bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Diversity in a North Western Mediterranean Sea Shallow Coastal Lagoon Under Contrasting Water Temperature Conditions
Authors: Trombetta Thomas , Bouget François-Yves , Félix Christine , Mostajir Behzad , Vidussi Francesca
Published: April 2022

Temperature and light mainly drive seasonal dynamics of microbial planktonic diversity in coastal ecosystems; however, disentangling their effects is challenging because they are always tightly coupled. Shallow coastal lagoons exhibit intense temperature changes throughout the year and high interannual temperature fluctuations, offering the opportunity to study temperature effects on microbial community diversity and succession. Weekly sampling at 16s and 18s rRNA gene OTU diversity associated with high-frequency meteorological and hydrological monitoring was conducted in the northwestern Mediterranean Thau Lagoon (South of France) from winter to spring in 2015 and 2016. While 2015 was a normal climatic year, 2016 had the warmest winter ever recorded in southern France. Water temperature was found to be the main driver of community diversity and succession from winter to spring. During the normal temperature year of 2015, bacterial communities were dominated by Proteobacteria and Bacteroidetes, archaeal community by Thaumarachaeota, and unicellular eukaryotes mainly by picochlorophytes (Bathycoccus prasinos, Micromonas bravo, and Ostreococcus spp.) in winter and diatoms (Chaetoceros spp.) in spring. The unusually warm year 2016 benefited Actinobacteria (ML602J-51), Cyanobacteria (Synechococcus), the picoeukaryote Ostreococcus spp., and several dinoflagellates. Our results suggest that in a warmer ocean, smaller organisms will dominate microbial communities in shallow coastal waters, potentially affecting ecosystem services.
Involvement of Ceramide Metabolism in Cerebral Ischemia
Authors: Ouro Alberto , Correa-Paz Clara , Maqueda Elena , Custodia Antía , Aramburu-Núñez Marta , Romaus-Sanjurjo Daniel , Posado-Fernández Adrián , Candamo-Lourido María , Alonso-Alonso Maria Luz , Hervella Pablo , Iglesias-Rey Ramón , Castillo José , Campos Francisco , Sobrino Tomás
Published: April 2022

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in worldwide. Although reperfusion therapies have shown efficacy in a limited number of patients with acute ischemic stroke, neuroprotective drugs and recovery strategies have been widely assessed, but none of them have been successful in clinical practice. Therefore, the search for new therapeutic approaches is still necessary. Sphingolipids consist of a family of lipidic molecules with both structural and cell signaling functions. Regulation of sphingolipid metabolism is crucial for cell fate and homeostasis in the body. Different works have emphasized the implication of its metabolism in different pathologies, such as diabetes, cancer, neurodegeneration, or atherosclerosis. Other studies have shown its implication in the risk of suffering a stroke and its progression. This review will highlight the implications of sphingolipid metabolism enzymes in acute ischemic stroke.
Global and Comparative Proteome Signatures in the Lens Capsule, Trabecular Meshwork, and Iris of Patients With Pseudoexfoliation Glaucoma
Authors: Sahay Prity , Chakraborty Munmun , Rao Aparna
Published: April 2022

Pseudoexfoliation (PXF) is characterized by the accumulation of the exfoliative material in the eye and high rates of blindness if left untreated. Pseudoexfoliation glaucoma (PXG) is generally diagnosed too late due to its asymptomatic nature, necessitating the development of new effective screening tools for the early diagnosis of the disease. Thus, the increasing prevalence of this disease due to an aging population has demanded the identification of suitable biomarkers for the early detection of the disease or detection of the onset of glaucoma in the eyes with PXF. We applied a proteomics strategy based on a high-throughput screening method for the determination of proteins involving PXF and PXG pathogenesis. The lens capsule (LC), iris, and trabecular meshwork (TM) samples with PXF and PXG were taken by surgical trabeculectomy, and control samples were taken from the donor corneal buttons obtained from the institutional eye bank to characterize the proteome profile. Peptides from the LC were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein of interest and cytokine/chemokine profiles were verified using immunohistochemistry and the bio-plex kit assay, respectively. There were a total of 1433 proteins identified in the human LC, of which 27 proteins were overexpressed and eight proteins were underexpressed in PXG compared with PXF. Overexpressed proteins such as fibromodulin, decorin, lysyl oxidase homolog 1, collagen alpha-1(I) chain, collagen alpha-3(VI) chain, and biglycan were the major components of the extracellular matrix (ECM) proteins involved in cell-matrix interactions or ECM proteoglycans and the assembly and cross-linking of collagen fibrils. The ECM composition and homeostasis are altered in glaucoma. Thus, quantitative proteomics is a method to discover molecular markers in the eye. Monitoring these events can help evaluate disease progression in future studies.
SLC7A11, a Potential Therapeutic Target Through Induced Ferroptosis in Colon Adenocarcinoma
Authors: Cheng Xin , Wang Yadong , Liu Liangchao , Lv Chenggang , Liu Can , Xu Jingyun
Published: April 2022

Background: Ferroptosis induced by SLC7A11 has an important translational value in the treatment of cancers. However, the mechanism of SLC7A11 in the pathogenesis of colon adenocarcinoma (COAD) is rarely studied in detail.

Methods: SLC7A11 expression was explored with The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, and Western blot assay. The correlation of SLC7A11 expression with the abundance of infiltrating immune cells was evaluated via the TIMER database. The relation of SLC7A11 expression with immune cell markers was investigated via Gene Expression Profiling Interactive Analysis (GEPIA). The co-expression genes of SLC7A11 were screened by R packages, and the PPI was constructed via the STRING database. SLC7A11 and co-expressed gene modulators were selected by NetworkAnalyst and DSigDB database. The correlations between SLC7A11 and cancer immune characteristics were analyzed via the TIMER and TISIDB databases.

Results: SLC7A11 is overexpressed in most tumors, including COAD. The expression level of SLC7A11 has a significant correlation with the infiltration levels of CD8+ T cells, neutrophils, and dendritic cells in COAD. The infiltrated lymphocyte markers of Th1 cell such as TBX21, IL12RB2, IL27RA, STAT1, and IFN-γ were strongly correlated with SLC7A11 expression. Five hub genes co-expressed with SLC7A11 that induce ferroptosis were identified, and mir-335-5p, RELA, and securinine have regulatory effects on it. SLC7A11 was negatively correlated with the expression of chemokines and chemokine receptors, such as CCL17, CCL19, CCL22, CCL23, CXCL14, CCR10, CX3CR1, and CXCR3, in COAD.

Conclusion: SLC7A11 may play a role in induced ferroptosis and regulating tumor immunity, which can be considered as potential therapeutic targets in COAD.
ENTT/ENTTR: A Family of Improved Emerging NVM-Based Trojan Triggers and Resets
Authors: Nagarajan Karthikeyan , Khan Mohammad Nasim Imtiaz , Ghosh Swaroop
Published: April 2022

Hardware Trojans in Integrated Circuits (ICs), that are inserted as hostile modifications in the design phase and/or the fabrication phase, are a security threat since the semiconductor manufacturing process is increasingly becoming globalized. These Trojans are devised to stay hidden during standard structural and functional testing procedures and only activate under pre-determined rare conditions (e.g., after a large number of clock cycles or the assertion of an improbable net). Once triggered, they can deliver malicious payloads (e.g., denial-of-service and information leakage attacks). Current literature identifies a collection of logic Trojans (both trigger circuits and payloads), but minimal research exists on memory Trojans despite their high feasibility. Emerging Non-Volatile Memories (NVMs), such as Resistive RAM (RRAM), have special properties such as non-volatility and gradual drift in bitcell resistance under a pulsing voltage input that make them prime targets to deploy hardware Trojans. In this paper, we present two delay-based and two voltage-based Trojan triggers using emerging NVM (ENTT) by utilizing RRAM’s resistance drift under a pulsing voltage input. Simulations show that ENTTs can be triggered by reading/writing to a specific memory address N times (N could be 2,500–3,500 or a different value for each ENTT design). Since the RRAM is non-volatile, address accesses can be intermittent and therefore stay undetected from system-level techniques that can identify continuous hammering as a possible security threat. We also present three reset techniques to de-activate the triggers. The resulting static/dynamic power overhead and maximum area overhead incurred by the proposed ENTTs are 104.24 μW/0.426 μW and 9.15 μm2, respectively in PTM 65 nm technology. ENTTs are effective against contemporary Trojan detection techniques and system level protocols. We also propose countermeasures to detect ENTT during the test phase and/or prevent fault-injection attacks during deployment.
Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes
Authors: Skauli Nadia , Savchenko Ekaterina , Ottersen Ole Petter , Roybon Laurent , Amiry-Moghaddam Mahmood
Published: April 2022

Aquaporin-4 (AQP4) is the predominant water channel in the brain; it is enriched in astrocytic foot processes abutting vessels where it is anchored through an interaction with the dystrophin-associated protein (DAP) complex. Enhanced expression with concomitant mislocalization of AQP4 along astrocyte plasma membranes is a hallmark of several neurological conditions. Thus, there is an urgent need to identify which signaling pathways dictate AQP4 microdistribution. Here we show that canonical bone morphogenetic proteins (BMPs), particularly BMP2 and 4, upregulate AQP4 expression in astrocytes and dysregulate the associated DAP complex by differentially affecting its individual members. We further demonstrate the presence of BMP receptors and Smad1/5/9 pathway activation in BMP treated astrocytes. Our analysis of adult mouse brain reveals BMP2 and 4 in neurons and in a subclass of endothelial cells and activated Smad1/5/9 in astrocytes. We conclude that the canonical BMP-signaling pathway might be responsible for regulating the expression of AQP4 and of DAP complex proteins that govern the subcellular compartmentation of this aquaporin.
A Comparison Study of Impulsiveness, Cognitive Function, and P300 Components Between Gamma-Hydroxybutyrate and Heroin-Addicted Patients: Preliminary Findings
Authors: Zeng Tingting , Li Shida , Wu Li , Feng Zuxing , Fan Xinxin , Yuan Jing , Wang Xin , Meng Junyu , Ma Huan , Zeng Guanyong , Kang Chuanyuan , Yang Jianzhong
Published: April 2022

Purpose

The aim of this study was to investigate and compare impulsiveness, negative emotion, cognitive function, and P300 components among gamma-hydroxybutyrate (GHB)-addicted patients, heroin-dependent patients, and methadone maintenance treatment (MMT) subjects.

Methods

A total of 48 men including 17 GHB addicts, 16 heroin addicts, 15 MMT subjects, and 15 male mentally healthy controls (HC) were recruited. All subjects were evaluated for symptoms of depression, anxiety, impulsiveness, and cognitive function through the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder 7-item (GAD-7), the Barratt Impulsiveness Scale version II (BIS-II), the Beijing version of the Montreal Cognitive Assessment (BJ-MoCA), the behavioral test (response time), and event-related potential P300 detection.

Results

(1) The mean scores of BIS-II in the GHB addiction group, heroin dependence group, and MMT group were significantly higher than those of the HC group (F = 30.339, P = 0.000). (2) The total scores of BJ-MOCA in GHB addiction group was the worst among the four groups, followed by heroin addiction, MMT group and HC group (F = 27.880, P = 0.000). (3) The response time in the GHB addiction group was the longest among the four groups, followed by the heroin addiction, MMT, and HC groups (F = 150.499, P = 0.000). (4) The amplitude and latency of P300 in GHB addiction subjects were significantly lower and longer than those of the MMT group and the HC group. (5) For the three types of addiction, the P300 amplitudes at Fz, Cz, Pz, T5, and T6 were negatively correlated with the scores of GAD-7, PHQ-9, and BIS-II; the P300 latencies were positively correlated with the response time and negatively correlated with the scores of the BJ-MoCA.

Conclusion

People with an addiction were likely to have increased impulsiveness. The cognitive function of the GHB and heroin-addicted subjects, including the heroin detoxification and the MMT groups, was severely impaired, especially for the GHB-addicted patients. The impairment manifested as abnormalities of BJ-MoCA, response time, and P300 components.
Deep Learning for Prediction of Progression and Recurrence in Nonfunctioning Pituitary Macroadenomas: Combination of Clinical and MRI Features
Authors: Chen Yan-Jen , Hsieh Hsun-Ping , Hung Kuo-Chuan , Shih Yun-Ju , Lim Sher-Wei , Kuo Yu-Ting , Chen Jeon-Hor , Ko Ching-Chung
Published: April 2022

Objectives

A subset of non-functioning pituitary macroadenomas (NFMAs) may exhibit early progression/recurrence (P/R) after tumor resection. The purpose of this study was to apply deep learning (DL) algorithms for prediction of P/R in NFMAs.

Methods

From June 2009 to December 2019, 78 patients diagnosed with pathologically confirmed NFMAs, and who had undergone complete preoperative MRI and postoperative MRI follow-up for more than one year, were included. DL classifiers including multi-layer perceptron (MLP) and convolutional neural network (CNN) were used to build predictive models. Categorical and continuous clinical data were fed into the MLP model, and images of preoperative MRI (T2WI and contrast enhanced T1WI) were analyzed by the CNN model. MLP, CNN and multimodal CNN-MLP architectures were performed to predict P/R in NFMAs.

Results

Forty-two (42/78, 53.8%) patients exhibited P/R after surgery. The median follow-up time was 42 months, and the median time to P/R was 25 months. As compared with CNN using MRI (accuracy 83%, precision 87%, and AUC 0.84) or MLP using clinical data (accuracy 73%, precision 73%, and AUC 0.73) alone, the multimodal CNN-MLP model using both clinical and MRI features showed the best performance for prediction of P/R in NFMAs, with accuracy 83%, precision 90%, and AUC 0.85.

Conclusions

DL architecture incorporating clinical and MRI features performs well to predict P/R in NFMAs. Pending more studies to support the findings, the results of this study may provide valuable information for NFMAs treatment planning.
The Landscape of Immunotherapy Resistance in NSCLC
Authors: Frisone Daniele , Friedlaender Alex , Addeo Alfredo , Tsantoulis Petros
Published: April 2022

Lung cancer is the leading cause of cancer mortality worldwide. Immunotherapy has demonstrated clinically significant benefit for non-small-cell lung cancer, but innate (primary) or acquired resistance remains a challenge. Criteria for a uniform clinical definition of acquired resistance have been recently proposed in order to harmonize the design of future clinical trials. Several mechanisms of resistance are now well-described, including the lack of tumor antigens, defective antigen presentation, modulation of critical cellular pathways, epigenetic changes, and changes in the tumor microenvironment. Host-related factors, such as the microbiome and the state of immunity, have also been examined. New compounds and treatment strategies are being developed to target these mechanisms with the goal of maximizing the benefit derived from immunotherapy. Here we review the definitions of resistance to immunotherapy, examine its underlying mechanisms and potential corresponding treatment strategies. We focus on recently published clinical trials and trials that are expected to deliver results soon. Finally, we gather insights from recent preclinical discoveries that may translate to clinical application in the future.
Synthetic MRI for Radiotherapy Planning for Brain and Prostate Cancers: Phantom Validation and Patient Evaluation
Authors: Gouel Pierrick , Hapdey Sebastien , Dumouchel Arthur , Gardin Isabelle , Torfeh Eva , Hinault Pauline , Vera Pierre , Thureau Sebastien , Gensanne David
Published: April 2022

Purpose

We aimed to evaluate the accuracy of T1 and T2 mappings derived from a multispectral pulse sequence (magnetic resonance image compilation, MAGiC®) on 1.5-T MRI and with conventional sequences [gradient echo with variable flip angle (GRE-VFA) and multi-echo spin echo (ME-SE)] compared to the reference values for the purpose of radiotherapy treatment planning.

Methods

The accuracy of T1 and T2 measurements was evaluated with 2 coils [head and neck unit (HNU) and BODY coils] on phantoms using descriptive statistics and Bland–Altman analysis. The reproducibility and repeatability of T1 and T2 measurements were performed on 15 sessions with the HNU coil. The T1 and T2 synthetic sequences obtained by both methods were evaluated according to quality assurance (QA) requirements for radiotherapy. T1 and T2in vivo measurements of the brain or prostate tissues of two groups of five subjects were also compared.

Results

The phantom results showed good agreement (mean bias, 8.4%) between the two measurement methods for T1 values between 490 and 2,385 ms and T2 values between 25 and 400 ms. MAGiC® gave discordant results for T1 values below 220 ms (bias with the reference values, from 38% to 1,620%). T2 measurements were accurately estimated below 400 ms (mean bias, 8.5%) by both methods. The QA assessments are in agreement with the recommendations of imaging for contouring purposes for radiotherapy planning. On patient data of the brain and prostate, the measurements of T1 and T2 by the two quantitative MRI (qMRI) methods were comparable (max difference, <7%).

Conclusion

This study shows that the accuracy, reproducibility, and repeatability of the multispectral pulse sequence (MAGiC®) were compatible with its use for radiotherapy treatment planning in a range of values corresponding to soft tissues. Even validated for brain imaging, MAGiC® could potentially be used for prostate qMRI.
Augmentation of Extracellular ATP Synergizes With Chemotherapy in Triple Negative Breast Cancer
Authors: Manouchehri Jasmine M. , Datta Jharna , Willingham Natalie , Wesolowski Robert , Stover Daniel , Ganju Ramesh K. , Carson William E. , Ramaswamy Bhuvaneswari , Cherian Mathew A.
Published: April 2022

Introduction

Breast cancer affects two million patients worldwide every year and is the most common cause of cancer-related death among women. The triple-negative breast cancer (TNBC) sub-type is associated with an especially poor prognosis because currently available therapies fail to induce long-lasting responses. Therefore, there is an urgent need to develop novel therapies that result in durable responses. One universal characteristic of the tumor microenvironment is a markedly elevated concentration of extracellular adenosine triphosphate (eATP). Chemotherapy exposure results in further increases in eATP through its release into the extracellular space of cancer cells via P2RX channels. eATP is degraded by eATPases. Given that eATP is toxic to cancer cells, we hypothesized that augmenting the release of eATP through P2RX channels and inhibiting extracellular ATPases would sensitize TNBC cells to chemotherapy.

Methods

TNBC cell lines MDA-MB 231, Hs 578t and MDA-MB 468 and non-tumorigenic immortal mammary epithelial MCF-10A cells were treated with increasing concentrations the chemotherapeutic agent paclitaxel in the presence of eATPases or specific antagonists of P2RXs with cell viability and eATP content being measured. Additionally, the mRNA, protein and cell surface expressions of the purinergic receptors P2RX4 and P2RX7 were evaluated in all examined cell lines via qRT-PCR, western blot, and flow cytometry analyses, respectively.

Results

In the present study, we observed dose-dependent declines of cell viability and increases in eATP of paclitaxel-treated TNBC cell lines in the presence of inhibitors of eATPases, but not of the MCF-10A cell line. These effects were reversed by specific antagonists of P2RXs. Similar results, as those observed with eATPase inhibitors, were seen with P2RX activators. All examined cell lines expressed both P2RX4 and P2RX7 at the mRNA, protein and cell surface levels.

Conclusion

These results reveal that eATP modulates the chemotherapeutic response in TNBC cell lines, which could be exploited to enhance the efficacy of chemotherapy regimens for TNBC.
Case Report: 18F-PSMA-1007 PET/CT Avid Solitary Penile Metastasis of Castration-Resistant Prostate Cancer With a PSA of 0.072 ng/ml
Authors: Li Yongliang , Li Yanmei , Dong Siying , Chen Jian , Yang Pengfei , Li Juan
Published: April 2022

Penile metastasis of prostate cancer is rare, with a poor prognosis, and only a limited number of relevant cases have been reported so far. With the application of 18F-PSMA-1007 PET/CT, the biochemical recurrence of prostate cancer can be detected at an early stage for providing important evidence, facilitating clinical decision-making. Here, we have reported a case of solitary penile metastatic recurrence in the context of mild PSA progression (PSA: 0.072 ng/ml). This case highlights the preferable sensitivity of 18F-PSMA-1007 PET/CT imaging in prostate cancer.
Identification of Premature Infants at High Risk of Late Respiratory Diseases: A Retrospective Cohort Study
Authors: Sun Ling , Bao Yingying , Zhang Hong , Zhu Jiajun
Published: April 2022

Aim

To identify infants with very low birth weight at risk of late respiratory diseases after discharge.

Methods

This retrospective longitudinal study included 388 preterm infants with gestational age of < 32 weeks and birth weight of < 1,500 g and evaluated perinatal information, assessments performed while in the neonatal intensive care unit, and longitudinal follow-up via questionnaire until the corrected gestational age of 18–24 months.

Results

The mean birth weight and gestational age were 1,191.2 ± 191.8 g and 29.1 ± 1.4 weeks, respectively. Sixty-four (16.5%) infants developed late respiratory diseases after discharge to the corrected gestational age of 18–24 months. Univariate analyses showed that gestational age, birth weight, respiratory support, oxygen use, bronchopulmonary dysplasia diagnosed at 36 weeks’ postmenstrual age and length of hospital stay were associated with late respiratory diseases. After adjusting for covariates, respiratory support was significantly associated with serious respiratory morbidities to 18–24 months corrected gestational age. With each day of respiratory support, the odds of late respiratory diseases increased by 1.033-fold.

Conclusion

Respiratory support was associated with increased odds of developing late respiratory diseases during early childhood, which may be an early predictor to late respiratory morbidities. Thus, it is imperative to identify a safe and effective strategy to prevent chronic dependency on respiratory support.
Comparison of the Efficacy and Safety of a Doravirine-Based, Three-Drug Regimen in Treatment-Naïve HIV-1 Positive Adults: A Bayesian Network Meta-Analysis
Authors: Zhang Ke , Zhang Yang , Zhou Jing , Xu Lulu , Zhou Chi , Chen Guanzhi , Huang Xiaojie
Published: April 2022

Introduction: Extensive use of antiretroviral therapy has remarkably improved the survival rates of people living with HIV. Doravirine (DOR) is a newly-approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors. Here, we compared the efficacy and safety of DOR + tenofovir dipivoxil fumarate (TDF)+Lamivudine (3TC)/Emtritabine (FTC) with traditional triple therapies in treatment-naïve HIV-1-positive adults.

Methods: Randomized controlled trials involving treatment-naïve HIV-1-positive adults that met inclusion criteria were systematically retrieved and data on the following outcomes extracted: virological suppression, adverse events, severe adverse events, and drug-related adverse events. A Bayesian network meta-analysis was then performed on the data.

Results: This study included a total of 39 randomized controlled trials involving 26 antiretroviral therapies and 21,110 HIV1-positive patients. At week 48, relative to the other 25 regimens included in the network of virological suppression, DOR + TDF+3TC/FTC exhibited superiority to some efavirenz, nevirapine, atazanavir, or lopinavir-based regimens, including efavirenz + abacavir+3TC [Odd Ratio (OR) = 0.52, 95% confidence interval (CrI) = 0.35–0.77]. At week 48, the performance of DOR + TDF+3TC/FTC was relatively similar to all other analyzed regimens in terms of adverse events. The DOR + TDF+3TC/FTC regimen performed better in terms of severe adverse events and drug-related adverse events.

Conclusion: The network meta-analysis showed that DOR + TDF+3TC/FTC has good efficacy and safety at 48 weeks.

Systematic Review Registration: Open Science Framework, https://osf.io/6ybp7.
The Unusual Cosubstrate Specificity of NQO2: Conservation Throughout the Amniotes and Implications for Cellular Function
Authors: Islam Faiza , Leung Kevin K. , Walker Matthew D. , Al Massri Shahed , Shilton Brian H.
Published: April 2022

Human Quinone Reductase 2 (NQO2) is a pharmacological target and has appeared in numerous screening efforts as an off-target interactor with kinase-targeted drugs. However the cellular functions of NQO2 are not known. To gain insight into the potential cellular functions of NQO2, we have carried out a detailed evolutionary analysis. One of the most striking characteristics of NQO2 is that it uses conventional dihydronicotinamide cosubstrates, NADH and NADPH, extremely inefficiently, raising questions about an enzymatic function in cells. To characterize the ability of NQO2 to serve as an enzyme, the NQO2 gene was disrupted in HCT116 cells. These NQO2 knockouts along with the parental cells were used to demonstrate that cellular NQO2 is unable to catalyze the activation of the DNA cross-linking reagent, CB1954, without the addition of exogenous dihydronicotinamide riboside (NRH). To find whether the unusual cosubstrate specificity of NQO2 has been conserved in the amniotes, recombinant NQO2 from a reptile,Alligator mississippiensis, and a bird,Anas platyrhynchos, were cloned, purified, and their catalytic activity characterized. Like the mammalian enzymes, the reptile and bird NQO2 were efficient catalysts with the small and synthetic cosubstrateN-benzyl-1,4-dihydronicotinamide but were inefficient in their use of NADH and NADPH. Therefore, the unusual cosubstrate preference of NQO2 appears to be conserved throughout the amniotes; however, we found that NQO2 is not well-conserved in the amphibians. A phylogenetic analysis indicates that NQO1 and NQO2 diverged at the time, approximately 450 MYA, when tetrapods were beginning to evolve.
Trends of Utilization of Antiseizure Medications Among Pregnant Women in Manitoba, Canada: A 20-Year Population-Based Study
Authors: Shouman Walid , Delaney Joseph A. , Kowalec Kaarina , Ng Marcus , Ruth Chelsea , Falk Jamieson , Leong Christine , Alessi-Severini Silvia , Lavu Alekhya , Peymani Payam , Eltonsy Sherif
Published: April 2022

Background: Evidence from developed countries demonstrates that the use of antiseizure medications (ASMs) has been increasing in the last decade. Pregnant women have a very challenging risk benefit trade-off in terms of ASM utilization, and it is crucial to know if increased utilization is seen among pregnant women.

Objective: To examine time-trends of utilization of ASM therapies among pregnant women in Manitoba, Canada.

Methods: We conducted a population-based cohort study using de-identified, linked administrative databases from Manitoba. Pregnancies between 1995 and 2018 were included. Four groups of pregnant people were created based on ASM exposure and epilepsy diagnosis.

Results: Of 273,492 pregnancies, 812 (3/1000) had epilepsy diagnosis and were exposed to ASMs, 963 (3.5/1000) had epilepsy diagnosis and were unexposed, and 2742 (10/1000) were exposed to ASMs and did not have epilepsy diagnosis. Overall, the number of pregnancies exposed to ASMs increased significantly from 0.56% in 1997 to 2.21% in 2018 (p < 0.0001). Subgroup analysis by epilepsy diagnosis showed no significant change in ASMs exposure among pregnant women with epilepsy [the proportion of women exposed to ASM from all pregnancies was 0.37% (in 1997) and 0.36% (in 2018), p = 0.24]. A drop in carbamazepine use was observed, while the number of lamotrigine prescriptions increased from 6.45% in 1997 to 52% by 2018. ASM use among pregnant women without epilepsy increased significantly from 0.19% in 1997 to 1.85% in 2018 (p < 0.0001). In the total cohort of pregnancies, 1439 (0.53%) were exposed during their entire pregnancy, and 1369 (0.5%) were exposed only in their first trimester. Clonazepam was the most used ASM during the study period (1953 users, 0.71%), followed by gabapentin (785 users, 0.29%) and carbamazepine (449 users, 0.16%).

Conclusion: No major shifts in the quantity of ASM use over the study period were observed among pregnant women with epilepsy. However, there was a significant increase in ASM use among pregnant women without epilepsy. The study results warrant further investigation into the implications of ASM use in pregnancy for indications other than epilepsy.
Restoration of Sarco/Endoplasmic Reticulum Ca2+-ATPase Activity Functions as a Pivotal Therapeutic Target of Anti-Glutamate-Induced Excitotoxicity to Attenuate Endoplasmic Reticulum Ca2+ Depletion
Authors: Zhang Wen , Ye Fanghua , Pang Nan , Kessi Miriam , Xiong Juan , Chen Shimeng , Peng Jing , Yang Li , Yin Fei
Published: April 2022

Glutamate-induced excitotoxicity is a pathological basis of many acute/chronic neurodegenerative diseases. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2b) is a membrane-embedded P-type ATPase pump that manages the translocation of calcium ions (Ca2+) from cytosol into the lumen of the endoplasmic reticulum (ER) calcium stores. It participates in a wide range of biological functions in the central nervous system (CNS). However, the role of SERCA2b in glutamate-induced excitotoxicity and its mechanism must be elucidated. Herein, we demonstrate that SERCA2b mutants exacerbate the excitotoxicity of hypo-glutamate stimulation on HT22 cells. In this study, SERCA2b mutants accelerated Ca2+ depletion through loss-of-function (reduced pumping capacity) or gain-of-function (acquired leakage), resulting in ER stress. In addition, the occurrence of ER Ca2+ depletion increased mitochondria-associated membrane formation, which led to mitochondrial Ca2+ overload and dysfunction. Moreover, the enhancement of SERCA2b pumping capacity or inhibition of Ca2+ leakage attenuated Ca2+ depletion and impeded excitotoxicity in response to hypo-glutamate stimulation. In conclusion, SERCA2b mutants exacerbate ER Ca2+-depletion-mediated excitotoxicity in glutamate-sensitive HT22 cells. The mechanism of disruption is mainly related to the heterogeneity of SERCA2b mutation sites. Stabilization of SRECA2b function is a critical therapeutic approach against glutamate-induced excitotoxicity. These data will expand understanding of organelle regulatory networks and facilitate the discovery and creation of drugs against excitatory/inhibitory imbalance in the CNS.
Aging Alters the Formation and Functionality of Signaling Microdomains Between L-type Calcium Channels and β2-Adrenergic Receptors in Cardiac Pacemaker Cells
Authors: Choi Sabrina , Vivas Oscar , Baudot Matthias , Moreno Claudia M.
Published: April 2022

Heart rate is accelerated to match physiological demands through the action of noradrenaline on the cardiac pacemaker. Noradrenaline is released from sympathetic terminals and activates β1-and β2-adrenergic receptors (ΑRs) located at the plasma membrane of pacemaker cells. L-type calcium channels are one of the main downstream targets potentiated by the activation of β-ARs. For this signaling to occur, L-type calcium channels need to be located in close proximity to β-ARs inside caveolae. Although it is known that aging causes a slowdown of the pacemaker rate and a reduction in the response of pacemaker cells to noradrenaline, there is a lack of in-depth mechanistic insights into these age-associated changes. Here, we show that aging affects the formation and function of adrenergic signaling microdomains inside caveolae. By evaluating the β1 and β2 components of the adrenergic regulation of the L-type calcium current, we show that aging does not alter the regulation mediated by β1-ARs but drastically impairs that mediated by β2-ARs. We studied the integrity of the signaling microdomains formed between L-type calcium channels and β-ARs by combining high-resolution microscopy and proximity ligation assays. We show that consistent with the electrophysiological data, aging decreases the physical association between β2-ARs and L-type calcium channels. Interestingly, this reduction is associated with a decrease in the association of L-type calcium channels with the scaffolding protein AKAP150. Old pacemaker cells also have a reduction in caveolae density and in the association of L-type calcium channels with caveolin-3. Together the age-dependent alterations in caveolar formation and the nano-organization of β2-ARs and L-type calcium channels result in a reduced sensitivity of the channels to β2 adrenergic modulation. Our results highlight the importance of these signaling microdomains in maintaining the chronotropic modulation of the heart and also pinpoint the direct impact that aging has on their function.
12 Weeks of Physical Exercise Attenuates Oxidative Stress, Improves Functional Tests Performance, and Reduces Fall Risk in Elderly Women Independently on Serum 25(OH)D Concentration
Authors: Rodziewicz-Flis Ewa Aleksandra , Kawa Małgorzata , Flis Damian Józef , Szaro-Truchan Marzena , Skrobot Wojciech Romuald , Kaczor Jan Jacek
Published: April 2022

The study aimed to evaluate if the 25(OH)D concentration is related to physical training responses. Moreover, to determine the association between serum 25(OH)D concentration and older women’s physical performance, oxidative stress markers, inflammation, and bone metabolism. 37 older women (age 72.9 ± 5.2 years) were assigned into two groups: supplemented (SG) and non-supplemented (NSG). Then, the participants from SG and NSG were randomly assigned into exercised and non-exercised groups: exercise sufficient vitamin D group (ESD; n = 10), exercise insufficient vitamin D group (EID; n = 9), control sufficient vitamin D group (CSD; n = 9), and control insufficient vitamin D group (CID; n = 9). To assess the study aims time up and go test (TUG), 6 min walk test (6MWT), fall risk test (FRT), blood osteocalcin (OC), parathormone (PTH), calcium (Ca2+), sulfhydryl groups (SH), malondialdehyde (MDA), and interleukin-6 (IL-6) were performed. The results showed that a higher 25(OH)D concentration was in line with better physical performance and bone metabolism as well as lower inflammation. After 12 weeks of training we noted an improvement in 6MWT (from 374.0 ± 17.3 to 415.0 ± 18.8; p = 0.001 and from 364.8 ± 32.8 to 419.4 ± 32.3; p = 0.001 for EID and ESD, respectively), TUG (from 7.9 ± 0.5 to 6.8 ± 0.8; p = 0.001 and from 7.3 ± 1.5 to 6.4 ± 0.9; p = 0.002, for EID and ESD, respectively), reduction of fall risk (from 2.8 ± 0.8 to 1.9 ± 0.4; p = 0.003 and from 2.1 ± 1.1 to 1.6 ± 0.5; p = 0.047, for EID and ESD, respectively) and increase in SH groups (from 0.53 ± 0.06 to 0.58 ± 0.08; p = 0.012 and from 0.54 ± 0.03 to 0.59 ± 0.04; p = 0.005, for EID and ESD, respectively), regardless of the baseline 25(OH)D concentration. A decrease in PTH and OC concentration was observed only in EID group (from 57.7 ± 15.7 to 49.4 ± 12.6; p = 0.013 for PTH and from 27.9 ± 17.2 to 18.0 ± 6.2; p = 0.004 for OC). To conclude, vitamin D concentration among older women is associated with physical performance, fall risk, inflammation, and bone metabolism markers. Moreover, 12 weeks of training improved physical performance and antioxidant protection, regardless of baseline vitamin D concentration.
Full-Length Transcriptome Sequencing Reveals Tissue-Specific Gene Expression Profile of Mangrove Clam Geloina erosa
Authors: Liao Xin , Liu Yunqing , Han Tingyu , Yang Mingliu , Liu Wenai , Wang Yadi , He Chunpeng , Lu Zuhong
Published: April 2022

Mollusca is the second largest animal phylum and represents one of the most evolutionarily successful animal groups. Geloina erosa, a species of Corbiculidae, plays an important role in mangrove ecology. It is highly adaptable and can withstand environmental pollution and microbial infections. However, there is no reference genome or full-length transcriptome available for G. erosa. This impedes the study of the biological functions of its different tissues because transcriptome research requires reference genome or full-length transcriptome as a reference to improve accuracy. In this study, we applied a combination of Illumina and PacBio single-molecule real-time sequencing technologies to sequence the full-length transcriptomes of G. erosa tissues. Transcriptomes of nine samples obtained from three tissues (hepatopancreas, gill, and muscle) were sequenced using Illumina. Furthermore, we obtained 87,310 full-length reads non-chimeric sequences. After removing redundancy, 22,749 transcripts were obtained. The average Q score of 30 was 94.48%. In total, 271 alternative splicing events were predicted. There were 14,496 complete regions and 3,870 lncRNAs. Differential expression analysis revealed tissue-specific physiological functions. The gills mainly express functions related to filtration, metabolism, identifying pathogens and activating immunity, and neural activity. The hepatopancreas is the main tissue related to metabolism, it also involved in the immune response. The muscle mainly express functions related to muscle movement and control, it contains more energy metabolites that gill and hepatopancreas. Our research provides an important reference for studying the gene expression of G. erosa under various environmental stresses. Moreover, we present a reliable sequence that will provide an excellent foundation for further research on G. erosa.
Students’ Perceptions of University Corruption in a Spanish Public University: A Path Analysis
Authors: Julián Martín , Bonavia Tomas
Published: April 2022

Most research on corruption in educational settings has focused on a cross-national and macro-level analysis; however, to our knowledge, few papers have sought to explore individual perceptions that explain corruption in higher education. The present research aimed to disentangle students’ predictors of corrupt intention in a Spanish public university. A total of 933 undergraduate, postgraduate, and Ph.D. students filled out an online survey measuring four corruption scenarios: favoritism, bribery, fraud, and embezzlement. Path analysis (PA) revealed that justifiability, risk perception, and perceived prevalence of corruption were significant factors in predicting corrupt intention. Moreover, willingness to report a corrupt act was predicted by corrupt intention, justifiability, and risk perception. Corrupt behavior is a complex phenomenon explained not only by peers’ behavior, but also by their individual justifications and perception of risk. Education is not free of corruption, and universities must address this urgent problem in order to avoid future economic, societal, and ethical problems.
Role of Efficient Human Resource Management in Managing Diversified Organizations
Authors: Minghua Huang
Published: April 2022

As the world has turned into a global village, it has created many challenges for human resource departments regarding the management of a diverse workforce in satisfying the employees and creating a diverse yet safe environment for them that does not make them uncomfortable. The current study has investigated the effect of human resource practices on the diversity climate with the mediation of job satisfaction. The data has been collected from human resource personnel of multinationals in China with the help of 316 participants. The study deployed SEM analysis to analyze and measure the effect of training and development along with performance appraisal on the diversity climate. The findings of the study revealed that training and growth or development do not have an impact on the diversity climate, however, performance appraisal has a strong positive impact. Similarly, the mediating role of job satisfaction has been found to ensure the relationship of training and development and performance appraisal with the diversity climate. This study has provided certain implications for the HR managers of multinationals to ensure a secure diversity climate for a diverse workforce.
Self-Regulated Writing Strategy Use When Revising Upon Automated, Peer, and Teacher Feedback in an Online English as a Foreign Language Writing Course
Authors: Tian Lili , Liu Qisheng , Zhang Xingxing
Published: April 2022

Research investigating the intricacies of how self-regulated writing strategies are used in a finely focused area of the second language (L2) writing process is still lacking. This study takes a mixed-methods approach to explore Chinese English as a Foreign Language (EFL) learners’ use of self-regulated writing strategies when revising based on automated, peer, and teacher feedback in an online EFL writing context. Thirty-six Chinese university learners filled in three questionnaires (one per feedback source). In addition, four learners followed a think-aloud protocol while revising and responding to a stimulated recall interview to provide further data. The results revealed that learners employed an array of self-regulated writing strategies to attain their feedback revision goals. Learners used more cognitive strategies when revising based on automated feedback compared with peer and teacher feedback and more motivational strategies when revising based on teacher feedback. The think-aloud data and stimulated recall interviews coincided with the quantitative findings. Textual analysis revealed that feedback type and quantity were associated with self-regulated writing strategy use.
Bipedal Walking of Underwater Soft Robot Based on Data-Driven Model Inspired by Octopus
Authors: Wu Qiuxuan , Wu Yan , Yang Xiaochen , Zhang Botao , Wang Jian , Chepinskiy Sergey A , Zhilenkov Anton A
Published: April 2022

The soft organisms in nature have always been a source of inspiration for the design of soft arms and this paper draws inspiration from the octopus’s tentacle, aiming at a soft robot for moving flexibly in three-dimensional space. In the paper, combined with the characteristics of an octopus’s tentacle, a cable-driven soft arm is designed and fabricated, which can motion flexibly in three-dimensional space. Based on the TensorFlow framework, a data-driven model is established, and the data-driven model is trained using deep reinforcement learning strategy to realize posture control of a single soft arm. Finally, two trained soft arms are assembled into an octopus-inspired biped walking robot, which can go forward and turn around. Experimental analysis shows that the robot can achieve an average speed of 7.78 cm/s, and the maximum instantaneous speed can reach 12.8 cm/s.
Rise and fall of fomivirsen, the first approved gene silencing medicine : A historical review
Authors: Bege Miklós , Borbás Anikó
Published: April 2022

Fomivirsent was approved by the FDA in 1998 and by the EMA in 1999 as the very first antisense drug used to treat CMV retinitis in patients with AIDS. To date, it has been the only first generation antisense oligonucleotide used in therapy. Fomivirsen has been a pioneer in this field and has demonstrated the usefulness of the antisense tehcnology for medicinal science. However, after three years of use, fomivirsen has been withdrawn from the market (in the US in 2001 and in the EU in 2002), and nowadays, gene silencing drugs with a more advanced chemical structure and more complex mechanism of action are used in medicine. On the occasion of the 20th anniversary of its European withdrawal, we briefly overview the history of fomivirsen.
Hot Water Disinfestation Treatment Does Not Affect Physical and Biochemical Properties of Export Quality Mango Fruit [Mangifera indica L.]
Authors: Ndlela Shepard , Obala Francis , Mwando Nelson L. , Mkiga Abdullah M. , Azrag Abdelmutalab G. A. , Mohamed Samira A.
Published: April 2022

There are various postharvest treatments currently available in the market. Among these, heat-based treatments are very effective. Several hot water treatment (HWT) protocols at various temperature regimes and time durations have been developed for different mango cultivars and varieties. However, many concerns have been raised regarding the quality of fruits subjected to HWT, particularly on physical and biochemical properties. The purpose of this study was to generate empirical evidence on the effect of the HWT protocol currently recognized and accepted by the EU for Apple mango cultivar from Africa. We subjected mango to HWT at 46.1 °C for 68, 75, and 84 min and evaluated various physical and biochemical properties at 1, 3, 5, and 7 days post-treatment. Conventional methods of analysis were used to test acidity, antioxidants, minerals, nutrients, and physical properties of treated mangoes, and comparisons against untreated controls were made. We found no significant differences in pH, various acid content, total carotenoids, β-carotene content, vitamin A, aromatic volatiles, total phenolics, total antioxidant activity, various minerals, electrolytic leakage, crude protein, total carbohydrates, total sugars, crude fat, moisture content, dry matter, total soluble solids, firmness, or weight between treated and untreated mangoes. We conclude that HWT presents a viable alternative for postharvest treatment of export mangoes provided that quality attributes are maintained from preharvest, harvesting, transportation, treatment, and post-treatment handling.
In Vitro Application of Exogenous Fibrolytic Enzymes from Trichoderma Spp. to Improve Feed Utilization by Ruminants
Authors: Iannaccone Francesco , Alborino Vittoria , Dini Irene , Balestrieri Anna , Marra Roberta , Davino Rosario , Di Francia Antonio , Masucci Felicia , Serrapica Francesco , Vinale Francesco
Published: April 2022

Treating ruminant feeds with exogenous fibrolytic enzymes may potentially increase forage cell wall degradability and thus feed efficiency. In nature, fungi biosynthesize lignocellulolytic enzymes that can break down lignocellulosic material into its sugar components, thereby providing ready fermentable substrates. This work showed the in vitro fibrolytic activity of three Trichoderma strains (T. atroviride strain P1, T. afroharzianum strain T22, T. reesei strain T67). Total protein concentration and enzymatic (e.g., glucanase, cellulase, and xylanase) activities were determined in fungal culture filtrates after 7 and 14 days of growth on different fiber-based media. The enzymatic mixtures produced by Trichoderma spp. showed the highest concentration of fibrolytic enzymes and were added to industrial feed to test their ability to hydrolyze insoluble fibers. The supplementation of industrial feeds containing medium-fiber or low-fiber concentrates with T22 enzymes produced in the presence of lyophilized mushrooms and durum wheat fiber reduced hemicellulose concentration up to 33% and 24%, respectively. These results may offer novel opportunities to develop livestock feeds with improved fiber digestibility.