bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells
Authors: Pisano Marina , Dettori Maria Antonietta , Fabbri Davide , Delogu Giovanna , Palmieri Giuseppe , Rozzo Carla
Published: May 2021

Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11 and 12—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50 values of 1.7 ± 0.5 μM for 11 and 2.0 ± 0.7 μM for 12) and no toxicity of normal fibroblasts up to 32 µM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed long-lasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11 or 12, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11 and 12 were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.
Human Chromosome 18 and Acrocentrics: A Dangerous Liaison
Authors: Villa Nicoletta , Redaelli Serena , Sala Elena , Conconi Donatella , Romitti Lorenza , Manfredini Emanuela , Crosti Francesca , Roversi Gaia , Lavitrano Marialuisa , Rodeschini Ornella , Recalcati Maria Paola , Piazza Rocco , Dalprà Leda , Riva Paola , Bentivegna Angela
Published: May 2021

The presence of thousands of repetitive sequences makes the centromere a fragile region subject to breakage. In this study we collected 31 cases of rearrangements of chromosome 18, of which 16 involved an acrocentric chromosome, during genetic screening done in three centers. We noticed a significant enrichment of reciprocal translocations between the centromere of chromosome 18 and the centromeric or pericentromeric regions of the acrocentrics. We describe five cases with translocation between chromosome 18 and an acrocentric chromosome, and one case involving the common telomere regions of chromosomes 18p and 22p. In addition, we bring evidence to support the hypothesis that chromosome 18 preferentially recombines with acrocentrics: (i) the presence on 18p11.21 of segmental duplications highly homologous to acrocentrics, that can justify a NAHR mechanism; (ii) the observation by 2D-FISH of the behavior of the centromeric regions of 18 respect to the centromeric regions of acrocentrics in the nuclei of normal subjects; (iii) the contact analysis among these regions on published Hi-C data from the human lymphoblastoid cell line (GM12878).
Embryonic Trophectoderm Secretomics Reveals Chemotactic Migration and Intercellular Communication of Endometrial and Circulating MSCs in Embryonic Implantation
Authors: Calle Alexandra , Toribio Víctor , Yáñez-Mó María , Ramírez Miguel Ángel
Published: May 2021

Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial–mesenchymal transition stages in these cells. BBT-secretomes contain early pregnancy-related proteins and angiogenic proteins both as cargo in EVs and the soluble fraction. We have demonstrated the functional transfer of protein-containing secretome between embryonic trophectoderm and maternal MSC in vitro using two BBT primary cultures eight endometrial MSC (eMSC) and five peripheral blood MSC (pbMSC) lines. We observed that eMSC and pbMSC chemotax to both the soluble fraction and EVs of the BBT secretome. In addition, in a complementary direction, we found that the pattern of expression of implantation proteins in BBT-EVs changes depending on: (i) their epithelial–mesenchymal phenotype; (ii) as a result of the uptake of eMSC- or pbMSC-EV previously stimulated or not with embryonic signals (IFN-); (iii) because of the stimulation with the endometrial cytokines present in the uterine fluid in the peri-implantation period.
Current Advances on the Important Roles of Enhancer RNAs in Molecular Pathways of Cancer
Authors: Wang Rui , Tang Qianzi
Published: May 2021

Enhancers are critical genomic elements that can cooperate with promoters to regulate gene transcription in both normal and cancer cells. Recent studies reveal that enhancer regions are transcribed to produce a class of noncoding RNAs referred to as enhancer RNAs (eRNAs). Emerging evidence shows that eRNAs play important roles in enhancer activation and enhancer-driven gene regulation, and the expression of eRNAs may be a critical factor in tumorigenesis. The important roles of eRNAs in cancer signaling pathways are also gradually unveiled, providing a new insight into cancer therapy. Here, we review the roles of eRNAs in regulating cancer signaling pathways and discuss the potential of eRNA-targeted therapy for human cancers.
Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance
Authors: Yurube Takashi , Hirata Hiroaki , Ito Masaaki , Terashima Yoshiki , Kakiuchi Yuji , Kuroda Ryosuke , Kakutani Kenichiro
Published: May 2021

The intervertebral disc is the largest avascular low-nutrient organ in the body. Thus, resident cells may utilize autophagy, a stress-response survival mechanism, by self-digesting and recycling damaged components. Our objective was to elucidate the involvement of autophagy in rat experimental disc degeneration. In vitro, the comparison between human and rat disc nucleus pulposus (NP) and annulus fibrosus (AF) cells found increased autophagic flux under serum deprivation rather in humans than in rats and in NP cells than in AF cells of rats (n = 6). In vivo, time-course Western blotting showed more distinct basal autophagy in rat tail disc NP tissues than in AF tissues; however, both decreased under sustained static compression (n = 24). Then, immunohistochemistry displayed abundant autophagy-related protein expression in large vacuolated disc NP notochordal cells of sham rats. Under temporary static compression (n = 18), multi-color immunofluorescence further identified rapidly decreased brachyury-positive notochordal cells with robust expression of autophagic microtubule-associated protein 1 light chain 3 (LC3) and transiently increased brachyury-negative non-notochordal cells with weaker LC3 expression. Notably, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic death was predominant in brachyury-negative non-notochordal cells. Based on the observed notochordal cell autophagy impairment and non-notochordal cell apoptosis induction under unphysiological mechanical loading, further investigation is warranted to clarify possible autophagy-induced protection against notochordal cell disappearance, the earliest sign of disc degeneration, through limiting apoptosis.
Expression and Prognostic Characteristics of Ferroptosis-Related Genes in Colon Cancer
Authors: Zhu Jie , Kong Weikaixin , Xie Zhengwei
Published: May 2021

Ferroptosis is a new type of programmed cell death, which occurs with iron dependence. Previous studies have showed that ferroptosis plays an important regulatory role in the occurrence and development of tumors. Colon cancer is one of the major morbidities and causes of mortality in the world. This study used RNA-seq and colon cancer clinical data to explore the relationship between ferroptosis-related genes and colon cancer. Based on the fifteen prognostic ferroptosis-related genes, two molecular subgroups of colon cancer were identified. Surprisingly, we also found cluster2 was characterized by lower mutation burden and expression of checkpoint genes, better survival, and higher expression of NOX1. Moreover, cluster2 has fewer BRAF mutations. We also found the expression of NOX1 is related to the status of BRAF. Finally, using 15 ferroptosis-related genes from The Cancer Genome Atlas cohort, we constructed a prognosis model, and this model may be used to predict the prognosis of patients in clinics.
Zebrafish as a Model for the Study of Lipid-Lowering Drug-Induced Myopathies
Authors: Dubińska-Magiera Magda , Migocka-Patrzałek Marta , Lewandowski Damian , Daczewska Małgorzata , Jagla Krzysztof
Published: May 2021

Drug-induced myopathies are classified as acquired myopathies caused by exogenous factors. These pathological conditions develop in patients without muscle disease and are triggered by a variety of medicaments, including lipid-lowering drugs (LLDs) such as statins, fibrates, and ezetimibe. Here we summarise the current knowledge gained via studies conducted using various models, such as cell lines and mammalian models, and compare them with the results obtained in zebrafish (Danio rerio) studies. Zebrafish have proven to be an excellent research tool for studying dyslipidaemias as a model of these pathological conditions. This system enables in-vivo characterization of drug and gene candidates to further the understanding of disease aetiology and develop new therapeutic strategies. Our review also considers important environmental issues arising from the indiscriminate use of LLDs worldwide. The widespread use and importance of drugs such as statins and fibrates justify the need for the meticulous study of their mechanism of action and the side effects they cause.
Proteomic Comparison of Bone Marrow Derived Osteoblasts and Mesenchymal Stem Cells
Authors: Aasebø Elise , Brenner Annette K. , Hernandez-Valladares Maria , Birkeland Even , Berven Frode S. , Selheim Frode , Bruserud Øystein
Published: May 2021

Mesenchymal stem cells (MSCs) can differentiate into osteoblasts, and therapeutic targeting of these cells is considered both for malignant and non-malignant diseases. We analyzed global proteomic profiles for osteoblasts derived from ten and MSCs from six healthy individuals, and we quantified 5465 proteins for the osteoblasts and 5420 proteins for the MSCs. There was a large overlap in the profiles for the two cell types; 156 proteins were quantified only in osteoblasts and 111 proteins only for the MSCs. The osteoblast-specific proteins included several extracellular matrix proteins and a network including 27 proteins that influence intracellular signaling (Wnt/Notch/Bone morphogenic protein pathways) and bone mineralization. The osteoblasts and MSCs showed only minor age- and sex-dependent proteomic differences. Finally, the osteoblast and MSC proteomic profiles were altered by ex vivo culture in serum-free media. We conclude that although the proteomic profiles of osteoblasts and MSCs show many similarities, we identified several osteoblast-specific extracellular matrix proteins and an osteoblast-specific intracellular signaling network. Therapeutic targeting of these proteins will possibly have minor effects on MSCs. Furthermore, the use of ex vivo cultured osteoblasts/MSCs in clinical medicine will require careful standardization of the ex vivo handling of the cells.
Dual Actions of A2A and A3 Adenosine Receptor Ligand Prevents Obstruction-Induced Kidney Fibrosis in Mice
Authors: Pak Eun Seon , Jeong Lak Shin , Hou Xiyan , Tripathi Sushil K. , Lee Jiyoun , Ha Hunjoo
Published: May 2021

Kidney fibrosis is the final outcome of chronic kidney disease (CKD). Adenosine plays a significant role in protection against cellular damage by activating four subtypes of adenosine receptors (ARs), A1AR, A2AAR, A2BAR, and A3AR. A2AAR agonists protect against inflammation, and A3AR antagonists effectively inhibit the formation of fibrosis. Here, we showed for the first time that LJ-4459, a newly synthesized dual-acting ligand that is an A2AAR agonist and an A3AR antagonist, prevents the progression of tubulointerstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed on 6-week-old male C57BL/6 mice. LJ-4459 (1 and 10 mg/kg) was orally administered for 7 days, started at 1 day before UUO surgery. Pretreatment with LJ-4459 improved kidney morphology and prevented the progression of tubular injury as shown by decreases in urinary kidney injury molecular-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion. Obstruction-induced tubulointerstitial fibrosis was attenuated by LJ-4459, as shown by a decrease in fibrotic protein expression in the kidney. LJ-4459 also inhibited inflammation and oxidative stress in the obstructed kidney, with reduced macrophage infiltration, reduced levels of pro-inflammatory cytokines, as well as reduced levels of reactive oxygen species (ROS). These data demonstrate that LJ-4459 has potential as a therapeutic agent against the progression of tubulointerstitial fibrosis.
The Importance of N186 in the Alpha-1-Antitrypsin Shutter Region Is Revealed by the Novel Bologna Deficiency Variant
Authors: Ronzoni Riccardo , Ferrarotti Ilaria , D’Acunto Emanuela , Balderacchi Alice M. , Ottaviani Stefania , Lomas David A. , Irving James A. , Miranda Elena , Fra Annamaria
Published: May 2021

Alpha-1-antitrypsin (AAT) deficiency causes pulmonary disease due to decreased levels of circulating AAT and consequently unbalanced protease activity in the lungs. Deposition of specific AAT variants, such as the common Z AAT, within hepatocytes may also result in liver disease. These deposits are comprised of ordered polymers of AAT formed by an inter-molecular domain swap. The discovery and characterization of rare variants of AAT and other serpins have historically played a crucial role in the dissection of the structural mechanisms leading to AAT polymer formation. Here, we report a severely deficient shutter region variant, Bologna AAT (N186Y), which was identified in five unrelated subjects with different geographical origins. We characterized the new variant by expression in cellular models in comparison with known polymerogenic AAT variants. Bologna AAT showed secretion deficiency and intracellular accumulation as detergent-insoluble polymers. Extracellular polymers were detected in both the culture media of cells expressing Bologna AAT and in the plasma of a patient homozygous for this variant. Structural modelling revealed that the mutation disrupts the hydrogen bonding network in the AAT shutter region. These data support a crucial coordinating role for asparagine 186 and the importance of this network in promoting formation of the native structure.
Genome Evolutionary Dynamics Meets Functional Genomics: A Case Story on the Identification of SLC25A44
Authors: Darbani Behrooz
Published: May 2021

Gene clusters are becoming promising tools for gene identification. The study reveals the purposive genomic distribution of genes toward higher inheritance rates of intact metabolic pathways/phenotypes and, thereby, higher fitness. The co-localization of co-expressed, co-interacting, and functionally related genes was found as genome-wide trends in humans, mouse, golden eagle, rice fish, Drosophila, peanut, and Arabidopsis. As anticipated, the analyses verified the co-segregation of co-localized events. A negative correlation was notable between the likelihood of co-localization events and the inter-loci distances. The evolution of genomic blocks was also found convergent and uniform along the chromosomal arms. Calling a genomic block responsible for adjacent metabolic reactions is therefore recommended for identification of candidate genes and interpretation of cellular functions. As a case story, a function in the metabolism of energy and secondary metabolites was proposed for Slc25A44, based on its genomic local information. Slc25A44 was further characterized as an essential housekeeping gene which has been under evolutionary purifying pressure and belongs to the phylogenetic ETC-clade of SLC25s. Pathway enrichment mapped the Slc25A44s to the energy metabolism. The expression of peanut and human Slc25A44s in oocytes and Saccharomyces cerevisiae strains confirmed the transport of common precursors for secondary metabolites and ubiquinone. These results suggest that SLC25A44 is a mitochondrion-ER-nucleus zone transporter with biotechnological applications. Finally, a conserved three-amino acid signature on the cytosolic face of transport cavity was found important for rational engineering of SLC25s.
Current Search through Liquid Biopsy of Effective Biomarkers for Early Cancer Diagnosis into the Rich Cargoes of Extracellular Vesicles
Authors: Tatischeff Irène
Published: May 2021

There exist many different human cancers, but regardless of the cancer type, an early diagnosis is a necessary condition for further optimal outcomes from the disease. Therefore, efficient specific and sensitive cancer biomarkers are urgently needed. This is especially true for the cancers depicting a silent progression, and those only diagnosed in an already metastatic state with a poor survival prognostic. After a rapid overview of the previous methods for cancer diagnosis, the outstanding characteristics of extracellular vesicles (EVs) will be presented, as new interesting candidates for early cancer diagnosis in human biofluid non-invasive liquid biopsy. The present review aims to give the state-of-the-art of the numerous searches of efficient EV-mediated cancer diagnosis. The corresponding literature quest was performed by means of an original approach, using a powerful Expernova Questel big data platform, which was specifically adapted for a literature search on EVs. The chosen collected scientific papers are presented in two parts, the first one drawing up a picture of the current general status of EV-mediated cancer diagnosis and the second one showing recent applications of such EV-mediated diagnosis for six important human-specific cancers, i.e., lung, breast, prostate, colorectal, ovary and pancreatic cancers. However, the promising perspective of finally succeeding in the worldwide quest for the much-needed early cancer diagnosis has to be moderated by the many remaining challenges left to solve before achieving the efficient clinical translation of the constantly increasing scientific knowledge.
Using Brain Activity Patterns to Differentiate Real and Virtual Attended Targets during Augmented Reality Scenarios
Authors: Vortmann Lisa-Marie , Schwenke Leonid , Putze Felix
Published: May 2021

Augmented reality is the fusion of virtual components and our real surroundings. The simultaneous visibility of generated and natural objects often requires users to direct their selective attention to a specific target that is either real or virtual. In this study, we investigated whether this target is real or virtual by using machine learning techniques to classify electroencephalographic (EEG) and eye tracking data collected in augmented reality scenarios. A shallow convolutional neural net classified 3 second EEG data windows from 20 participants in a person-dependent manner with an average accuracy above 70% if the testing data and training data came from different trials. This accuracy could be significantly increased to 77% using a multimodal late fusion approach that included the recorded eye tracking data. Person-independent EEG classification was possible above chance level for 6 out of 20 participants. Thus, the reliability of such a brain–computer interface is high enough for it to be treated as a useful input mechanism for augmented reality applications.
Assessment of the Effectiveness of Different Safety Measures at Tunnel Lay-Bys and Portals to Protect Occupants in Passenger Cars
Authors: Tomasch Ernst , Heindl Simon Franz , Gstrein Gregor , Sinz Wolfgang , Steffan Hermann
Published: May 2021

Tunnel portals and tunnel lay-bys are hazardous spots for road users. Different infrastructure safety measures are in use, but the protection level is not known. In this study the following safety measures for reducing the injury risk are investigated: angular positioned 4 m and 8 m concrete barrier, crash cushion Alpina F1-50 and Alpina  crash cushion. A passenger car equipped with a data acquisition unit is accelerated to 100 km/h and impacts the safety measure. The assessment of the latter is based on the EN 1317 criteria, specifically the Acceleration Severity Index (ASI), Theoretical Head Impact Velocity (THIV). Further assessment criteria are related to intrusions into the passenger compartment and post-crash motion. The best result in terms of ASI and THIV was achieved by the 8 m (ASI: 1.6, THIV: 30 km/h) concrete barrier. The crash cushion Alpina  showed good results for the ASI (1.8) but the THIV (57 km/h) was less satisfactory, while the angular positioned 4 m concrete barrier (ASI: 2.9, THIV: 53 km/h) and the crash cushion Alpina F1-50 (ASI: 3.3, THIV: 74 km/h) performed worst. Even though some of the measures showed good results, no protection measure tested currently complies with all the assessment criteria used.
Assessment of Infestation of Selected Blackcurrant (Ribes nigrum L.) Genotypes by the Blackcurrant Leaf Midge (Dasineura tetensi Rübs.) in Poland
Authors: Piotrowski Wojciech , Łabanowska Barbara H. , Kozak Marcin
Published: May 2021

Blackcurrant leaf midge (Dasineura tetensi) is a widespread pest of blackcurrant. Attacks by this pest can cause up to 60% reduction in the growth of shoots resulting in yield decreases. Our study, conducted (2012–2014) in Poland, aimed to assess the susceptibility of blackcurrant genotypes to D. tetensi, in order to select genotypes as parental lines for breeding new blackcurrant genotypes. Among tested blackcurrant genotypes, none were found to be completely resistant to this pest. The pest colonized genotypes Big Ben, Nr 8/72, Ben Connan, Ben Alder, Ben Hope, Foxendown, Ben Nevis, Fariegh, Ojebyn, and Ben Tirran below the threshold level (10%). In contrast, genotypes Nr 7/15, Ben Lomond, Ben Finlay, Tisel, Polares, Polonus, Tiben, PC-110, Polben, Gofert, Ruben, and Ores suffered pest levels above the threshold. With regard to egg numbers, the fewest were recorded on genotypes Big Ben, Ben Connan, Ben Alder, and Ben Nevis, and the most on Gofert and Ores. Fewer larvae were recorded on genotypes Big Ben, Nr 8/72, Ben Connan, and Foxendown compared to Ben Lomond, PC-110, Gofert, Tiben, Polben, and Ores. Developing blackcurrant genotype resistance to leaf midge strongly supports the IPM strategy.
Warm Temperatures Reduce Flower Attractiveness and Bumblebee Foraging
Authors: Descamps Charlotte , Jambrek Anne , Quinet Muriel , Jacquemart Anne-Laure
Published: May 2021

(1) Background: Plants attract pollinators using several visual signals, mainly involving the display, size, shape, and color of flowers. Each signal is relevant for pollinators foraging for floral rewards, pollen, and nectar. Changes in floral signals and rewards can be induced by an increase in temperature, drought, or other abiotic stresses and are expected to increase as global temperatures rise. In this study, we explored how pollinators respond to modified floral signals and rewards following an increase in temperature; (2) Methods: We tested the effects of warmer temperatures on bee-pollinated starflower (Borago officinalis, Boraginaceae) and determined the behavior of one of its main pollinators, the buff-tailed bumblebee (Bombus terrestris). We measured visual floral traits (display and size) and rewards (nectar and pollen) for plants cultivated at 21 °C or 26 °C. We investigated bumblebee behavior by tracking insect visits in a binary choice experiment in an indoor flight arena; (3) Results: Plants cultivated at 26 °C exhibited a smaller floral area (i.e., corolla sizes summed for all flowers per plant, 34.4 ± 2.3 cm2 versus 71.2 ± 2.7 cm2) and a greater flower height (i.e., height of the last inflorescence on the stem, 87 ± 1 cm versus 75 ± 1 cm) compared to plants grown at 21 °C. Nectar production per flower was lower in plants grown at 26 °C than in plants grown at 21 °C (2.67 ± 0.37 µL versus 4.15 ± 0.22 µL), and bumblebees visited flowers from plants grown at 26 °C four times less frequently than they visited those from plants grown at 21 °C; (4) Conclusions: These results show that warmer temperatures affect floral signals and reduce overall floral resources accessible to pollinators. Thus, the global increases in temperature caused by climate change could reduce plant pollination rates and reproductive success by reducing flower visitation.
Pinyon Engraver Beetle Acoustics: Stridulation Apparatus, Sound Production and Behavioral Response to Vibroacoustic Treatments in Logs
Authors: Lukic Ivan , Bedoya Carol L. , Hofstetter Evan M. , Hofstetter Richard W.
Published: May 2021

Bark beetles are among the most influential biotic agents in conifer forests, and forest management often focuses on bark beetle chemical communication for tree protection. Although acoustic communication occurs in many bark beetle species, we have yet to utilize acoustic communication for bark beetle control. Here, we describe the stridulatory organs and ‘stress’ chirps of the pinyon engraver, Ips confusus, a significant pest and mortality agent of pinyon pine in western North America. Only females possessed stridulatory organs and their stress chirps varied significantly in duration, pulses per chirp, and dominant frequency. We tested an array of acoustic-vibrational treatments into logs but were unable to disrupt male entry into logs or alter female–male interactions, female tunneling, and female oviposition. We found acoustic–vibrational treatments had little effect on I. confusus behavior and suggest further studies if acoustic methods are to be utilized for bark beetle control.
Explanatory Factors for Periprosthetic Infection in Total Knee Arthroplasty
Authors: Delgado-González Alberto , Morales-Viaji Juan José , Criado-Albillos Guillermo , Martín-Rodríguez Adoración del Pilar , González-Santos Josefa , López-Liria Remedios , Collazo-Riobo Carla , Soto-Cámara Raúl , González-Bernal Jerónimo J.
Published: May 2021

There are many studies whose results reveal possible risk factors for developing an infection after a total knee arthroplasty (TKA). The objective of this study is to analyse the risk factors that depend on the hospital and, especially, if the patellar replacement influences the appearance of periprosthetic infection. A retrospective study was performed, where data from the electronic registry of patients of people over 18 and who had undergone TKA, between the years 2015 and 2018, were reviewed. Dependent variables on the patients and the health care system were collected. The possible associations between the factors and the appearance of infection after TKA were studied using univariate and multivariate regression analyses. A total of 907 primary knee arthroplasties were included in the study. Those patients who had their patella replaced had a significantly higher risk of developing an infection (OR 2.07; 95% confidence interval 1.01–6.31). Likewise, patients who underwent surgery by surgeons with more than 10 years of experience were more than twice as likely to become infected than those operated on by younger surgeons (OR 2.64; 95%CI 1.01–6.97). Male patients were also found to be three times more likely to be infected than women (OR 2.99; 95%CI 1.32–5.74). Those interventions that were longer had a higher risk of infection. The same happened with patients who stayed in the hospital for a longer period of time. The rest of the variables did not show statistically significant results. In this study, it was found that the replacement of the patella may be a factor of infection, but it should be corroborated with randomized clinical trials. Furthermore, patients who underwent longer surgeries or those with prolonged hospital stays should be closely monitored to detect infection as soon as possible and establish the most appropriate treatment.
Old and New Challenges in Uveitis Associated with Behçet’s Disease
Authors: Gueudry Julie , Leclercq Mathilde , Saadoun David , Bodaghi Bahram
Published: May 2021

Behçet’s disease (BD) is a systemic vasculitis disease of unknown origin occurring in young people, which can be venous, arterial or both, classically occlusive. Ocular involvement is particularly frequent and severe; vascular occlusion secondary to retinal vasculitis may lead to rapid and severe loss of vision. Biologics have transformed the management of intraocular inflammation. However, the diagnosis of BD is still a major challenge. In the absence of a reliable biological marker, diagnosis is based on clinical diagnostic criteria and may be delayed after the appearance of the onset sign. However, therapeutic management of BD needs to be introduced early in order to control inflammation, to preserve visual function and to limit irreversible structural damage. The aim of this review is to provide current data on how innovations in clinical evaluation, investigations and treatments were able to improve the prognosis of uveitis associated with BD.
Predicting Silent Atrial Fibrillation in the Elderly: A Report from the NOMED-AF Cross-Sectional Study
Authors: Mitrega Katarzyna , Lip Gregory Y. H. , Sredniawa Beata , Sokal Adam , Streb Witold , Przyludzki Karol , Zdrojewski Tomasz , Wierucki Lukasz , Rutkowski Marcin , Bandosz Piotr , Kazmierczak Jaroslaw , Grodzicki Tomasz , Opolski Grzegorz , Kalarus Zbigniew
Published: May 2021

Background: Silent atrial fibrillation (SAF) is common and is associated with poor outcomes. Aims: to study the risk factors for AF and SAF in the elderly (≥65 years) general population and to develop a risk stratification model for predicting SAF. Methods: Continuous ECG monitoring was performed for up to 30 days using a vest-based system in a cohort from NOMED-AF, a cross-sectional study based on a nationwide population sample. The independent risk factors for AF and SAF were determined using multiple logistic regression. ROC analysis was applied to validate the developed risk stratification score. Results: From the total cohort of 3014 subjects, AF was diagnosed in 680 individuals (mean age, 77.5 ± 7.9; 50.1% men) with AF, and, of these, 41% had SAF. Independent associations with an increased risk of AF were age, male gender, coronary heart disease, thyroid diseases, prior ischemic stroke or transient ischemic attack (ICS/TIA), diabetes, heart failure, chronic kidney disease (CKD), obesity, and NT-proBNP >125 ng/mL. The risk factors for SAF were age, male gender, ICS/TIA, diabetes, heart failure, CKD, and NT-proBNP >125 ng/mL. We developed a clinical risk scale (MR-DASH score) that achieved a good level of prediction in the derivation cohort (AUC 0.726) and the validation cohort (AUC 0.730). Conclusions: SAF is associated with various clinical risk factors in a population sample of individuals ≥65 years. Stratifying individuals from the general population according to their risk for SAF may be possible using the MR-DASH score, facilitating targeted screening programs of individuals with a high risk of SAF.
Post-Exertional Malaise May Be Related to Central Blood Pressure, Sympathetic Activity and Mental Fatigue in Chronic Fatigue Syndrome Patients
Authors: Kujawski Sławomir , Słomko Joanna , Hodges Lynette , Pheby Derek F. H. , Murovska Modra , Newton Julia L. , Zalewski Paweł
Published: May 2021

Post-exertional malaise (PEM) is regarded as the hallmark symptom in chronic fatigue syndrome (CFS). The aim of the current study is to explore differences in CFS patients with and without PEM in indicators of aortic stiffness, autonomic nervous system function, and severity of fatigue. One-hundred and one patients met the Fukuda criteria. A Chronic Fatigue Questionnaire (CFQ) and Fatigue Impact Scale (FIS) were used to assess the level of mental and physical fatigue. Aortic systolic blood pressure (sBPaortic) and the autonomic nervous system were measured with the arteriograph and Task Force Monitor, respectively. Eighty-two patients suffered prolonged PEM according to the Fukuda criteria, while 19 did not. Patients with PEM had higher FIS scores (p = 0.02), lower central systolic blood pressure (p = 0.02) and higher mental fatigue (p = 0.03). For a one-point increase in the mental fatigue component of the CFQ scale, the risk of PEM increases by 34%. For an sBPaortic increase of 1 mmHg, the risk of PEM decreases by 5%. For a one unit increase in sympathovagal balance, the risk of PEM increases by 330%. Higher mental fatigue and sympathetic activity in rest are related to an increased risk of PEM, while higher central systolic blood pressure is related to a reduced risk of PEM. However, none of the between group differences were significant after FDR correction, and therefore conclusions should be treated with caution and replicated in further studies.
Triads and Rogue Events for Internal Waves in Stratified Fluids with a Constant Buoyancy Frequency
Authors: Pan Qing , Yin Hui-Min , Chow Kwok W.
Published: May 2021

Internal waves in a stratified fluid with a constant buoyancy frequency were studied, with special attention given to rogue modes, extreme waves, dynamical evolution, and Fermi–Pasta–Ulam–Tsingou type recurrence phenomena. Rogue waves for triads in a general physical setting have recently been derived analytically, but the implications in a fluid mechanics context have not yet been fully assessed. Numerical simulations were conducted for cases of coupled triads where the common member is a daughter wave mode. In sharp contrast with previous studies, rogue modes instead of plane waves were used as the initial condition. Furthermore, spatial dependence was incorporated. Rogue or extreme waves in one set of triads provided a possible mechanism for significant energy transfer among modes of the internal wave spectrum, in addition to the other known theories, e.g., weak turbulence. Remarkably, Fermi–Pasta–Ulam–Tsingou recurrence types of growth and decay cycles arose, similar to those observed for surface gravity wave groups governed by the cubic nonlinear Schrödinger equation. These mechanisms will enhance our understanding of transport processes in oceans.
Cost-Effectiveness of Serum Galactomannan Surveillance during Mould-Active Antifungal Prophylaxis
Authors: Khoo Ai Leng , Zhao Ying Jiao , Tan Glorijoy Shi En , Teng Monica , Yap Jenny , Tambyah Paul Anantharajah , Ng Chin Hin , Lim Boon Peng , Chai Louis Yi Ann
Published: May 2021

Serial galactomannan (GM) monitoring can aid the diagnosis of invasive aspergillosis (IA) and optimise treatment decisions. However, widespread adoption of mould-active prophylaxis has reduced the incidence of IA and challenged its use. We evaluated the cost-effectiveness of prophylaxis-biomarker strategies. A Markov model simulating high-risk patients undergoing routine GM surveillance with mould-active versus non-mould-active prophylaxis was constructed. The incremental cost for each additional quality-adjusted life-year (QALY) gained over a lifetime horizon was calculated. In 40- and 60-year-old patients receiving mould-active prophylaxis coupled with routine GM surveillance, the total cost accrued was the lowest at SGD 11,227 (USD 8255) and SGD 9234 (USD 6790), respectively, along with higher QALYs gained (5.3272 and 1.1693). This strategy, being less costly and more effective, dominated mould-active prophylaxis with no GM monitoring or GM surveillance during non-mould-active prophylaxis. The prescription of empiric antifungal treatment was influential in the cost-effectiveness. When the GM test sensitivity was reduced from 80% to 30%, as might be anticipated with the use of mould-active prophylactic agents, the conclusion remained unchanged. The likelihood of GM surveillance with concurrent mould-active prophylaxis being cost-effective was 77%. Routine GM surveillance remained cost-effective during mould-active prophylaxis despite lower IA breakthroughs. Cost-saving from reduced empirical antifungal treatment was an important contributing factor.
Genetic Counselling Improves the Molecular Characterisation of Dementing Disorders
Authors: Zampatti Stefania , Ragazzo Michele , Peconi Cristina , Luciano Serena , Gambardella Stefano , Caputo Valerio , Strafella Claudia , Cascella Raffaella , Caltagirone Carlo , Giardina Emiliano
Published: May 2021

Dementing disorders are a complex group of neurodegenerative diseases characterised by different, but often overlapping, pathological pathways. Genetics have been largely associated with the development or the risk to develop dementing diseases. Recent advances in molecular technologies permit analyzing of several genes in a small time, but the interpretation analysis is complicated by several factors: the clinical complexity of neurodegenerative disorders, the frequency of co-morbidities, and the high phenotypic heterogeneity of genetic diseases. Genetic counselling supports the diagnostic path, providing an accurate familial and phenotypic characterisation of patients. In this review, we summarise neurodegenerative dementing disorders and their genetic determinants. Genetic variants and associated phenotypes will be divided into high and low impact, in order to reflect the pathologic continuum between multifactorial and mendelian genetic factors. Moreover, we report a molecular characterisation of genes associated with neurodegenerative disorders with cognitive impairment. In particular, the high frequency of rare coding genetic variants in dementing genes strongly supports the role of geneticists in both, clinical phenotype characterisation and interpretation of genotypic data. The smart application of exome analysis to dementia patients, with a pre-analytical selection on familial, clinical, and instrumental features, improves the diagnostic yield of genetic test, reduces time for diagnosis, and allows a rapid and personalised management of disease.
Implementing Personalized Medicine in COVID-19 in Andalusia: An Opportunity to Transform the Healthcare System
Authors: Dopazo Joaquín , Maya-Miles Douglas , García Federico , Lorusso Nicola , Calleja Miguel Ángel , Pareja María Jesús , López-Miranda José , Rodríguez-Baño Jesús , Padillo Javier , Túnez Isaac , Romero-Gómez Manuel
Published: May 2021

The COVID-19 pandemic represents an unprecedented opportunity to exploit the advantages of personalized medicine for the prevention, diagnosis, treatment, surveillance and management of a new challenge in public health. COVID-19 infection is highly variable, ranging from asymptomatic infections to severe, life-threatening manifestations. Personalized medicine can play a key role in elucidating individual susceptibility to the infection as well as inter-individual variability in clinical course, prognosis and response to treatment. Integrating personalized medicine into clinical practice can also transform health care by enabling the design of preventive and therapeutic strategies tailored to individual profiles, improving the detection of outbreaks or defining transmission patterns at an increasingly local level. SARS-CoV2 genome sequencing, together with the assessment of specific patient genetic variants, will support clinical decision-makers and ultimately better ways to fight this disease. Additionally, it would facilitate a better stratification and selection of patients for clinical trials, thus increasing the likelihood of obtaining positive results. Lastly, defining a national strategy to implement in clinical practice all available tools of personalized medicine in COVID-19 could be challenging but linked to a positive transformation of the health care system. In this review, we provide an update of the achievements, promises, and challenges of personalized medicine in the fight against COVID-19 from susceptibility to natural history and response to therapy, as well as from surveillance to control measures and vaccination. We also discuss strategies to facilitate the adoption of this new paradigm for medical and public health measures during and after the pandemic in health care systems.
Epithelial–Mesenchymal Transition Gene Signature Related to Prognostic in Colon Adenocarcinoma
Authors: Busuioc Constantin , Ciocan-Cartita Cristina Alexandra , Braicu Cornelia , Zanoaga Oana , Raduly Lajos , Trif Monica , Muresan Mihai-Stefan , Ionescu Calin , Stefan Cristina , Crivii Carmen , Al Hajjar Nadim , Mǎrgǎrit Simona , Berindan-Neagoe Ioana
Published: May 2021

Colon adenocarcinoma (COAD) remains an important cause of cancer-related mortality worldwide. Epithelial–mesenchymal transition (EMT) is a key mechanism, promoting not only the invasive or metastatic phenotype but also resistance to therapy. Using bioinformatics approaches, we studied the alteration on EMT related genes and its implication on COAD prognostic based on public datasets. For the EMT mechanisms, two overexpressed genes were identified (NOX4 and IGF2BP3), as well as five downregulated genes (BMP5, DACT3, EEF1A2, GCNT2 and SFRP1) that were related to prognosis in COAD. A qRT-PCR validation step was conducted in a COAD patient cohort comprising of 29 tumor tissues and 29 normal adjacent tissues, endorsing the expression level for BMP5, as well as for two of the miRNAs targeting key EMT related genes, revealing upregulation of miR-27a-5p and miR-146a-5p. The EMT signature can be used to develop a panel of biomarkers for recurrence prediction in COAD patients, which may contribute to the improvement of risk stratification for the patients.
Plant Diversity in the Dynamic Mosaic Landscape of an Agricultural Heritage System: The Minabe-Tanabe Ume System
Authors: Hara Yuji , Oki Shinji , Uchiyama Yoshiyuki , Ito Kyuichi , Tani Yuto , Naito Asako , Sampei Yuki
Published: May 2021

The Minabe-Tanabe Ume System in central Japan is defined as a Globally Important Agricultural Heritage System (GIAHS) by the United Nations Food and Agriculture Organization. This study examined relationships between parcel-level plant diversity and land use, management, and development in traditional sloped Ume (Japanese apricot; Prunus mume) orchards and adjoining level orchards recently developed through large-scale cut-fill land development. We constructed and overlaid past (1974) and present (2015) digital land-use maps to assess land use and topography. We conducted field vegetation surveys in land parcels with different development and management histories. Although 249 ha (4.6% of the total 2015 area) were developed using cut-fill methods, 5148 ha remain a traditional orchard surrounded by coppice forests. Vegetation surveys and a two-way indicator species analysis revealed that traditional orchards had more native species and a higher plant diversity index. Cut-fill orchards contained a higher proportion of alien species; however, the degree depended on parcel history and management. Overall, this area remains a dynamic mosaic landscape containing a core of long-standing Ume orchards. We suggest that biodiversity conservation in this area should focus on conservation measures such as indirect land-use regulations, including some acceptable landform transformations, to promote continued farming of this ecologically important area.
Therapeutic Nanoparticles for the Different Phases of Ischemic Stroke
Authors: Bernardo-Castro Sara , Albino Inês , Barrera-Sandoval Ángela María , Tomatis Francesca , Sousa João André , Martins Emanuel , Simões Susana , Lino Miguel M. , Ferreira Lino , Sargento-Freitas João
Published: May 2021

Stroke represents the second leading cause of mortality and morbidity worldwide. Ischemic strokes are the most prevalent type of stroke, and they are characterized by a series of pathological events prompted by an arterial occlusion that leads to a heterogeneous pathophysiological response through different hemodynamic phases, namely the hyperacute, acute, subacute, and chronic phases. Stroke treatment is highly reliant on recanalization therapies, which are limited to only a subset of patients due to their narrow therapeutic window; hence, there is a huge need for new stroke treatments. Nonetheless, the vast majority of promising treatments are not effective in the clinical setting due to their inability to cross the blood-brain barrier and reach the brain. In this context, nanotechnology-based approaches such as nanoparticle drug delivery emerge as the most promising option. In this review, we will discuss the current status of nanotechnology in the setting of stroke, focusing on the diverse available nanoparticle approaches targeted to the different pathological and physiological repair mechanisms involved in each of the stroke phases.
A Novel Assay for Phosphoserine Phosphatase Exploiting Serine Acetyltransferase as the Coupling Enzyme
Authors: Marchesani Francesco , Zangelmi Erika , Bruno Stefano , Bettati Stefano , Peracchi Alessio , Campanini Barbara
Published: May 2021

Phosphoserine phosphatase (PSP) catalyzes the final step of de novo L-serine biosynthesis—the hydrolysis of phosphoserine to serine and inorganic phosphate—in humans, bacteria, and plants. In published works, the reaction is typically monitored through the discontinuous malachite green phosphate assay or, more rarely, through a continuous assay that couples phosphate release to the phosphorolysis of a chromogenic nucleoside by the enzyme purine nucleoside phosphorylase (PNP). These assays suffer from numerous drawbacks, and both rely on the detection of phosphate. We describe a new continuous assay that monitors the release of serine by exploiting bacterial serine acetyltransferase (SAT) as a reporter enzyme. SAT acetylates serine, consuming acetyl-CoA and releasing CoA-SH. CoA-SH spontaneously reacts with Ellman’s reagent to produce a chromophore that absorbs light at 412 nm. The catalytic parameters estimated through the SAT-coupled assay are fully consistent with those obtained with the published methods, but the new assay exhibits several advantages. Particularly, it depletes L-serine, thus allowing more prolonged linearity in the kinetics. Moreover, as the SAT-coupled assay does not rely on phosphate detection, it can be used to investigate the inhibitory effect of phosphate on PSP.
Multigene Phylogeny Reveals Haploanthostomella elaeidis gen. et sp. nov. and Familial Replacement of Endocalyx (Xylariales, Sordariomycetes, Ascomycota)
Authors: Konta Sirinapa , Hyde Kevin D. , Eungwanichayapant Prapassorn D. , Karunarathna Samantha C. , Samarakoon Milan C. , Xu Jianchu , Dauner Lucas A. P. , Aluthwattha Sasith Tharanga , Lumyong Saisamorn , Tibpromma Saowaluck
Published: May 2021

During our investigation of palm fungi in Thailand, two interesting taxa from Elaeis guineensis and Metroxylon sagu (Arecaceae) were collected. Based on phylogenetic analyses of a combined dataset of ITS, LSU, rpb2, and tub2 nucleotide sequences as well as unique morphological characteristics, we introduce the new genus Haploanthostomella within Xylariales, and a new species Endocalyx metroxyli. Additionally, in our study, the genus Endocalyx is transferred to the family Cainiaceae based on its brown conidia and molecular phylogenetic evidence.