bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Liver Function With MRI: Where Do We Stand?
Authors: Río Bártulos Carolina , Senk Karin , Schumacher Mona , Plath Jan , Kaiser Nico , Bade Ragnar , Woetzel Jan , Wiggermann Philipp
Published: April 2022

Liver disease and hepatocellular carcinoma (HCC) have become a global health burden. For this reason, the determination of liver function plays a central role in the monitoring of patients with chronic liver disease or HCC. Furthermore, assessment of liver function is important, e.g., before surgery to prevent liver failure after hepatectomy or to monitor the course of treatment. Liver function and disease severity are usually assessed clinically based on clinical symptoms, biopsy, and blood parameters. These are rather static tests that reflect the current state of the liver without considering changes in liver function. With the development of liver-specific contrast agents for MRI, noninvasive dynamic determination of liver function based on signal intensity or using T1 relaxometry has become possible. The advantage of this imaging modality is that it provides additional information about the vascular structure, anatomy, and heterogeneous distribution of liver function. In this review, we summarized and discussed the results published in recent years on this technique. Indeed, recent data show that the T1 reduction rate seems to be the most appropriate value for determining liver function by MRI. Furthermore, attention has been paid to the development of automated tools for image analysis in order to uncover the steps necessary to obtain a complete process flow from image segmentation to image registration to image analysis. In conclusion, the published data show that liver function values obtained from contrast-enhanced MRI images correlate significantly with the global liver function parameters, making it possible to obtain both functional and anatomic information with a single modality.
Optimizing Dosage-Specific Treatments in a Multi-Scale Model of a Tumor Growth
Authors: Ponce-de-Leon Miguel , Montagud Arnau , Akasiadis Charilaos , Schreiber Janina , Ntiniakou Thaleia , Valencia Alfonso
Published: April 2022

The emergence of cell resistance in cancer treatment is a complex phenomenon that emerges from the interplay of processes that occur at different scales. For instance, molecular mechanisms and population-level dynamics such as competition and cell–cell variability have been described as playing a key role in the emergence and evolution of cell resistances. Multi-scale models are a useful tool for studying biology at very different times and spatial scales, as they can integrate different processes occurring at the molecular, cellular, and intercellular levels. In the present work, we use an extended hybrid multi-scale model of 3T3 fibroblast spheroid to perform a deep exploration of the parameter space of effective treatment strategies based on TNF pulses. To explore the parameter space of effective treatments in different scenarios and conditions, we have developed an HPC-optimized model exploration workflow based on EMEWS. We first studied the effect of the cells’ spatial distribution in the values of the treatment parameters by optimizing the supply strategies in 2D monolayers and 3D spheroids of different sizes. We later study the robustness of the effective treatments when heterogeneous populations of cells are considered. We found that our model exploration workflow can find effective treatments in all the studied conditions. Our results show that cells’ spatial geometry and population variability should be considered when optimizing treatment strategies in order to find robust parameter sets.
SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases
Authors: Sun Yilun , Nitiss John L. , Pommier Yves
Published: April 2022

Topoisomerases play crucial roles in DNA metabolism that include replication, transcription, recombination, and chromatin structure by manipulating DNA structures arising in double-stranded DNA. These proteins play key enzymatic roles in a variety of cellular processes and are also likely to play structural roles. Topoisomerases allow topological transformations by introducing transient breaks in DNA by a transesterification reaction between a tyrosine residue of the enzyme and DNA. The cleavage reaction leads to a unique enzyme intermediate that allows cutting DNA while minimizing the potential for damage-induced genetic changes. Nonetheless, topoisomerase-mediated cleavage has the potential for inducing genome instability if the enzyme-mediated DNA resealing is impaired. Regulation of topoisomerase functions is accomplished by post-translational modifications including phosphorylation, polyADP-ribosylation, ubiquitylation, and SUMOylation. These modifications modulate enzyme activity and likely play key roles in determining sites of enzyme action and enzyme stability. Topoisomerase-mediated DNA cleavage and rejoining are affected by a variety of conditions including the action of small molecules, topoisomerase mutations, and DNA structural forms which permit the conversion of the short-lived cleavage intermediate to persistent topoisomerase DNA–protein crosslink (TOP-DPC). Recognition and processing of TOP-DPCs utilizes many of the same post-translational modifications that regulate enzyme activity. This review focuses on SUMOylation of topoisomerases, which has been demonstrated to be a key modification of both type I and type II topoisomerases. Special emphasis is placed on recent studies that indicate how SUMOylation regulates topoisomerase function in unperturbed cells and the unique roles that SUMOylation plays in repairing damage arising from topoisomerase malfunction.
Identification of Sodium Transients Through NaV1.5 Channels as Regulators of Differentiation in Immortalized Dorsal Root Ganglia Neurons
Authors: Martínez Antón L. , Brea José , Domínguez Eduardo , Varela María J. , Allegue Catarina , Cruz Raquel , Monroy Xavier , Merlos Manuel , Burgueño Javier , Carracedo Ángel , Loza María Isabel
Published: April 2022

Neuronal differentiation is a complex process through which newborn neurons acquire the morphology of mature neurons and become excitable. We employed a combination of functional and transcriptomic approaches to deconvolute and identify key regulators of the differentiation process of a DRG neuron-derived cell line, and we focused our study on the NaV1.5 ion channel (encoded by Scn5a) as a channel involved in the acquisition of DRG neuronal features. Overexpression of Scn5a enhances the acquisition of neuronal phenotypic features and increases the KCl-elicited hyperexcitability response in a DRG-derived cell line. Moreover, pharmacologic inhibition of the NaV1.5 channel during differentiation hinders the acquisition of phenotypic features of neuronal cells and the hyperexcitability increase in response to changes in the extracellular medium ionic composition. Taken together, these data highlight the relevance of sodium transients in regulating the neuronal differentiation process in a DRG neuron-derived cell line.
Examining for Cavum Septum Pellucidum and Ventricular Enlargement in Retired Elite-Level Rugby League Players
Authors: Stanwell Peter , Iverson Grant L. , Van Patten Ryan , Castellani Rudolph J. , McCrory Paul , Gardner Andrew J.
Published: April 2022

Objective

A cavum septum pellucidum (CSP) has been reported as a visible brain anomaly in normal individuals as well in some former combat and collision sport athletes. The appearance of CSP with fenestrations and ventricular enlargement are considered associated features of the neuropathological diagnosis of chronic traumatic encephalopathy. The current study examined CSP anatomic features and lateral ventricle size in retired elite rugby league players and controls.

Methods

Forty-one retired rugby league players and 41 healthy community controls, similar in age and education, underwent structural MRI scans. CSP grade, CSP length, corpus callosum septal length, and Evans' ratio (for lateral ventricle size) were rated by two of the current study authors. All participants also self-reported concussion exposure histories, depressive symptoms, daytime sleepiness, and impulsivity. They completed a neuropsychological test battery assessing premorbid intellectual functioning, attention, processing speed, language, visuospatial skills, memory, and aspects of executive functioning.

Results

The two raters had high agreement for CSP grade (Cohen's κ = 0.80), CSP length [intraclass correlation (ICC) = 0.99], corpus callosum septal length (ICC = 0.73), the CSP/septal ratio (ICC = 0.99), and the Evans' ratio (ICC = 0.75). Twenty-five retired players (61.0%) had an abnormal CSP compared to 17 controls [41.5%; χ(1, 82)2 = 3.12, p = 0.08, odds ratio = 2.21]. The CSP/septal ratio was larger for retired players than for the controls. The Evans' ratio did not differ between the two groups. In the retired rugby league players (n = 41), those with normal (n = 16) and abnormal (n = 25) CSP grades did not differ across age, age of first exposure to collision sport, years of sport exposure, concussion history, or 23 clinical and cognitive variables.

Conclusion

This study revealed a difference in the size of the CSP between retired professional rugby league players and controls. There was no significant difference in the size of the ventricles between the two groups. There were no significant differences between those with vs. without an abnormal CSP on age of first exposure to rugby league, years of exposure to repetitive neurotrauma, number of lifetime concussions, depression, impulsivity, perceived cognitive decline, or on any neuropsychological test.
Grace Under Pressure: Resiliency of Quality Monitoring of Stroke Care During the Covid-19 Pandemic in Mexico City
Authors: Medina-Rioja Raul , González-Calderón Gina , Saldívar-Dávila Sergio , Estrada Saúl Alexander , Gayón-Lombardo Erika , Somerville-Briones Nicole , Calleja-Castillo Juan Manuel
Published: April 2022

Stroke is one of the leading causes of death and disability among adults worldwide. The World Health Organization (WHO) officially declared a COVID-19 pandemic on March 11, 2020. The first case in Mexico was confirmed in February 2020, subsequently becoming one of the countries most affected by the pandemic. In 2020, The National Institute of Neurology of Mexico started a Quality assurance program for stroke care, consisting of registering, monitoring and feedback of stroke quality measures through the RES-Q platform. We aim to describe changes in the demand for stroke healthcare assistance at the National Institute of Neurology and Neurosurgery during the pandemic and the behavior of stroke quality metrics during the prepandemic and the pandemic periods. For this study, we analyzed data for acute stroke patients registered in the RES-Q platform, in the prepandemic (November 2019 to February 2020) and pandemic (March-December 2020) periods in two groups, one prior to the pandemic. During the pandemic, there was an increase in the total number of assessed acute stroke patients at our hospital, from 474 to 574. The average time from the onset of symptoms to hospital arrival (Onset to Door Time—OTD) for all stroke patients (thrombolyzed and non-thrombolyzed) increased from 9 h (542 min) to 10.3 h (618.3 min) in the pandemic group. A total of 135 acute stroke patients were enrolled in this registry. We found the following results: Patients in both groups were studied with non-contrast computed tomography (NNCT), computed tomography angiography (CTA), magnetic resonance angiography (MRA), digital subtraction angiography (DSA) or more frequently in the pandemic period (early carotid imaging, Holter monitoring) as needed. Treatment for secondary prevention (antihypertensives, antiplatelets, statins) did not differ. Frequency of performing and documenting the performance of NIHSS scale at arrival and early dysphagia test improved. There was an increase in alteplase use from 21 to 42% (p = 0.03). There was a decrease in door to needle time (46 vs. 39 min p = 0.30). After the implementation of a stroke care protocol and quality monitoring system, acute stroke treatment in our institution has gradually improved, a process that was not thwarted during the COVID-19 pandemic.
Role of Inner Ear Macrophages and Autoimmune/Autoinflammatory Mechanisms in the Pathophysiology of Inner Ear Disease
Authors: Miwa Toru , Okano Takayuki
Published: April 2022

Macrophages play important roles in tissue homeostasis and inflammation. Recent studies have revealed that macrophages are dispersed in the inner ear and may play essential roles in eliciting an immune response. Autoinflammatory diseases comprise a family of immune-mediated diseases, some of which involve sensorineural hearing loss, indicating that similar mechanisms may underlie the pathogenesis of immune-mediated hearing loss. Autoimmune inner ear disease (AIED) is an idiopathic disorder characterized by unexpected hearing loss. Tissue macrophages in the inner ear represent a potential target for modulation of the local immune response in patients with AIED/autoinflammatory diseases. In this review, we describe the relationship between cochlear macrophages and the pathophysiology of AIED/autoinflammatory disease.
Dietary Nutrition and Gut Microbiota Composition in Patients With Hypertensive Disorders of Pregnancy
Authors: Yu Jinran , Zhang Bo , Miao Tingting , Hu Haiting , Sun Yongye
Published: April 2022

Objective

The aim is to explore the intakes of dietary nutrients and the changes of gut microbiota composition among patients with hypertensive disorders of pregnancy (HDP) and provide a theoretical basis for the prevention and treatment of HDP.

Methods

This study was conducted at the Maternal and Child Health Care Hospital of Changzhou. A total of 170 pregnant women (72 patients with HDP in the case group and 98 healthy pregnant women in the control group) in the third trimester were enrolled. Dietary nutrient intakes were assessed through a food frequency questionnaire survey. Fresh fecal samples were aseptically collected, and 16S rDNA sequencing was conducted. The intakes of dietary nutrients and the diversity and relative abundance of gut microbiota were compared between pregnant women with and without HDP. A logistic regression model was used to investigate the association between differential gut microbial genera and the risk of HDP.

Results

The daily dietary intakes of vitamin A and vitamin C in pregnant women with HDP were significantly lower than those in the control group. The relative abundances of Bacteroidota, Bacteroidaceae, and Bacteroides were increased, and the relative abundances of Actinobacteriota, Lachnospiraceae, Prevotellaceae, Bifidobacteriaceae, Blautia, Prevotella, and Bifidobacterium were decreased in women with HDP compared with those in the controls. In addition, the relative abundance of Bifidobacterium was positively correlated with dietary intakes of vitamin C and vitamin E in patients with HDP. After adjustment for confounding factors, the odds ratio (95% confidence interval) of HDP for the relative abundance of Bifidobacterium was 0.899 (0.813, 0.995).

Conclusion

The composition of gut microbiota in pregnant women with HDP was significantly changed compared with that of healthy controls. The relative abundance of Bifidobacterium was negatively associated with HDP. Moreover, dietary vitamin C and gut Bifidobacterium may cooperatively contribute to reduce the risk of HDP.
Gestational Age Variation in Human Placental Drug Transporters
Authors: Goetzl Laura , Darbinian Nune , Merabova Nana , Devane Lindsay C. , Ramamoorthy Sammanda
Published: April 2022

Patient and providers’ fear of fetal exposure to medications may lead to discontinuation of treatment, disease relapse, and maternal morbidity. Placental drug transporters play a critical role in fetal exposure through active transport but the majority of data are limited to the 3rd trimester, when the majority of organogenesis has already occurred. Our objective was to define gestational age (GA) dependent changes in protein activity, expression and modifications of five major placental drug transporters: SERT, P-gp, NET, BCRP and MRP3. Apical brush border membrane fractions were prepared from fresh 1st, 2nd and 3rd trimester human placentas collected following elective pregnancy termination or planned cesarean delivery. A structured maternal questionnaire was used to identify maternal drug use and exclude exposed subjects. Changes in placental transporter activity and expression relative to housekeeping proteins were quantified. There was evidence for strong developmental regulation of SERT, NET, P-gp, BCRP and MRP3. P-gp and BCRP decreased with gestation (r = −0.72, p < 0.001 and r = −0.77, p < 0.001, respectively). Total SERT increased with gestation but this increase was due to a decrease in SERT cleavage products across trimesters. Uncleaved SERT increased with GA (r = 0.89, p < 0.001) while cleaved SERT decreased with GA (r = −0.94, p < 0.001). Apical membrane NET overall did not appear to be developmentally regulated (r = −0.08, p = 0.53). Two forms of MRP3 were identified; the 50 kD form did not change across GA; the 160 kD form was steady in the 1st and 2nd trimester and increased in the 3rd trimester (r = 0.24, p = 0.02). The 50 kD form was expressed at higher levels. The observed patterns of SERT, NET P-gp, BCRP and MRP3 expression and activity may be associated with transporter activity or decreased placental permeability in the 1st trimester to transporter specific substrates including commonly used psychoactive medications such as anti-depressants, anti-psychotics, and amphetamines, while transport of nutrients and serotonin is important in the 1st trimester. Overall these observations are consistent with a strong protective effect during organogenesis. 3rd trimester estimates of fetal exposure obtained from cord blood likely significantly overestimate early fetal exposure to these medications at any fixed maternal dose.
SHP2 Inhibitors Show Anti-Myeloma Activity and Synergize With Bortezomib in the Treatment of Multiple Myeloma
Authors: Zhou Pan , Xiao Mengyu , Li Weiya , Sun Xiaobai , Bai Yanliang , Meng Feiying , Zhu Zunmin , Yuan Weiping , Sun Kai
Published: April 2022

Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. The protein tyrosine phosphatase SHP2 is a central node regulating RAS/mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) signaling pathway which plays a crucial role in the pathogenesis and proteasome inhibitor (PI) resistance of MM. Several preclinical studies have demonstrated that SHP2 inhibitors exerted antitumor activity in cancer-harboring diverse mutations in the RAS pathway, offering the potential for targeting myeloma. In this study, we showed that pharmacological inhibition of SHP2 activity using SHP099 and RMC-4550 efficiently inhibited the proliferation of MM cells by inducing apoptosis and cell cycle arrest. As per the mechanism, SHP2 inhibitors activated the level of cleaved caspase3, BAK, and P21 and downregulated ERK phosphorylation in MM cells. Moreover, the blockade of SHP2 exhibited anti-myeloma effect in vivo in a mouse xenograft model. In addition, SHP2 inhibitors synergized the antineoplastic effect of bortezomib in bortezomib-sensitive MM cells and showed identical efficacy in targeting bortezomib-resistant MM cells. Overall, our findings suggest that SHP2-specific inhibitors trigger anti-myeloma activity in vitro and in vivo by regulating the ERK pathway and enhancing cytotoxicity of bortezomib, providing therapeutic benefits for both bortezomib naïve and resistant MM.
Impact of the CYP2D6 Genotype on Metoprolol Tolerance and Adverse Events in Elderly Chinese Patients With Cardiovascular Diseases
Authors: Chen Jianqiao , Zheng Jin , Zhu Zifan , Hao Benchuan , Wang Miao , Li Huiying , Cai Yulun , Wang Shiqi , Li Jun , Liu Hongbin
Published: April 2022

The latest consensus has changed CYP2D6 genotyping among Chinese population, while its impact on metoprolol tolerance and adverse events in elderly Chinese patients with cardiovascular diseases remains unclear. In this study, we prospectively included elderly patients who started metoprolol treatment for cardiovascular indications. According to the latest consensus on CYP2D6 genotype-to-phenotype translation, the patients were categorized as normal, intermediate, or poor metabolizers (NMs, IMs, or PMs, respectively) by detecting the presence of the CYP2D6*1, *2, *5, *10, and *14. Logistic regression model was used to analyze the correlation between the CYP2D6 phenotype and incidence of adverse events, which were assessed over a 12-week period. In this study, there were 651 (62.7%) NMs, 385 (37.1%) IMs, and 3 (0.3%) PMs. After 12 weeks of follow-up, compared with NMs, IMs had the lower maintenance dose [50.0 (25.0–50.0) mg/day vs. 25.0 (25.0–50.0) mg/day, p < 0.001] and lower weight-adjusted maintenance doses (0.52 ± 0.25 mg/day/kg vs. 0.42 ± 0.22 mg/day/kg, p < 0.001), and had higher incidence of postural hypotension (6.0% vs. 10.9%, p = 0.006), bradycardia (21.5% vs. 28.6%, p = 0.011), asystole (0.8% vs. 3.1%, p = 0.009) and syncope (2.0% vs. 6.2%, p = 0.001). In logistic regression model, the overall incidence of adverse events was 1.37-fold larger in IMs than in NMs (odds ratio = 1.37, 95% confidence interval = 1.05–1.79, p = 0.021). We conclude that IMs have lower tolerance and higher incidence of metoprolol-related adverse events than NMs in elderly Chinese patients with cardiovascular diseases. CYP2D6 genotyping is justifiable in elderly patients to minimize the risk of adverse events and ensure the benefits of metoprolol.
Cascaded Progressive Generative Adversarial Networks for Reconstructing Three-Dimensional Grayscale Core Images From a Single Two-Dimensional Image
Authors: Li Yang , Jian Pengpeng , Han Guanghui
Published: April 2022

It is very challenging to accurately understand and characterize the internal structure of three-dimensional (3D) rock masses using geological monitoring and conventional laboratory measures. One important method for obtaining 3D core images involves reconstructing their 3D structure from two-dimensional (2D) core images. However, traditional 2D–3D reconstruction methods are mostly designed for binary core images, rather than grayscale images. Furthermore, the reconstruction structure cannot reflect the gray level distribution of the core. Here, by combining the dimension promotion theory in super-dimension (SD) reconstruction and framework of deep learning, we propose a novel convolutional neural network framework, the cascaded progressive generative adversarial network (CPGAN), to reconstruct 3D grayscale core images. Within this network, we propose a loss function based on the gray level distribution and pattern distribution to maintain the texture information of the reconstructed structure. Simultaneously, by adopting SD dimension promotion theory, we set the input and output of every single node of the CPGAN network to be deep gray-padding structures of equivalent size. Through the cascade of every single node network, we thus ensured continuity and variability between the reconstruction layers. In addition, we used 3D convolution to determine the spatial characteristics of the core. The reconstructed 3D results showed that the gray level information in the 2D image were accurately reflected in the 3D space. This proposed method can help us to understand and analyze various parameter characteristics in cores.
The Relationship Between e-Health Literacy and Breast Cancer Literacy Among Saudi Women
Authors: Almoajel Alia , Alshamrani Samar , Alyabsi Mesnad
Published: April 2022

Breast cancer is the most common cancer in women and represents a significant burden among women worldwide. The concept of health literacy is relatively new to the Gulf states, particularly to Saudi Arabia. Research on this topic is scarce, and no study has empirically explored the influence of e-health literacy on breast cancer literacy. The purpose of this study was to measure the impact of e-health literacy on breast cancer literacy among Saudi women in Riyadh city, Saudi Arabia. A cross-sectional survey was conducted online in a cohort of 336 women and disseminated via social media using the e-Health Literacy Scale (eHEALS) and Breast Cancer Literacy Assessment Tool (Breast-CLAT). Multiple regression analysis was executed to identify the sociodemographic factors that influence the e-health literacy and breast cancer literacy of participants. The participants showed high level of e-health literacy with total eHEALS score of 28.79, and better breast cancer literacy with total Breast-CLAT score of 23.44. This study yielded three significant findings: (1) e-health literacy is influenced by age and education which implies that youngest participants showed higher eHEALS scores than their older counterparts and that having increased education level reflected increased eHEALS scores, (2) breast cancer literacy is predicted by education and income which suggests that those who have higher levels of education and higher monthly incomes have increased levels of breast cancer literacy, and (3) breast cancer literacy and e-health literacy were associated which shows that participants with higher eHEALS scores were more likely have increased level of breast cancer literacy. The study revealed that the participants had high level of e-health literacy which correlated to their increased level of breast cancer literacy. The study findings implied that it is important for Saudi women to possess high levels of e-health literacy about breast cancer as more breast cancer educational resources are online nowadays.
An Implementation Strategy to Develop Sustainable Surveillance Activities Through Adoption of a Target Operating Model
Authors: Lee Natalie K. , Stewart Miles A. , Dymond Jessica S. , Lewis Sheri L.
Published: April 2022

The increasing threat of emerging and re-emerging pathogens calls for a shared vision toward developing and maintaining global surveillance mechanisms to enable rapid characterization of pathogens, a foundational requirement for effective outbreak response. Efforts establishing new surveillance programs in low- and middle-income countries (LMICs) have repeatedly led to siloed systems that prove unsustainable or ineffective due to narrowly focused approaches, competing priorities, or lack of resourcing. Barriers inherent to LMICs, such as resource limitations, workforce strain, unreliable supply chains, and lack of enduring champions exacerbate implementation and sustainability challenges. In order to improve adoption and endurance of new surveillance programs, more effective design and implementation of programs is needed to adequately reflect stakeholder needs and simultaneously support population-level disease monitoring and clinical decision-making across a range of chronic and acute health issues. At the heart of this cross-sectorial integration between clinical care and public health initiatives are emerging technologies and data modalities, including sequencing data. In this prospective, we propose an implementation strategy for genomics-based surveillance initiatives in LMICs founded on the use of a target operating model. Adoption of a target operating model for the design and implementation of genomic surveillance programs will ensure programs are agile, relevant, and unified across diverse stakeholder communities, thereby increasing their overall impact and sustainability.
Treatment of a Double Cancer Patient With Primary Inferior Vena Cava Sarcoma and Lung Adenocarcinoma: A Case Report and Literature Review
Authors: Guo Xiaohu , Wei Zhengang , Wang Mancai , Zhang Youcheng
Published: April 2022

Background

Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignancy. Here, we present the case of a 38-year-old woman with a primary IVC leiomyosarcoma and lung adenocarcinoma.

Case Report

The patient, a 38-year-old Chinese female, presented to the general surgical outpatients clinic with a 18-month history of intermittent right upper abdominal pain. Contrast-enhanced computed tomography (CT) showed a tumor of IVC (3.4*2.7 cm) extending to the renal veins. In addition, chest CT revealed a mass lesion in the upper left lung lobe. Then, the patient underwent resection of the IVC tumor and wedge resection of the upper lobe of the left lung. The patient then received gefitinib (250 mg/day) as a maintenance therapy until the tumor recurrence or metastasis in the follow-up period. Pulmonary metastasis of the sarcoma were first diagnosed 20 month after the resection of the IVC leiomyosarcoma. So the patient again received thoracoscopic wedge pneumonectomy, and it was confirmed to be metastasis of IVC leiomyosarcoma. The patient received oral anlotinib treatment (12 mg once daily) after the last operation. During on-going regular follow-up visits no evidence of recurrence or metastasis was observed from December 2020 to October 2021.

Conclusions

The patient with a primary IVC leiomyosarcoma and lung adenocarcinoma is extremely rare. Surgery is still an effective treatment for patients with a primary IVC leiomyosarcoma and lung adenocarcinoma at present.
Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants
Authors: Rainard Pascal , Foucras Gilles , Martins Rodrigo P.
Published: April 2022

Mastitis is one of the greatest issues for the global dairy industry and controlling these infections by vaccination is a long-sought ambition that has remained unfulfilled so far. In fact, gaps in knowledge of cell-mediated immunity in the mammary gland (MG) have hampered progress in the rational design of immunization strategies targeting this organ, as current mastitis vaccines are unable to elicit a strong protective immunity. The objectives of this article are, from a comprehensive and critical review of available literature, to identify what characterizes adaptive immunity in the MG of ruminants, and to derive from this analysis research directions for the design of an optimal vaccination strategy. A peculiarity of the MG of ruminants is that it does not belong to the common mucosal immune system that links the gut immune system to the MG of rodents, swine or humans. Indeed, the MG of ruminants is not seeded by lymphocytes educated in mucosal epithelia of the digestive or respiratory tracts, because the mammary tissue does not express the vascular addressins and chemokines that would allow the homing of memory T cells. However, it is possible to elicit an adaptive immune response in the MG of ruminants by local immunization because the mammary tissue is provided with antigen-presenting cells and is linked to systemic mechanisms. The optimal immune response is obtained by luminal exposure to antigens in a non-lactating MG. The mammary gland can be sensitized to antigens so that a local recall elicits neutrophilic inflammation and enhanced defenses locally, resulting from the activation of resident memory lymphocytes producing IFN-γ and/or IL-17 in the mammary tissue. The rational exploitation of this immunity by vaccination will need a better understanding of MG cell-mediated immunity. The phenotypic and functional characterization of mammary antigen-presenting cells and memory T cells are amongst research priorities. Based on current knowledge, rekindling research on the immune cells that populate the healthy, infected, or immunized MG appears to be a most promising approach to designing efficacious mastitis vaccines.
An Improved Proximal Policy Optimization Method for Low-Level Control of a Quadrotor
Authors: Xue Wentao , Wu Hangxing , Ye Hui , Shao Shuyi
Published: April 2022

In this paper, a novel deep reinforcement learning algorithm based on Proximal Policy Optimization (PPO) is proposed to achieve the fixed point flight control of a quadrotor. The attitude and position information of the quadrotor is directly mapped to the PWM signals of the four rotors through neural network control. To constrain the size of policy updates, a PPO algorithm based on Monte Carlo approximations is proposed to achieve the optimal penalty coefficient. A policy optimization method with a penalized point probability distance can provide the diversity of policy by performing each policy update. The new proxy objective function is introduced into the actor–critic network, which solves the problem of PPO falling into local optimization. Moreover, a compound reward function is presented to accelerate the gradient algorithm along the policy update direction by analyzing various states that the quadrotor may encounter in the flight, which improves the learning efficiency of the network. The simulation tests the generalization ability of the offline policy by changing the wing length and payload of the quadrotor. Compared with the PPO method, the proposed method has higher learning efficiency and better robustness.
Multi-Mode Shape Control of Active Compliant Aerospace Structures Using Anisotropic Piezocomposite Materials in Antisymmetric Bimorph Configuration
Authors: Wang Xiaoming , Hu Xinhan , Huang Chengbin , Zhou Wenya
Published: April 2022

The mission performance of future advanced aerospace structures can be synthetically improved via active shape control utilizing piezoelectric materials. Multiple work modes are required. Bending/twisting mode control receives special attention for many classic aerospace structures, such as active reflector systems, active blades, and compliant morphing wings. Piezoelectric fiber composite (Piezocomposite) material features in-plane anisotropic actuation, which is very suitable for multiple work modes. In this study, two identical macro-fiber composite (MFC) actuators of the F1 type were bonded to the base plate structure in an “antisymmetric angle-ply bimorph configuration” in order to achieve independent bending/twisting shape control. In terms of the finite element model and homogenization strategy, the locations of bimorph MFCs were determined by considering the effect of trade-off control capabilities on the bending and twisting shapes. The modal characteristics were investigated via both experimental and theoretical approaches. The experimental tests implied that the shape control accuracy was heavily reduced due to various uncertainties and nonlinearities, including hysteresis and the creep effect of the actuators, model errors, and external disturbances. A multi-mode feedback control law was designed and the experimental tests indicated that synthetic (independent and coupled) bending/twisting deformations were achieved with improved shape accuracy. This study provides a feasible multi-mode shape control approach with high surface accuracy, especially by employing piezocomposite materials.
Extraction of Bioactive Metabolites from Achillea millefolium L. with Choline Chloride Based Natural Deep Eutectic Solvents: A Study of the Antioxidant and Antimicrobial Activity
Authors: Ivanović Milena , Grujić Dragana , Cerar Janez , Islamčević Razboršek Maša , Topalić-Trivunović Ljiljana , Savić Aleksandar , Kočar Drago , Kolar Mitja
Published: April 2022

In this study, the extraction efficiency of natural deep eutectic solvents (NADES) based on choline chloride as a hydrogen bond acceptor (HBA) and five different hydrogen bond donors (HBD; lactic acid, 1,4-butanediol, 1,2-propanediol, fructose and urea) was evaluated for the first time for the isolation of valuable bioactive compounds from Achillea millefolium L. The phytochemical profiles of NADES extracts obtained after ultrasound-assisted extraction were evaluated both spectrophotometrically (total phenolic content (TPC) and antioxidant assays) and chromatographically (UHPLC-MS and HPLC-UV). The results were compared with those obtained with 80% ethanol, 80% methanol, and water. The highest TPC value was found in the lactic acid-based NADES (ChCl-LA), which correlated with the highest antioxidant activity determined by the FRAP analysis. On the other hand, the highest antiradical potential against ABTS+• was determined for urea-based NADES. Phenolic acids (chlorogenic acid and dicaffeoylquinic acid isomers), flavones (luteolin and apigenin), and their corresponding glucosides were determined as the dominant individual phenolic compounds in all extracts. The antibacterial and antifungal properties of the extracts obtained against four bacterial cultures and two yeasts were evaluated using two methods: the agar dilution method to obtain the minimum inhibitory concentration (MIC) and the minimum bactericidal or fungicidal concentration (MBC or MFC), and the disc diffusion method. ChCl-LA had the lowest MIC and MBC/MFC with respect to all microorganisms, with an MIC ranging from 0.05 mg mL−1 to 0.8 mg mL−1, while the water extract had the weakest inhibitory activity with MIC and MBC/MFC higher than 3.2 mg mL−1.
Identification of Coenzyme Q10 and Skeletal Muscle Protein Biomarkers as Potential Factors to Assist in the Diagnosis of Sarcopenia
Authors: Yen Chi-Hua , Chang Po-Sheng , Chang Yu-Hsun , Lin Ping-Ting
Published: April 2022

The aim of this study was to explore the use of coenzyme Q10 and skeletal muscle protein biomarkers in the diagnosis of sarcopenia. Subjects with or without sarcopenia were recruited. The anthropometric, muscle strength and endurance measurements were assessed. Muscle proteins (albumin and creatine kinase), myokines (irisin and myostatin), and the coenzyme Q10 level were measured. Approximately half of the subjects suffered from a low coenzyme Q10 concentration (<0.5 μM). The levels of creatinine kinase and irisin were significantly lower in subjects with sarcopenia (p ≤ 0.05). In receiver operating characteristic analyses, irisin and creatine kinase showed a better prediction capability for sarcopenia (area under the curve, irisin: 0.64 vs. creatinine kinase: 0.61) than other biomarkers. Additionally, a low level of irisin (<118.0 ng/mL, odds ratio, 6.46, p < 0.01), creatine kinase (<69.5 U/L, odds ratio, 3.31, p = 0.04), or coenzyme Q10 (<0.67 μM, odds ratio, 9.79, p < 0.01) may increase the risk for sarcopenia even after adjusting for confounders. Since the levels of coenzyme Q10 and muscle biomarkers, such as irisin and creatine kinase, are associated with sarcopenia, we suggest they could be used as candidate markers to assist in the diagnosis of sarcopenia.
Estradiol and Estrogen-like Alternative Therapies in Use: The Importance of the Selective and Non-Classical Actions
Authors: Farkas Szidónia , Szabó Adrienn , Hegyi Anita Emőke , Török Bibiána , Fazekas Csilla Lea , Ernszt Dávid , Kovács Tamás , Zelena Dóra
Published: April 2022

Estrogen is one of the most important female sex hormones, and is indispensable for reproduction. However, its role is much wider. Among others, due to its neuroprotective effects, estrogen protects the brain against dementia and complications of traumatic injury. Previously, it was used mainly as a therapeutic option for influencing the menstrual cycle and treating menopausal symptoms. Unfortunately, hormone replacement therapy might be associated with detrimental side effects, such as increased risk of stroke and breast cancer, raising concerns about its safety. Thus, tissue-selective and non-classical estrogen analogues have become the focus of interest. Here, we review the current knowledge about estrogen effects in a broader sense, and the possibility of using selective estrogen-receptor modulators (SERMs), selective estrogen-receptor downregulators (SERDs), phytoestrogens, and activators of non-genomic estrogen-like signaling (ANGELS) molecules as treatment.
Isolation of Neoantigen-Specific Human T Cell Receptors from Different Human and Murine Repertoires
Authors: Grunert Corinna , Willimsky Gerald , Peuker Caroline Anna , Rhein Simone , Hansmann Leo , Blankenstein Thomas , Blanc Eric , Beule Dieter , Keller Ulrich , Pezzutto Antonio , Busse Antonia
Published: April 2022

(1) Background: Mutation-specific T cell receptor (TCR)-based adoptive T cell therapy represents a truly tumor-specific immunotherapeutic strategy. However, isolating neoepitope-specific TCRs remains a challenge. (2) Methods: We investigated, side by side, different TCR repertoires—patients’ peripheral lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs), PBLs of healthy donors, and a humanized mouse model—to isolate neoepitope-specific TCRs against eight neoepitope candidates from a colon cancer and an ovarian cancer patient. Neoepitope candidates were used to stimulate T cells from different repertoires in vitro to generate neoepitope-specific T cells and isolate the specific TCRs. (3) Results: We isolated six TCRs from healthy donors, directed against four neoepitope candidates and one TCR from the murine T cell repertoire. Endogenous processing of one neoepitope, for which we isolated one TCR from both human and mouse-derived repertoires, could be shown. No neoepitope-specific TCR could be generated from the patients’ own repertoire. (4) Conclusion: Our data indicate that successful isolation of neoepitope-specific TCRs depends on various factors such as the heathy donor’s TCR repertoire or the presence of a tumor microenvironment allowing neoepitope-specific immune responses of the host. We show the advantage and feasibility of using healthy donor repertoires and humanized mouse TCR repertoires to generate mutation-specific TCRs with different specificities, especially in a setting when the availability of patient material is limited.
RBM24 in the Post-Transcriptional Regulation of Cancer Progression: Anti-Tumor or Pro-Tumor Activity?
Authors: Shi De-Li
Published: April 2022

RNA-binding proteins are critical post-transcriptional regulators of gene expression. They are implicated in a wide range of physiological and pathological processes by modulating nearly every aspect of RNA metabolisms. Alterations in their expression and function disrupt tissue homeostasis and lead to the occurrence of various cancers. RBM24 is a highly conserved protein that binds to a large spectrum of target mRNAs and regulates many post-transcriptional events ranging from pre-mRNA splicing to mRNA stability, polyadenylation and translation. Studies using different animal models indicate that it plays an essential role in promoting cellular differentiation during organogenesis and tissue regeneration. Evidence is also accumulating that its dysregulation frequently occurs across human cancers. In several tissues, RBM24 clearly functions as a tumor suppressor, which is consistent with its inhibitory potential on cell proliferation. However, upregulation of RBM24 in other cancers appears to promote tumor growth. There is a possibility that RBM24 displays both anti-tumor and pro-tumor activities, which may be regulated in part through differential interactions with its protein partners and by its post-translational modifications. This makes it a potential biomarker for diagnosis and prognosis, as well as a therapeutic target for cancer treatment. The challenge remains to determine the post-transcriptional mechanisms by which RBM24 modulates gene expression and tumor progression in a context- or background-dependent manner. This review discusses recent findings on the potential function of RBM24 in tumorigenesis and provides future directions for better understanding its regulatory role in cancer cells.
Bone Development and Disease in Infants
Authors: Pavone Vito
Published: April 2022

The aim of this Editorial is to introduce the content of the present Special Issue, entitled “Bone Development and Disease in Infants” [...]
Sources and Types of Social Supports and Their Association with Mental Health Symptoms and Life Satisfaction among Young Adults with a History of Out-of-Home Care
Authors: Evans Rhiannon , Katz Colleen C. , Fulginiti Anthony , Taussig Heather
Published: April 2022

Young adults with a history of out-of-home care report poorer mental health and life satisfaction compared to non-care-experienced peers. Social support is a known protective factor for mental health. There is limited evidence, however, on the relationship between sources (e.g., family members) and types (e.g., information) of social support and mental health symptoms and life satisfaction in this population. Reporting cross-sectional survey data from 215 young adults aged 18–22 years with a history of out-of-home care, the current study conducted descriptive, bivariate, and linear regression analysis to examine the different sources and types of support young adults receive and their relation to mental health symptoms and life satisfaction. Participants had high levels of support from family members, friends, and other adults. Most participants had informational support, but less than half had consistent material support. Regression analyses demonstrated that having enough informational and material support were associated with fewer mental health symptoms. Having family support and material support were associated with greater life satisfaction. Further longitudinal research is needed to understand the trajectory between social supports and mental health functioning and life satisfaction.
Individual and Contextual Risk and Protective Factors for Suicidal Thoughts and Behaviors among Black Adolescents with Arrest Histories
Authors: Quinn Camille R. , Duprey Erinn B. , Boyd Donte T. , Lynch Raven , Mitchell Micah , Ross Andrew , Handley Elizabeth D. , Cerulli Catherine
Published: April 2022

Black adolescents in the United States have experienced an increase in suicidal thoughts and behaviors (STBs). Since Black adolescents are overrepresented in the youth punishment system, more research is needed to investigate correlates of STBs for this population. The purpose of this paper is to explore and establish correlates of individual, family, and community risk and protective factors and their relationship to lifetime STBs in a national sample of Black youth with arrest histories. Guided by an intersectional eco-behavioral lens, we investigated individual, family and contextual risk and protective factors for STBs among a national sample of justice-involved Black youth aged 12–17 with a history of arrest (n = 513). We used logistic regression models to test risk and protective factors for STBs. Among the sample, 9.78% endorsed suicidal ideation, and 7.17% endorsed a previous suicide attempt. Further, gender (female) and depression severity were risk factors for STBs, while positive parenting and religiosity were protective factors for STBs. School engagement was associated with lower levels of suicidal ideation. The findings suggest suicide prevention and intervention efforts should identify developmentally salient risk and protective factors to reduce mental health burden associated with STBs and concurrent alleged law-breaking activity of Black youth.
Relevance of Colloid Inherent Salt Estimated by Surface Complexation Modeling of Surface Charge Densities for Different Silica Colloids
Authors: Goel Alok , Lützenkirchen Johannes
Published: April 2022

Potentiometric titrations have been routinely used to measure the proton-related surface charge density (SCD) of particles in solution. Here, we quantify the SCD of silica nanoparticles (NPs) that are commercially available as charge-stabilized colloids (by the addition of NaOH) in the presence of known amounts of added NaCl. The experimental results are simulated by surface complexation models (SCMs) of the electrical double layer (EDL). The modeling results suggest that involving only the added NaCl electrolyte yields poor agreement between the experiment and the best achievable fit. An increase in the Na concentration accounting for the colloid inherent salt (CIS) associated with these charge-stabilized colloids results in much better simulations. In the available literature, this CIS has often been disregarded. However, in the modeling, the total concentration of Na must be known for a consistent mole balance and derivation of reliable ion-pair binding constants. If the CIS is not accounted for or the original suspensions are not dialyzed, the presence of CIS renders the study of those colloids difficult, particularly when investigating specific ion effects, since the CIS always interferes. In the present work, we show that the SCM-estimated amount of CIS from varying the total salt and solid concentration agrees surprisingly well with the manufacturer specification.