bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucosal Associated Invariant T Cells Were Activated and Polarized Toward Th17 in Chronic Obstructive Pulmonary Disease
Authors: Qiu Wenjia , Kang Ning , Wu Yanxu , Cai Yongjun , Xiao Li , Ge Haiyan , Zhu Huili
Published: March 2021

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airway limitation accompanied with infiltration of inflammatory cells. Mucosal associated invariant T (MAIT) cells can recognize bacteria and play an important role in controlling host immune responses by producing cytokines. In this study, we characterized the function and the ability of MAIT cells to secrete cytokines measured by flow cytometry. In COPD patients, MAIT cells have the ability to produce more IL-17 and less IFN-γ compared to healthy individuals. We found that HLA-DR expression levels reflected the degree of inflammation and the proportion of IL-17 was significantly correlated with lung function in peripheral blood. In addition, we found that MAIT cells were highly expressed in the lung, and the increased expression of CXCR2, CXCL1 indicated that MAIT cells had the potential to migrate to inflammatory tissues. This evidence implies that MAIT cells may play a potential role in COPD immunopathology.
Serum Levels of Inflammatory Proteins Are Associated With Peripheral Neuropathy in a Cross-Sectional Type-1 Diabetes Cohort
Authors: Purohit Sharad , Tran Paul Minh Huy , Tran Lynn Kim Hoang , Satter Khaled Bin , He Mingfang , Zhi Wenbo , Bai Shan , Hopkins Diane , Gardiner Melissa , Wakade Chandramohan , Bryant Jennifer , Bernard Risa , Morgan John , Bode Bruce , Reed John Chip , She Jin-Xiong
Published: March 2021

Chronic low-grade inflammation is involved in the pathogenesis of type-1 diabetes (T1D) and its complications. In this cross-section study design, we investigated association between serum levels of soluble cytokine receptors with presence of peripheral neuropathy in 694 type-1 diabetes patients. Sex, age, blood pressure, smoking, alcohol intake, HbA1c and lipid profile, presence of DPN (peripheral and autonomic), retinopathy and nephropathy was obtained from patient’s chart. Measurement of soluble cytokine receptors, markers of systemic and vascular inflammation was done using multiplex immunoassays. Serum levels were elevated in in DPN patients, independent of gender, age and duration of diabetes. Crude odds ratios were significantly associated with presence of DPN for 15/22 proteins. The Odds ratio (OR) remained unchanged for sTNFRI (1.72, p=0.00001), sTNFRII (1.45, p=0.0027), sIL2Rα (1.40, p=0.0023), IGFBP6 (1.51, p=0.0032) and CRP (1.47, p=0.0046) after adjusting for confounding variables, HbA1C, hypertension and dyslipidemia. Further we showed risk of DPN is associated with increase in serum levels of sTNFRI (OR=11.2, p<10), sIL2Rα (8.69, p<10-15), sNTFRII (4.8, p<10-8) and MMP2 (4.5, p<10-5). We combined the serum concentration using ridge regression, into a composite score, which can stratify the DPN patients into low, medium and high-risk groups. Our results here show activation of inflammatory pathway in DPN patients, and could be a potential clinical tool to identify T1D patients for therapeutic intervention of anti-inflammatory therapies.
Understanding and Managing Sepsis in Patients With Cancer in the Era of Antimicrobial Resistance
Authors: Gudiol Carlota , Albasanz-Puig Adaia , Cuervo Guillermo , Carratalà Jordi
Published: March 2021

Sepsis is a frequent complication in immunosuppressed cancer patients and hematopoietic stem cell transplant recipients that is associated with high morbidity and mortality rates. The worldwide emergence of antimicrobial resistance is of special concern in this population because any delay in starting adequate empirical antibiotic therapy can lead to poor outcomes. In this review, we aim to address: (1) the mechanisms involved in the development of sepsis and septic shock in these patients; (2) the risk factors associated with a worse prognosis; (3) the impact of adequate initial empirical antibiotic therapy given the current era of widespread antimicrobial resistance; and (4) the optimal management of sepsis, including adequate and early source control of infection, optimized antibiotic use based on the pharmacokinetic and pharmacodynamics changes in these patients, and the role of the new available antibiotics.
The Association Between Alpha-1 Adrenergic Receptor Antagonists and In-Hospital Mortality From COVID-19
Authors: Rose Liam , Graham Laura , Koenecke Allison , Powell Michael , Xiong Ruoxuan , Shen Zhu , Mench Brett , Kinzler Kenneth W. , Bettegowda Chetan , Vogelstein Bert , Athey Susan , Vogelstein Joshua T. , Konig Maximilian F. , Wagner Todd H.
Published: March 2021

Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed, and pre-clinical data suggest alpha-1 adrenergic receptor antagonists (α1-AR antagonists) may be effective in reducing mortality related to hyperinflammation independent of etiology. Using a retrospective cohort design with patients in the Department of Veterans Affairs healthcare system, we use doubly robust regression and matching to estimate the association between baseline use of α1-AR antagonists and likelihood of death due to COVID-19 during hospitalization. Having an active prescription for any α1-AR antagonist (tamsulosin, silodosin, prazosin, terazosin, doxazosin, or alfuzosin) at the time of admission had a significant negative association with in-hospital mortality (relative risk reduction 18%; odds ratio 0.73; 95% CI 0.63–0.85; p ≤ 0.001) and death within 28 days of admission (relative risk reduction 17%; odds ratio 0.74; 95% CI 0.65–0.84; p ≤ 0.001). In a subset of patients on doxazosin specifically, an inhibitor of all three alpha-1 adrenergic receptors, we observed a relative risk reduction for death of 74% (odds ratio 0.23; 95% CI 0.03–0.94; p = 0.028) compared to matched controls not on any α1-AR antagonist at the time of admission. These findings suggest that use of α1-AR antagonists may reduce mortality in COVID-19, supporting the need for randomized, placebo-controlled clinical trials in patients with early symptomatic infection.
New Bioactive Sesquiterpeniods From the Plant Endophytic Fungus Pestalotiopsis theae
Authors: Liu Gaoran , Huo Ruiyun , Zhai Yanan , Liu Ling
Published: March 2021

Three new secondary metabolites pestalothenins A–C (1–3), including two new humulane-derived sesquiterpeniods (1 and 2) and one new caryophyllene-derived sesquiterpeniod (3), together with five known compounds (4–8) were isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae (N635). Their structures were elucidated by the extensive analyses of HRESIMS and NMR spectroscopic data. The absolute configurations of 1–3 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The cytotoxic effects of these compounds were evaluated in vitro. Compound 6 showed moderate cytotoxicity against T24 and MCF7 cell lines. In addition, compounds 1–8 were also evaluated for antibacterial activity.
Applications of Transcriptomics and Proteomics for Understanding Dormancy and Resuscitation in Mycobacterium tuberculosis
Authors: Kundu Manikuntala , Basu Joyoti
Published: March 2021

Mycobacterium tuberculosis can survive within its host for extended periods of time without any clinical symptoms of disease and reactivate when the immune system is weakened. A detailed understanding of how M. tuberculosis enters into and exits out of dormancy, is necessary in order to develop new strategies for tackling tuberculosis. Omics methodologies are unsupervised and unbiased to any hypothesis, making them useful tools for the discovery of new drug targets. This review summarizes the findings of transcriptomic and proteomic approaches toward understanding dormancy and reactivation of M. tuberculosis. Within the granuloma of latently infected individuals, the bacteria are dormant, with a marked slowdown of growth, division and metabolism. In vitro models have attempted to simulate these features by subjecting the bacterium to hypoxia, nutrient starvation, potassium depletion, growth in the presence of vitamin C, or growth in the presence of long-chain fatty acids. The striking feature of all the models is the upregulation of the DosR regulon, which includes the transcriptional regulator Rv0081, one of the central hubs of dormancy. Also upregulated are chaperone proteins, fatty acid and cholesterol degrading enzymes, the sigma factors SigE and SigB, enzymes of the glyoxylate and the methylcitrate cycle, the Clp proteases and the transcriptional regulator ClgR. Further, there is increased expression of genes involved in mycobactin synthesis, fatty acid degradation, the glyoxylate shunt and gluconeogenesis, in granulomas formed in vitro from peripheral blood mononuclear cells from latently infected individuals compared to naïve individuals. Genes linked to aerobic respiration, replication, transcription, translation and cell division, are downregulated during dormancy in vitro, but upregulated during reactivation. Resuscitation in vitro is associated with upregulation of genes linked to the synthesis of mycolic acids, phthiocerol mycocerosate (PDIM) and sulfolipids; ribosome biosynthesis, replication, transcription and translation, cell division, and genes encoding the five resuscitation promoting factors (Rpfs). The expression of proteases, transposases and insertion sequences, suggests genome reorganization during reactivation.
Changes in the Community Structure of Under-Ice and Open-Water Microbiomes in Urban Lakes Exposed to Road Salts
Authors: Fournier Isabelle B. , Lovejoy Connie , Vincent Warwick F.
Published: March 2021

Salinization of freshwater is increasingly observed in regions where chloride de-icing salts are applied to the roads in winter, but little is known about the effects on microbial communities. In this study, we analyzed the planktonic microbiomes of four lakes that differed in degree of urbanization, eutrophication and salinization, from an oligotrophic reference lake with no surrounding roads, to a eutrophic, salinized lake receiving runoff from a highway. We tested the hypothesis that an influence of road salts would be superimposed on the effects of season and trophic status. We evaluated the microbial community structure by 16S rRNA sequencing for Bacteria, and by four methods for eukaryotes: 16S rRNA chloroplast analysis, 18S rRNA sequencing, photosynthetic pigment analysis and microscopy. Consistent with our hypothesis, chloride and total nitrogen concentrations were among the most important statistical factors explaining the differences in taxonomic composition. These factors were positively correlated with the abundance of cryptophytes, haptophytes, and cyanobacteria. Ice-cover was also a major structuring factor, with clear differences between the winter communities and those of the open-water period. Nitrifying and methane oxidizing bacteria were more abundant in winter, suggesting the importance of anaerobic sediment processes and release of reduced compounds into the ice-covered water columns. The four methods for eukaryotic analysis provided complementary information. The 18S rRNA observations were strongly influenced by the presence of ribosome-rich ciliates, but revealed a much higher degree of taxonomic richness and greater separation of lakes, seasonal changes and potential salinity effects than the other methods.
White Matter Structural Network Analysis to Differentiate Alzheimer’s Disease and Subcortical Ischemic Vascular Dementia
Authors: Feng Mengmeng , Zhang Yue , Liu Yuanqing , Wu Zhiwei , Song Ziyang , Ma Mengya , Wang Yueju , Dai Hui
Published: March 2021

To explore the evaluation of white matter structural network analysis in the differentiation of Alzheimer’s disease (AD) and subcortical ischemic vascular dementia (SIVD), 67 participants [31 AD patients, 19 SIVD patients, and 19 normal control (NC)] were enrolled in this study. Each participant underwent 3.0T MRI scanning. Diffusion tensor imaging (DTI) data were analyzed by graph theory (GRETNA toolbox). Statistical analyses of global parameters [gamma, sigma, lambda, global shortest path length (Lp), global efficiency (Eg), and local efficiency (Eloc)] and nodal parameters [betweenness centrality (BC)] were obtained. Network-based statistical analysis (NBS) was employed to analyze the group differences of structural connections. The diagnosis efficiency of nodal BC in identifying different types of dementia was assessed by receiver operating characteristic (ROC) analysis. There were no significant differences of gender and years of education among the groups. There were no significant differences of sigma and gamma in AD vs. NC and SIVD vs. NC, whereas the Eg values of AD and SIVD were statistically decreased, and the lambda values were increased. The BC of the frontal cortex, left superior parietal gyrus, and left precuneus in AD patients were obviously reduced, while the BC of the prefrontal and subcortical regions were decreased in SIVD patients, compared with NC. SIVD patients had decreased structural connections in the frontal, prefrontal, and subcortical regions, while AD patients had decreased structural connections in the temporal and occipital regions and increased structural connections in the frontal and prefrontal regions. The highest area under curve (AUC) of BC was 0.946 in the right putamen for AD vs. SIVD. White matter structural network analysis may be a potential and promising method, and the topological changes of the network, especially the BC change in the right putamen, were valuable in differentiating AD and SIVD patients.
Nanotechnology to the Rescue: Treatment Perspective for the Immune Dysregulation Observed in COVID-19
Authors: Peter Angela E. , Sandeep B. V. , Rao B. Ganga , Kalpana V. Lakshmi
Published: March 2021

The study of the use of nanotechnology for drug delivery has been extensive. Nanomedical approaches for therapeutics; drug delivery in particular is superior to conventional methods in that it allows for controlled targeted delivery and release, higher stability, extended circulation time, minimal side-effects, and improved pharmacokinetic clearance (of the drug) form the body, to name a few. The magnitude of COVID-19, the current ongoing pandemic has been severe; it has caused widespread the loss of human life. In individuals with severe COVID-19, immune dysregulation and a rampant state of hyperinflammation is observed. This kind of an immunopathological response is detrimental and results in rapid disease progression, development of secondary infections, sepsis and can be fatal. Several studies have pin-pointed the reason for this immune dysregulation; deviations in the signaling pathways involved in the mediation and control of immune responses. In severe COVID-19 patients, many signaling cascades including JAK/STAT, NF-κB, MAPK/ERK, TGF beta, VEGF, and Notch signaling were found to be either upregulated or inactivated. Targeting these aberrant signaling pathways in conjunction with antiviral therapy will effectuate mitigation of the hyperinflammation, hypercytokinemia, and promote faster recovery. The science of the use of nanocarriers as delivery agents to modulate these signaling pathways is not new; it has already been explored for other inflammatory diseases and in particular, cancer therapy. Numerous studies have evaluated the efficacy and potential of nanomedical approaches to modulate these signaling pathways and have been met with positive results. A treatment regime, that includes nanotherapeutics and antiviral therapies will prove effective and holds great promise for the successful treatment of COVID-19. In this article, we review different nanomedical approaches already studied for targeting aberrant signaling pathways, the host immune response to SARS-CoV-2, immunopathology and the dysregulated signaling pathways observed in severe COVID-19 and the current treatment methods in use for targeting signaling cascades in COVID-19. We then conclude by suggesting that the use of nanomedical drug delivery systems for targeting signaling pathways can be extended to effectively target the aberrant signaling pathways in COVID-19 for best treatment results.
Memristors With Controllable Data Volatility by Loading Metal Ion-Added Ionic Liquids
Authors: Sato Hiroshi , Shima Hisashi , Nokami Toshiki , Itoh Toshiyuki , Honma Yusei , Naitoh Yasuhisa , Akinaga Hiroyuki , Kinoshita Kentaro
Published: March 2021

We demonstrate a new memristive device (IL-Memristor), in which an ionic liquid (IL) serve as a material to control the volatility of the resistance. ILs are ultra-low vapor pressure liquids consisting of cations and anions at room temperature, and their introduction into solid-state processes can provide new avenues in electronic device fabrication. Because the device resistance change in IL-Memristor is governed by a Cu filament formation/rupture in IL, we considered that the Cu filament stability affects the data retention characteristics. Therefore, we controlled the data retention time by clarifying the corrosion mechanism and performing the IL material design based on the results. It was found out that the corrosion of Cu filaments in the IL was ruled by the comproportionation reaction, and that the data retention characteristics of the devices varied depending on the valence of Cu ions added to the IL. Actually, IL-Memristors involving Cu(II) and Cu(I) show volatile and non-volatile nature with respect to the programmed resistance value, respectively. Our results showed that data volatility can be controlled through the metal ion species added to the IL. The present work indicates that IL-memristor is suitable for unique applications such as artificial neuron with tunable fading characteristics that is applicable to phenomena with a wide range of timescale.
Protocol for LASER: A Randomized Evaluation and an Associated Registry of Early Anticoagulation With Edoxaban After Ischemic Stroke in Patients With Atrial Fibrillation
Authors: Alrohimi Anas , Jickling Glen , Jeerakathil Thomas , Shuaib Ashfaq , Khan Khurshid , Kate Mahesh , Hill Michael D. , Buck Brian , Butcher Ken
Published: March 2021

Background: The optimal timing of anticoagulation after stroke in patients with atrial fibrillation (AF) is unknown.

Aim and Hypothesis: Our primary aim is to demonstrate the safety of edoxaban initiation within 5 days of AF related stroke. Our secondary aim is to determine predictors of hemorrhagic transformation (HT) after AF related stroke. We hypothesize that the rate of radiological HT will not be increased in patients starting edoxaban within 5 days of AF related stroke, relative to those in whom initiation is delayed. We hypothesize that the risk of HT in patients treated with edoxaban can be predicted using RNA expressed in leukocytes at time of stroke.

Methods and Design: LASER (Lixiana Acute Stroke Evaluation Registry) is a randomized controlled trial with an associated registry (clinicaltrials.gov NCT03494530). One hundred and fifty patients with ischemic stroke and AF will undergo baseline Computed Tomography (CT) scan and will be randomized 2:1 within 5 days of symptom onset to early (≤5 days, n = 100) or delayed (6–14 days, n = 50) edoxaban initiation. Participants will undergo clinical assessment and repeat CT at 7 days and clinical assessment at 90 days.

Study Outcomes: The primary outcome is the rate of incident radiological HT. Secondary outcomes include symptomatic HT, recurrent ischemic stroke, recurrent sub-clinical infarcts on follow up CT, systemic hemorrhagic complication rate, National Institute of Health Stroke Scale and modified Rankin Scale at day 7 and 90, mortality within 90 days, quality of life assessments at day 90, and predictors of HT, including RNA expression by 6 pre-selected candidate genes.

Discussion: Event rates for both HT and recurrent ischemic events, in patients treated with early vs. delayed edoxaban initiation are unknown. The primary study endpoint of LASER is an objective performance criterion relevant to clinical decision making in patients with AF related stroke. This study will provide data required for a definitive safety/efficacy study sample size power calculation.
Self-Powered Memristive Systems for Storage and Neuromorphic Computing
Authors: Shi Jiajuan , Wang Zhongqiang , Tao Ye , Xu Haiyang , Zhao Xiaoning , Lin Ya , Liu Yichun
Published: March 2021

A neuromorphic computing chip that can imitate the human brain’s ability to process multiple types of data simultaneously could fundamentally innovate and improve the von-neumann computer architecture, which has been criticized. Memristive devices are among the best hardware units for building neuromorphic intelligence systems due to the fact that they operate at an inherent low voltage, use multi-bit storage, and are cost-effective to manufacture. However, as a passive device, the memristor cell needs external energy to operate, resulting in high power consumption and complicated circuit structure. Recently, an emerging self-powered memristive system, which mainly consists of a memristor and an electric nanogenerator, had the potential to perfectly solve the above problems. It has attracted great interest due to the advantages of its power-free operations. In this review, we give a systematic description of self-powered memristive systems from storage to neuromorphic computing. The review also proves a perspective on the application of artificial intelligence with the self-powered memristive system.
Effect of Enzymatic Hydrolysis on the Zinc Binding Capacity and in vitro Gastrointestinal Stability of Peptides Derived From Pumpkin (Cucurbita pepo L.) Seeds
Authors: Lu Dan , Peng Mengyao , Yu Min , Jiang Bo , Wu Hong , Chen Jingjing
Published: March 2021

Zinc is a crucial micronutrient for maintaining body immune system and metabolism function. However, insufficient intake from diet may lead to zinc deficiency and impair normal body function. In addition, conventional zinc salts supplementation has the disadvantage of low bioavailability since the zinc ions may be easily chelated by dietary fiber or phytate commonly found in diets rich in plants, and form precipitates that cannot be absorbed. Therefore, the objective of the present study is to prepare pumpkin seed derived peptides and to evaluate the effect of structure and surface properties on the zinc binding behavior of the pumpkin seed protein hydrolysate (PSPH), as well as their gastrointestinal stability. Briefly, different PSPHs were prepared using enzymatic hydrolysis method with bromelain, papain, flavourzyme, alcalase, and pepsin. The particle size, zeta potential, surface hydrophobicity, degree of hydrolysis, ATR-FTIR spectra, and zinc binding capacity were determined. The representative samples were chosen to characterize the binding energy and surface morphology of PSPH-Zn. At last, the in vitro gastrointestinal stability of PSPH and PSPH-Zn were evaluated. Our results showed that peptides hydrolyzed by papain had the largest average molecular weight, smallest particle size, highest hydrophobicity, and the greatest zinc binding capacity. Zinc showed better gastrointestinal stability in PSPHs chelates than in its salt. Meanwhile, PSPH-Zn with higher zinc binding capacity showed better stability. The result of this study indicated pumpkin seed hydrolyzed by papain may be used as a potential source for zinc fortification. The findings in this study may provide important implications for developing plant-based zinc chelating peptides.
Light-To-Moderate Raw Garlic Consumption Frequency Is Inversely Associated With Thickened Carotid Intima-Media Thickness: A Population-Based Study
Authors: Liu Yunyun , Meng Ge , Zhang Qing , Liu Li , Wu Hongmei , Gu Yeqing , Zhang Shunming , Zhang Tingjing , Wang Xuena , Sun Shaomei , Zhou Ming , Jia Qiyu , Song Kun , Tan Fengling , Niu Kaijun
Published: March 2021

Background: Previous animal and clinical studies have reported beneficial effects of garlic preparations on carotid intima-media thickness (cIMT). However, no epidemiological study has yet investigated the association between dietary raw garlic consumption and cIMT in the general population. The objective of this study was investigating the association between dietary raw garlic consumption and thickened cIMT in Chinese adults.

Methods: This cross-sectional study used data from the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study. A total of 4,329 general adults from 2015 to 2017 were included in this study. Frequency of consumption of raw garlic was summarized as four categories for analysis: < 1 time/week, 1 time/week, 2-3 times/week, ≥4 times/week with a validated food frequency questionnaire. The thickened cIMT was defined as common carotid artery IMT ≥ 1.0 mm or a carotid bifurcation IMT ≥ 1.2 mm by ultrasonography. Multivariable logistic regression analysis was used to examine the association between frequency of raw garlic consumption and thickened cIMT.

Results: The prevalence of thickened cIMT is 22.9% among these participants. The adjusted odds ratios (95% confidence intervals) associated with the different frequencies were 1.00 (reference) for < 1 time/week, 0.74 (0.59, 0.94) for 1 time/week, 0.71 (0.55, 0.92) for 2–3 times/week, and 0.94 (0.71, 1.25) for ≥ 4 times/week.

Conclusions: Light-to-moderate raw garlic consumption was inversely associated with thickened cIMT, whereas greater raw garlic consumption (i.e., ≥4 times/week) was not associated with thickened cIMT. Future longitudinal studies should be conducted to test these findings.
Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma
Authors: Wang Ling , Sparks-Wallace Ayrianna , Casteel Jared L. , Howell Mary E. A. , Ning Shunbin
Published: March 2021

Non-small-cell lung carcinoma (NSCLC) is the major type of lung cancer, which is among the leading causes of cancer-related deaths worldwide. LIMD1 was previously identified as a tumor suppressor in lung cancer, but their detailed interaction in this setting remains unclear. In this study, we have carried out multiple genome-wide bioinformatic analyses for a comprehensive understanding of LIMD1 in NSCLC, using various online algorithm platforms that have been built for mega databases derived from both clinical and cell line samples. Our results indicate that LIMD1 expression level is significantly downregulated at both mRNA and protein levels in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), with a considerable contribution from its promoter methylation rather than its gene mutations. The Limd1 gene undergoes mutation only at a low rate in NSCLC (0.712%). We have further identified LIMD1-associated molecular signatures in NSCLC, including its natural antisense long non-coding RNA LIMD1-AS1 and a pool of membrane trafficking regulators. We have also identified a subgroup of tumor-infiltrating lymphocytes, especially neutrophils, whose tumor infiltration levels significantly correlate with LIMD1 level in both LUAD and LUSC. However, a significant correlation of LIMD1 with a subset of immune regulatory molecules, such as IL6R and TAP1, was only found in LUAD. Regarding the clinical outcomes, LIMD1 expression level only significantly correlates with the survival of LUAD (p<0.01) but not with that of LUSC (p>0.1) patients. These findings indicate that LIMD1 plays a survival role in LUAD patients at least by acting as an immune regulatory protein. To further understand the mechanisms underlying the tumor-suppressing function of LIMD1 in NSCLC, we show that LIMD1 downregulation remarkably correlates with the deregulation of multiple pathways that play decisive roles in the oncogenesis of NSCLC, especially those mediated by EGFR, KRAS, PIK3CA, Keap1, and p63, in both LUAD and LUSC, and those mediated by p53 and CDKN2A only in LUAD. This study has disclosed that LIMD1 can serve as a survival prognostic marker for LUAD patients and provides mechanistic insights into the interaction of LIMD1 with NSCLC, which provide valuable information for clinical applications.
Pancreatic Leiomyosarcoma With Schistosomiasis Hematobia: A Case Report and Literature Review
Authors: Li Qiang , Staiculescu Daniel , Zhou Yurong , Chen Jiang
Published: March 2021

Pancreatic leiomyosarcoma (PL) is a very rare, malignant neoplasm with a very poor prognosis. Here, we examine a novel case of PL with schistosomiasis hematobia. The patient had been initially misdiagnosed by the first magnetic resonance imaging (MRI). The second imaging examination demonstrated an enlarged heterogeneous tumor mass in the body-tail of pancreas. Following image analysis, the patient underwent a pancreatectomy, splenectomy and lymph node dissections. Sixteen months after the tumor resection, follow-up computed tomography (CT) and MRI revealed tumor metastasis in the liver and lung. PL has non-specific clinical manifestations and imaging characteristics, making early diagnosis very challenging. When it is difficult to distinguish between benign and malignant pancreatic lesions, short-term imaging follow-up is preferred. In this case report, we discuss the relationship between PL and schistosomiasis hematobia.
Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis
Authors: Oranratnachai Songporn , Rattanasiri Sasivimol , Pooprasert Anantaporn , Tansawet Amarit , Reungwetwattana Thanyanan , Attia John , Thakkinstian Ammarin
Published: March 2021

Background

Hepatocellular carcinoma (HCC) is the third most fatal cancer, with a 5-year survival rate of 18%. Standard frontline-therapy is multikinase inhibitors (MKIs), but accessibility is still limited, particularly in developing countries. This network meta-analysis (NMA) aimed to compare the efficacy of usual chemotherapy vs MKIs.

Method

Randomised-controlled trials (RCTs) comparing any among chemotherapy vs MKIs in treatment-naïve patients with advanced HCCs were identified from MEDLINE and SCOPUS databases. Overall survival (OS) and progression-free survival (PFS) probabilities and times were extracted from Kaplan-Meier curves using Digitizer, and then converted to individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate median OS and PFS. A two-stage NMA was applied for the overall response rate and adverse events (AEs) outcome.

Results

A total of 20 RCTs were eligible for NMA. Lenvatinib was the best treatment among single MKIs, with median OS and PFS of 9 and 6.3 months, without significant differences in AEs relative to other MKIs. Median OS and PFS were 0.70 (-0.42, 1.83) and 2.17 (1.41, 2.93) months longer with Lenvatinib than Sorafenib. Among chemotherapy agents, FOLFOX4 had the longest median OS and PFS at 7.9 and 4.3 months, respectively, without significant AEs compared to other chemotherapies. The combination of Sorafenib+Doxorubicin prolonged median OS and PFS to 12.7 and 6.3 months, respectively.

Conclusion

Use of the MKIs Lenvatinib or Sorafenib as first line systemic treatment for advanced HCC could be beneficial. However, FOLFOX4 might be the optimal choice in a developing country where the health-care budget is limited.
Early Interleukin-22 and Neutrophil Proteins Are Correlated to Future Lung Damage in Children With Cystic Fibrosis
Authors: Renwick Julie , Reece Emma , Walsh Jamie , Walsh Ross , Persaud Thara , O'Leary Cathal , Donnelly Seamas C. , Greally Peter
Published: March 2021

Cystic Fibrosis (CF) lung damage begins early in life. Lung function decline is associated with pulmonary infections, neutrophil infiltration and inflammation. In CF, neutrophils have an altered phenotype. In this pilot study, we aimed to determine if signals of dysfunctional neutrophil responses were evident early in life and whether these signals may be associated with lung damage in later childhood. We examined the pulmonary protein profiles of 14 clinical stable infants and pre-school children with CF employing the aptamer-based affinity platform, SOMAscan®. High resolution computed tomography (HRCT) was performed on all children after age 6 years and Brody score calculated. A Spearman's rank order correlation analysis and Benjamini-Hochberg adjustment was used to correlate protein concentrations in early life to Brody scores in later childhood. Early life concentrations of azurocidin and myeloperoxidase, were positively correlated with Brody score after age 6 (p = 0.0041 and p = 0.0182, respectively). Four other neutrophil associated proteins; Complement C3 (p = 0.0026), X-ray repair CCP 6 (p = 0.0059), C3a anaphylatoxin des Arginine (p = 0.0129) and cytokine receptor common subunit gamma (p = 0.0214) were all negatively correlated with Brody scores. Interestingly, patients with more severe lung damage after age 6 had significantly lower levels of IL-22 in early years of life (p = 0.0243). IL-22 has scarcely been reported to have implications in CF. Identification of early biomarkers that may predict more severe disease progression is particularly important for the future development of early therapeutic interventions in CF disease. We recommend further corroboration of these findings in prospective validation studies.
Clinical Characteristics According to Age and Duration of Symptoms to Be Considered for Rapid Diagnosis of Pediatric Intussusception
Authors: Park In Kyu , Cho Min Jeng
Published: March 2021

Purpose:The purpose of this study was to evaluate whether clinical findings in children with ileocolic intussusception differ based on age and duration of symptoms and to assess the clinical characteristics of diagnosed and undiagnosed patients to determine which symptoms make diagnosis more difficult.

Methods:We reviewed 536 medical records of <15-year-old children diagnosed with ileocolic intussusception between 2008 and 2019. We divided the children into three categories according to age (<1 year, 1–2 years, and ≥2 years). The children were also divided into two groups based on whether symptoms lasted for more or <6 h. Diagnosed and undiagnosed children were assessed separately during for the initial evaluation.

Results:Following analysis of the three age groups, bloody stool, post-enema bloody stool, diarrhea, vomiting, poor oral intake, and lethargy were more frequent in children aged <1 year. In children aged ≥2 years, non-specific abdominal pain was more frequent and the undiagnosed rate was higher. Following analysis of the duration of symptoms, paroxysmal pain was significantly more frequent in the early group (<6 h), and bloody stool and fever were significantly more frequent in the late group (≥6 h). Nonspecific abdominal pain was more frequent and the door-to-diagnosis time was significantly longer in the undiagnosed group than in the diagnosed group.

Conclusions:Clinical findings of ileocolic intussusception vary depending on the age and duration of symptoms. Younger children with paroxysmal pain, vomiting, bloody stool, poor oral intake, or lethargy should be suspected of having intussusception. In older children, non-specific abdominal pain without bloody stool may be a symptom of intussusception. Glycerin enema is helpful in diagnosing intussusception in children with no typical symptoms.
Gastrointestinal Symptoms in Children With Life-Limiting Conditions Receiving Palliative Home Care
Authors: Hauch Holger , Kriwy Peter , Hahn Andreas , Dettmeyer Reinhard , Zimmer Klaus-Peter , Neubauer Bernd , Brill Sabine , Vaillant Vera , de Laffolie Jan , Schaefer Kristine , Tretiakowa Irina , Hach Michaela , Sibelius Ulf , Berthold Daniel
Published: March 2021

Context: Children with life-limiting diseases suffer from gastrointestinal (GI) symptoms. Since the introduction of specialized palliative home care (SPHC) in Germany, it is possible to care for these children at home. In phase 1 of care the aim is to stabilize the patient. In phase 2, terminal support is provided.

Objectives: Analysis were performed of the differences between these phases. The causes and modalities/outcome of treatment were evaluated.

Methods: A retrospective study was performed from 2014 to 2020. All home visits were analyzed with regard to the abovementioned symptoms, their causes, treatment and results.

Results: In total, 149 children were included (45.9% female, mean age 8.17 ± 7.67 years), and 126 patients were evaluated. GI symptoms were common in both phases. Vomiting was more common in phase 2 (59.3 vs. 27.1%; p < 0.001). After therapy, the proportion of asymptomatic children in phase 1 increased from 40.1 to 75.7%; (p < 0.001). Constipation was present in 52.3% (phase 1) and 54.1% (phase 2). After treatment, the proportion of asymptomatic patients increased from 47.3 to 75.7% in phase 1 (p < 0.001), and grade 3 constipation was reduced from 33.9 to 15% in phase 2 (p < 0.05).

Conclusion: Painful GI symptoms occur in both palliative care phases but are more common in phase 2. The severity and frequency can usually be controlled at home. The study limitations were the retrospective design and small number of patients, but the study had a representative population, good data quality and a unique perspective on the reality of outpatient pediatric palliative care in Germany.
Automatically Controlled Frequency-Tunable rf Plasma Thruster: Ion Beam and Thrust Measurements
Authors: Takahashi Kazunori , Imai Ryoji , Hanaoka Kengo
Published: March 2021

A fast and automatically controlled frequency-tunable radiofrequency (rf) system is installed in an rf plasma thruster consisting of a stepped-diameter insulator source tube wound by a single-turn loop antenna and a solenoid providing a magnetic nozzle, and immersed in vacuum. The frequency and the output power are controlled so as to minimize the reflection coefficient and to maintain the net power corresponding to the forward minus reflected powers at a constant level. The reproducibility of the impedance matching and the stability of the net rf power are assessed, showing the fast impedance matching within about 10 msec and the long and stable delivery of the rf power to the thruster. When increasing the rf power up to 500 W, discontinuous changes in the source plasma density, the imparted thrust, and the signal intensity of the ion beam downstream of the thruster are observed, indicating effects of the discharge mode on the thruster performance and the ion energy distribution.
Changes in DNA Methylation in Arabidopsis thaliana Plants Exposed Over Multiple Generations to Gamma Radiation
Authors: Laanen Pol , Saenen Eline , Mysara Mohamed , Van de Walle Jorden , Van Hees May , Nauts Robin , Van Nieuwerburgh Filip , Voorspoels Stefan , Jacobs Griet , Cuypers Ann , Horemans Nele
Published: March 2021

Previous studies have found indications that exposure to ionising radiation (IR) results in DNA methylation changes in plants. However, this phenomenon is yet to be studied across multiple generations. Furthermore, the exact role of these changes in the IR-induced plant response is still far from understood. Here, we study the effect of gamma radiation on DNA methylation and its effect across generations in youngArabidopsisplants. A multigenerational set-up was used in which three generations (Parent, generation 1, and generation 2) of 7-day oldArabidopsis thalianaplants were exposed to either of the different radiation treatments (30, 60, 110, or 430 mGy/h) or to natural background radiation (control condition) for 14 days. The parental generation consisted of previously non-exposed plants, whereas generation 1 and generation 2 plants had already received a similar irradiation in the previous one or two generations, respectively. Directly after exposure the entire methylomes were analysed with UPLC-MS/MS to measure whole genome methylation levels. Whole genome bisulfite sequencing was used to identify differentially methylated regions (DMRs), including their methylation context in the three generations and this for three different radiation conditions (control, 30 mGy/h, and 110 mGy/h). Both intra- and intergenerational comparisons of the genes and transposable elements associated with the DMRs were made. Taking the methylation context into account, the highest number of changes were found for cytosines followed directly by guanine (CG methylation), whereas only limited changes in CHG methylation occurred and no changes in CHH methylation were observed. A clear increase in IR-induced DMRs was seen over the three generations that were exposed to the lowest dose rate, where generation 2 had a markedly higher number of DMRs than the previous two generations (Parent and generation 1). Counterintuitively, we did not see significant differences in the plants exposed to the highest dose rate. A large number of DMRs associated with transposable elements were found, the majority of them being hypermethylated, likely leading to more genetic stability. Next to that, a significant number of DMRs were associated with genes (either in their promoter-associated region or gene body). A functional analysis of these genes showed an enrichment for genes related to development as well as various stress responses, including DNA repair, RNA splicing, and (a)biotic stress responses. These observations indicate a role of DNA methylation in the regulation of these genes in response to IR exposure and shows a possible role for epigenetics in plant adaptation to IR over multiple generations.
Trait Diversity of Pulse Species Predicts Agroecosystem Properties Trade-Offs
Authors: Guiguitant Julie , Vile Denis , Marrou Hélène
Published: March 2021

Crop diversity management in agriculture is a fundamental principle of agroecology and a powerful way to promote resilient and sustainable production systems. Pulses are especially relevant for diversification issues. Yet, the specific diversity of legumes is poorly represented in most cropping systems. We used the trait-based approach to quantify the functional diversity of 30 pulses varieties, belonging to 10 species, grown under common field conditions. Our aim was to test relationships between traits, yield, and supporting agroecosystem properties. Our experimental results highlighted trade-offs between agroecosystem properties supported by different combinations of traits. Also, results demonstrated the relevance of leaf nitrogen content (LNC), leaf area ratio (LAR), and reproductive phenology to predict most of the trade-offs observed between agroecosystem properties. A comparison with a previous analysis based on literature data collected in diverse agronomic situations suggested that some traits are more plastic than others and therefore contribute differently to frame legumes diversity depending on the conditions of observation. Present results suggested that the implementation of such trait-based approach would rapidly benefit the selection of species/varieties for specific targeted agroecosystem services provisioning under specific (environmental or management) conditions.
Dynamic Responses of Barley Root Succinyl-Proteome to Short-Term Phosphate Starvation and Recovery
Authors: Wang Juncheng , Ma Zengke , Li Chengdao , Ren Panrong , Yao Lirong , Li Baochun , Meng Yaxiong , Ma Xiaole , Si Erjing , Yang Ke , Shang Xunwu , Wang Huajun
Published: March 2021

Barley (Hordeum vulgare L.)—a major cereal crop—has low Pi demand, which is a distinct advantage for studying the tolerance mechanisms of phosphorus deficiency. We surveyed dynamic protein succinylation events in barley roots in response to and recovery from Pi starvation by firstly evaluating the impact of Pi starvation in a Pi-tolerant (GN121) and Pi-sensitive (GN42) barley genotype exposed to long-term low Pi (40 d) followed by a high-Pi recovery for 10 d. An integrated proteomics approach involving label-free, immune-affinity enrichment, and high-resolution LC-MS/MS spectrometric analysis was then used to quantify succinylome and proteome in GN121 roots under short-term Pi starvation (6, 48 h) and Pi recovery (6, 48 h). We identified 2,840 succinylation sites (Ksuc) across 884 proteins; of which, 11 representative Ksuc motifs had the preferred amino acid residue (lysine). Furthermore, there were 81 differentially abundant succinylated proteins (DFASPs) from 119 succinylated sites, 83 DFASPs from 110 succinylated sites, 93 DFASPs from 139 succinylated sites, and 91 DFASPs from 123 succinylated sites during Pi starvation for 6 and 48 h and during Pi recovery for 6 and 48 h, respectively. Pi starvation enriched ribosome pathways, glycolysis, and RNA degradation. Pi recovery enriched the TCA cycle, glycolysis, and oxidative phosphorylation. Importantly, many of the DFASPs identified during Pi starvation were significantly overexpressed during Pi recovery. These results suggest that barley roots can regulate specific Ksuc site changes in response to Pi stress as well as specific metabolic processes. Resolving the metabolic pathways of succinylated protein regulation characteristics will improve phosphate acquisition and utilization efficiency in crops.
The Analysis of Interpersonal Communication in Sport From Mixed Methods Strategy: The Integration of Qualitative-Quantitative Elements Using Systematic Observation
Authors: Izquierdo Conrad , Anguera M. Teresa
Published: March 2021

The objective to which this manuscript is oriented to is focused on the analysis of interpersonal communication in sport. The multimodal essence of human nature adopts special characteristics in individual and team sports, given the roles that athletes adopt in different circumstances, depending on the contingencies that characterize each competition or each training session. Themixed methodsframework allows us to advance in the ways of integration between qualitative and quantitative elements, taking advantage of the proven possibilities of systematic observation, which we can considermixed methodin itself, and which provides rigor and flexibility in the study of the communicative flow in sport. In any sport, the procedure followed by systematic observation may require direct observation, which is characterized by its high perceptiveness, or indirect observation, when it comes to verbal behavior or documentary material. In all cases, the procedure is structured in three macro-stages: QUAL-QUAN-QUAL. In this work we start from a conceptual positioning about interpersonal communication, to later show the sequential gear in sports about obtaining qualitative data, its transformation into other types of data that are still qualitative but have been structured, analyze them quantitatively, and return to a qualitative stage where the interpretation of the results is possible. This process ofquantitizingconstitutes the cornerstone that gives shape and structure to any research on interpersonal communication in sport that combines the fine nuances of qualitative data (a motor action, a gesture, an exclamation,…) with the power of robust quantitative data analysis suitable for the treatment of organized qualitative data, which will provide qualitativefeed-back.