bluuebunny/crossref_metadata_2025 huggingface dataset:
Camrelizumab-Related Myocarditis and Myositis With Myasthenia Gravis: A Case Report and Literature Review
Authors: Bai Jing , Li Dan , Yang Peidan , Xu Kunyan , Wang Yingnan , Li Qian , Liu Jiang , Du Wenli , Zhang Fengbin , Feng Rui
Published: January 2022

Immune checkpoint inhibitors (ICIs) have substantially changed the treatment of a variety of malignant tumors. With the increasing of their usage, the unique immune-mediated toxicity profile of ICIs has become apparent. We report a case of esophageal squamous cell carcinoma in a patient who received anti-programmed cell death protein 1 (PD-1) (camrelizumab) therapy and the occurrence of sequential immune-related adverse events (irAEs). Although many irAEs have been reported, severe myositis caused by camrelizumab with simultaneous involvement of multiple organs, including the myocardium, respiratory muscles, and skeletal muscles, has rarely been described in literature. This 69-year-old male patient developed a grade 4 camrelizumab-induced adverse reaction according to the Common Terminology Criteria for Adverse Events (CTCAE) and was successfully treated with methylprednisolone and immunoglobulins. The early identification of irAEs, immediate discontinuation of immunotherapy, use of steroids and/or immunosuppressants, and adjuvant supportive treatment are critical to the clinical prognosis of patients. It should be aware that autoimmune complications can occur even when ICI treatment is ceased.
Chemotherapy Combined With Recombinant Human Endostatin (Endostar) Significantly Improves the Progression-Free Survival of Stage IV Soft Tissue Sarcomas
Authors: Liao Zhichao , Zhang Chao , Yang Tielong , Liu Haotian , Yang Songwei , Li Ting , Xing Ruwei , Teng Sheng , Yang Yun , Zhao Jun , Zhao Gang , Bai Xu , Zhu Lei , Yang Jilong
Published: January 2022

Purpose

Our previously study showed that recombinant human endostatin (Endostar) combined with chemotherapy had significant activity to increase the mPFS in patients with advanced sarcomas with tolerable side effects. However, the small cohort size and short follow-up time made it difficult to screen sensitive sarcoma subtypes and determine whether there is an overall survival benefit. With the largest sarcoma cohort to our knowledge, we try to confirm the efficacy and safety of chemotherapy combined with Endostar in stage IV sarcomas, with the specific purpose of finding out the sensitive sarcoma types for this combined treatment.

Methods

After the exclusion of ineligible patients, 156 patients with stage IV bone and soft tissue sarcomas were included in this study according to the inclusion criteria.

Results

By the end of follow-up, the ORR was 10.7% (9/84) vs 1.4% (1/72) (p=0.041), the DCR was 26.2% (22/84) vs 5.6% (4/72) (p=0.001) in the combined group and chemotherapy group, respectively. The mPFS of combined group was significantly longer than the chemotherapy group (10.42 vs 6.87 months, p=0.003). The mOS were 26.84 months and 23.56 months, without significant difference (p= 0.481). In osteogenic sarcoma, there was no statistically significant difference in the mPFS between the two groups (p=0.59), while in the soft tissue sarcoma, the mPFS in the combined group was significantly higher than that of the chemotherapy group (11.27 vs 8.05 months, p=0.004). Specifically, undifferentiated polymorphic sarcoma (UPS) was the possible sarcoma subtypes that benefited from the combined therapy. For the 38 UPS patients (28 patients in the combined group and 10 patients in the chemotherapy group), the mPFS in the combined group was up to 14.88 months, while it was only 7.1 months in the chemotherapy group, with a significant difference (p=0.006). The most common adverse events in the combined group were myelosuppression, gastrointestinal reactions and abnormal liver function, without significant difference in two groups.

Conclusion

Chemotherapy plus Endostar could prolong mPFS and improve ORR and DCR in patients with stage IV soft tissue sarcoma, suggesting that the combined therapy could improve the patient prognosis in soft tissue sarcomas, especially the UPS patients.
Amide Proton Transfer Weighted and Intravoxel Incoherent Motion Imaging in Evaluation of Prognostic Factors for Rectal Adenocarcinoma
Authors: Li Juan , Lin Liangjie , Gao Xuemei , Li Shenglei , Cheng Jingliang
Published: January 2022

Objectives

To analyze the value of amide proton transfer (APT) weighted and intravoxel incoherent motion (IVIM) imaging in evaluation of prognostic factors for rectal adenocarcinoma, compared with diffusion weighted imaging (DWI).

Materials and Methods

Preoperative pelvic MRI data of 110 patients with surgical pathologically confirmed diagnosis of rectal adenocarcinoma were retrospectively evaluated. All patients underwent high-resolution T2-weighted imaging (T2WI), APT, IVIM, and DWI. Parameters including APT signal intensity (APT SI), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADC) were measured in different histopathologic types, grades, stages, and structure invasion statuses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy, and the corresponding area under the curves (AUCs) were calculated.

Results

APT SI, D and ADC values of rectal mucinous adenocarcinoma (MC) were significantly higher than those of rectal common adenocarcinoma (AC) ([3.192 ± 0.661%] vs. [2.333 ± 0.471%], [1.153 ± 0.238×10-3 mm2/s] vs. [0.792 ± 0.173×10-3 mm2/s], and [1.535 ± 0.203×10-3 mm2/s] vs. [0.986 ± 0.124×10-3 mm2/s], respectively; all P<0.001). In AC group, the APT SI and D values showed significant differences between low- and high-grade tumors ([2.226 ± 0.347%] vs. [2.668 ± 0.638%], and [0.842 ± 0.148×10-3 mm2/s] vs. [0.777 ± 0.178×10-3 mm2/s], respectively, both P<0.05). The D value had significant difference between positive and negative extramural vascular invasion (EMVI) tumors ([0.771 ± 0.175×10-3 mm2/s] vs. [0.858 ± 0.151×10-3 mm2/s], P<0.05). No significant difference of APT SI, D, D*, f or ADC was observed in different T stages, N stages, perineural and lymphovascular invasions (all P>0.05). The ROC curves showed that the AUCs of APT SI, D and ADC values for distinguishing MC from AC were 0.921, 0.893 and 0.995, respectively. The AUCs of APT SI and D values in distinguishing low- from high-grade AC were 0.737 and 0.663, respectively. The AUC of the D value for evaluating EMVI involvement was 0.646.

Conclusion

APT and IVIM were helpful to assess the prognostic factors related to rectal adenocarcinoma, including histopathological type, tumor grade and the EMVI status.
Expression of TIMPs and MMPs in Ovarian Tumors, Ascites, Ascites-Derived Cells, and Cancer Cell Lines: Characteristic Modulatory Response Before and After Chemotherapy Treatment
Authors: Escalona Ruth M. , Kannourakis George , Findlay Jock K. , Ahmed Nuzhat
Published: January 2022

Background

The tissue inhibitors of metalloproteinase (TIMPs) and their associated metalloproteinase (MMPs) are essential regulators of tissue homeostasis and are essential for cancer progression. This study analyzed the expression of TIMP-1,-2,-3 and the associated MMPs (MMP-2,-9,-11,-14) in different Stages, Grades and World Health Organization (WHO) classifications of serous ovarian tumors, ascites, ascites-derived cells from chemo-naïve (CN) and relapsed (CR) patients, and in ovarian cancer cell lines. The status of TIMPs and associated MMPs in response to chemotherapy treatment was assessed in cancer cell lines; TCGA data was interrogated to gauge TIMPs and associated MMPs as prognostic and platinum-response indicators.

Methods

The levels of TIMP-1, -2 and -3 were assessed by immunohistochemistry. The mRNA expression of TIMPs and MMPs was quantified by real time PCR (qRT-PCR). The chemosensitivity (IC50 values) to Cisplatin or Paclitaxel in cell lines was evaluated by MTT assay. The levels of TIMPs in ascites and cell lysates were analyzed by an ELISA assay.

Results

The expression of TIMP-2 was significantly upregulated in Type 2 compared to Type 1 tumors and normal/benign ovarian tissues. TIMP-3 expression was significantly enhanced in Stage III, Grade 3 and Type 2 tumors compared to normal/benign ovarian tissues. The mRNA expression of MMP-9,-11 and -14 was significantly upregulated in Stage IV compared to normal/benign ovarian tissues. The expression of TIMP-1 was highest, followed by TIMP-2 and then TIMP-3 in CN ascites. At the cellular level, TIMP-2 mRNA expression was significantly higher in CN compared to CR epithelial cells in patients. The expression of TIMP-1 and -2, MMPs and cancer stem cells (CSCs) were upregulated in response to chemotherapy treatments in cancer cell lines. Interrogation of the TCGA dataset suggests shifts in platinum responses in patients consistent with genetic alterations in TIMP-2, -3 and MMP-2, -11 genes in tumors; and decreased overall survival (OS) and progression-free survival (PFS) in patients with altered MMP-14 genes.

Conclusions

TIMPs and related MMPs are differentially expressed in serous ovarian tumors, ascites, ascites-derived cells and ovarian cancer cell lines. Chemotherapy treatment modulates expression of TIMPs and MMPs in association with increased expression of genes related to cancer stem cells.
Cancer Stem Cells and the Tumor Microenvironment in Gastric Cancer
Authors: Yang Ying , Meng Wen-Jian , Wang Zi-Qiang
Published: January 2022

Gastric cancer (GC) remains one of the leading causes of cancer-related death worldwide. Cancer stem cells (CSCs) might be responsible for tumor initiation, relapse, metastasis and treatment resistance of GC. The tumor microenvironment (TME) comprises tumor cells, immune cells, stromal cells and other extracellular components, which plays a pivotal role in tumor progression and therapy resistance. The properties of CSCs are regulated by cells and extracellular matrix components of the TME in some unique manners. This review will summarize current literature regarding the effects of CSCs and TME on the progression and therapy resistance of GC, while emphasizing the potential for developing successful anti-tumor therapy based on targeting the TME and CSCs.
The Inhibition Effect of Linezolid With Reyanning Mixture on MRSA and its Biofilm is More Significant than That of Linezolid Alone
Authors: Zhang Lulu , Yang Weifeng , Chu Yajun , Wen Bo , Cheng Yungchi , Mahmood Tariq , Bao Mei , Ge Feng , Li Li , Yi Jianfeng , Du Chengqiang , Lu Cheng , Tan Yong
Published: January 2022

Methicillin-resistant Staphylococcus aureus (MRSA) is a superbacterium, and when it forms biofilms, it is difficult to treat even with the first-line of antibiotic linezolid (LNZ). Reyanning mixture (RYN), a compound-based Chinese medicine formula, has been found to have inhibitory effects on biofilms. This study aims to explore the synergistic inhibitory effect and corresponding mechanisms of their (LNZ&RYN) combination on the planktonic as well as biofilm cells of MRSA. Broth microdilution and chessboard methods were employed for the determination of minimum inhibitory concentrations (MICs) and synergistic concentration of LNZ&RYN, respectively. The effect of the combined medication on biofilm and mature biofilm of MRSA were observed by biofilm morphology and permeability experiments, respectively. To unveil the molecular mechanism of action of the synergistic combination of LNZ and RYN, RT-PCR based biofilm-related gene expression analysis and ultra-high pressure liquid chromatography-time-of-flight mass spectrometry based endogenous metabonomic analysis were deployed. The results indicated that 1/16RYN as the best combined dose reduced LNZ (4 μg/ml) to 2 μg/ml. The combined treatment inhibited living MRSA before and after biofilm formation, removed the residual structure of dead bacteria in MRSA biofilms and affected the shape and size of bacteria, resulting in the improvement of biofilm permeability. The mechanism was that biofilm-related genes such as agrC, atlA, and sarA, as well as amino acid uptake associated with the metabolism of 3-dehydrocarnitine, kynurenine, L-leucine, L-lysine and sebacic acid were inhibited. This study provides evidence for the treatment of MRSA and its biofilms with LNZ combined with RYN.
Adverse Events During Pregnancy Associated With Entecavir and Adefovir: New Insights From a Real-World Analysis of Cases Reported to FDA Adverse Event Reporting System
Authors: Yang Renjun , Yin Nuoya , Zhao Ying , Li Dandan , Zhang Xuanling , Li Xingang , Zhang Yang , Faiola Francesco
Published: January 2022

Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring.

Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP).

Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value >2, and lower limit of 95% confidence interval (CI)> 1.

Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09–2.30) and 2.13 (95% CI, 1.04–4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54–8.18) and 2.85 (95% CI, 1.15–7.08), respectively.

Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice.
Identification of Novel Chemical Scaffolds that Inhibit the Growth of Mycobacterium tuberculosis in Macrophages
Authors: Ahmed Sara , Manning Alyssa , Flint Lindsay , Awasthi Divya , Ovechkina Yulia , Parish Tanya
Published: January 2022

Mycobacterium tuberculosis is an important global pathogen for which new drugs are urgently required. The ability of the organism to survive and multiply within macrophages may contribute to the lengthy treatment regimen with multiple drugs that are required to cure the infection. We screened the MyriaScreen II diversity library of 10,000 compounds to identify novel inhibitors of M. tuberculosis growth within macrophage-like cells using high content analysis. Hits were selected which inhibited the intramacrophage growth of M. tuberculosis without significant cytotoxicity to infected macrophages. We selected and prioritized compound series based on their biological and physicochemical properties and the novelty of the chemotypes. We identified five chemical classes of interest and conducted limited catalog structure-activity relationship studies to determine their tractability. We tested activity against intracellular and extracellular M. tuberculosis, as well as cytoxicity against murine RAW264.7 and human HepG2 cells. Benzene amide ethers, thiophene carboxamides and thienopyridines were only active against intracellular bacteria, whereas the phenylthiourea series was also active against extracellular bacteria. One member of a phenyl pyrazole series was moderately active against extracellular bacteria. We identified the benzene amide ethers as an interesting series for further work. These new compound classes serve as starting points for the development of novel drugs to target intracellular M. tuberculosis.
Comparative Evaluation of the Effect of Metformin and Insulin on Gut Microbiota and Metabolome Profiles of Type 2 Diabetic Rats Induced by the Combination of Streptozotocin and High-Fat Diet
Authors: Hu Nan , Zhang Qi , Wang Hui , Yang Xuping , Jiang Yan , Chen Rong , Wang Liying
Published: January 2022

Lately, an increasing number of studies have investigated the relationship between metformin and gut microbiota, suggesting that metformin exerts part of its hypoglycemic effect through the microbes. However, its underlying mechanism remains largely undetermined. In the present study, we investigated the effects of metformin on gut microbiota and metabolome profiles in serum and compared it with insulin treatment in rats with type 2 diabetes mellitus (T2DM). Diabetic rats (DM group) were induced by a combination of streptozotocin and high-fat diet (HFD). After 7 days, DM rats were treated with metformin (MET group) or insulin (INS group) for 3 weeks. The 16S rRNA sequencing of the gut microbiota and non-targeted metabolomics analysis of serum were conducted. A total of 13 bile acids (BAs) in serum were further determined and compared among different groups. The rat model of T2DM was well established with the typical diabetic symptoms, showing significantly increased blood glucose, AUC of OGTT, HOMA-IR, TC, TG, LDL-C and TBA. Metformin or insulin treatment could ameliorate symptoms of diabetes and partly recover the abnormal biochemical indicators. Compared with DM rats, the relative abundances of 13 genera were significantly changed after metformin treatment, while only three genera were changed after insulin treatment. The metformin and insulin treatments also exhibited different serum metabolome profiles in T2DM rats. Moreover, 64 differential metabolites were identified between MET and DM groups, whereas 206 were identified between INS and DM groups. Insulin treatment showed greater influence on amino acids, glycerophospholipids/glycerolipids, and acylcarnitine compared with the metformin treatment, while metformin had an important impact on BAs. Furthermore, metformin could significantly decrease the serum levels of CA, GCA, UDCA, and GUDCA, but increase the level of TLCA in DM rats. Insulin treatment significantly decreased the levels of CA, UDCA, and CDCA. Besides, several metabolites in serum or microbiota were positively or negatively correlated with some bacteria. Collectively, our findings indicated that metformin had a stronger effect on gut microbiota than insulin, while insulin treatment showed greater influence on serum metabolites, which provided novel insights into the therapeutic effects of metformin on diabetes.
Clinical and Immunological Factors Associated with Recommended Trough Levels of Adalimumab and Infliximab in Patients with Crohn’s Disease
Authors: Orts Beatriz , Gutierrez Ana , Madero Lucía , Sempere Laura , Frances Ruben , Zapater Pedro
Published: January 2022

Introduction: Up to 40% of patients with Crohn’s disease do not respond to treatment with anti-TNF or lose response after the initial benefit. Low drug concentrations have been proposed as the main predictor of treatment failure. Our aim was to study the immunological profile and clinical evolution of patients with Crohn’s disease according to the anti-TNF dose and serum trough levels.

Methods: Crohn’s disease patients in remission treated with infliximab or adalimumab at stable doses for at least for 3 months were included. Serum levels of anti-TNF, TNF-α, interferon-γ, and interleukin IL-12, IL-10, and IL-26 were determined in blood samples taken just before drug administration. Patients were classified according to anti-TNF levels below, within, or above the target level range and the use of intensified doses. Clinical evolution at 6 months was analyzed.

Results: A total of 62 patients treated with infliximab (8 on intensified schedule) and 49 treated with adalimumab (7 on intensified schedule) were included. All infliximab-treated patients showed levels within the recommended range, but half of adalimumab-treated patients were below the recommended range. A significant negative relationship between body weight and adalimumab levels was observed, especially in patients treated with intensified doses. Patients with infliximab levels over 8 µg/ml presented higher median IL-10 than patients with in-range levels (84.0 pg/ml, interquartile range [IQR] 77.0–84.8 vs. 26.2 pg/mL, IQR 22.6–38.0; p < 0.001), along with lower values of interferon-γ (312.9 pg/ml, IQR 282.7–350.4 vs. 405.6 pg/ml, IQR 352.2–526.6; p = 0.005). Patients receiving intensified versus non-intensified doses of infliximab showed significantly higher IL-26 levels (91.8 pg/ml, IQR 75.6–109.5 vs. 20.5 pg/ml, IQR 16.2–32.2; p = 0.012), irrespective of serum drug levels. Patients with in-range levels of adalimumab showed higher values of IL-10 than patients with below-range levels (43.3 pg/ml, IQR 35.3–54.0 vs. 26.3 pg/ml, IQR 21.6–33.2; p = 0.001). Patients treated with intensified vs regular doses of adalimumab had increased levels of IL-12 (612.3 pg/ml, IQR 570.2–1353.7 vs. 516.4 pg/mL, IQR 474.5–591.2; p = 0.023). Four patients with low adalimumab levels (19%) and four treated with intensified doses were admitted to a hospital during a follow-up compared to none of the patients with levels within the range.

Conclusion: Patients with Crohn’s disease treated with infliximab and adalimumab exhibit differences in serum levels of cytokines depending on the drug, dose intensification, and steady state trough serum levels.
Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity
Authors: Morgese Maria Grazia , Bove Maria , Di Cesare Mannelli Lorenzo , Schiavone Stefania , Colia Anna Laura , Dimonte Stefania , Mhillaj Emanuela , Sikora Vladyslav , Tucci Paolo , Ghelardini Carla , Trabace Luigia
Published: January 2022

Alzheimer’s disease (AD), one of the most widespread neurodegenerative disorder, is a fatal global burden for the elder population. Although many efforts have been made, the search of a curative therapy is still ongoing. Individuating phenotypic traits that might help in investigating treatment response is of growing interest in AD research. AD is a complex pathology characterized by many comorbidities, such as depression and increased susceptibility to pain perception, leading to postulate that these conditions may rely on common biological substrates yet to be determined. In order to investigate those biological determinants to be associable with phenotypic traits, we used the rat model of amyloid beta-induced toxicity. This established model of early phase of AD is obtained by the intracerebroventricular injection of soluble amyloid beta1-42 (Aβ) peptide 7 days before performing experiments. In this model, we have previously reported increased immobility in the forced swimming test, reduced cortical serotonin levels and subtle alterations in the cognitive domain a depressive-like phenotype associated with subtle alteration in memory processes. In light of evaluating pain perception in this animal model, we performed two different behavioral tests commonly used, such as the paw pressure test and the cold plate test, to analyze mechanical hyperalgesia and thermal allodynia, respectively. Behavioural outcomes confirmed the memory impairment in the social recognition test and, compared to sham, Aβ-injected rats showed an increased selective susceptibility to mechanical but not to thermal stimulus. Behavioural data were then corroborated by neurochemical and biochemical biomarker analyses either at central or peripheral level. Data showed that the peptide injection evoked a significant increase in hypothalamic glutamate, kynurenine and dopamine content, while serotonin levels were reduced. Plasma Cystatin-C, a cysteine protease, was increased while serotonin and melatonin levels were decreased in Aβ-injected rats. Urinary levels paralleled plasma quantifications, indicating that Aβ-induced deficits in pain perception, mood and cognitive domain may also depend on these biomarkers. In conclusion, in the present study, we demonstrated that this animal model can mimic several comorbid conditions typical of the early phase of AD. Therefore, in the perspective of generating novel therapeutic strategies relevant to precision medicine in AD, this animal model and the biomarkers evaluated herein may represent an advantageous approach.
Durvalumab-Induced Demyelinating Lesions in a Patient With Extensive-Stage Small-Cell Lung Cancer: A Case Report
Authors: Liu Wenhui , Chen Bo , Liu Yiping , Luo Zhiying , Sun Bao , Ma Fang
Published: January 2022

It is of great clinical value to investigate the immune-related adverse events (irAEs), especially demyelinating lesions, caused by immune checkpoint inhibitors (ICIs). The incidence of demyelinating lesions is less frequent in irAEs, but once it occurs, it will seriously affect the survival of patients. The present study reports a case of durvalumab-induced demyelinating lesions in a patient with extensive-stage small-cell lung cancer. Subsequently, the patient receives a high intravenous dose of methylprednisolone and his condition is improved after 21 days of treatment. Altogether, early diagnosis and treatment of ICIs-related neurological irAEs is of great significance to the outcome of the patient’s condition.
Identifying Multiple Influential Spreaders in Complex Networks by Considering the Dispersion of Nodes
Authors: Tao Li , Liu Mutong , Zhang Zili , Luo Liang
Published: January 2022

Identifying multiple influential spreaders, which relates to finding k (k > 1) nodes with the most significant influence, is of great importance both in theoretical and practical applications. It is usually formulated as a node-ranking problem and addressed by sorting spreaders’ influence as measured based on the topological structure of interactions or propagation process of spreaders. However, ranking-based algorithms may not guarantee that the selected spreaders have the maximum influence, as these nodes may be adjacent, and thus play redundant roles in the propagation process. We propose three new algorithms to select multiple spreaders by taking into account the dispersion of nodes in the following ways: (1) improving a well-performed local index rank (LIR) algorithm by extending its key concept of the local index (an index measures how many of a node’s neighbors have a higher degree) from first-to second-order neighbors; (2) combining the LIR and independent set (IS) methods, which is a generalization of the coloring problem for complex networks and can ensure the selected nodes are non-adjacent if they have the same color; (3) combining the improved second-order LIR method and IS method so as to make the selected spreaders more disperse. We evaluate the proposed methods against six baseline methods on 10 synthetic networks and five real networks based on the classic susceptible-infected-recovered (SIR) model. The experimental results show that our proposed methods can identify nodes that are more influential. This suggests that taking into account the distances between nodes may aid in the identification of multiple influential spreaders.
Observation of the Rotational Doppler Effect With Structured Beams in Atomic Vapor
Authors: Qiu Shuwei , Wang Jinwen , Yang Xin , Cao Mingtao , Zhang Shougang , Gao Hong , Li Fuli
Published: January 2022

A vector beam with the spatial variation polarization has attracted keen interest and is progressively applied in quantum information, quantum communication, precision measurement, and so on. In this letter, the spectrum observation of the rotational Doppler effect based on the coherent interaction between atoms and structured light in an atomic vapor is realized. The geometric phase and polarization of the structured beam are generated and manipulated by using a flexible and efficacious combination optical elements, converting an initial linearly polarized Gaussian beam into a phase vortex beam or an asymmetric or symmetric vector beam. These three representative types of structured beam independently interact with atoms under a longitudinal magnetic field to explore the rotational Doppler shift associated with the topological charge. We find that the rotational Doppler broadening increases obviously with the topological charge of the asymmetric and symmetric vector beam. There is no rotational Doppler broadening observed from the spectrum of the phase vortex beam, although the topological charge, and spatial profile of the beam change. This study can be applied to estimate the rotational velocity of the atom-level or molecule-level objects, measure the intensity of magnetic fields and study the quantum coherence in atomic ensembles.
Research on Calibration Method of Infrared Temperature Measurement System Near Room Temperature Field
Authors: Cui Shuanglong , Xing Jian
Published: January 2022

The calibration accuracy of the infrared temperature measurement system near room temperature field is easily affected by the calibration environment. In this paper, an equivalent blackbody calibration method is proposed for this problem. In this method, the target radiation and ambient radiation superimposed in calibration data are separated by two calibration functions at different ambient temperatures, and an equivalent blackbody calibration function is constructed. The experimental verification of the proposed method is carried out, and the results show that the proposed method has a better calibration effect for the surface blackbody than the commonly used environmental compensation methods. This method can effectively improve the calibration accuracy of infrared temperature measurement system near room temperature field, and further improve the infrared temperature measurement theory.
Polarization-Based Haze Removal Using Self-Supervised Network
Authors: Shi Yingjie , Guo Enlai , Bai Lianfa , Han Jing
Published: January 2022

Atmospheric scattering caused by suspended particles in the air severely degrades the scene radiance. This paper proposes a method to remove haze by using a neural network that combines scene polarization information. The neural network is self-supervised and online globally optimization can be achieved by using the atmospheric transmission model and gradient descent. Therefore, the proposed method does not require any haze-free image as the constraint for neural network training. The proposed approach is far superior to supervised algorithms in the performance of dehazing and is highly robust to the scene. It is proved that this method can significantly improve the contrast of the original image, and the detailed information of the scene can be effectively enhanced.
Massively Multidimensional Diffusion-Relaxation Correlation MRI
Authors: Narvaez Omar , Svenningsson Leo , Yon Maxime , Sierra Alejandra , Topgaard Daniel
Published: January 2022

Diverse approaches such as oscillating gradients, tensor-valued encoding, and diffusion-relaxation correlation have been used to study microstructure and heterogeneity in healthy and pathological biological tissues. Recently, acquisition schemes with free gradient waveforms exploring both the frequency-dependent and tensorial aspects of the encoding spectrum b(ω) have enabled estimation of nonparametric distributions of frequency-dependent diffusion tensors. These “D(ω)-distributions” allow investigation of restricted diffusion for each distinct component resolved in the diffusion tensor trace, anisotropy, and orientation dimensions. Likewise, multidimensional methods combining longitudinal and transverse relaxation rates, R1 and R2, with (ω-independent) D-distributions capitalize on the component resolution offered by the diffusion dimensions to investigate subtle differences in relaxation properties of sub-voxel water populations in the living human brain, for instance nerve fiber bundles with different orientations. By measurements on an ex vivo rat brain, we here demonstrate a “massively multidimensional” diffusion-relaxation correlation protocol joining all the approaches mentioned above. Images acquired as a function of the magnitude, normalized anisotropy, orientation, and frequency content of b(ω), as well as the repetition time and echo time, yield nonparametric D(ω)-R1-R2-distributions via a Monte Carlo data inversion algorithm. The obtained per-voxel distributions are converted to parameter maps commonly associated with conventional lower-dimensional methods as well as unique statistical descriptors reporting on the correlations between restriction, anisotropy, and relaxation.
Adaptive Synchronization for Hyperchaotic Liu System
Authors: Li Shunjie , Wu Yawen , Zheng Gang
Published: January 2022

In this paper, the adaptive control design is investigated for the chaos synchronization of two identical hyperchaotic Liu systems. First, an adaptive control law with two inputs is proposed based on Lyapunov stability theory. Secondly, two other control schemes are obtained based on a further analysis of the proposed adaptive control law. Finally, numerical simulations are presented to validate the effectiveness and correctness of these results.
Effectiveness of Light-Quality and Dark-White Growth Light Shifts in Short-Term Light Acclimation of Photosynthesis in Arabidopsis
Authors: Hommel Elisabeth , Liebers Monique , Offermann Sascha , Pfannschmidt Thomas
Published: January 2022

Photosynthesis needs to run efficiently under permanently changing illumination. To achieve this, highly dynamic acclimation processes optimize photosynthetic performance under a variety of rapidly changing light conditions. Such acclimation responses are acting by a complex interplay of reversible molecular changes in the photosynthetic antenna or photosystem assemblies which dissipate excess energy and balance uneven excitation between the two photosystems. This includes a number of non-photochemical quenching processes including state transitions and photosystem II remodeling. In the laboratory such processes are typically studied by selective illumination set-ups. Two set-ups known to be effective in a highly similar manner are (i) light quality shifts (inducing a preferential excitation of one photosystem over the other) or (ii) dark-light shifts (inducing a general off-on switch of the light harvesting machinery). Both set-ups result in similar effects on the plastoquinone redox state, but their equivalence in induction of photosynthetic acclimation responses remained still open. Here, we present a comparative study in which dark-light and light-quality shifts were applied to samples of the same growth batches of plants. Both illumination set-ups caused comparable effects on the phosphorylation of LHCII complexes and, hence, on the performance of state transitions, but generated different effects on the degree of state transitions and the formation of PSII super-complexes. The two light set-ups, thus, are not fully equivalent in their physiological effectiveness potentially leading to different conclusions in mechanistic models of photosynthetic acclimation. Studies on the regulation of photosynthetic light acclimation, therefore, requires to regard the respective illumination test set-up as a critical parameter that needs to be considered in the discussion of mechanistic and regulatory aspects in this subject.
Manipulation of Barley Development and Flowering Time by Exogenous Application of Plant Growth Regulators
Authors: Kupke Brendan M. , Tucker Matthew R. , Able Jason A. , Porker Kenton D.
Published: January 2022

Matching flowering time to the optimal flowering period in Mediterranean cropping zones is pivotal to maximize yield. Aside from variety selection and sowing date, growers have limited options to alter development in season. Plant hormones and growth regulators are used in perennial horticultural systems to manipulate development and floral initiation. In this study, a range of plant hormonal products were tested to analyze their effects on barley (Hordeum vulgare L) development by exogenous spray applications. Plants were grown in controlled conditions under long and short photoperiods with different vernalization treatments. The gibberellin (GA) products demonstrated the greatest potential for altering development. The GA inhibitor trinexapac-ethyl was able to delay the time to flowering in genetically divergent barley cultivars by up to 200 degree days under controlled conditions. A similar delay in flowering could be achieved via application at both early (GS13) and late (GS33) stages, with higher rates delaying flowering further. Notably, trinexapac-ethyl was able to extend the duration of pre-anthesis phases of development. By contrast, GA3 was unable to accelerate development under extreme short (8 h) or long (16 h) day lengths. There was also little evidence that GA3 could reproducibly accelerate development under intermediate 10–12 h day lengths. In addition, sprays of the cytokinin 6-benzyladenine (6-BA) were unable to reduce the vernalization requirement of the winter genotype Urambie. The present study provides baseline data for plant growth regulator treatments that delay cereal development. These treatments might be extended in field studies to align flowering of early sown crops to the optimal flowering period.
Spatiotemporal Variations in Seed Set and Pollen Limitation in Populations of the Rare Generalist Species Polemonium caeruleum in Poland
Authors: Ryniewicz Justyna , Roguz Katarzyna , Mirski Paweł , Brzosko Emilia , Skłodowski Mateusz , Wróblewska Ada , Ostrowiecka Beata , Tałałaj Izabela , Jermakowicz Edyta , Zych Marcin
Published: January 2022

A vast majority of angiosperms are pollinated by animals, and a decline in the number and diversity of insects often affects plant reproduction through pollen limitation. This phenomenon may be particularly severe in rare plant species, whose populations are shrinking. Here, we examined the variability in factors shaping reproductive success and pollen limitation in red-listed Polemonium caeruleum L. During a 5-year study in several populations of P. caeruleum (7–15, depending on year), we assessed the degree of pollen limitation based on differences in seed set between open-pollinated (control) and hand-pollinated flowers. We analysed the effects of flower visitors, population size, and meteorological data on plant reproductive success and pollen limitation. Our study showed that pollen limitation rarely affected P. caeruleum populations, and was present mainly in small populations. Pollen limitation index was negatively affected by the size of population, visitation frequency of all insects, and when considering the visitation frequency of individual groups, also by honeybee visits. Seed production in control treatment was positively influenced by the population size, average monthly precipitation in June and visits of hoverflies, while visits of honeybees, average monthly temperature in September, and average monthly precipitation in August influenced seed production negatively. As generalist plant P. caeruleum can be pollinated by diverse insect groups, however, in small populations their main visitors, the honeybees and bumblebees, may be less attracted, eventually leading to the disappearance of these populations. In pollination of P. caeruleum managed honeybees may play a dual role: while they are the most frequent and efficient flower visitors, their presence decreases seed set in open-pollinated flowers, which is most probably related to efficient pollen collection by these insects.
Novel Mutant Alleles Reveal a Role of the Extra-Large G Protein in Rice Grain Filling, Panicle Architecture, Plant Growth, and Disease Resistance
Authors: Biswal Akshaya K. , Wu Ting-Ying , Urano Daisuke , Pelissier Rémi , Morel Jean-Benoit , Jones Alan M. , Biswal Ajaya K.
Published: January 2022

Plant growth and grain filling are the key agronomical traits for grain weight and yield of rice. The continuous improvement in rice yield is required for a future sustainable global economy and food security. The heterotrimeric G protein complex containing a canonical α subunit (RGA1) couples extracellular signals perceived by receptors to modulate cell function including plant development and grain weight. We hypothesized that, besides RGA1, three atypical, extra-large GTP-binding protein (XLG) subunits also regulate panicle architecture, plant growth, development, grain weight, and disease resistance. Here, we identified a role of XLGs in agronomic traits and stress tolerance by genetically ablating all three rice XLGs individually and in combination using the CRISPR/Cas9 genome editing in rice. For this study, eight (three single, two double, and three triple) null mutants were selected. Three XLG proteins combinatorically regulate seed filling, because loss confers a decrease in grain weight from 14% with loss of one XLG and loss of three to 32% decrease in grain weight. Null mutations in XLG2 and XLG4 increase grain size. The mutants showed significantly reduced panicle length and number per plant including lesser number of grains per panicle compared to the controls. Loss-of-function of all individual XLGs contributed to 9% more aerial biomass compared to wild type (WT). The double mutant showed improved salinity tolerance. Moreover, loss of the XLG gene family confers hypersensitivity to pathogens. Our findings suggest that the non-canonical XLGs play important roles in regulating rice plant growth, grain filling, panicle phenotype, stress tolerance, and disease resistance. Genetic manipulation of XLGs has the potential to improve agronomic properties in rice.
Coordinated Epigenetic Regulation in Plants: A Potent Managerial Tool to Conquer Biotic Stress
Authors: Huang Chien-Yu , Jin Hailing
Published: January 2022

Plants have evolved variable phenotypic plasticity to counteract different pathogens and pests during immobile life. Microbial infection invokes multiple layers of host immune responses, and plant gene expression is swiftly and precisely reprogramed at both the transcriptional level and post-transcriptional level. Recently, the importance of epigenetic regulation in response to biotic stresses has been recognized. Changes in DNA methylation, histone modification, and chromatin structures have been observed after microbial infection. In addition, epigenetic modifications may be preserved as transgenerational memories to allow the progeny to better adapt to similar environments. Epigenetic regulation involves various regulatory components, including non-coding small RNAs, DNA methylation, histone modification, and chromatin remodelers. The crosstalk between these components allows precise fine-tuning of gene expression, giving plants the capability to fight infections and tolerant drastic environmental changes in nature. Fully unraveling epigenetic regulatory mechanisms could aid in the development of more efficient and eco-friendly strategies for crop protection in agricultural systems. In this review, we discuss the recent advances on the roles of epigenetic regulation in plant biotic stress responses.
The Chromosome-Level Genome of Miracle Fruit (Synsepalum dulcificum) Provides New Insights Into the Evolution and Function of Miraculin
Authors: Yang Zhuang , Liu Zhenhuan , Xu Hang , Chen Yayu , Du Pengmeng , Li Ping , Lai Wenjie , Hu Haiyan , Luo Jie , Ding Yuanhao
Published: January 2022

Miracle fruit (Synsepalum dulcificum) is a rare valuable tropical plant famous for a miraculous sweetening glycoprotein, miraculin, which can modify sour flavors to sweet flavors tasted by humans. Here, we present a chromosome-level high-quality genome of S. dulcificum with an assembly genome size of ∼550 Mb, contig N50 of ∼14.14 Mb, and 37,911 annotated protein-coding genes. Phylogenetic analysis revealed that S. dulcificum was most closely related to Camellia sinensis and Diospyros oleifera, and that S. dulcificum diverged from the Diospyros genus ∼75.8 million years ago (MYA), and that C. sinensis diverged from Synsepalum ∼63.5 MYA. Ks assessment and collinearity analysis with S. dulcificum and other species suggested that a whole-genome duplication (WGD) event occurred in S. dulcificum and that there was good collinearity between S. dulcificum and Vitis vinifera. On the other hand, transcriptome and metabolism analysis with six tissues containing three developmental stages of fleshes and seeds of miracle fruit revealed that Gene Ontology (GO) terms and metabolic pathways of “cellular response to chitin,” “plant–pathogen interaction,” and “plant hormone signal transduction” were significantly enriched during fruit development. Interestingly, the expression of miraculin (Chr10G0299340) progressively increased from vegetative organs to reproductive organs and reached an incredible level in mature fruit flesh, with an fragments per kilobase of transcript per million (FPKM) value of ∼113,515, which was the most highly expressed gene among all detected genes. Combining the unique signal peptide and the presence of the histidine-30 residue together composed the main potential factors impacting miraculin’s unique properties in S. dulcificum. Furthermore, integrated analysis of weighted gene coexpression network analysis (WGCNA), enrichment and metabolite correlation suggested that miraculin plays potential roles in regulating plant growth, seed germination and maturation, resisting pathogen infection, and environmental pressure. In summary, valuable genomic, transcriptomic, and metabolic resources provided in this study will promote the utilization of S. dulcificum and in-depth research on species in the Sapotaceae family.
Measuring Achievement, Affiliation, and Power Motives in Mobility Situations: Development of the Multi-Motive Grid Mobility
Authors: Mertens Alica , Theisen Maximilian , Funke Joachim
Published: January 2022

The current study introduces the Multi-Motive Grid Mobility (MMG-M) in an age-stratified sample (N = 206) that aims to disentangle six motive components – hope of success, hope of affiliation, hope of power, fear of failure, fear of rejection, and fear of power – in mobility-related and mobility-unrelated scenarios. Similar to the classical Multi-Motive Grid (MMG), we selected 14 picture scenarios representing seven mobility and seven non-mobility situations. The scenarios were combined with 12 statements from the MMG. Both the MMG-M and MMG were assessed to allow comparability between psychometric criteria. The results of confirmatory factor analyses yielded a good model fit for a six-factor solution with an additional mobility factor for the MMG-M. Internal consistency of the items was similar to the MMG. Lastly, we investigated associations between the motive components and mobility-related variables. We found that risk awareness was positively related to all fear components in both mobility and non-mobility scenarios. Most importantly, physical constraint was positively associated with fear of rejection and fear of power in mobility situations underlining the importance to create support systems to reduce these concerns in people’s everyday lives.