bluuebunny/crossref_metadata_2025 huggingface dataset:
An Information Theoretical Multilayer Network Approach to Breast Cancer Transcriptional Regulation
Authors: Ochoa Soledad , de Anda-Jáuregui Guillermo , Hernández-Lemus Enrique
Published: March 2021

Breast cancer is a complex, highly heterogeneous disease at multiple levels ranging from its genetic origins and molecular processes to clinical manifestations. This heterogeneity has given rise to the so-called intrinsic or molecular breast cancer subtypes. Aside from classification, these subtypes have set a basis for differential prognosis and treatment. Multiple regulatory mechanisms—involving a variety of biomolecular entities—suffer from alterations leading to the diseased phenotypes. Information theoretical approaches have been found to be useful in the description of these complex regulatory programs. In this work, we identified the interactions occurring between three main mechanisms of regulation of the gene expression program: transcription factor regulation, regulation via noncoding RNA, and epigenetic regulation through DNA methylation. Using data from The Cancer Genome Atlas, we inferred probabilistic multilayer networks, identifying key regulatory circuits able to (partially) explain the alterations that lead from a healthy phenotype to different manifestations of breast cancer, as captured by its molecular subtype classification. We also found some general trends in the topology of the multi-omic regulatory networks: Tumor subtype networks present longer shortest paths than their normal tissue counterpart; epigenomic regulation has frequently focused on genes enriched for certain biological processes; CpG methylation and miRNA interactions are often part of a regulatory core of conserved interactions. The use of probabilistic measures to infer information regarding theoretical-derived multilayer networks based on multi-omic high-throughput data is hence presented as a useful methodological approach to capture some of the molecular heterogeneity behind regulatory phenomena in breast cancer, and potentially other diseases.
Functional Characterization of the Effects of N-acetyltransferase 2 Alleles on N-acetylation of Eight Drugs and Worldwide Distribution of Substrate-Specific Diversity
Authors: Fukunaga Koya , Kato Ken , Okusaka Takuji , Saito Takeo , Ikeda Masashi , Yoshida Teruhiko , Zembutsu Hitoshi , Iwata Nakao , Mushiroda Taisei
Published: March 2021

Variability in the enzymatic activity of N-acetyltransferase 2 (NAT2) is an important contributor to interindividual differences in drug responses. However, there is little information on functional differences in N-acetylation activities according to NAT2 phenotypes, i.e., rapid, intermediate, slow, and ultra-slow acetylators, between different substrate drugs. Here, we estimated NAT2 genotypes in 990 Japanese individuals and compared the frequencies of different genotypes with those of different populations. We then calculated in vitro kinetic parameters of four NAT2 alleles (NAT2∗4, ∗5, ∗6, and ∗7) for N-acetylation of aminoglutethimide, diaminodiphenyl sulfone, hydralazine, isoniazid, phenelzine, procaineamide, sulfamethazine (SMZ), and sulfapyrizine. NAT2∗5, ∗6, and ∗7 exhibited significantly reduced N-acetylation activities with lower Vmax and CLint values of all drugs when compared with NAT2∗4. Hierarchical clustering analysis revealed that 10 NAT2 genotypes were categorized into three or four clusters. According to the results of in vitro metabolic experiments using SMZ as a substrate, the frequencies of ultra-slow acetylators were calculated to be 29.05–54.27% in Europeans, Africans, and South East Asians, whereas Japanese and East Asian populations showed lower frequencies (4.75 and 11.11%, respectively). Our findings will be helpful for prediction of responses to drugs primarily metabolized by NAT2.
Experimental Study of the Dynamic Compressive and Tensile Strengths of Fly Ash and Slag Based Alkali-Activated Concrete Reinforced With Basalt Fibers
Authors: Lian Chong , Wang Yubo , Liu Shan , Hao Yifei
Published: March 2021

The use of industrial by-products, e.g., fly ash, slag, as complete replacement of Portland cement to make alkali-activated concrete (AAC) has become a hot topic due to the contribution to sustainability in construction industry. AAC has comparable compressive strength compared to the ordinary Portland cement concrete (OPC) and has many advantages, such as excellent durability and corrosion resistance. However, similar to OPC, AACmaterial still has certain shortcomings such as brittleness, low tensile strength, and poor impact resistance, which can be improved by incorporating fibers in the matrix. This paper considers the basalt fiber-reinforced alkali-activated concrete (BFRAAC), and explores the dynamic compressive and tensile strengths through a series of impact tests. The test results show that the dynamic strength of BFRAAC exhibits significant strain rate effect, that is, the material strength increases with the strain rate. Compared to the compressive strength of the material, the strain rate sensitivity of its tensile strength is more marked. Based on the test results, empirical formulas describing the relation between dynamic strength and strain rate of BFRAAC are proposed.
Biologic Drug Survival in Psoriasis: A Systematic Review & Comparative Meta-Analysis
Authors: Mourad Ahmed I. , Gniadecki Robert
Published: March 2021

Drug survival studies have been utilized to evaluate the real-world effectiveness of biologics used in psoriasis. However, the increasing volume of drug survival data suffers from large variability due to regional differences in drug availability, patient selection and biologic reimbursement. The objective of this study was to conduct a meta-analysis of biologic drug survival to determine comparative effectiveness of the biologics in a real-world setting. Studies reporting drug survival for biologic therapy in psoriasis were identified by a systematic literature search. Hazard ratio data for drug discontinuation were estimated directly from published Kaplan-Meier estimator curves at year 1, 2, and 5 of treatment and compared pairwise for the following biologics: ustekinumab, adalimumab, etanercept, infliximab, secukinumab, and ixekizumab. This pooled hazard ratios were used to estimate 2- and 5-year overall drug survival rates. Ustekinumab had the longest persistence at 2 and 5 years among all biologics included in this meta-analysis. Adalimumab was superior to etanercept and infliximab at 5 years. Pooled 5-year drug survival rates for adalimumab, etanercept, and infliximab were 46.3, 35.9, and 34.7%, respectively. Two- and five-year data were not available for anti-IL-17 drugs, but at 1-year ustekinumab outperformed secukinumab, the latter being equal to anti-TNFs. In conclusion, ustekinumab is characterized by longer drug survival than TNF inhibitors and IL-17 inhibitors. Estimated pooled 2- and 5-year drug survival rates may serve as a useful tool for patient communication and clinical decision-making.
Plant Growth and Drought Tolerance-Promoting Bacterium for Bioremediation of Paraquat Pesticide Residues in Agriculture Soils
Authors: Inthama Phatcharida , Pumas Pamon , Pekkoh Jeeraporn , Pathom-aree Wasu , Pumas Chayakorn
Published: March 2021

Thailand is an agricultural country. However, agricultural productivity relies on the heavy use of herbicides, especially paraquat. Paraquat accumulation is emerging as a problem in an ever-growing portion of agricultural land. Paraquat residues are toxic to plants, animals, and aquatic organisms in the environment. Biological remediation is a process that can mitigate agricultural chemical contaminants. One of the interesting bioremediators is bacteria. Not only do certain soil bacteria remediate paraquat, but some of them also possess plant growth-promoting properties, which provide advantages in field application. Thus, this study aimed to screen soil bacteria that could degrade paraquat and, at the same time, promote plant growth. Bacteria were isolated from paraquat-treated agricultural soil in Mueang Kaen Pattana municipality, Chiang Mai province, Thailand. On the basis of morphological and 16S rDNA sequence analyses, the selected bacterium was identified as Bacillus aryabhattai strain MoB09. It is capable of growing in nitrogen-free media. B. aryabhattai growth and paraquat degradation were found to be optimum at pH 7 and 30°C. This selected strain also possessed plant growth-promoting abilities, including indole production, siderophore production, phosphate solubilization, and 1-aminocyclopropane-1-carboxylic acid deaminase activity. Paraquat degradation was also evaluated in pot experiments of cowpea (Vigna unguiculata). It was found that this strain could remediate the paraquat residue in both sterilized and non-sterilized soils. The cowpea plants grown in paraquat-contaminated soil with B. aryabhattai showed longer root and shoot lengths than those grown in soil without bacterial inoculation. In addition, B. aryabhattai also promoted the growth of cowpea under induced drought stress. These results suggested that B. aryabhattai could be applied to mitigate paraquat residue in soil and also to promote plant productivity for the organic crop production.
Re-evaluation of a Neonatal Mouse Model of Infection With Enterotoxigenic Escherichia coli
Authors: Carroll Carla J. , Hocking Dianna M. , Azzopardi Kristy I. , Praszkier Judyta , Bennett-Wood Vicki , Almeida Kaylani , Ingle Danielle J. , Baines Sarah L. , Tauschek Marija , Robins-Browne Roy M.
Published: March 2021

Enterotoxigenic E. coli (ETEC) is a common cause of diarrhea in children in low- and middle-income countries, and in travelers to these countries. ETEC is also an important cause of morbidity and premature mortality in piglets, calves, goat kids and lambs. The major virulence determinants of ETEC are enterotoxins and colonization factors, which enable the pathogen to colonize the small intestine and deliver enterotoxins, such as the heat-stable enterotoxins, STp and STh, to epithelial cells. Because most ETEC strains are host-specific, there are few convenient animal models to investigate the pathogenesis of ETEC infections or to evaluate specific anti-ETEC interventions, such as drugs and vaccines. An exception is ETEC strains bearing F41 pili, which mediate intestinal colonization of various young animals, including neonatal mice, to cause disease and in some cases death. In this study, we used the archetypal F41-producing bovine ETEC strain, B41 (O101:NM; K99, F41, STp) to validate and further explore the contribution of F41 and STp to bacterial virulence. By using targeted gene deletion and trans-complementation studies, augmented by whole genome sequencing, and in vitro and animal studies of virulence, we established that F41 mediates colonization of the mouse intestine and is essential for bacterial virulence. In addition, we showed for the first time that STp is as important as F41 for virulence. Together, these findings validate the use of neonatal mice to study the pathogenesis of F41-bearing ETEC and to investigate possible specific anti-ETEC interventions including vaccines that target heat-stable enterotoxins.
An Extracellular Matrix-Based Signature Associated With Immune Microenvironment Predicts the Prognosis and Therapeutic Responses of Patients With Oesophageal Squamous Cell Carcinoma
Authors: Zhang Hongpan , Shi Qi , Yang Zhihao , Wang Kaige , Zhang Zhiyu , Huang Zheng , Cui Xiaobin , Li Feng
Published: March 2021

Evidence has suggested that the cancer-associated extracellular matrix (ECM) could be recognised as immune-related biomarkers that modulate tumour progression and expansion. However, the ECM-associated immune effect on esophageal squamous cell carcinoma (ESCC) prognosis and therapy has not been well characterised. In our study, we first constructed an ECM-related signature including four genes CST1, NELL2, ADAMTSL4, and ANGPTL7 by multivariate Cox regression analyses. This signature could serve as a marker to evaluate the prognosis of patients with ESCC and was successfully validated in testing and combined (training plus testing) cohorts. We also found that there were significant different therapeutic responses to chemotherapy and targeted drugs between the high-risk and low-risk groups of patients defined by the signature. Furthermore, the expression of four genes and immune function analysis suggested that this ECM-related signature gene might play important roles in the changes of the tumour microenvironment. In conclusion, our findings demonstrated that the ECM-related signature might serve as an independent prognostic factor and provide a potential biomarker for chemotherapy responses for patients with ESCC.
Modulation of the Corticomotor Excitability by Repetitive Peripheral Magnetic Stimulation on the Median Nerve in Healthy Subjects
Authors: Jia Yanbing , Liu Xiaoyan , Wei Jing , Li Duo , Wang Chun , Wang Xueqiang , Liu Hao
Published: March 2021

Objective: We aimed to examine the effects of repetitive peripheral nerve magnetic stimulation (rPNMS) on the excitability of the contralateral motor cortex and motor function of the upper limb in healthy subjects.

Methods: Forty-six healthy subjects were randomly assigned to either a repetitive peripheral nerve magnetic stimulation group (n = 23) or a sham group (n = 23). The repetitive peripheral nerve magnetic stimulation group received stimulation using magnetic pulses at 20 Hz, which were applied on the median nerve of the non-dominant hand, whereas the sham group underwent the same protocol without the stimulation output. The primary outcome was contralateral transcranial magnetic stimulation (TMS)-induced corticomotor excitability for the abductor pollicis brevis of the stimulated hand in terms of resting motor threshold (rMT), the slope of recruitment curve, and peak amplitude of motor evoked potential (MEP), which were measured at baseline and immediately after each session. The secondary outcomes were motor hand function including dexterity and grip strength of the non-dominant hand assessed at baseline, immediately after stimulation, and 24 h post-stimulation.

Results: Compared with the sham stimulation, repetitive peripheral nerve magnetic stimulation increased the peak motor evoked potential amplitude immediately after the intervention. The repetitive peripheral nerve magnetic stimulation also increased the slope of the recruitment curve immediately after intervention and enhanced hand dexterity after 24 h. However, the between-group difference for the changes was not significant. The significant changes in hand dexterity and peak amplitude of motor evoked potential after repetitive peripheral nerve magnetic stimulation were associated with their baseline value.

Conclusions: Repetitive peripheral nerve magnetic stimulation may modulate the corticomotor excitability together with a possible lasting improvement in hand dexterity, indicating that it might be helpful for clinical rehabilitation.
Long-Term BCI Training of a Tetraplegic User: Adaptive Riemannian Classifiers and User Training
Authors: Benaroch Camille , Sadatnejad Khadijeh , Roc Aline , Appriou Aurélien , Monseigne Thibaut , Pramij Smeety , Mladenovic Jelena , Pillette Léa , Jeunet Camille , Lotte Fabien
Published: March 2021

While often presented as promising assistive technologies for motor-impaired users, electroencephalography (EEG)-based Brain-Computer Interfaces (BCIs) remain barely used outside laboratories due to low reliability in real-life conditions. There is thus a need to design long-term reliable BCIs that can be used outside-of-the-lab by end-users, e.g., severely motor-impaired ones. Therefore, we propose and evaluate the design of a multi-class Mental Task (MT)-based BCI for longitudinal training (20 sessions over 3 months) of a tetraplegic user for the CYBATHLON BCI series 2019. In this BCI championship, tetraplegic pilots are mentally driving a virtual car in a racing video game. We aimed at combining a progressive user MT-BCI training with a newly designed machine learning pipeline based on adaptive Riemannian classifiers shown to be promising for real-life applications. We followed a two step training process: the first 11 sessions served to train the user to control a 2-class MT-BCI by performing either two cognitive tasks (REST and MENTAL SUBTRACTION) or two motor-imagery tasks (LEFT-HAND and RIGHT-HAND). The second training step (9 remaining sessions) applied an adaptive, session-independent Riemannian classifier that combined all 4 MT classes used before. Moreover, as our Riemannian classifier was incrementally updated in an unsupervised way it would capture both within and between-session non-stationarity. Experimental evidences confirm the effectiveness of this approach. Namely, the classification accuracy improved by about 30% at the end of the training compared to initial sessions. We also studied the neural correlates of this performance improvement. Using a newly proposed BCI user learning metric, we could show our user learned to improve his BCI control by producing EEG signals matching increasingly more the BCI classifier training data distribution, rather than by improving his EEG class discrimination. However, the resulting improvement was effective only on synchronous (cue-based) BCI and it did not translate into improved CYBATHLON BCI game performances. For the sake of overcoming this in the future, we unveil possible reasons for these limited gaming performances and identify a number of promising future research directions. Importantly, we also report on the evolution of the user's neurophysiological patterns and user experience throughout the BCI training and competition.
Disposition of Proteins and Lipids in Synaptic Membrane Compartments Is Altered in Q175/Q7 Huntington’s Disease Mouse Striatum
Authors: Iuliano Maria , Seeley Connor , Sapp Ellen , Jones Erin L. , Martin Callie , Li Xueyi , DiFiglia Marian , Kegel-Gleason Kimberly B.
Published: March 2021

Dysfunction at synapses is thought to be an early change contributing to cognitive, psychiatric and motor disturbances in Huntington’s disease (HD). In neurons, mutant Huntingtin collects in aggregates and distributes to the same sites as wild-type Huntingtin including on membranes and in synapses. In this study, we investigated the biochemical integrity of synapses in HD mouse striatum. We performed subcellular fractionation of striatal tissue from 2 and 6-month old knock-in Q175/Q7 HD and Q7/Q7 mice. Compared to striata of Q7/Q7 mice, proteins including GLUT3, Na+/K+ ATPase, NMDAR 2b, PSD95, and VGLUT1 had altered distribution in Q175/Q7 HD striata of 6-month old mice but not 2-month old mice. These proteins are found on plasma membranes and pre- and postsynaptic membranes supporting hypotheses that functional changes at synapses contribute to cognitive and behavioral symptoms of HD. Lipidomic analysis of mouse fractions indicated that compared to those of wild-type, fractions 1 and 2 of 6 months Q175/Q7 HD had altered levels of two species of PIP2, a phospholipid involved in synaptic signaling, increased levels of cholesterol ester and decreased cardiolipin species. At 2 months, increased levels of species of acylcarnitine, phosphatidic acid and sphingomyelin were measured. EM analysis showed that the contents of fractions 1 and 2 of Q7/Q7 and Q175/Q7 HD striata had a mix of isolated synaptic vesicles, vesicle filled axon terminals singly or in clusters, and ER and endosome-like membranes. However, those of Q175/Q7 striata contained significantly fewer and larger clumps of particles compared to those of Q7/Q7. Human HD postmortem putamen showed differences from control putamen in subcellular distribution of two proteins (Calnexin and GLUT3). Our biochemical, lipidomic and EM analysis show that the presence of the HD mutation conferred age dependent disruption of localization of synaptic proteins and lipids important for synaptic function. Our data demonstrate concrete biochemical changes suggesting altered integrity of synaptic compartments in HD mice that may mirror changes in HD patients and presage cognitive and psychiatric changes that occur in premanifest HD.
PLAU1 Facilitated Proliferation, Invasion, and Metastasis via Interaction With MMP1 in Head and Neck Squamous Carcinoma
Authors: Wu Kun , Mao Yuan-Yuan , Han Nan-Nan , Wu Hanjiang , Zhang Sheng
Published: March 2021

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant neoplasm; it is associated with high morbidity and mortality. Thus, understanding the molecular mechanisms underlying its initiation and progression is critical for establishing the most appropriate treatment strategies. We found that urokinase-type plasminogen activator (PLAU1) was upregulated and associated with poor prognosis in HNSCC. Silencing of PLAU1 inhibited the proliferation, colony-formation, migration, and invasion abilities of HNSCC cells in vitro and reduced the expression of matrix metalloproteinase 1 (MMP1), whereas PLAU1 overexpression significantly enhanced the growth, the colony-formation, migration, and invasion abilities, and the xenograft tumor growth of HNSCC cells in vivo and increased the expression of MMP1. The Co-IP assay verified that PLAU1 interacted with MMP1. A positive correlation between PLAU1 and MMP1 expression was observed in HNSCC samples. si-RNAs against MMP1 reversed the aggressive effects of PLAU1 overexpression in HNSCC. Taken together, our data revealed that PLAU1 facilitated HNSCC cell proliferation, invasion, and metastasis via interaction with MMP1.
Case Report: Severe COVID-19 Pneumonia in a Patient With Relapsed/Refractory Hodgkin’s Lymphoma
Authors: Yonal-Hindilerden Ipek , Hindilerden Fehmi , Mastanzade Metban , Tiryaki Tarik Onur , Tasan-Yenigun Sevim , Bilen Yusuf , Aksoz Selcuk , Cagatay Arif Atahan , Nalcaci Meliha
Published: March 2021

First identified in China in December 2019, coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. The presence of haematological malignancies are expected to increase the risk of adverse outcomes from this viral infection due to the immunosuppression brought about by the underlying cancer and the effects of therapy. We present a 55-year-old woman diagnosed with relapsed/refractory Hodgkin’s lymphoma (HL) who had been heavily pretreated with multiagent chemotherapy, autologous hematopoietic stem cell transplantation (autoHCT), allogeneic hematopoietic stem cell transplantation (alloHCT) and was complicated with EBV associated posttransplant lymphoproliferative disease (PTLD) and chronic graft-versus-host-disease (GVHD). The patient was recently treated with brentuximab and donor lymphocyte infusion (DLI) for relapse after alloHCT. She suffered from severe COVID-19 pneumonia and eventually succumbed to acute respiratory distress syndrome (ARDS) and multiorgan failure. Of note, this is the first reported case of COVID-19 in a HL patient who was being treated with brentuximab for relapse after alloHCT.
The Impact of Prolonged Mechanical Ventilation on Overall Survival in Patients With Surgically Treated Brain Metastases
Authors: Schuss Patrick , Schäfer Niklas , Bode Christian , Borger Valeri , Eichhorn Lars , Giordano Frank A. , Güresir Erdem , Heimann Muriel , Ko Yon-Dschun , Landsberg Jennifer , Lehmann Felix , Potthoff Anna-Laura , Radbruch Alexander , Schaub Christina , Schwab Katjana S. , Weller Johannes , Vatter Hartmut , Herrlinger Ulrich , Schneider Matthias
Published: March 2021

Objective

Surgical resection represents a common treatment modality in patients with brain metastasis (BM). Postoperative prolonged mechanical ventilation (PMV) might have an enormous impact on the overall survival (OS) of these patients suffering from advanced cancer disease. We therefore have analyzed our institutional database with regard to a potential impact of PMV on OS of patients who had undergone surgery for brain metastases.

Methods

360 patients with surgically treated brain metastases were included. The definition of PMV consisted of postoperative mechanical ventilation lasting for more than 48 hours. Analysis of survival incorporating established prognostic factors such as age, location of BM, and preoperative physical status was performed.

Results

14 of 360 patients with BM (4%) suffered from postoperative PMV after surgical treatment of BM. Patients with PMV presented in a significantly more impaired neurological condition preoperatively than patients without (p<0.0001). Multivariate analysis determined PMV to be a significant prognostic factor for OS after surgical treatment in patients with BM, independent of other predictive factors (p<0.0001).

Conclusions

The present study demonstrates postoperative PMV as significantly related to poor OS in patients with surgically treated BM. Postoperative PMV is a so far underestimated prognostic predictor, but might be utilized for optimized patient management early in the postoperative phase. For this purpose, the results of the present study should encourage the initiation of further scientific efforts.
The Efficacy of Ginsenoside Rg3 Combined with First-line Chemotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Peng Ze , Wu Wen Wen , Yi Ping
Published: March 2021

Background: For advanced non-small cell lung cancer (NSCLC) patients, first-line chemotherapy is the main treatment in the clinic despite its efficacy is limited and adverse effects are always inescapable. Ginsenoside Rg3, an anti-cancer active ingredient by suppressing angiogenesis, has been increasingly widely used as an adjuvant in first-line chemotherapy for advanced NSCLC to optimize treatment in China. However, no comprehensive meta-analyses have been conducted to estimate the efficacy and safety of the therapy combining ginsenoside Rg3 and first-line chemotherapy in advanced NSCLC patients.

Methods: Randomized controlled trails using a combination of first-line chemotherapy and ginsenoside Rg3 for advanced NSCLC patients were searched and selected from six databases. The Cochrane Risk of Bias tool was used to assessed the quality of these selected original researches. And we used Review Manager 5.3 and STATA to analyze the data.

Results: Twenty-two RCTs that matched our selection criteria with a number of 2202 patients were included in our review. The results showed that compared with first-line chemotherapy alone, the combination of ginsenoside Rg3 and first-line chemotherapy could better improve the objective response rate (ORR) (RR [95% CI], 1.44 [1.27, 1.63], p < 0.00001 ), the disease control rate (DCR) (RR [95% CI], 1.24 [1.12, 1.38], p < 0.0001), karnofsky performance status (KPS) (RR [95% CI], 1.62 [1.42, 1.84], p < 0.00001), one-year survival rate (RR [95% CI], 1.49 [1.08, 2.06], p = 0.01), two-year survival rate (RR [95% CI], 6.22 [1.68, 22.95], p = 0.006), weight change (RR [95% CI], 1.31 [1.04, 1.66], p = 0.02), and higher reduce the VEGF levels (RR [95% CI], -2.21 [-4.03, -0.38], p = 0.02), the incidence of gastrointestinal reactions (RR [95% CI], 0.66 [0.47, 0.93], p = 0.02) and bone marrow suppression (RR [95% CI], 0.43 [0.30, 0.61], p < 0.00001).

Conclusion: Ginsenoside Rg3 can enhance drug efficacy and reduce drug-induced toxicity from chemotherapy. These findings provide helpful information for clinicians indicating that a therapy combined of ginsenoside Rg3 and first-line chemotherapy may be used to optimal the treatment of advanced NSCLC.
High Expression of Lysophosphatidic Acid Induces Nerve Injury in LSS Patients via AKT Mediated NF-κB p65 Pathway
Authors: Zhai Guiliang , Liang Wenfei , Xu Yongjun
Published: March 2021

Lumbar spinal stenosis (LSS) is a spinal degenerative disease, complicated with nerve injury. Lysophosphatidic acid (LPA), a kind of glycerophospholipid molecule is elevated in the initial stages of neural injury. This research aimed to investigate the patho-mechanism of nerve injury caused by LPA in LSS patients. Twenty-five LSS patients and fifteen idiopathic scoliosis patients (without neurological symptoms) were recruited from Xianyang Central Hospital of Shanxi Province. We measured the concentration of LPA in cerebrospinal fluid samples of all subjects. Different concentrations (0.1, 1, and 10 mol/L) of LPA were used to stimulate Rat Neurons-spinal cord (RN-SC) cells. The effects of LPA on cell injury was detected by MTT and LDH (lactate dehydrogenase) assay. Cell apoptosis was determined by FCM (flow cytometry) and TUNEL staining. The changes in the expression of key proteins involved in Akt mediated NF-κB p65 pathway intervened by LPA were determined by western blot. RN-SC cells were pretreated with JSH-23 (NF-κB inhibitor) before LPA exposure, followed by cell apoptosis measurement. The concentration of LPA in LSS patients was notably higher than that in control patients (p < 0.01). The level of LPA was positively correlated with the severity of LSS. LPA treatment induced RN-SC cells displaying oval or rounded cell body with degenerated protrusion dose dependently. In addition, LPA decreased RN-SC cell viability and promoted cell apoptosis in a dose-dependent manner. LPA initiated Akt phosphorylation, IKB phosphorylation, and NF-κB nuclear translocation in a dose-dependent manner. However, JSH-23 (NF-κB inhibitor) pre-treatment prevented effects of LPA. The high levels of LPA induced nerve injury by reducing the viability of RN-SC cells and promoted cell apoptosis through Akt mediated NF-κB p65 signaling pathway. LPA might be a new therapeutic target for relieving nerve injury in LSS patients.
Hermansky-Pudlak Syndrome and Lung Disease: Pathogenesis and Therapeutics
Authors: Velázquez-Díaz Pamela , Nakajima Erika , Sorkhdini Parand , Hernandez-Gutierrez Ashley , Eberle Adam , Yang Dongqin , Zhou Yang
Published: March 2021

Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches.
SabaTracheid 1.0: A Novel Program for Quantitative Analysis of Conifer Wood Anatomy — A Demonstration on African Juniper From the Blue Nile Basin
Authors: Gebregeorgis Eyob Gebrehiwot , Boniecka Justyna , Pia̧tkowski Marcin , Robertson Iain , Rathgeber Cyrille B. K.
Published: March 2021

Knowledge about past climates, especially at a seasonal time scale, is important as it allows informed decisions to be made to mitigate future climate change. However, globally, and especially in semi-arid Tropics, instrumental climatic data are scarce. A dendroclimatic approach may fill this gap, but tropical dendrochronological data are rare and do not yet provide fine resolution intra-annual information about past climates. Unlike in the Tropics, in the Mediterranean, temperate, alpine, and arctic regions, dendroanatomy and quantitative wood anatomy (QWA) are progressing fast attaining an intra-annual resolution, which allows a better understanding of seasonal climate dynamics and climate–growth relationships. The existing dendroanatomical and QWA methods aren’t suitable for tropical trees because they do not consider the high variation in tree ring width and the frequent occurrence of micro-rings containing only a few tracheids per radial file. The available tracheid analysis programs generally fail to provide multiple sectors for micro-rings and they are unable to compute most of the useful dendroanatomical parameters at fine temporal resolutions. Here, we present a program (SabaTracheid) that addresses the three main standard tasks that are necessary for QWA and dendroanatomy before running a climate analysis: (1) tracheidogram standardization, (2) sectoring, and (3) computing QWA and dendroanatomical variables. SabaTracheid is demonstrated on African Juniper (Juniperus procera Hochst. ex Endl), but it is potentially able to provide fine-resolution QWA and dendroanatomic data that could be used for dendroanatomical studies in all regions of the world. SabaTracheid is a freeware that quickly and accurately standardizes tracheidograms, divides tree rings into multiple regular sectors, computes useful dendroanatomic and QWA variables for the whole tree rings, early- and latewood portions, and each sector separately. This program is particularly adapted to deal with high inter-annual growth variations observed in tropical trees so that it assures the provision of complete sectoral QWA and dendroanatomical data for micro-rings as well. We demonstrate SabaTracheid using a dataset of 30 Juniperus procera tree rings from the Blue Nile basin, in Ethiopia. SabaTracheid’s ability to provide fine resolution QWA and dendroanatomic data will help the discipline develop in tropical as well as in the Mediterranean and temperate regions.
Construction of ddRADseq-Based High-Density Genetic Map and Identification of Quantitative Trait Loci for Trans-resveratrol Content in Peanut Seeds
Authors: Luo Huaiyong , Guo Jianbin , Yu Bolun , Chen Weigang , Zhang Huan , Zhou Xiaojing , Chen Yuning , Huang Li , Liu Nian , Ren Xiaoping , Yan Liying , Huai Dongxin , Lei Yong , Liao Boshou , Jiang Huifang
Published: March 2021

Resveratrol (trans-3,4′,5-trihydroxystilbene) is a natural stilbene phytoalexin which is also found to be good for human health. Cultivated peanut (Arachis hypogaea L.), a worldwide important legume crop, is one of the few sources of human's dietary intake of resveratrol. Although the variations of resveratrol contents among peanut varieties were observed, the variations across environments and its underlying genetic basis were poorly investigated. In this study, the resveratrol content in seeds of a recombination inbred line (RIL) population (Zhonghua 6 × Xuhua 13, 186 progenies) were quantified by high performance liquid chromatography (HPLC) method across four environments. Genotypes, environments and genotype × environment interactions significantly influenced the resveratrol contents in the RIL population. A total of 8,114 high-quality single nucleotide polymorphisms (SNPs) were identified based on double-digest restriction-site-associated DNA sequencing (ddRADseq) reads. These SNPs were clustered into bins using a reference-based method, which facilitated the construction of high-density genetic map (2,183 loci with a total length of 2,063.55 cM) and the discovery of several chromosome translocations. Through composite interval mapping (CIM), nine additive quantitative trait loci (QTL) for resveratrol contents were identified on chromosomes A01, A07, A08, B04, B05, B06, B07, and B10 with 5.07–8.19% phenotypic variations explained (PVE). Putative genes within their confidential intervals might play roles in diverse primary and secondary metabolic processes. These results laid a foundation for the further genetic dissection of resveratrol content as well as the breeding and production of high-resveratrol peanuts.
An Event-Related Brain Potential (ERP) Study of Complex Anaphora in Spanish
Authors: García-Sierra Adrián , Silva-Pereyra Juan , Alatorre-Cruz Graciela Catalina , Wig Noelle
Published: March 2021

This study examines the event- related brain potential (ERP) of 25 Mexican monolingual Spanish-speakers when reading Spanish sentences with single entity anaphora or complex anaphora. Complex anaphora is an expression that refer to propositions, states, facts or events while, a single entity anaphora is an expression that refers back to a concrete object. Here we compare the cognitive cost in processing a single entity anaphora [éstafeminine; La renuncia (resignation)] from a complex anaphora [estoneuter; La renuncia fue aceptada (The resignation was accepted)].Éstaelicited a larger positive peak at 200 ms, andestoelicited a larger frontal negativity around 400 ms. The positivity resembles the P200 component, and its amplitude is thought to represent an interaction between predictive qualities in sentence processing (i.e., graphical similarity and frequency of occurrence). Unlike parietal negativities (typical N400), frontal negativities are thought to represent the ease by which pronouns are linked with its antecedent, and how easy the information is recovered from short-term memory. Thus, the complex anaphora recruited more cognitive resources than the single entity anaphora. We also included an ungrammatical control sentence [éstemasculine; La renuncia (resignation)] to better understand the unique processes behind complex anaphoric resolution, as opposed to just general difficulty in sentence processing. In this case, event-related potentials (ERPs) elicited byéstemasculineandéstafemininewere compared. Again,éstaelicited a larger P200. However, different from the experimental condition, a left anterior negativity (LAN) effect was observed foréste; the ungrammatical condition. Altogether, the present research provides electrophysiological evidence indicating that demonstrative pronouns with different morphosyntactic features (i.e., gender) and discourse parameters (i.e., single entity or complex referent) interact during the first stage of anaphoric processing of anaphora. This stage initiated as early as 200 milliseconds after the pronoun onset and probably ends around 400 ms.
An Exploratory Study of Police Officers’ Perceptions of Health Risk, Work Stress, and Psychological Distress During the COVID-19 Outbreak in China
Authors: Huang Qiufeng , Bodla Ali Ahmad , Chen Chiyin
Published: March 2021

Background

How do the police officers perceive health risk, psychological distress, and work stress during the COVID-19 outbreak in China? This study explores the health risk perception, work stress, and psychological distress of police officers who worked at the front line to implement lockdown measures.

Materials and Methods

We conducted a large-scale field survey (N = 5,611) with police officers sample in the northwestern part of China from February 29 to March 7, 2020. Independent-sample T-test and ANOVA were used to analyze whether there are differences in health risk perception, work stress, and psychological distress between different groups. The regression analysis was employed to figure out the factors that influence police officers’ psychological distress.

Results

Results showed a gender difference in perceiving work stress among police officers. Also, police officers with chronic disease perceived higher health risks, more psychological distress, and higher work stress. Additionally, police officers above 45 years old significantly perceived higher health risks than young officers did. It also revealed that working hours contribute to police officers’ health risk perception, psychological distress, and work stress. Finally, our results highlight that age, working hours, chronic disease, health risk perception, and work stress significantly contribute to police officers’ psychological distress.

Conclusion

Our research verifies that there is a gender difference in perceiving work stress among police officers. Police officers with ongoing medical issues and above 45 years old suffer more during the COVID-19 outbreak in China. Our research suggests that the government should pay more attention to their physical health and mental health. The heavy workload containing the COVID-19 extends police officers’ working hours, causing higher health risks, work stress, and psychological distress. This study contributes to the psychological distress literature and provides a way forward to other countries struggling to contain the COVID-19.
A Household-Based Cross-Sectional Survey of Knowledge, Awareness and Practice Regarding Malaria in Western Area Rural District, Sierra Leone
Authors: Wang Lili , Yin Jianhai , Zheng Canjun , Smith Samuel Juana , Ngegba Esther , Huang Xiaoxia , Kamara Anitta , Chen Xia , Wang Xu , Luo Wei , Kan Biao
Published: March 2021

Sierra Leone is a highly endemic area for malaria, and the implementation of the National Malaria Strategic Plan (2016–2020) has reached its midpoint in 2018. To provide more specific guidance for interventions in the future, a household-based cross-sectional survey was conducted to elucidate the knowledge, awareness and practices regarding malaria and malarial control measures among the general public. Three communities (Grafton, Jui, and Kossoh) in the Western Area Rural District that were in close proximity to Sierra Leone's capital city of Freetown were included. Households were randomly selected and interviewed with a structured questionnaire covering malaria infection, diagnosis, treatment and prevention, as well as knowledge of malaria prevention. As a result, a total of 262 qualified questionnaires were included. The average cost for meals per day is ~30,000 Leones in each household. The rate of awareness, indicated by reporting having heard of malaria, was 98.1% (257/262), and 86.6% (227/262) of the respondents knew that mosquito bites are the main route of transmission. In addition, 80.9% (212/262) of the respondents sought health advice or treatment for the illness, and a similar percentage of respondents had been tested for malaria, mostly with rapid diagnostic tests (RDTs). A high demand for long-lasting insecticidal nets (72.1%) matched the serious shortage (61.8%, 162/262), and of the households that reported a lack of nets, 66 had children younger than 5 years old. In conclusion, public awareness of malaria prevention is high, based on this survey, although there was a limited use of preventive measures in these three communities and the malaria burden was still high. Therefore, the public's knowledge of malaria should be sustained and reinforced, and the distribution and use of malaria prevention measures should be promoted to supprt the achievement of the planned objectives.
Evaluating a Laboratory Flume Microbiome as a Window Into Natural Riverbed Biogeochemistry
Authors: Kaufman Matthew H. , Warden John G. , Cardenas M. Bayani , Stegen James C. , Graham Emily B. , Brown Joseph
Published: March 2021

Riverbeds are hotspots for microbially-mediated reactions that exhibit pronounced variability in space and time. It is challenging to resolve biogeochemical mechanisms in natural riverbeds, as uncontrolled settings complicate data collection and interpretation. To overcome these challenges, laboratory flumes are often used as proxies for natural riverbed systems. Flumes capture spatiotemporal variability and thus allow for controlled investigations of riverbed biogeochemistry. These investigations implicitly rely on the assumption that the flume microbiome is similar to the microbiome of natural riverbeds. However, this assumption has not been tested and it is unknown how the microbiome of a flume compares to natural aquatic settings, including riverbeds. To evaluate the fundamental assumption that a flume hosts a microbiome similar to natural riverbed systems, we used 16s rRNA gene sequencing and publicly available data to compare the sediment microbiome of a single large laboratory flume to a wide variety of natural ecosystems including lake and marine sediments, river, lake, hyporheic, soil, and marine water, and bank and wetland soils. Richness and Shannon diversity metrics, analyses of variance, Bray-Curtis dissimilarity, and analysis of the common microbiomes between flume and river sediment all indicated that the flume microbiome more closely resembled natural riverbed sediments than other ecosystems, supporting the use of flume experiments for investigating natural microbially-mediated biogeochemical processes in riverbeds.
Covid-19 Response From Global Makers: The Careables Cases of Global Design and Local Production
Authors: Kieslinger Barbara , Schaefer Teresa , Fabian Claudia Magdalena , Biasin Elisabetta , Bassi Enrico , Freire Ricardo Ruiz , Mowoh Nadine , Arif Nawres , Melis Paulien
Published: March 2021

Makerspaces—informal shared spaces that offer access to technologies, resources and a community of peer learners for making—across the globe initiated a rapid response to the lack of medical hardware supplies during the global pandemic outbreak in early 2020 caused by the Corona virus (COVID-19). As our health systems faced unexperienced pressure, being close to collapsing in some countries, and global supply chains failing to react immediately, makers started to prototype, locally produce and globally share designs of Open Source healthcare products, such as face shields and other medical supplies. Local collaboration with hospitals and healthcare professionals were established. These bottom-up initiatives from maker networks across the globe are showing us how responsible innovation is happening outside the constraints of profit-driven large industries. In this qualitative study we present five cases from a global network of makers that contributed to the production of personal protective equipment (PPE) and healthcare-related products. We draw our cases from the experiences made in Careables, a mixed community of people and organizations committed to the co-design and making of open, personalized healthcare for everyone. With the presented cases we reflect on the potential implications for post-pandemic local production of healthcare products and analyze them from a social innovation perspective. These global experiences are valuable indications of transformative innovations that can reduce dependencies from international supply chains and mainstream mass production.
Temporal and Spatial Analysis of Forward and Backward Microbial Contamination in a Mars Analog Mission
Authors: Yair Yael , Reshef Leah , Shopen-Gochev Camelia , Yoffe Gal , Azulay Gil , Aharonson Oded , Sorek-Abramovich Reut
Published: March 2021

As human exploration missions to Mars are on the horizon, microbial cross-contamination remains a key issue to address. These issues can be approached today using advances in molecular metagenomics methods, which include rapid and sensitive sequencing platforms for characterizing microbial populations. Combined with analog missions, these methods provide powerful tools for assessing the challenges associated with planetary exploration. Here, we designed a protocol to monitor forward and backward contamination events and progression in an 11-days Mars analog mission in the Ramon crater in Israel. Forward contamination soil samples were collected daily from three sites–two sites in close proximity to the habitat and one isolated site. Backward contamination was determined in samples from nitrile gloves of six analog astronauts before and after extravehicular activities Temperature, relative humidity and soil composition data were also collected for all sites. Environmental DNA samples were extracted in the main habitat and 16S (bacterial) and 18S (eukaryotic, fungal) rRNA gene amplicons were sequenced and analyzed to study microbial population diversity and composition. Shannon Diversity index analysis and Principal Coordinates analysis (PCoA) of rRNA genes indicated that differences in the diversity and population composition were significant in sites closer to the habitat when compared to a reference site. These samples also demonstrated the introduction of human-associated taxa to the environment. Backward contamination consisted of bacterial taxa found on gloves upon return from EVA and also detected in soil, altogether 44 genera, indicating backward contamination events. To our knowledge, this is the first protocol to utilize advanced molecular technologies to investigate forward and backward contamination in a Mars analog mission.