bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Osimertinib Followed by Osimertinib Plus Bevacizumab, Personalized Treatment Strategy for a Lung Cancer Patient With a Novel EGFR Exon 20 Insertion D770_N771insGT and Multiple Brain Metastases
Authors: Zhi Xiaoyu , Luo Jiancheng , Li Weiwei , Wang Jinliang , Wang Yuying , Cai Yi , Yan Xiang
Published: October 2021

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) are the standard of care for non–small cell lung cancer (NSCLC) patients with EGFR exon 19 deletion and L858R mutations. However, no EGFR TKI has been approved for NSCLC patients harboring insertion mutations in EGFR exon 20 (EGFRex20ins), a subgroup of uncommon EGFR mutations resistant to first-generation EGFR TKIs. This unmet clinical challenge is further complicated by disease progression due to brain metastases (BMs), which limits the use of EGFR TKIs with low intracranial activity. Osimertinib, a third-generation EGFR TKI with high CNS activity, has demonstrated superior efficacy as a first-line treatment for EGFR-mutant NSCLC with or without BM. The VEGF pathway is a key mediator of cancer metastasis and resistance to EGFR TKIs. Accumulating evidence has demonstrated that the addition of anti-VEGF agents to EGFR TKIs provides an alternative treatment option for the clinical management of EGFR-mutant NSCLC. We herein report an NSCLC case with a novel EGFRex20ins mutation D770_N771insGT and multiple brain metastases who briefly responded to first-line osimertinib treatment and subsequently achieved prolonged disease control with osimertinib plus bevacizumab as second-line treatment. Our case suggests that osimertinib in combination with bevacizumab may be an effective option for NSCLC patients with specific EGFRex20ins mutations and brain metastases.
Photostable Red-Emitting Fluorescent Rhein-Magnesium(Ⅱ) Coordination Polymer Nanodot-Based Nanostructures With a Large Stokes Shift for Imaging Mitochondria in Cancer Cell
Authors: Jiang Qin , Du Ke , Jiang Yuhang , Liu Yuhan , Han Chen , Yin Zhihui , Wang Ying , Gao Xiaoyan
Published: October 2021

The mitochondria play a significant role in many cellular processes and are recognized as one of the most important therapeutic targets in cancer. Direct long-term imaging of the mitochondria is very crucial for treating cancer. However, the development of a red-emitting mitochondrial probe with a large Stokes shift and photostability remains highly challenging. Fluorescent metal complexes with superior physicochemical property have emerged as new fluorescent nanomaterials due to their increasing advantages in bioimaging. Herein, a luminescent pitaya-type nanostructure based on rhein-magnesium(II) (Rh-Mg) coordination polymer nanodots was used as a fluorescent nanoprobe to selectively image the mitochondria benefiting from the introduction of triphenylphosphine. The as-prepared Rh-Mg nanodot-based nanoprobe showed red emission peaking at 620 nm, a large Stokes shift (100 nm), and excellent photostability as compared with commercial mitochondrial probes. Due to these extraordinary features, this fluorescent nanoprobe was successfully used for mitochondrial targeting imaging of live cancer cell line Neuro-2a (mouse neuroblastoma) and BV2 microglial cells. Therefore, our results pave a new way for the design of fluorescent nanoprobes for imaging mitochondria in cancer cell.
Wireless Textile Moisture Sensor for Wound Care
Authors: Tessarolo Marta , Possanzini Luca , Gualandi Isacco , Mariani Federica , Torchia Leo Davide , Arcangeli Danilo , Melandri Federico , Scavetta Erika , Fraboni Beatrice
Published: October 2021

One of the main problems of hard-to-heal wounds regards the monitoring of their healing progress. Currently, clinicians monitor the wound’s status by removing the dressing, disturbing the healing process. A relevant parameter that they need to monitor is wound moisture. Indeed, a low amount of exudate can desiccate the wound, while a high level of moisture will lead to maceration. Thus, to optimize the healing process, it is particularly important to maintain an optimum level of moisture, while limiting unnecessary dressing changes. An innovative solution to address this issue is the design of a bandage with an integrated moisture sensor. In this work, we developed a textile sensor based on a conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) that discriminates wound’s moisture level. PEDOT:PSS is screen printed on a gauze in a specific geometry. Exploiting its intrinsic electrochemical properties, the sensor operates in real time by monitoring impedance variations that span over several orders of magnitude between dry and wet states. The sensor is directly integrated with an RFID chip, implementing a real-time wireless monitoring. The final device results in a low-cost, user friendly, disposable and wirelessly connected patch.
Assessing the Structural Vulnerability of Online Social Networks in Empirical Data
Authors: Zhang Dayong , Guo Changyong , Zhang Zhaoxin , Long Gang
Published: October 2021

Assessing the structural vulnerability of online social networks has been one of the most engaging topics recently, which is quite essential and beneficial to holding the network connectivity and facilitating information flow, but most of the existing vulnerability assessment measures and the corresponding solutions fail to accurately reveal the global damage done to the network. In order to accurately measure the vulnerability of networks, an invulnerability index based on the concept of improved tenacity is proposed in the present study. Compared with existing measurements, the new method does not measure a single property performance, such as giant component size or the number of components after destruction, but pays special attention to the potential equilibrium between the removal cost and the removal effect. Extensive experiments on real-world social networks demonstrate the accuracy and effectiveness of the proposed method. Moreover, compared with results of attacks based on the different centrality indices, we found an individual node’s prominence in a network is inherently related to the structural properties of network. In high centralized networks, the nodes with higher eigenvector are more important than the others in maintaining stability and connectivity. But in low centralized networks, the nodes with higher betweenness are more powerful than the others. In addition, the experimental results indicate that low centralized networks can tolerate high intentional attacks and has a better adaptability to attacks than high centralized networks.
Suppression of Optical Rogue Waves by Dispersion Oscillating Fiber in the Mid-infrared Supercontinuum
Authors: Liu Shuo , Han Xin , lv Jiaqi , Feng Yanhui , Xia Yuanqin , Bai Zhenxu
Published: October 2021

We further numerically study the mid-infrared supercontinuum (SC) and the rare optical rogue wave (ORW) generated by femtosecond pulse pumping in chalcogenide fibers. Specifically, it is shown via ensembles of numerical simulations that the compression of the spectrum by dispersion oscillating fiber (DOF) effectively controls the generation of ORW. A comparison is made between uniform fiber (UF) and DOF, the spectral bandwidth is compressed from 5,800 nm of UF to 2,300 nm of DOF, and the ORW of high peak power is suppressed. In addition, the oscillation amplitude, oscillation period and initial phase of DOF dispersion are further changed. It has been proved that the suppression effect of ORW is the best when the oscillation amplitude is 300 ps2/km, the oscillation period is 0.5 cm and the initial phase is 0. We believe that our research results will provide some enlightenment for controlling the direction of ORW by changing the characteristics of optical fiber, improving the performance of SC.
NSAIDs Naproxen, Ibuprofen, Salicylate, and Aspirin Inhibit TRPM7 Channels by Cytosolic Acidification
Authors: Chokshi Rikki , Bennett Orville , Zhelay Tetyana , Kozak J. Ashot
Published: October 2021

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for relieving pain and inflammation accompanying numerous disease states. The primary therapeutic mechanism of these widely used drugs is the inhibition of cyclooxygenase 1 and 2 (COX1, 2) enzymes that catalyze the conversion of arachidonic acid into prostaglandins. At higher doses, NSAIDs are used for prevention of certain types of cancer and as experimental treatments for Alzheimer’s disease. In the immune system, various NSAIDs have been reported to influence neutrophil function and lymphocyte proliferation, and affect ion channels and cellular calcium homeostasis. Transient receptor potential melastatin 7 (TRPM7) cation channels are highly expressed in T lymphocytes and are inhibited by Mg2+, acidic pH, and polyamines. Here, we report a novel effect of naproxen, ibuprofen, salicylate, and acetylsalicylate on TRPM7. At concentrations of 3–30mM, they reversibly inhibited TRPM7 channel currents. By measuring intracellular pH with the ratiometric indicator BCECF, we found that at 300μM to 30mM, these NSAIDs reversibly acidified the cytoplasm in a concentration-dependent manner, and propose that TRPM7 channel inhibition is a consequence of cytosolic acidification, rather than direct. NSAID inhibition of TRPM7 channels was slow, voltage-independent, and displayed use-dependence, increasing in potency upon repeated drug applications. The extent of channel inhibition by salicylate strongly depended on cellular PI(4,5)P2 levels, as revealed when this phospholipid was depleted with voltage-sensitive lipid phosphatase (VSP). Salicylate inhibited heterologously expressed wildtype TRPM7 channels but not the S1107R variant, which is insensitive to cytosolic pH, Mg2+, and PI(4,5)P2 depletion. NSAID-induced acidification was also observed in Schneider 2 cells from Drosophila, an organism that lacks orthologous COX genes, suggesting that this effect is unrelated to COX enzyme activity. A 24-h exposure to 300μM–10mM naproxen resulted in a concentration-dependent reduction in cell viability. In addition to TRPM7, the described NSAID effect would be expected to apply to other ion channels and transporters sensitive to intracellular pH.
Cellular Size, Gap Junctions, and Sodium Channel Properties Govern Developmental Changes in Cardiac Conduction
Authors: Nowak Madison B. , Veeraraghavan Rengasayee , Poelzing Steven , Weinberg Seth H.
Published: October 2021

Electrical conduction in cardiac ventricular tissue is regulated via sodium (Na+) channels and gap junctions (GJs). We and others have recently shown that Na+channels preferentially localize at the site of cell-cell junctions, the intercalated disc (ID), in adult cardiac tissue, facilitating coupling via the formation of intercellular Na+nanodomains, also termed ephaptic coupling (EpC). Several properties governing EpC vary with age, including Na+channel and GJ expression and distribution and cell size. Prior work has shown that neonatal cardiomyocytes have immature IDs with Na+channels and GJs diffusively distributed throughout the sarcolemma, while adult cells have mature IDs with preferentially localized Na+channels and GJs. In this study, we perform an in silico investigation of key age-dependent properties to determine developmental regulation of cardiac conduction. Simulations predict that conduction velocity (CV) biphasically depends on cell size, depending on the strength of GJ coupling. Total cell Na+channel conductance is predictive of CV in cardiac tissue with high GJ coupling, but not correlated with CV for low GJ coupling. We find that ephaptic effects are greatest for larger cells with low GJ coupling typically associated with intermediate developmental stages. Finally, simulations illustrate how variability in cellular properties during different developmental stages can result in a range of possible CV values, with a narrow range for both neonatal and adult myocardium but a much wider range for an intermediate developmental stage. Thus, we find that developmental changes predict associated changes in cardiac conduction.
Exercising With Embodied Young Avatars: How Young vs. Older Avatars in Virtual Reality Affect Perceived Exertion and Physical Activity Among Male and Female Elderly Individuals
Authors: Tammy Lin Jih-Hsuan , Wu Dai-Yun
Published: October 2021

This study demonstrated that implementation of the Proteus effect via manipulation of avatar age in VR is effective among elderly individuals in the context of exercise. One hundred and four elderly adults aged 60 years and older who did not engage in vigorous physical activities participated in this experiment with a 2 (avatar age: young vs. older) × 2 (sex: male vs. female) design. The results showed that the embodiment of younger avatars (age approximately 20 years) in VR leads to greater perceived exercise exertion regardless of sex after controlling for age and emotion. Older adults with young avatars perceived a greater contribution of efforts to exercise. This study also found that among those who did not engage in vigorous exercise, female older adults who embodied young avatars reported greater self-efficacy for future exercise and greater physical activity during the exercise phase than those who embodied older avatars. This study suggests that females are more likely to be motivated to continue exercising through young avatar embodiment. In contrast, female elderly who embodied old avatars reported significant fewer physical activity than male elderly who embodied old avatars. This indicated that the Proteus effect had stronger effects among females than among older males. Although we found the Proteus effect through VR avatar manipulation, the effect was temporary and limited to the experimental phase. This study is the first to examine the Proteus effect among elderly individuals in the context of exercise. It also contributes to the literature by indicating that avatar age manipulation is an effective means of promoting exercise among elderly individuals and helping them achieve exercise outcomes. This study further demonstrates that female elderly individuals respond to young avatars differently than male elderly individuals, with female elderly individuals showing more positive effects of young avatar embodiment than males. Implications and theoretical contributions are discussed.
Perceived Motivational Climate and Stages of Exercise Behavior Change: Mediating Roles of Motivation Within and Beyond Physical Education Class
Authors: Wu Xiaojing , Gai Xiaosong , Yu Tianfeng , Yu Haifeng , Zhang Yu
Published: October 2021

This study examined the relationship between the perceived motivational climate in physical education (PE) classes and the stage of exercise behavior change among 322 high school students in northeastern China. Furthermore, the chain-mediating effects of autonomous motivation in PE and the five types of motivation (interest, competence, social relatedness, appearance, and health) in leisure-time physical activity (PA) were examined. Results showed that autonomous motivation in PE and the five types of motivation in leisure-time PA had chain-mediating effects on the relationships between the perceived mastery- and performance-oriented motivational climate and the stage of exercise behavior change in the whole sample (controlling for gender). Specifically, a perceived mastery-oriented motivational climate promoted autonomous motivation in PE, which, in turn, increased the five types of motivation in leisure-time PA and led to a higher stage of exercise behavior change. Conversely, a perceived performance-oriented motivational climate reduced autonomous motivation in PE which, in turn, decreased the five types of motivation in leisure-time PA and led to earlier stages of exercise behavior change. The patterns of the chain-mediating effects of autonomous motivation in PE and the five types of motivation in leisure-time PA were somewhat similar in girls and boys. The results suggested that PE teachers should create mastery-oriented climates and avoid performance-oriented motivational climates, which may promote intrinsic or identified motivations of students for PA within and beyond PE classes, thereby affecting the leisure-time PA of students.
Integrated Care for Pregnant Women and Parents With Methamphetamine-Related Mental Disorders
Authors: Petzold Johannes , Spreer Maik , Krüger Maria , Sauer Cathrin , Kirchner Tobias , Hahn Susanna , Zimmermann Ulrich S. , Pilhatsch Maximilian
Published: October 2021

Background: Methamphetamine use is a rapidly increasing cause of morbidity and mortality. Pregnant women and new parents who consume methamphetamine are at high risk since they seldom seek health services despite having multiple needs. We addressed this care gap by implementing an easily accessible program that pools resources from psychiatric, obstetric, and pediatric departments as well as community and government agencies.

Method: This real-life observational study evaluated an integrated care program in 27 expecting parents and 57 parents of minors. The outcome criteria were treatment retention, psychosocial functioning, and abstinence. We compared participant demographics according to outcome and applied ordinal logistic regression to predict treatment success.

Results: Patients received integrated care for almost 7 months on average. Nearly half achieved stable abstinence and functional recovery. Only one pregnant woman dropped out before a care plan could be implemented, and all women who gave birth during treatment completed it successfully. Three-fourths of patients had psychiatric comorbidities. Patients with depressive disorders were almost 5 times less likely to succeed with treatment. Attention-deficit hyperactivity disorder (ADHD) was diagnosed in nearly 30% of patients who dropped out of a care plan, which was about 4 times more often than in the successful outcome group.

Conclusion: Our program engaged pregnant women and parents in treatment and helped them recover from methamphetamine-related mental disorders. Management of comorbid ADHD and depression should be an integral part of care initiatives to counter the methamphetamine crisis that affects parents and children across the globe.
Prevalence and Socio-Demographic Correlates of Body Weight Categories Among South African Women of Reproductive Age: A Cross-Sectional Study
Authors: Akokuwebe Monica Ewomazino , Idemudia Erhabor Sunday
Published: October 2021

Background:The shift in disease patterns has been connected with increased body weight burden, becoming a major public health concern in South Africa, as previous studies have assessed overweight or obesity among certain populations. However, little is known about bodyweight burden (underweight, overweight, and obesity) among women aged 15–49 years. Therefore, this study was conducted to identify the prevalence and its associated socio-demographic correlates of bodyweight categories among women of reproductive age in South Africa.

Methods:The present study used the South Africa Demographic Health Survey (2016 SADHS) data for 2016. A total of 3,263 women of reproductive age were included in the analysis. Both bivariable and multivariable logistics regressions were performed to determine the prevalence and socio-demographic correlates of bodyweight categories among women in South Africa. Thus, this study used the criteria of the WHO standard body mass index (BMI) cut-offs to classify bodyweight categories. The odds ratios (ORs) with 95% CIs were estimated for potential determinants included in the final model.

Results:The overall prevalence of body weight burden was 66.5%, with 4.9% underweight, 27.1% overweight, and 34.5% obese (p< 0.05). The identified factors associated with underweight among women of reproductive age were those from “other” population group [adjusted odds ratio (AOR) 2.65: 95% CI 1.40–5.00], rural residence (AOR 1.23: 95% CI 0.75–2.02), and Northern Cape Province (AOR 1.58: 95% CI 0.65–3.87). For overweight/obese, the main factors were those aged 45–49 years (AOR 10.73: 95% CI 7.41–15.52), tertiary education (AOR 1.41: 95% CI 0.97–2.03), and residing in Eastern Cape (AOR 1.27: 95% CI 0.82–1.99) and KwaZulu-Natal Provinces (AOR 1.20: 95% CI 0.78–1.84).

Conclusion:The findings presented in this study indicate the concurrence of underweight and overweight/obese among women aged 15–49 years in South Africa. Despite underweight prevalence being on the decline, yet overweight/obese is increasing over time. The health implication of body weight burden needs rapid and effective interventions, focusing on factors such as rural, education, population group, older age 45–49 years, and Provinces (Northern Cape, Eastern Cape, and KwaZulu-Natal) – the high-risk groups identified herein are of most importance to curb the growing burden among South African women of reproductive age.
Impacts of Professionalization and Wellbeing Policies on Scottish Prison Workers
Authors: Fletcher Andrew , McKie Linda , MacPherson Isobel , Tombs Jackie
Published: October 2021

Prison workers occupy a niche role. Balancing the care and welfare of prisoners while simultaneously restricting their freedoms is a stressful job, laced with danger, that occurs entirely within the bounded context of the prison. Here, wellbeing and professionalism are closely linked and articulated through a range of policies. This article explores the perceptions and experiences of staff in relation to a range of wellbeing and training policies in the Scottish Prison Service (SPS). We interviewed 10 SPS employees, some working directly with prisoners and others in more centralised policy development and support roles. Thematic analysis found a high degree of contentment with such policies but highlighted tensions between their implementation and specific challenges of the prison context. Emerging themes included: supporting wellbeing within the complex dynamic of the prison world; addressing inherent tensions borne out of the underlying threat of violence; and the impact of professionalization. We conclude that while the prison service aspires to offer employees wellbeing and professionalization opportunities similar to those in other sectors, there is a need for such policies to more clearly reflect the unique context of prison work. This might involve co-design of policies and more careful consideration of the pressures, tensions and idiosyncrasies of that rarefied environment.
Psicopatologías de la libertad (I): la agorafobia o la restricción del espacio
Authors: Villegas Besora Manuel
Published: October 2021

En este artículo se parte de la concepción de la agorafobia como una limitación de la libertad, pero no entendida únicamente en su aspecto de movilidad física, característica de la dimensión sintomática del trastorno, sino como capacidad de decisión y de compromiso. Las situaciones en las que la persona se halla ante un conflicto relacional implican con frecuencia serias limitaciones a la libertad personal, que pueden materializarse a través de la sintomatología agorafóbica. La naturaleza última de estos conflictos relacionales requiere, en parte, la superación de verdaderos dilemas de carácter moral, tal como se muestra en los casos que ilustran el artículo.
WSPM-System: Providing Real Data of Rotor Speed and Pitch Angle for Numerical Simulation of Downwash Airflow from a Multirotor UAV Sprayer
Authors: Zhang Hao , Qi Lijun , Wan Junjie , Musiu Elizabeth M. , Zhou Jiarui , Lu Zhongao , Wang Pei
Published: October 2021

The accurate setting of input parameters in the numerical simulation of downwash airflow from a UAV sprayer is important for acceptable simulation results. To provide real data of simulation parameters (rotor speed and pitch angle) for the numerical simulation of downwash airflow, a wireless simulation parameter measurement system (WSPM-System) was designed and tested in this study. The system consists of hardware and software designed based on Arduino and LabVIEW, respectively. Wireless communication was realized by nRF24L01. The lattice Boltzmann method (LBM) was applied for the numerical simulation of downwash airflow. The results showed that the valid communication distance of the WSPM-System was 100 m, with a packet loss rate of less than 1%. While hovering, the rotor speed dropped by about 30% when the load of the UAV sprayer changed from 16 kg to 4 kg, which resulted in the maximum vertical downward velocity (VVD) on the horizontal detection surface dropping by about 23%. Under forward flight, the rotor speed in the front (n1, n6) and rear (n3, n4) of the UAV sprayer, respectively, showed a negative linear correlation and positive linear correlation with flight speed (R2 > 0.95). Meanwhile, the rotor speed in the middle (n2, n5) was consistent with the rotor speed while hovering under the same load; the pitch angle showed a positive linear correlation with flight speed (R2 > 0.94). A correlation analysis of measured and simulated values of the VVD revealed that the numerical simulation of downwash airflow with the parameters provided by the WSPM-System was reliable (R2 = 0.91). This study confirmed that the input value of the rotor speed in the fluid software needed to be determined according to the application parameters of the UAV sprayer, thus providing a feasible method and system for obtaining real simulation parameters.
Measuring On-Farm Phosphorus Fertiliser Use—Lessons Learned from Surveying Data of Five Regions in Northern Germany
Authors: Winklhofer Paul , Andert Sabine , Hüttel Silke , Gerowitt Bärbel
Published: October 2021

Phosphorus (P) is essential for agriculture; however, local P surpluses can have adverse environmental effects, such as eutrophication. Optimal P fertiliser use, therefore, means balancing these effects. Although P fluxes from soil to plants are key research areas, little is known about on-farm use of P fertilisers. As, typically, not all fields or crops are treated with P annually, the transferability of measurements for other nutrients, such as nitrogen, appears limited. This study aims to close this knowledge gap. On-farm P use was described using the farm records of 50 farms in five regions of northern Germany for the period of 2010 to 2018. All sources for P fertilisation were taken into account as either P mineral, P organic or P total. Two indicators for on-farm P use were suggested: frequency, which gives the percentage of the treated area, and amount, which gives the quantity used per ha of the treated area. The frequency for P total ranged from 55.9% to 93.1% of the total farm area being fertilised. Amounts between 24.8 and 41.6 kg ha−1 P total were applied on the treated area of the farm. The results supported the separation of the quantity and frequency in on-farm P use. No decrease in P use was found during the period investigated. Using mixed models, the results further show that explanatory variables, including the farm characteristics and crop choice, explain the substantial variations in P use. It is recommended for the example of Germany to establish an official digital database for P fertilisers that can be updated professionally and is mandatory for all documentation on P use.
Effects of a Combination of Lysolecithin, Synthetic Emulsifier, and Monoglycerides on Growth Performance, Intestinal Morphology, and Selected Carcass Traits in Broilers Fed Low-Energy Diets
Authors: Ghazalah Abdallah , Abd-Elsamee Mamdouh , Ibrahim Moataz , Abdelgayed Sherein S. , Abdelkader Mohamed , Gonzalez-Sanchez David , Wealleans Alexandra
Published: October 2021

This study aimed to evaluate the effect of supplementing a combination of lysolecithin, synthetic emulsifier, and monoglycerides (LEX) on growth performance, intestinal morphology, and selected carcass traits in broilers fed low-energy diets without added oil. Three hundred one-day-old Arbor Acres (AA) broilers (40.3 ± 3.3 g) were assigned to two dietary treatments with six replicates of 25 birds each and were fed a control low-energy diet without added oil supplemented with 0 and 250 g/t of LEX for 30 days. Growth performance was measured and recorded throughout the study. At slaughter, 60 birds per treatment were used to assess the effect of LEX on the carcass traits. Final average body weight and feed conversion ratio were improved (p < 0.05) in LEX treated birds compared to control. LEX supplementation was linked to higher (p < 0.05) carcass weight and yield and to lower (p < 0.05) abdominal fat and liver weight. Moisture content was higher (p < 0.05) in ground deboned broilers from LEX treatment. Villus height was increased (p < 0.05), and crypt depth reduced (p < 0.05) in the jejunum of birds treated with LEX. This study demonstrates that supplementation of LEX to a low-energy diet without added oil improved performance, carcass weight and yield, reduced abdominal fat deposition, and improved intestinal morphology in broiler chickens.
The Effect of Feeding Restriction on the Microbiota and Metabolome Response in Late-Phase Laying Hens
Authors: Artdita Clara Ajeng , Zhuang Yi-Ru , Liu Tzu-Yu , Cheng Chih-Yuan , Hsiao Felix Shih-Hsiang , Lin Yuan-Yu
Published: October 2021

This study investigated cecal bacterial community profile, cecal and serum metabolites, and its biosynthesis pathway in late-phase laying hens during 6 weeks feeding restriction (FR), using 16S rDNA as gene sequencing and non-targeted LC-MS/MS as metabolomics approach. We used three groups (ad libitum, FR20, and FR40). FR can reduce excessive fat in late-phase laying hens, while egg production rate is not affected, except for the FR40 group. In phylum level, FR20 had more population of Bacteriodetes and Firmicutes amongst groups. The same result is at genus level, FR20 were higher of the predominant genus (Bacteroides and Rikenellaceae_RC9_gut_group). Both of FR20 and FR40 reduced Proteobacteria as potential pathogenic bacteria. Non-targeted metabolomic analysis revealed that FR20 modified 20 metabolites in cecal and 10 metabolites in serum of laying hens, whereas 48 cecal metabolites and 31 serum metabolites has revealed in FR40. KEGG assay showed FR20 and FR40 upregulated lipid, carbohydrate, amino acid, nucleic acid pathway, and FR40 modified steroid metabolism in cecal analysis. In serum, only FR40 modified lipid, amino acid pathway, and carbohydrate biosynthesis were shown. This study showed that FR during late-phase laying hens altered the microbiome composition, modified metabolites profile and biosynthesis of the cecal as well as serum.
Aβ1–40-Induced Platelet Adhesion Is Ameliorated by Rosmarinic Acid through Inhibition of NADPH Oxidase/PKC-δ/Integrin αIIbβ3 Signaling
Authors: Lee Bo Kyung , Jee Hye Jin , Jung Yi-Sook
Published: October 2021

In platelets, oxidative stress reportedly increases platelet adhesion to vessels, thus promoting the vascular pathology of various neurodegenerative diseases, including Alzheimer’s disease (AD). Recently, it has been shown that β-amyloid (Aβ) can increase oxidative stress in platelets; however, the underlying mechanism remains elusive. In the present study, we aimed to elucidate the signaling pathway of platelet adhesion induced by Aβ1–40, the major form of circulating Aβ, through Western blotting, immunofluorescence confocal microscopy, and fluorescence-activated cell sorting analysis. Additionally, we examined whether rosmarinic acid (RA), a natural polyphenol antioxidant, can modulate these processes. Our results show that Aβ1–40-induced platelet adhesion is mediated through NADPH oxidase/ROS/PKC-δ/integrin αIIbβ3 signaling, and these signaling pathways are significantly inhibited by RA. Collectively, these results suggest that RA may have beneficial effects on platelet-associated vascular pathology in AD.
Air-Water Bubbly Flow by Multiple Vents on a Hydrofoil in a Steady Free-Stream
Authors: Kim Kiseong , Nagarathinam David , Ahn Byoung-Kwon , Park Cheolsoo , Kim Gun-Do , Moon Il-Sung
Published: October 2021

Flow features, due to air injection through multiple vents on the surface of a hydrofoil inclined at an angle with respect to the free-stream in a cavitation tunnel, are presented here. The hydrofoil, with a chord length, c, is oriented at the angle of inclination, α = 3.5°. The Froude number, Fn, based on the free-stream velocity, V∞, and air injection vent diameter, dh, is 30.30, 50.51 and 70.71. Air is injected through multiple vents on the hydrofoil at the non-dimensional air injection coefficient, Cq∼16−8917. The air bubble packing per unit area is quantified using spatial density, SD, at various combinations of Fn,Cq based on a high-speed video from the side view. The time-averaged spatial density, , is observed to increase in a logarithmic manner with an increase in the air injection rate, Q, at various Froude numbers. There is an increase in the mean spatial density of the bubbles with the increase in Cq at all Fn. A power–law relation is shown to exist between the time-averaged spatial density, , and the non-dimensional flow variables, Reynolds number, Reair, Fn and Cq based on a regression analysis. By tracking individual finite volume bubbles flowing with the free-stream, the bubble dimensions in pixels are quantified using quantities such as the deformation rate, ϵ, and standardization, ϵS, from the side-view videos. It is observed that ϵ and ϵS change with time, even as they become advected with the free-stream. Through high-speed imaging from the top view, we characterize the bubbly flow features’ time-averaged thickness, t, at various combinations of Fn,Cq at α = 3.5°. We obtain a power-law relation between the non-dimensional time-averaged jet thickness, t/c, and the non-dimensional flow parameters such as, Reair, Fn,Cq and the non-dimensional streamwise distance, x/xref, based on a regression analysis, where xref is a reference distance. The results are relevant to engineering applications where the air–water bubbly flow in a free-stream is important.
Enhanced Efficiency and Reduced Side Lobe Level Convex Conformal Reflectarray
Authors: Beccaria Michele , Addamo Giuseppe , Orefice Mario , Peverini Oscar , Manfredi Diego , Calignano Flaviana , Virone Giuseppe , Pirinoli Paola
Published: October 2021

In this work, the design of a convex conformal reflectarray (CRA), suitable to be used for high gain on board antenna in mobile communication systems, is presented. The reflector is not planar, as in usual reflectarray configurations, but the re-radiating elements are printed on a surface conformed to a cylinder to mimic a curved surface, such as the fuselage of an airplane, on which the reflectarray could be mounted. To compensate for the loss in efficiency due to the curvature, an ad hoc feed is designed; the results obtained with the simulation of the entire structure and the measurements of its prototype prove the effectiveness of the design procedure and its capability in enhancing the CRA features, in comparison with similar but more conventional solutions.
Extracellular Vesicles in Airway Homeostasis and Pathophysiology
Authors: Fucarino Alberto , Pitruzzella Alessandro , Burgio Stefano , Zarcone Maria Concetta , Modica Domenico Michele , Cappello Francesco , Bucchieri Fabio
Published: October 2021

The epithelial–mesenchymal trophic unit (EMTU) is a morphofunctional entity involved in the maintenance of the homeostasis of airways as well as in the pathogenesis of several diseases, including asthma and chronic obstructive pulmonary disease (COPD). The “muco-microbiotic layer” (MML) is the innermost layer of airways made by microbiota elements (bacteria, viruses, archaea and fungi) and the surrounding mucous matrix. The MML homeostasis is also crucial for maintaining the healthy status of organs and its alteration is at the basis of airway disorders. Nanovesicles produced by EMTU and MML elements are probably the most important tool of communication among the different cell types, including inflammatory ones. How nanovesicles produced by EMTU and MML may affect the airway integrity, leading to the onset of asthma and COPD, as well as their putative use in therapy will be discussed here.
Revising of the Near Ground Helicopter Hover: The Effect of Ground Boundary Layer Development
Authors: Andronikos Theologos , Papadakis George , Riziotis Vasilis , Voutsinas Spyros
Published: October 2021

The interaction of a helicopter rotor with the ground in hover flight is addressed numerically using a hybrid Eulerian–Lagrangian CFD model. When a helicopter takes off or lands, its wake interferes with the ground. This interaction, depending on the height-to-rotor diameter ratio, causes the altering of the rotor loading and performance as compared to the unconstrained case and gives rise to the development of a complex outwash flow field in the surrounding of the helicopter. The present study aims to characterize the interactional phenomena occurring in the early stages of the rotor wake development and in particular the interference of the starting vortex with the ground boundary layer and the effect of this interaction in the motion of the vortex in the rotor outwash flow. The hybrid CFD method employed combines a standard URANS compressible finite volume solver, the use of which is restricted to confined grids around solid bodies, and a Lagrangian approximation of the entire flow field in which conservation equations are solved in their material form, disctretized using particle representation of the flow quantities. The two methods are strongly coupled to each other through an appropriate iterative scheme. The main advantage of the proposed methodology is that it can conveniently handle complex configurations with several bodies that move independently from one another, with affordable computational cost. In this paper, thrust coefficient predictions of the hybrid model are compared to predictions of a free wake code and to experimental data indicating that consistent prediction of the rotor load requires the inclusion of the ground boundary layer in the analysis. Moreover, detailed comparisons of the rotor wake evolution predicted by the hybrid model are presented.
Smoke Patterns around Prescribed Fires in Australian Eucalypt Forests, as Measured by Low-Cost Particulate Monitors
Authors: Price Owen Francis , Forehead Hugh
Published: October 2021

Prescribed burns produce smoke pollution, but little is known about the spatial and temporal pattern because smoke plumes are usually small and poorly captured by State air-quality networks. Here, we sampled smoke around 18 forested prescribed burns in the Sydney region of eastern Australia using up to 11 Nova SDS011 particulate sensors and developed a Generalised Linear Mixed Model to predict hourly PM2.5 concentrations as a function of distance, fire size and weather conditions. During the day of the burn, PM2.5 tended to show hourly exceedances (indicating poor air quality) up to ~2 km from the fire but only in the downwind direction. In the evening, this zone expanded to up to 5 km and included upwind areas. PM2.5 concentrations were higher in still, cool weather and with an unstable atmosphere. PM2.5 concentrations were also higher in larger fires. The statistical model confirmed these results, identifying the effects of distance, period of the day, wind angle, fire size, temperature and C-Haines (atmospheric instability). The model correctly identified 78% of hourly exceedance and 72% of non-exceedance values in retained test data. Applying the statistical model predicts that prescribed burns of 1000 ha can be expected to cause air quality exceedances over an area of ~3500 ha. Cool weather that reduces the risk of fire escape, has the highest potential for polluting nearby communities, and fires that burn into the night are particularly bad.
Species-Specific Proteins in the Oviducts of Snail Sibling Species: Proteotranscriptomic Study of Littorina fabalis and L. obtusata
Authors: Lobov Arseniy A. , Babkina Irina Y. , Danilov Lavrentii G. , Masharskiy Alexey E. , Predeus Alexander V. , Mikhailova Natalia A. , Granovitch Andrei I. , Maltseva Arina L.
Published: October 2021

Genus Littorina subgenus Neritrema (Mollusca, Caenogastropoda) includes the “obtusata” group of closely related species (Littorina obtusata and L. fabalis). The anatomy of the adult reproductive system (pallial oviduct) is the only reliable feature used for species identification in females of these species. Reproductive system anatomy and reproduction-associated proteins often diverge between sibling species. Despite being of high evolutionary interest, the molecular basis of this divergence remains poorly understood. We performed proteotranscriptomic comparison of oviducts of L. obtusata and L. fabalis by RNA-seq on Illumina HiSeq 2500 and two-dimensional protein electrophoresis (2D DIGE) with MS/MS identification of the species-specific proteins. The interspecies differences in the oviduct were associated with (1) metabolic proteins reflecting overall physiological differences between L. obtusata and L. fabalis, (2) receptor proteins, and (3) transcripts related to transposable elements (TEs). Various receptors identified may recognize a wide variety of ligands from pathogen-associated molecular patterns to specific carbohydrates on the sperm surface. Therefore, these may participate in immune defense as well as in sperm storage and regulation. Species-specificity of multiple TE sequences (coding for reverse transcriptase and ribonuclease H) may indicate the important role of these genomic elements in the Littorina species divergence, which has not been reported previously.
A Meta-Analysis Indicates Positive Correlation between Genetic Diversity and Species Diversity
Authors: Xie Lei , Yang Yuan , Li Yao , Chen Shuifei , Feng Yueyao , Wang Ningjie , Lv Ting , Ding Hui , Wang Lu , Fang Yanming
Published: October 2021

Species diversity (SD) and genetic diversity (GD) are the two basic levels of biodiversity. In general, according to the consensus view, the parallel effects of environmental heterogeneity, area, and connectivity on two levels, can drive a positive correlation between GD and SD. Conversely, a negative correlation or no correlation would be expected if these effects are not parallel. Our understanding of the relationships between SD and GD among different ecosystems, sampling methods, species, and under climate change remains incomplete. In the present study, we conducted a hierarchical meta-analysis based on 295 observations from 39 studies and found a positive correlation between genetic diversity and species diversity (95% confidence interval, 7.6–22.64%). However, significant relationships were not found in some ecosystems when we conducted species–genetic diversity correlation analysis based on a single ecosystem. Moreover, the magnitudes of the correlations generally decreased with the number of sampling units and the annual average the temperature of sampling units. Our results highlight the positive correlation between GD and SD, thereby indicating that protecting SD involves protecting GD in conservation practice. Furthermore, our results also suggest that global increases in temperature during the 21st century will have significant impacts on global biodiversity.
Modeling Prostate Cancer Treatment Responses in the Organoid Era: 3D Environment Impacts Drug Testing
Authors: Van Hemelryk Annelies , Mout Lisanne , Erkens-Schulze Sigrun , French Pim J. , van Weerden Wytske M. , van Royen Martin E.
Published: October 2021

Organoid-based studies have revolutionized in vitro preclinical research and hold great promise for the cancer research field, including prostate cancer (PCa). However, experimental variability in organoid drug testing complicates reproducibility. For example, we observed PCa organoids to be less affected by cabazitaxel, abiraterone and enzalutamide as compared to corresponding single cells prior to organoid assembly. We hypothesized that three-dimensional (3D) organoid organization and the use of various 3D scaffolds impact treatment efficacy. Live-cell imaging of androgen-induced androgen receptor (AR) nuclear translocation and taxane-induced tubulin stabilization was used to investigate the impact of 3D scaffolds, spatial organoid distribution and organoid size on treatment effect. Scaffolds delayed AR translocation and tubulin stabilization, with Matrigel causing a more pronounced delay than synthetic hydrogel as well as incomplete tubulin stabilization. Drug effect was further attenuated the more centrally organoids were located in the scaffold dome. Moreover, cells in the organoid core revealed a delayed treatment effect compared to cells in the organoid periphery, underscoring the impact of organoid size. These findings indicate that analysis of organoid drug responses needs careful interpretation and requires dedicated read-outs with consideration of underlying technical aspects.
Glucocorticoid/Adiponectin Axis Mediates Full Activation of Cold-Induced Beige Fat Thermogenesis
Authors: Luo Liping , Wang Lu , Luo Yan , Romero Estevan , Yang Xin , Liu Meilian
Published: October 2021

Glucocorticoids (GCs), a class of corticosteroids produced by the adrenal cortex in response to stress, exert obesity-promoting effects. Although adaptive thermogenesis has been considered an effective approach to counteract obesity, whether GCs play a role in regulating cold stress-induced thermogenesis remains incompletely understood. Here, we show that the circulating levels of stress hormone corticosterone (GC in rodents) were significantly elevated, whereas the levels of adiponectin, an adipokine that was linked to cold-induced adaptive thermogenesis, were decreased 48 h post cold exposure. The administration of a glucocorticoid hydrocortisone downregulated adiponectin protein and mRNA levels in both WAT and white adipocytes, and upregulated thermogenic gene expression in inguinal fat. In contrast, mifepristone, a glucocorticoid receptor antagonist, enhanced adiponectin expression and suppressed energy expenditure in vivo. Mechanistically, hydrocortisone suppressed adiponectin expression by antagonizing PPARγ in differentiated 3T3-L1 adipocytes. Ultimately, adiponectin deficiency restored mifepristone-decreased oxygen consumption and suppressed the expression of thermogenic genes in inguinal fat. Taken together, our study reveals that the GCs/adiponectin axis is a key regulator of beige fat thermogenesis in response to acute cold stress.
The Role of Endogenous Metal Nanoparticles in Biological Systems
Authors: Vodyanoy Vitaly
Published: October 2021

The blood and tissues of vertebrate animals and mammals contain small endogenous metal nanoparticles. These nanoparticles were observed to be composed of individual atoms of iron, copper, zinc, silver, gold, platinum, and other metals. Metal nanoparticles can bind proteins and produce proteinaceous particles called proteons. A small fraction of the entire pool of nanoparticles is usually linked with proteins to form proteons. These endogenous metal nanoparticles, along with engineered zinc and copper nanoparticles at subnanomolar levels, were shown to be lethal to cultured cancer cells. These nanoparticles appear to be elemental crystalline metal nanoparticles. It was discovered that zinc nanoparticles produce no odor response but increase the odor reaction if mixed with an odorant. Some other metal nanoparticles, including copper, silver, gold, and platinum nanoparticles, do not affect the responses to odorants. The sources of metal nanoparticles in animal blood and tissues may include dietary plants and gut microorganisms. The solid physiological and biochemical properties of metal nanoparticles reflect their importance in cell homeostasis and disease.