios including four representative concentration pathways (RCPs) and five general circulation models (GCMs) at two extremes of its climatic niche; (iii) estimate uncertainty in population tree height linked to the main drivers of local adaptation that may change among RCPs and GCMs in the Nordic countries and Spain. Our models revealed that tree height adaptation is mostly driven by drought in Spain and by photoperiod in the Nordic countries, whereas the literature review also highlighted temperature as a climatic driver for the Nordic region. Model predictions for the Nordic countries showed an overall increase in tree height but with high uncertainty in magnitude depending on the RCPs and GCMs whereas predictions for Spain showed tree height to be maintained in the north and reduced in the south, but with similar magnitudes among RCPs and GCMs. Both models predicted tree height outside the data range used to develop the models (extrapolation). Predictions using higher emission RCPs resulted in larger extrapolated areas, constituting a further source of uncertainty. An expanded network of Scots pine field trials throughout Europe, facilitated by data collection and international research collaboration, would limit the need for uncertain predictions based on extrapolation.
The Evolution of Predator Resemblance in Avian Brood Parasites
Authors: York Jennifer E.
Published: November 2021

Predators have profound effects on prey behavior and some adult brood parasites use predator resemblance to exploit the antipredator defenses of their hosts. Clarifying host perception of such stimuli is important for understanding the adaptive significance of adult brood parasite characteristics, and the mechanisms by which they misdirect hosts. Here I review the literature to explore the adaptive basis of predator resemblance in avian brood parasites, and natural variation in host responses to these stimuli. I also provide a framework for the information ecology of predator resemblance, which is based on the principles of signal detection theory and draws from empirical evidence from the common cuckoo,Cuculus canorus, as the most widely studied system. In this species, visual and acoustic hawk-like stimuli are effective in manipulating host defenses. Overall, contrasts across host responses suggest that different modalities of information can have independent effects on hosts, and that predator resemblance takes advantage of multiple sensory and cognitive processes. Host perception of these stimuli and the degree to which they are processed in an integrated manner, and the physiological processes underlying regulation of the responses, present new avenues for brood parasitism research.
Development of the European Ladybirds Smartphone Application: A Tool for Citizen Science
Authors: Skuhrovec Jiří , Roy Helen E. , Brown Peter M. J. , Kazlauskis Karolis , Inghilesi Alberto F. , Soares Antonio O. , Adriaens Tim , Roy David B. , Nedvěd Oldřich , Zach Peter , Viglášová Sandra , Kulfan Ján , Honek Alois , Martinkova Zdenka
Published: November 2021

Wildlife observations submitted by volunteers through citizen science initiatives are increasingly used within research and policy. Ladybirds are popular and charismatic insects, with most species being relatively easy to identify from photographs. Therefore, they are considered an appropriate taxonomic group for engaging people through citizen science initiatives to contribute long-term and large-scale datasets for use in many different contexts. Building on the strengths of a mass participation citizen science survey on ladybirds in the United Kingdom, we have developed a mobile application for ladybird recording and identification across Europe. The main aims of the application are to: (1) compile distribution data for ladybird species throughout Europe, and use this to assess changes in distribution over time; (2) connect and engage people in nature and increase awareness about the diversity and ecological importance of ladybirds. In developing the application we first constructed a database including ladybird species from the United Kingdom, Czech Republic, Slovakia, Italy, Belgium, and Portugal with associated information on relevant morphological features (e.g., size, main color, pronotum pattern) to inform identification. Additionally, the species were assessed on the basis of probability of occurrence within each country which enables users to reduce the number of species to only those with relevance to the location of the recorder. This is amongst the first collaborative citizen science approaches aimed at involving participants across Europe in recording a group of insects. In the near future, we aim to expand the use of the application to all countries in Europe.
RNF4 Regulates the BLM Helicase in Recovery From Replication Fork Collapse
Authors: Ellis Nathan , Zhu Jianmei , Yagle Mary K , Yang Wei-Chih , Huang Jing , Kwako Alexander , Seidman Michael M. , Matunis Michael J.
Published: November 2021

Sumoylation is an important enhancer of responses to DNA replication stress and the SUMO-targeted ubiquitin E3 ligase RNF4 regulates these responses by ubiquitylation of sumoylated DNA damage response factors. The specific targets and functional consequences of RNF4 regulation in response to replication stress, however, have not been fully characterized. Here we demonstrated that RNF4 is required for the restart of DNA replication following prolonged hydroxyurea (HU)-induced replication stress. Contrary to its role in repair of γ-irradiation-induced DNA double-strand breaks (DSBs), our analysis revealed that RNF4 does not significantly impact recognition or repair of replication stress-associated DSBs. Rather, using DNA fiber assays, we found that the firing of new DNA replication origins, which is required for replication restart following prolonged stress, was inhibited in cells depleted of RNF4. We also provided evidence that RNF4 recognizes and ubiquitylates sumoylated Bloom syndrome DNA helicase BLM and thereby promotes its proteosome-mediated turnover at damaged DNA replication forks. Consistent with it being a functionally important RNF4 substrate, co-depletion of BLM rescued defects in the firing of new replication origins observed in cells depleted of RNF4 alone. We concluded that RNF4 acts to remove sumoylated BLM from collapsed DNA replication forks, which is required to facilitate normal resumption of DNA synthesis after prolonged replication fork stalling and collapse.
Maintenance of Complex Trait Variation: Classic Theory and Modern Data
Authors: Koch Evan M. , Sunyaev Shamil R.
Published: November 2021

Numerous studies have found evidence that GWAS loci experience negative selection, which increases in intensity with the effect size of identified variants. However, there is also accumulating evidence that this selection is not entirely mediated by the focal trait and contains a substantial pleiotropic component. Understanding how selective constraint shapes phenotypic variation requires advancing models capable of balancing these and other components of selection, as well as empirical analyses capable of inferring this balance and how it is generated by the underlying biology. We first review the classic theory connecting phenotypic selection to selection at individual loci as well as approaches and findings from recent analyses of negative selection in GWAS data. We then discuss geometric theories of pleiotropic selection with the potential to guide future modeling efforts. Recent findings revealing the nature of pleiotropic genetic variation provide clues to which genetic relationships are important and should be incorporated into analyses of selection, while findings that effect sizes vary between populations indicate that GWAS measurements could be misleading if effect sizes have also changed throughout human history.
A Multilayer Interactome Network Constructed in a Forest Poplar Population Mediates the Pleiotropic Control of Complex Traits
Authors: Gong Huiying , Zhu Sheng , Zhu Xuli , Fang Qing , Zhang Xiao-Yu , Wu Rongling
Published: November 2021

The effects of genes on physiological and biochemical processes are interrelated and interdependent; it is common for genes to express pleiotropic control of complex traits. However, the study of gene expression and participating pathways in vivo at the whole-genome level is challenging. Here, we develop a coupled regulatory interaction differential equation to assess overall and independent genetic effects on trait growth. Based on evolutionary game theory and developmental modularity theory, we constructed multilayer, omnigenic networks of bidirectional, weighted, and positive or negative epistatic interactions using a forest poplar tree mapping population, which were organized into metagalactic, intergalactic, and local interstellar networks that describe layers of structure between modules, submodules, and individual single nucleotide polymorphisms, respectively. These multilayer interactomes enable the exploration of complex interactions between genes, and the analysis of not only differential expression of quantitative trait loci but also previously uncharacterized determinant SNPs, which are negatively regulated by other SNPs, based on the deconstruction of genetic effects to their component parts. Our research framework provides a tool to comprehend the pleiotropic control of complex traits and explores the inherent directional connections between genes in the structure of omnigenic networks.
Improving the Classification of Alzheimer’s Disease Using Hybrid Gene Selection Pipeline and Deep Learning
Authors: Mahendran Nivedhitha , Vincent P. M. Durai Raj , Srinivasan Kathiravan , Chang Chuan-Yu
Published: November 2021

Alzheimer’s is a progressive, irreversible, neurodegenerative brain disease. Even with prominent symptoms, it takes years to notice, decode, and reveal Alzheimer’s. However, advancements in technologies, such as imaging techniques, help in early diagnosis. Still, sometimes the results are inaccurate, which delays the treatment. Thus, the research in recent times focused on identifying the molecular biomarkers that differentiate the genotype and phenotype characteristics. However, the gene expression dataset’s generated features are huge, 1,000 or even more than 10,000. To overcome such a curse of dimensionality, feature selection techniques are introduced. We designed a gene selection pipeline combining a filter, wrapper, and unsupervised method to select the relevant genes. We combined the minimum Redundancy and maximum Relevance (mRmR), Wrapper-based Particle Swarm Optimization (WPSO), and Auto encoder to select the relevant features. We used the GSE5281 Alzheimer’s dataset from the Gene Expression Omnibus We implemented an Improved Deep Belief Network (IDBN) with simple stopping criteria after choosing the relevant genes. We used a Bayesian Optimization technique to tune the hyperparameters in the Improved Deep Belief Network. The tabulated results show that the proposed pipeline shows promising results.
New Insights About the Behavioral Ecology of the Coelacanth Latimeria chalumnae Video Recorded in the Absence of Humans Off South Africa
Authors: Sakaue Jiro , Maeda Kazuhiko , Miller Michael J. , Sakai Ryuichi , Tahara Koh-ichi , Abe Hideki , Maeda Kazuya , Ida Hitoshi
Published: November 2021

Graphical Abstract
Commercial Potential of Pelagic Sargassum spp. in Mexico
Authors: López Miranda José Luis , Celis Lourdes B. , Estévez Miriam , Chávez Valeria , van Tussenbroek Brigitta I. , Uribe-Martínez Abigail , Cuevas Eduardo , Rosillo Pantoja Izarelly , Masia Luis , Cauich-Kantun Citlali , Silva Rodolfo
Published: November 2021

The recent periodic influx of massive quantities of pelagic Sargassum spp. (sargasso) into the Caribbean has posed ecological, social, and economic challenges to the region. Sustainable use of the biomass is crucial to mitigate negative impacts of beached algae. The current uses of sargasso in Mexico are reviewed, and a biorefinery approach is proposed to optimize its commercialization. The commercialization potential of sargasso in the Mexican Caribbean is analyzed using the strengths, weaknesses, opportunities, and threats (SWOT) analysis. The unpredictability of the influx to the Mexican shores is considerable, both in time and space, also, some areas receive consistently more sargasso than others. The lack of available technology, local infrastructure and regulations concerning sargasso are relevant, as is the urgent need to establish proper regulatory measures. In the context of the Mexican legal system, the category “special waste” can best be applied to sargasso that is collected from the beach or nearshore waters for the purpose of regulation. Lessons learnt from in Mexico may be applied elsewhere, with adaptations for each specific location. More importantly, mutual understanding of the constraints and possibilities of sargasso management in other countries, or territories, may facilitate the coordinated management of this transboundary macroalgae bloom.
Review of Self-sensing Capability of Ultra-high Performance Concrete
Authors: Lian Jinkang , Hu Chao , Fu Tengfei , Wang Yulin
Published: November 2021

Ultra-high performance concrete (UHPC) has the inherent potential to self-sensing capability due to its inclusion of steel fibers or other electrically conductive materials. Many studies have investigated the electrical and piezoresistive properties of UHPC. With the incorporation of micro steel fibers, carbon nanotubes, carbon nanofibrils, or nano graphite platelets, it opens up great potential to allow UHPC to effectively sense stress, strain, and crack damage. Therefore, the UHPC-based structures can achieve the functionality of structure health monitoring (SHM). This article reviews the recent advances in self-sensing capability of various UHPC-based materials with the focus on sensing capability and mechanisms. Future applications and challenges are also discussed.
Extracorporeal Membrane Oxygenation for COVID-19: Case Report of Nine Patients
Authors: Hua Jing , Zhang Xin , Wang Na , Ran Linyu , Wang Shengyun , Huang Chiungwei , Gao Wei , Qian Chenchen , Guo Wei , Liu Zhongmin , Li Qiang , Wang Feilong
Published: November 2021

Covid-19, Coronavirus disease 2019; ARDS, Acute respiratory distress syndrome; ECMO, Extracorporeal Membrane Oxygenation; WHO, World Health Organization; ICUs, Intensive care units. Acute respiratory distress syndrome (ARDS) is a fatal comorbidity of critically ill patients with COVID-19, who often end up on respiratory support. However, the safety and effectiveness of Extracorporeal Membrane Oxygenation (ECMO) in the treatment of COVID-19 remains to be elucidated at present. Here, we report on nine patients who received ECMO due to severe SARS-CoV-2 infection in Wuhan, China. Our initial experiences suggest that carefully selecting patients, as well as management by a well-trained team, are critical to implementing ECMO in patients with COVID-19. More randomized controlled trials with larger sample sizes are needed to evaluate the usefulness of ECMO in patients with COVID-19.