bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspects of Comic Representation in A Play of the May 18th Democratic Uprising: Focusing on The Champon and The Blue Days
Authors:   The Korean Society of Culture and Convergence, Baek so youn
Published: March 2023

Plays to remember and recreate the May 18 Democratic Uprising continued to be made. Among them, Yoon Jung-hwan's The Champon and Ko Sun-woong's The Blue days were popularly successful, utilizing comedic elements, unlike the existing plays based on May 18. The Champon sharply satirizes the reality of the time through the ignorance of the character and the coincidence of the incident, but induces laughter and empathy from the audience. On the other hand, in the case of The Blue Days, the original work with a strong melodramatic character is newly interpreted in the production process and is comicly transformed. Comic elements seen in the character's lines and acting block the audience from fully immersed in the situation in the play. Through this, the meaning of the case was made to be considered. These two works are of value and significance in that they summon the past to the living present and show new possibilities to continuously remember and commemorate May 18.
Studies on Maxwell Equations, Electromagnetic Wave Equations and Functions in Cosmological Special Relativity Theory
Authors: CHEN WEN-XIANG
Published: March 2023

In this paper, we explore various aspects of the Cosmological Special Relativity theory. Our investigations include Maxwell equations, electromagnetic wave equations and functions, energy-momentum relations, the Klein-Gordon equation and wave function, the Yukawa potential in the Cosmological Inertial Frame (CIF), the Schrdinger equation, the Dirac equation, and their respective solutions. We also analyze the interaction between A-type wave function and B-type extended distance.Our particular focus is on the time evolution of the Yukawa potential in the CIF and the quantification of the Klein-Gordon scalar field. Through our analysis, we have established a connection between the newly modified Friedman-Lematre-Robertson-Walker metric, the Dirac equation, and the Klein-Gordon equation.
PVC containing silver nanoparticles with antimicrobial properties effective against SARS-CoV-2
Authors: da Silva Daniel J. , Gramcianinov Guilherme B. , Jorge Pamela Z. , Malaquias Vanessa B. , Mori Augusto A. , Hirata Mário H. , Lopes Sergio A. M. , Bueno Luciano A. , Champeau Mathilde , Carastan Danilo J.
Published: March 2023

Poly (vinyl chloride) (PVC) is commonly used to manufacture biomedical devices and hospital components, but it does not present antimicrobial activity enough to prevent biofouling. With the emergence of new microorganisms and viruses, such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that was responsible for the global pandemic caused by Coronavirus Disease 2019 (COVID-19), it is evident the importance of the development of self-disinfectant PVC for hospital environments and medical clinics where infected people remain for a long time. In this contribution, PVC nanocomposites with silver nanoparticles (AgNPs) were prepared in the molten state. AgNPs are well-known as antimicrobial agents suitable for designing antimicrobial polymer nanocomposites. Adding 0.1 to 0.5 wt% AgNPs significantly reduced Young’s modulus and ultimate tensile strength of PVC due to the emergence of microstructural defects in the PVC/AgNP nanocomposites, but the impact strength did not change significantly. Furthermore, nanocomposites have a higher yellowness index (YI) and lower optical bandgap values than PVC. The PVC/AgNP nanocomposites present virucidal activity against SARS-CoV-2 (B.1.1.28 strain) within 48 h when the AgNP content is at least 0.3 wt%, suitable for manufacturing furniture and hospital equipment with self-disinfectant capacity to avoid secondary routes of COVID-19 contagion.
Palladium-catalyzed asymmetric three-component reaction between glyoxylic acid, sulfonamides and arylboronic acids for the synthesis of α-arylglycine derivatives
Authors: Jakob Bastian , Diehl Andreas M. , Horst Kathrin , Kelm Harald , Manolikakes Georg
Published: March 2023

A palladium-catalyzed asymmetric three-component synthesis ofα-arylglycine derivatives starting from glyoxylic acid, sulfonamides and arylboronic acids is reported. This novel, operationally simple method offers access to theα-arylglycine scaffold in good yields and enantioselectivities. The utilization of α tailored catalyst system enables the enantioselective synthesis of the desiredα-arylglycines despite a fast racemic background reaction. The obtained products can be directly employed as building blocks in peptide synthesis.
Subject-specific factors affecting particle residence time distribution of left atrial appendage in atrial fibrillation: A computational model-based study
Authors: Sanatkhani Soroosh , Nedios Sotirios , Menon Prahlad G. , Saba Samir F. , Jain Sandeep K. , Federspiel William J. , Shroff Sanjeev G.
Published: March 2023

Background

Atrial fibrillation (AF) is a prevalent arrhythmia, that causes thrombus formation, ordinarily in the left atrial appendage (LAA). The conventional metric of stroke risk stratification, CHA2DS2-VASc score, does not account for LAA morphology or hemodynamics. We showed in our previous study that residence time distribution (RTD) of blood-borne particles in the LAA and its associated calculated variables (i.e., mean residence time, tm, and asymptotic concentration, C∞) have the potential to improve CHA2DS2-VASc score. The purpose of this research was to investigate the effects of the following potential confounding factors on LAA tm and C∞: (1) pulmonary vein flow waveform pulsatility, (2) non-Newtonian blood rheology and hematocrit level, and (3) length of the simulation.

Methods

Subject-Specific data including left atrial (LA) and LAA cardiac computed tomography, cardiac output (CO), heart rate, and hematocrit level were gathered from 25 AF subjects. We calculated LAA tm and C∞ based on series of computational fluid dynamics (CFD) analyses.

Results

Both LAA tm and C∞ are significantly affected by the CO, but not by temporal pattern of the inlet flow. Both LAA tm and C∞ increase with increasing hematocrit level and both calculated indices are higher for non-Newtonian blood rheology for a given hematocrit level. Further, at least 20,000 s of CFD simulation is needed to calculate LAA tm and C∞ values reliably.

Conclusions

Subject-specific LA and LAA geometries, CO, and hematocrit level are essential to quantify the subject-specific proclivity of blood cell tarrying inside LAA in terms of the RTD function.
Efficient temporal high-order staggered-grid scheme with a dispersion-relation-preserving method for the scalar wave modeling
Authors: Zhang Chunlin , Fan Liyong , Chen Guiting , Zeng Xu
Published: March 2023

Staggered-grid finite-difference (FD) method is widely used to solve the wave equation for the numerical seismic modeling, and it is a key step of the advanced seismic imaging and inversion problem. However, the conventional FD method is prone to instability and dispersion error due to the insufficient approximation accuracy. In this work, we propose an efficient temporal high-order finite-difference (FD) scheme with the cross-rhombus stencil. Compared with the standard cross-rhombus method, the new method has less computational cost due to we simplify the FD scheme. Moreover, the dispersion relation of the new method is easy to obtain the dispersion-relation-preserving (DRP) FD coefficients, which can significantly alleviate the spatial and temporal dispersion errors. Dispersion and stability analyses indicate that the new scheme has better performance in seismic modeling than the conventional method, and numerical experiments also indicate that the new scheme can effectively mitigate dispersion error and improve the numerical accuracy.
Prospective study and proposal of an outcome predictive nomogram in a consecutive prospective series of differentiated thyroid cancer based on the new ATA risk categories and TNM
Authors: Sapuppo Giulia , Grasso Sonia , Di Benedetto Guenda , Belfiore Antonino , Pellegriti Gabriella
Published: March 2023

Introduction

The personalized management of differentiated thyroid cancer (DTC) is currently based on the postoperative TNM staging system and the ATA risk stratification system (RSS), both updated in 2018 and 2015, respectively.

Purpose

We aimed to evaluate the impact of the last two editions of TNM and ATA RSS in the prediction of persistent/recurrent disease in a large series of DTC patients.

Patients and methods

Our prospective study included 451 patients undergone thyroidectomy for DTC. We classified the patients according to TNM (both VIII and VII ed.) and stratified them according to the ATA RSS (both 2015 and 2009). We then evaluated the response to the initial therapy after 12-18 months according to the ATA “ongoing” risk stratification, and analyzed the variables associated with persistent/recurrent disease by multivariate analysis.

Results

The performance of the last two ATA RSSs was not significantly different. By staging patients according to the VIII or VII TNM editions, we found significant differences only in the distribution of patients with structural disease classified in stages III and IV. At multivariate analysis, only T-status and N-status were independently associated with persistent/recurrent disease. Overall, ATA RSSs and TNMs showed low predictive power in terms of persistent/recurrent disease (by Harrell’s test).

Conclusions

In our series of DTC patients, the new ATA RSS as well as the VIII TNM staging provided no additional benefit compared to the previous editions. Moreover, the VIII TNM staging system may underestimate disease severity in patients with large and numerous lymph node metastases at diagnosis.
Path analysis of energy economic management standardization in the context of carbon neutralization and carbon peak
Authors: Liu Jilu
Published: March 2023

Carbon neutrality and carbon peak are two important measures to control climate change. They have a huge impact on many companies in the fields of energy, industry, construction, transportation, etc. They can change the development pattern of related industries and increase many new investment and development opportunities. This paper proposes a path analysis of the standardization of energy economic management under the background of carbon neutrality and carbon peak, aiming to study the development forecast of energy economic management under low-carbon conditions. The algorithm proposed in this paper is an energy consumption analysis algorithm based on the IPAT model, which can be combined with the IPAT model to analyze and process energy consumption data. In addition, by analyzing and evaluating the contribution of various factors, people can better understand the impact of energy consumption on the environment and formulate corresponding solutions. The experimental analysis results of energy economic management based on carbon neutrality and carbon peak show that, from 2013 to 2017, under the baseline scenario, carbon emissions increased year by year, from 9.25 billion tons to 10.48 billion tons. Under the carbon neutral scenario, its carbon emissions are 9.22 billion tons, 9.24 billion tons, 9.22 billion tons, 9.19 billion tons and 9.21 billion tons respectively. Obviously, under the carbon neutral scenario, carbon emissions can be better controlled through carbon neutral and carbon peak strategies. Through these experimental prediction results, it can be proved that carbon neutrality and carbon peaking have excellent effects on promoting energy economic management. At the same time, this study also provides valuable reference information for further research on carbon neutrality and carbon peaks.
Evaluation of lung function in a German single center cohort of young patients with sickle cell disease using EIT and standard techniques
Authors: Rein Alina , Ngo Chuong , van den Berg Maike , Böll Svenja , Lassay Lisa , Kontny Udo , Wagner Norbert , Leonhardt Steffen , Tenbrock Klaus , Verjans Eva
Published: March 2023

Background and objective

Sickle cell disease (SCD) is a very common autosomal recessive hemoglobinopathy leading to multiple pulmonary complications that are closely associated with mortality. The pathophysiology of chronic pulmonary involvement is not yet fully understood and no specific therapies are available.

Methods

The aim of this cross-sectional study was to characterize the lung function of children and young adolescents with SCD in a German single-center cohort and to extend conventional lung function testing by the use of a new imaging method. We performed spirometry and body plethysmography in 35 children and young adults with hemoglobin SS, SC, S/β-thalassemia as well as 50 controls. These data were compared with clinical characteristics and typical laboratory parameters of hemolysis and disease activity in SCD. To identify lung inhomogeneities, for example due to atelectasis, hyperinflation, air trapping or vascular occlusions, we used the promising new method of electrical impedance tomography (EIT) and calculated global inhomogeneity indices.

Results

Lung function of patients with SCD was significantly reduced compared to that of healthy controls. When the result was found to be pathological, the most commonly observed type of breathing disorder was classified as restrictive. Laboratory parameters showed typical features of SCD including decreased levels of hemoglobin and hematocrit and elevated levels of leucocytes, platelets, lactate dehydrogenase and total bilirubin. However, there was no correlation between blood values and reduced lung function. Electrical impedance tomography (EIT) revealed no abnormalities in SCD patients compared to healthy controls. In particular, we were unable to demonstrate any regional inhomogeneities in lung ventilation.

Conclusion

In our study, SCD patients showed impaired lung function, with a relevant percentage of patients suffering from restrictive breathing disorder. Signs of obstruction could not be detected. Electrical impedance tomography (EIT) measurements revealed no unevenness that would suggest air entrapment, blockage of blood vessels, excessive inflation, obstruction, or other forms of lung disease. Additionally, the reduction in lung function observed in SCD patients was not related to the disease severity or laboratory test results.
Cold-tolerant phosphate-solubilizing Pseudomonas strains promote wheat growth and yield by improving soil phosphorous (P) nutrition status
Authors: Dasila Hemant , Sah V. K. , Jaggi Vandana , Kumar Arun , Tewari Lakshmi , Taj Gohar , Chaturvedi Sumit , Perveen Kahkashan , Bukhari Najat A. , Siang Tan Ching , Sahgal Manvika
Published: March 2023

It is well-known that phosphate-solubilizing bacteria (PSB) promote crop growth and yield. The information regarding characterization of PSB isolated from agroforestry systems and their impact on wheat crops under field conditions is rarely known. In the present study, we aim to develop psychrotroph-based P biofertilizers, and for that, four PSB strains (Pseudomonas sp. L3, Pseudomonas sp. P2, Streptomyces sp. T3, and Streptococcus sp. T4) previously isolated from three different agroforestry zones and already screened for wheat growth under pot trial conditions were evaluated on wheat crop under field conditions. Two field experiments were employed; set 1 includes PSB + recommended dose of fertilizers (RDF) and set 2 includes PSB – RDF. In both field experiments, the response of the PSB-treated wheat crop was significantly higher compared to the uninoculated control. In field set 1, an increase of 22% in grain yield (GY), 16% in biological yield (BY), and 10% in grain per spike (GPS) was observed in consortia (CNS, L3 + P2) treatment, followed by L3 and P2 treatments. Inoculation of PSB mitigates soil P deficiency as it positively influences soil alkaline phosphatase (AP) and soil acid phosphatase (AcP) activity which positively correlated with grain NPK %. The highest grain NPK % was reported in CNS-treated wheat with RDF (N–0.26%, P–0.18%, and K-1.66%) and without RDF (N-0.27, P-0.26, and K-1.46%), respectively. All parameters, including soil enzyme activities, plant agronomic data, and yield data were analyzed by principal component analysis (PCA), resulting in the selection of two PSB strains. The conditions for optimal P solubilization, in L3 (temperature-18.46, pH–5.2, and glucose concentration–0.8%) and P2 (temperature-17°C, pH–5.0, and glucose concentration–0.89%), were obtained through response surface methodology (RSM) modeling. The P solubilizing potential of selected strains at <20°C makes them a suitable candidate for the development of psychrotroph-based P biofertilizers. Low-temperature P solubilization of the PSB strains from agroforestry systems makes them potential biofertilizers for winter crops.
Role of gut symbionts of insect pests: A novel target for insect-pest control
Authors: Rupawate Pravara S. , Roylawar Praveen , Khandagale Kiran , Gawande Suresh , Ade Avinash B. , Jaiswal Durgesh Kumar , Borgave Seema
Published: March 2023

Insects possess beneficial and nuisance values in the context of the agricultural sector and human life around them. An ensemble of gut symbionts assists insects to adapt to diverse and extreme environments and to occupy every available niche on earth. Microbial symbiosis helps host insects by supplementing necessary diet elements, providing protection from predators and parasitoids through camouflage, modulation of signaling pathway to attain homeostasis and to trigger immunity against pathogens, hijacking plant pathways to circumvent plant defence, acquiring the capability to degrade chemical pesticides, and degradation of harmful pesticides. Therefore, a microbial protection strategy can lead to overpopulation of insect pests, which can drastically reduce crop yield. Some studies have demonstrated increased insect mortalityviathe destruction of insect gut symbionts; through the use of antibiotics. The review summarizes various roles played by the gut microbiota of insect pests and some studies that have been conducted on pest control by targeting the symbionts. Manipulation or exploitation of the gut symbionts alters the growth and population of the host insects and is consequently a potential target for the development of better pest control strategies. Methods such as modulation of gut symbiontsviaCRISPR/Cas9, RNAi and the combining of IIT and SIT to increase the insect mortality are further discussed. In the ongoing insect pest management scenario, gut symbionts are proving to be the reliable, eco-friendly and novel approach in the integrated pest management.
Target-driven machine learning-enabled virtual screening (TAME-VS) platform for early-stage hit identification
Authors: Bian Yuemin , Kwon Jason J. , Liu Cong , Margiotta Enrico , Shekhar Mrinal , Gould Alexandra E.
Published: March 2023

High-throughput screening (HTS) methods enable the empirical evaluation of a large scale of compounds and can be augmented by virtual screening (VS) techniques to save time and money by using potential active compounds for experimental testing. Structure-based and ligand-based virtual screening approaches have been extensively studied and applied in drug discovery practice with proven outcomes in advancing candidate molecules. However, the experimental data required for VS are expensive, and hit identification in an effective and efficient manner is particularly challenging during early-stage drug discovery for novel protein targets. Herein, we present our TArget-driven Machine learning-Enabled VS (TAME-VS) platform, which leverages existing chemical databases of bioactive molecules to modularly facilitate hit finding. Our methodology enables bespoke hit identification campaigns through a user-defined protein target. The input target ID is used to perform a homology-based target expansion, followed by compound retrieval from a large compilation of molecules with experimentally validated activity. Compounds are subsequently vectorized and adopted for machine learning (ML) model training. These machine learning models are deployed to perform model-based inferential virtual screening, and compounds are nominated based on predicted activity. Our platform was retrospectively validated across ten diverse protein targets and demonstrated clear predictive power. The implemented methodology provides a flexible and efficient approach that is accessible to a wide range of users. The TAME-VS platform is publicly available at https://github.com/bymgood/Target-driven-ML-enabled-VS to facilitate early-stage hit identification.
Mawangdui-Guidance Qigong Exercise for patients with chronic non-specific low back pain: Study protocol of a randomized controlled trial
Authors: Zhang Guilong , Gao Liang , Zhang Di , Li Hongjian , Shen Yuquan , Zhang Zhengsong , Huang Yong
Published: March 2023

Introduction

Worldwide, there is a high frequency of chronic non-specific low back pain (CNLBP), which is a significant public health concern. The etiology is complicated and diverse, and it includes a number of risk factors such as diminished stability and weak core muscles. Mawangdui-Guidance Qigong has been employed extensively to bolster the body in China for countless years. However, the effectiveness of treating CNLBP has not been assessed by a randomized controlled trial (RCT). In order to verify the results of the Mawangdui-Guidance Qigong Exercise and examine its biomechanical mechanism, we intend to perform a randomized controlled trial.

Methods and analysis

Over the course of 4 weeks, 84 individuals with CNLBP will be randomly assigned to receive either Mawangdui-Guidance Qigong Exercise, motor control exercise, or medication (celecoxib). Electromyographic data, including muscle activation time, iEMGs, root mean square value (RMS) and median frequency (MF), will be the main outcomes. The Japanese Orthopedic Association (JOA) Score, the Mcgill Pain Questionnaire (MPQ), beta-endorphin, and substance P are examples of secondary outcomes. At the start of treatment and 4 weeks later, all outcomes will be evaluated. SPSS version 20.0 (SPSS Inc., Chicago, IL, USA) will be used for all of the analysis.

Discussion

The prospective findings are anticipated to offer an alternative treatment for CNLBP and provide a possible explanation of the mechanism of Mawangdui-Guidance Qigong Exercise on CNLBP.

Ethics and dissemination

The Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine has given the study approval (Approval No. 2020KL-067). It has also registered at the website of China Clinical Trial Center Registration. The application adheres to the Declaration of Helsinki’s tenets (Version Edinburgh 2000). Peer-reviewed papers will be used to publicize the trial’s findings.

Trial registration number

ClinicalTrials.gov, identifier ChiCTR2000041080.
Risk factors and nomogram-based prediction of the risk of limb weakness in herpes zoster
Authors: Li Shao-jun , Feng Dan
Published: March 2023

Background

Limb weakness is a less common complication of herpes zoster (HZ). There has been comparatively little study of limb weakness. The aim of this study is to develop a risk nomogram for limb weakness in HZ patients.

Methods

Limb weakness was diagnosed using the Medical Research Council (MRC) muscle power scale. The entire cohort was assigned to a training set (from January 1, 2018 to December 30, 2019, n = 169) and a validation set (from October 1, 2020 to December 30, 2021, n = 145). The least absolute shrinkage and selection operator (LASSO) regression analysis method and multivariable logistic regression analysis were used to identify the risk factors of limb weakness. A nomogram was established based on the training set. The discriminative ability and calibration of the nomogram to predict limb weakness were tested using the receiver operating characteristic (ROC) curve, calibration plots, and decision curve analysis (DCA). A validation set was used to further assess the model by external validation.

Results

Three hundred and fourteen patients with HZ of the extremities were included in the study. Three significant risk factors: age (OR = 1.058, 95% CI: 1.021–1.100, P = 0.003), VAS (OR = 2.013, 95% CI: 1.101–3.790, P = 0.024), involving C6 or C7 nerve roots (OR = 3.218, 95% CI: 1.180–9.450, P = 0.027) were selected by the LASSO regression analysis and the multivariable logistic regression analysis. The nomogram to predict limb weakness was constructed based on the three predictors. The area under the ROC was 0.751 (95% CI: 0.673–0.829) in the training set and 0.705 (95% CI: 0.619–0.791) in the validation set. The DCA indicated that using the nomogram to predict the risk of limb weakness would be more accurate when the risk threshold probability was 10–68% in the training set and 15–57% in the validation set.

Conclusion

Age, VAS, and involving C6 or C7 nerve roots are potential risk factors for limb weakness in patients with HZ. Based on these three indicators, our model predicted the probability of limb weakness in patients with HZ with good accuracy.
Alcohol and lactation: Developmental deficits in a mouse model
Authors: Perez Roberto F. , Conner Kathleen E. , Erickson Michael A. , Nabatanzi Mirembe , Huffman Kelly J.
Published: March 2023

It is well documented that prenatal ethanol exposure via maternal consumption of alcohol during pregnancy alters brain and behavioral development in offspring. Thus, the Centers for Disease Control (CDC) advises against maternal alcohol consumption during pregnancy. However, little emphasis has been placed on educating new parents about alcohol consumption while breastfeeding. This is partly due to a paucity of research on lactational ethanol exposure (LEE) effects in children; although, it has been shown that infants exposed to ethanol via breast milk frequently present with reduced body mass, low verbal IQ scores, and altered sleeping patterns. As approximately 36% of breastfeeding mothers in the US consume alcohol, continued research in this area is critical. Our study employed a novel murine LEE model, where offspring were exposed to ethanol via nursing from postnatal day (P) 6 through P20, a period correlated with infancy in humans. Compared to controls, LEE mice had reduced body weights and neocortical lengths at P20 and P30. Brain weights were also reduced in both ages in males, and at P20 for females, however, female brain weights recovered to control levels by P30. We investigated neocortical features and found that frontal cortex thickness was reduced in LEE males compared to controls. Analyses of dendritic spines in the prelimbic subdivision of medial prefrontal cortex revealed a trend of reduced densities in LEE mice. Results of behavioral tests suggest that LEE mice engage in higher risk-taking behavior, show abnormal stress regulation, and exhibit increased hyperactivity. In summary, our data describe potential adverse brain and behavioral developmental outcomes due to LEE. Thus, women should be advised to refrain from consuming alcohol during breastfeeding until additional research can better guide recommendations of safe maternal practices in early infancy.
Recent advances on anti-angiogenic multi-receptor tyrosine kinase inhibitors in osteosarcoma and Ewing sarcoma
Authors: Fleuren Emmy D. G. , Vlenterie Myrella , van der Graaf Winette T. A.
Published: March 2023

Osteosarcoma (OS) and Ewing sarcoma (ES) are the two most common types of primary bone cancer that predominantly affect the young. Despite aggressive multimodal treatment, survival has not improved significantly over the past four decades. Clinical efficacy has historically been observed for some mono-Receptor Tyrosine Kinase (RTK) inhibitors, albeit in small subsets of OS and ES patients. Clinical efficacy in larger groups of OS or ES patients was reported recently with several newer generation multi-RTK inhibitors. All these inhibitors combine a strong anti-angiogenic (VEGFRs) component with simultaneous inhibition of other key RTKs implicated in OS and ES progression (PDGFR, FGFR, KIT and/or MET). However, despite interesting clinical data, none of these agents have obtained a registration for these indications and are thus difficult to implement in routine OS and ES patient care. It is at present also unclear which of these drugs, with largely overlapping molecular inhibition profiles, would work best for which patient or subtype, and treatment resistance almost uniformly occurs. Here, we provide a critical assessment and systemic comparison on the clinical outcomes to the six most tested drugs in this field in OS and ES to date, including pazopanib, sorafenib, regorafenib, anlotinib, lenvatinib and cabozantinib. We pay special attention to clinical response evaluations in bone sarcomas and provide drug comparisons, including drug-related toxicity, to put these drugs into context for OS and ES patients, and describe how future trials utilizing anti-angiogenic multi-RTK targeted drugs could be designed to ultimately improve response rates and decrease toxicity.
Cancer, more than a “COVID-19 co-morbidity”
Authors: Jani Chinmay T. , Schooley Robert T. , Mckay Rana R. , Lippman Scott M.
Published: March 2023

Patients with cancer represent a particularly vulnerable population at risk of adverse outcomes related to COVID-19. Collectively, the initial studies, including patients with and without cancer, confirmed that patients with cancer had a higher risk of complications and death related to COVID-19. Subsequent studies on patients with COVID-19 and cancer investigated patient and disease-related factors associated with COVID-19 severity and morality. Multiple interconnected factors include demographics, comorbidities, cancer-associated variables, treatment side effects, and other parameters. However, there is a lack of clarity on the contributions of any one factor. In this commentary, we deconvolute the data of specific risk factors associated with worse outcomes due to COVID-19 in cancer patients and focus on understanding the recommended guidelines to mitigate COVID-19 risk in this vulnerable population. In the first section, we highlight the key parameters, including age and race, cancer status, type of malignancy, cancer therapy, smoking status and comorbidities that impact outcomes for cancer patients with COVID-19. Next, we discuss efforts made at the patient, health system, and population levels to mitigate the effects of the ongoing outbreak for patients with cancer, including (1) screening, barrier and isolation strategies (2), Masking/PPE (3), vaccination, and (4) systemic therapies (e.g., evusheld) to prevent disease onset in patients. In the last section, we discuss optimal treatment strategies for COVID-19, including additional therapies for patients with COVID-19 and cancer. Overall, this commentary focuses on articles with high yield and impact on understanding the evolving evidence of risk factors and management guidelines in detail. We also emphasize the ongoing collaboration between clinicians, researchers, health system administrators and policymakers and how its role will be important in optimizing care delivery strategies for patients with cancer. Creative patient-centered solutions will be critical in the coming years, post the pandemic.
Case Report: A case of COL1A1–PDGFB fusion uterine sarcoma at cervix and insights into the clinical management of rare uterine sarcoma
Authors: Lu Linghui , Wang Shunni , Shen Haoran , Zhang Feiran , Ma Fenghua , Shi Yue , Ning Yan
Published: March 2023

COL1A1–PDGFB gene fusion uterine sarcoma is an especially rare malignant mesenchymal tumor that was previously classified as an undifferentiated uterine sarcoma due to the lack of specific features of differentiation. Till now, only five cases have been reported, and here we presented another case recently diagnosed in a Chinese woman who had vaginal bleeding. She presented with a cervical mass at the anterior lip of the cervix invading the vagina and was treated with laparoscopic total hysterectomy plus bilateral salpingo-oophorectomy (TH+BSO) and partial vaginal wall resection with the final pathology of COL1A1–PDGFB fusion uterine sarcoma. Our aim is to emphasize the importance of differential diagnosis of this rare tumor, as early precise diagnosis may allow patients to benefit from the targeted therapy imatinib. This article also serves as further clinical evidence of this disease, serving to increase clinical awareness of this rare sarcoma to avoid misdiagnosis.
Non-invasive neuromodulation of the cervical vagus nerve in rare primary headaches
Authors: Villar-Martinez Maria Dolores , Goadsby Peter J.
Published: March 2023

Primary headache disorders can be remarkably disabling and the therapeutic options available are usually limited to medication with a high rate of adverse events. Here, we discuss the mechanism of action of non-invasive vagal nerve stimulation, as well as the findings of the main studies involving patients with primary headaches other than migraine or cluster headache, such as hemicrania continua, paroxysmal hemicrania, cough headache, or short-lasting neuralgiform headache attacks (SUNCT/SUNA), in a narrative analysis. A bibliographical search of low-prevalence disorders such as rare primary headaches retrieves a moderate number of studies, usually underpowered. Headache intensity, severity, and duration showed a clinically significant reduction in the majority, especially those involving indomethacin-responsive headaches. The lack of response of some patients with a similar diagnosis could be due to a different stimulation pattern, technique, or total dose. The use of non-invasive vagal nerve stimulation for the treatment of primary headache disorders represents an excellent option for patients with these debilitating and otherwise refractory conditions, or that cannot tolerate several lines of preventive medication, and should always be considered before contemplating invasive, non-reversible stimulation techniques.
Case report: Diagnostic clues for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy in pediatric patients
Authors: Watanuki Keisuke , Koga Hiroshi
Published: March 2023

Introduction

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is a recently recognized pathology, but appears less common in children and the characteristics of pediatric cases remain unclear.

Case report

We report a pediatric case of anti-HMGCR myopathy accompanied by skin rash. Motor function and serum creatine kinase level normalized after combinational treatment including early intravenous immunoglobulin, methotrexate, and corticosteroid.

Literature review

We searched PubMed and identified reports with detailed clinical information of 33 pediatric patients <18 years old with anti-HMGCR myopathy. Among these 33 patients and our own case, skin rash and maximum serum creatine kinase level >5,000 IU/L were observed in 44% (15 patients) and 94% (32 patients), respectively. Skin rash was present in 15 of the 22 patients (68%) ≥7 years old and none of the 12 patients (0%) <7 years old. Among the 15 patients with skin rash, 12 (80%) presented with erythematous rash.

Conclusion

Erythematous skin rash may offer a clue to the diagnosis of anti-HMGCR myopathy in children with muscle weakness and serum creatine kinase level >5,000 IU/L in the absence of other myositis-specific antibodies, particularly in patients ≥7 years old. Our results suggest the importance of early anti-HMGCR testing in pediatric patients with these manifestations.
The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation
Authors: Owen Josephine C. , Garrick Steven P. , Peterson Briana M. , Berger Philip J. , Nold Marcel F. , Sehgal Arvind , Nold-Petry Claudia A.
Published: March 2023

Preterm birth is defined as delivery at <37 weeks of gestational age (GA) and exposes 15 million infants worldwide to serious early life diseases. Lowering the age of viability to 22 weeks GA entailed provision of intensive care to a greater number of extremely premature infants. Moreover, improved survival, especially at extremes of prematurity, comes with a rising incidence of early life diseases with short- and long-term sequelae. The transition from fetal to neonatal circulation is a substantial and complex physiologic adaptation, which normally happens rapidly and in an orderly sequence. Maternal chorioamnionitis or fetal growth restriction (FGR) are two common causes of preterm birth that are associated with impaired circulatory transition. Among many cytokines contributing to the pathogenesis of chorioamnionitis-related perinatal inflammatory diseases, the potent pro-inflammatory interleukin (IL)-1 has been shown to play a central role. The effects of utero-placental insufficiency-related FGR and in-utero hypoxia may also be mediated, in part, via the inflammatory cascade. In preclinical studies, blocking such inflammation, early and effectively, holds great promise for improving the transition of circulation. In this mini-review, we outline the mechanistic pathways leading to abnormalities in transitional circulation in chorioamnionitis and FGR. In addition, we explore the therapeutic potential of targeting IL-1 and its influence on perinatal transition in the context of chorioamnionitis and FGR.
Effect and mechanism of longkui yinxiao soup in treating psoriasis in mice
Authors: Zhu Congcong , Chen Ya , Tai Zongguang , Pan Huijun , Shen Min , Chen Zhongjian , Zhu Quangang
Published: March 2023

Objective: Longkui Yinxiao Soup is a traditional Chinese medicine formula used to treat psoriasis for decades. Although Longkui Yinxiao Soup showed promising efficacy in clinical practice, the regulatory mechanisms of Longkui Yinxiao Soup remain elusive. This study aimed to explore the underlying mechanisms of Longkui Yinxiao Soup in a psoriasis-like mouse model.

Methods: Longkui Yinxiao Soup was quality controlled by determining the contents of imperatorin and rhoifolin using high-performance liquid chromatography. The imiquimod-induced psoriasis-like mouse model was used to study the therapeutic effect and mechanism of Longkui Yinxiao Soup. The histopathological skin changes were observed by hematoxylin and eosin staining; the infiltration of proliferating proteins, proliferating cell nuclear antigen and Ki67, in skin tissues were observed by immunohistochemical analysis; and the inflammatory factors such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-23, and IL-17 in serum were detected using enzyme-linked immunosorbent assay. RNA sequencing and bioinformatic analysis were used to predict the mechanism of LYS against psoriasis. mRNA expressions of p38, extracellular regulated protein kinases (ERK), mitogen-activated protein kinase 3 (MEK3), mitogen-activated protein kinase 6 (MEK6), RAP1 GTPase activating protein (Rap1gap), and Rap1 were determined using real-time quantitative polymerase chain reaction. The expression levels of proteins related to Rap1–mitogen-activated protein kinase signaling pathways were measured by Western blotting.

Results: A quality-control method for Longkui Yinxiao Soup was successfully established using imperatorin and rhoifolin as content determination indexes. Longkui Yinxiao Soup significantly ameliorated the psoriatic symptoms in mice. The serum levels of inflammatory cytokines such as IL-6, TNF-α, IL-23, and IL-17 were decreased, and the expression levels of antigen identified by monoclonal antibody Ki67 (Ki67) and PCNA in skin tissues were downregulated. Moreover, the inhibition of Rap1–MAPK signaling pathways by Longkui Yinxiao Soup was detected.

Conclusion: This study confirmed the antipsoriatic activity of Longkui Yinxiao Soup in psoriasis-like mice. This might be due to the inhibition of inflammatory factor secretion, keratinocyte proliferation, and the Rap1–MAPK signal pathway.
Decoupling the effects of nutrition, age, and behavioral caste on honey bee physiology, immunity, and colony health
Authors: Corona Miguel , Branchiccela Belen , Alburaki Mohamed , Palmer-Young Evan C. , Madella Shayne , Chen Yanping , Evans Jay D.
Published: March 2023

Nutritional stress, especially a dearth of pollen, has been linked to honey bee colony losses. Colony-level experiments are critical for understanding the mechanisms by which nutritional stress affects individual honey bee physiology and pushes honey bee colonies to collapse. In this study, we investigated the impact of pollen restriction on key markers of honey bee physiology, main elements of the immune system, and predominant honey bee viruses. To achieve this objective, we uncoupled the effects of behavior, age, and nutritional conditions using a new colony establishment technique designed to control size, demography, and genetic background. Our results showed that the expression of storage proteins, including vitellogenin (vg) and royal jelly major protein 1 (mrjp1), were significantly associated with nursing, pollen ingestion, and older age. On the other hand, genes involved in hormonal regulation including insulin-like peptides (ilp1 and ilp2) and methyl farnesoate epoxidase (mfe), exhibited higher expression levels in young foragers from colonies not experiencing pollen restriction. In contrast, pollen restriction induced higher levels of insulin-like peptides in old nurses. On the other hand, we found a strong effect of behavior on the expression of all immune genes, with higher expression levels in foragers. In contrast, the effects of nutrition and age were significant only the expression of the regulatory gene dorsal. We also found multiple interactions of the experimental variables on viral titers, including higher Deformed wing virus (DWV) titers associated with foraging and age-related decline. In addition, nutrition significantly affected DWV titers in young nurses, with higher titers induced by pollen ingestion. In contrast, higher levels of Black queen cell virus (BQCV) were associated with pollen restriction. Finally, correlation, PCA, and NMDS analyses proved that behavior had had the strongest effect on gene expression and viral titers, followed by age and nutrition. These analyses also support multiple interactions among genes and virus analyzed, including negative correlations between the expression of genes encoding storage proteins associated with pollen ingestion and nursing (vg and mrjp1) with the expression of immune genes and DWV titers. Our results provide new insights into the proximal mechanisms by which nutritional stress is associated with changes in honey bee physiology, immunity, and viral titers.
Two major chromosome evolution events with unrivaled conserved gene content in pomegranate
Authors: Akparov Zeynal , Hajiyeva Sabina , Abbasov Mehraj , Kaur Sukhjiwan , Hamwieh Aladdin , Alsamman Alsamman M. , Hajiyev Elchin , Babayeva Sevda , Izzatullayeva Vusala , Mustafayeva Ziyafat , Mehdiyeva Sabina , Mustafayev Orkhan , Shahmuradov Ilham , Kosarev Peter , Solovyev Victor , Salamov Asaf , Jighly Abdulqader
Published: March 2023

Pomegranate has a unique evolutionary history given that different cultivars have eight or nine bivalent chromosomes with possible crossability between the two classes. Therefore, it is important to study chromosome evolution in pomegranate to understand the dynamics of its population. Here, we de novo assembled the Azerbaijani cultivar “Azerbaijan guloyshasi” (AG2017; 2n = 16) and re-sequenced six cultivars to track the evolution of pomegranate and to compare it with previously published de novo assembled and re-sequenced cultivars. High synteny was observed between AG2017, Bhagawa (2n = 16), Tunisia (2n = 16), and Dabenzi (2n = 18), but these four cultivars diverged from the cultivar Taishanhong (2n = 18) with several rearrangements indicating the presence of two major chromosome evolution events. Major presence/absence variations were not observed as >99% of the five genomes aligned across the cultivars, while >99% of the pan-genic content was represented by Tunisia and Taishanhong only. We also revisited the divergence between soft- and hard-seeded cultivars with less structured population genomic data, compared to previous studies, to refine the selected genomic regions and detect global migration routes for pomegranate. We reported a unique admixture between soft- and hard-seeded cultivars that can be exploited to improve the diversity, quality, and adaptability of local pomegranate varieties around the world. Our study adds body knowledge to understanding the evolution of the pomegranate genome and its implications for the population structure of global pomegranate diversity, as well as planning breeding programs aiming to develop improved cultivars.
Inversion models of aboveground grassland biomass in Xinjiang based on multisource data
Authors: Zhang R. P. , Zhou J. H. , Guo J. , Miao Y. H. , Zhang L. L.
Published: March 2023

Grassland biomass monitoring is essential for assessing grassland health and carbon cycling. However, monitoring grassland biomass in drylands based on satellite remote sensing is challenging.Statistical regression models and machine learning have been used for the construction of grassland biomass models, but the predictive power for different grassland types is unclear. Additionally, the selection of the most appropriate variables to construct a biomass inversion model for different grassland types must be explored. Therefore,1201 ground-truthed data points collected from 2014-2021,including 15 Moderate Resolution Imaging Spectroradiometer (MODIS) vegetation indices,geographic location and topographic data,and meteorological factors and vegetation biophysical indicators were screened for key variables using principal component analysis (PCA). The accuracy of multiple linear regression models, exponential regression models, power function models, support vector machine (SVM) models, random forest (RF) models, and neural network models was evaluated for the inversion of three types of grassland biomass. The results were as follows: (1) The biomass inversion accuracy of single vegetation indices was low, and the optimal vegetation indices were the soil-adjusted vegetation index (SAVI) (R2 = 0.255), normalized difference vegetation index (NDVI) (R2 = 0.372) and optimized soil-adjusted vegetation index (OSAVI) (R2 = 0.285). (2)Grassland above-ground biomass (AGB) was affected by various factors such as geographic location,topography, and meteorological factors, and the inverse models using a single environmental variable had large errors. (3) The main variables used to model biomass in the three types of grasslands were different. SAVI, aspect, slope, and precipitation (Prec.) were selected for desert grasslands; NDVI,shortwave infrared 2 (SWI2), longitude, mean temperature, and annual precipitation were selected for steppe;and OSAVI, phytochrome ratio (PPR), longitude, precipitation, and temperature were selected for meadows. (4) The non-parametric meadow biomass model was superior to the statistical regression model. (5) The RF model was the best model for the inversion of grassland biomass in Xinjiang, and this model had the highest accuracy for grassland biomass inversion (R2 = 0.656, root mean square error (RMSE) = 815.6 kg/ha),followed by meadow (R2 = 0.610, RMSE = 547.9 kg/ha) and desert grassland (R2 = 0.441, RMSE = 353.6 kg/ha).