bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Profile Analysis of Triple-Negative Breast Cancer Cells in Response to a Novel Cytostatic Tetrahydroisoquinoline Compared to Paclitaxel
Authors: Gangapuram Madhavi , Mazzio Elizabeth A. , Redda Kinfe K. , Soliman Karam F. A.
Published: July 2021

The absence of chemotherapeutic target hormone receptors in breast cancer is descriptive of the commonly known triple-negative breast cancer (TNBC) subtype. TNBC remains one of the most aggressive invasive breast cancers, with the highest mortality rates in African American women. Therefore, new drug therapies are continually being explored. Microtubule-targeting agents such as paclitaxel (Taxol) interfere with microtubules dynamics, induce mitotic arrest, and remain a first-in-class adjunct drug to treat TNBC. Recently, we synthesized a series of small molecules of substituted tetrahydroisoquinolines (THIQs). The lead compound of this series, with the most potent cytostatic effect, was identified as 4-Ethyl-N-(7-hydroxy-3,4-dihydroisoquinolin-2(1H)-yl) benzamide (GM-4-53). In our previous work, GM-4-53 was similar to paclitaxel in its capacity to completely abrogate cell cycle in MDA-MB-231 TNBC cells, with the former not impairing tubulin depolymerization. Given that GM-4-53 is a cytostatic agent, and little is known about its mechanism of action, here, we elucidate differences and similarities to paclitaxel by evaluating whole-transcriptome microarray data in MDA-MB-231 cells. The data obtained show that both drugs were cytostatic at non-toxic concentrations and caused deformed morphological cytoskeletal enlargement in 2D cultures. In 3D cultures, the data show greater core penetration, observed by GM-4-53, than paclitaxel. In concentrations where the drugs entirely blocked the cell cycle, the transcriptome profile of the 48,226 genes analyzed (selection criteria: (p-value, FDR p-value < 0.05, fold change −2< and >2)), paclitaxel evoked 153 differentially expressed genes (DEGs), GM-4-53 evoked 243 DEGs, and, of these changes, 52/153 paclitaxel DEGs were also observed by GM-4-53, constituting a 34% overlap. The 52 DEGS analysis by String database indicates that these changes involve transcripts that influence microtubule spindle formation, chromosome segregation, mitosis/cell cycle, and transforming growth factor-β (TGF-β) signaling. Of interest, both drugs effectively downregulated “inhibitor of DNA binding, dominant negative helix-loop-helix” (ID) transcripts; ID1, ID3 and ID4, and amphiregulin (AREG) and epiregulin (EREG) transcripts, which play a formidable role in cell division. Given the efficient solubility of GM-4-53, its low molecular weight (MW; 296), and capacity to penetrate a small solid tumor mass and effectively block the cell cycle, this drug may have future therapeutic value in treating TNBC or other cancers. Future studies will be required to evaluate this drug in preclinical models.
Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells
Authors: Wu Ying-Chieh , Sonninen Tuuli-Maria , Peltonen Sanni , Koistinaho Jari , Lehtonen Šárka
Published: July 2021

The blood–brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer’s disease and Parkinson’s disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.
Biodirected Synthesis of Silver Nanoparticles Using Aqueous Honey Solutions and Evaluation of Their Antifungal Activity against Pathogenic Candida Spp.
Authors: Czernel Grzegorz , Bloch Dominika , Matwijczuk Arkadiusz , Cieśla Jolanta , Kędzierska-Matysek Monika , Florek Mariusz , Gagoś Mariusz
Published: July 2021

Silver nanoparticles (AgNPs) were synthesized using aqueous honey solutions with a concentration of 2%, 10%, and 20%—AgNPs-H2, AgNPs-H10, and AgNPs-H20. The reaction was conducted at 35 °C and 70 °C. Additionally, nanoparticles obtained with the citrate method (AgNPs-C), while amphotericin B (AmB) and fluconazole were used as controls. The presence and physicochemical properties of AgNPs was affirmed by analyzing the sample with ultraviolet–visible (UV–Vis) and fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The 20% honey solution caused an inhibition of the synthesis of nanoparticles at 35 °C. The antifungal activity of the AgNPs was evaluated using opportunistic human fungal pathogens Candida albicans and Candida parapsilosis. The antifungal effect was determined by the minimum inhibitory concentration (MIC) and disc diffusion assay. The highest activity in the MIC tests was observed in the AgNPs-H2 variant. AgNPs-H10 and AgNPs-H20 showed no activity or even stimulated fungal growth. The results of the Kirby–Bauer disc diffusion susceptibility test for C. parapsilosis strains indicated stronger antifungal activity of AgNPs-H than fluconazole. The study demonstrated that the antifungal activity of AgNPs is closely related to the concentration of honey used for the synthesis thereof.
Research on Behavior Incentives of Prefabricated Building Component Manufacturers
Authors: Yao Pinbo , Liu Hongda
Published: July 2021

Based on the positive externalities of prefabricated buildings, this paper constructs an evolutionary game model between the government and material component vendors and analyzes the changes in the behavior of the government and component vendors in different stages of the advancement of prefabricated buildings. Based on data modeling and equation prediction analysis, it can be found that the expansion of the incremental cost of construction at the initial stage inhibits the enthusiasm of the government. Thus, the government’s incentive behavior effectively affects the behavior of component vendors, and fiscal taxation and punishment policies will promote component vendors to provide prefabricated components. In the development stage, the government’s fiscal policy influence that weakens and affects component vendors’ behavior mainly comes from the incremental costs and benefits of components. Additionally, the difference between the builder’s incremental cost and the sales revenue narrowed. At this time, the behavior prediction of both parties tends to be steady. In the mature stage, prefabricated buildings will mainly rely on market forces, and the government can gradually withdraw from the market. The cost variable tends to be lower, and it can be predicted that component vendors tend to supply components, while the government tends to restrict policies.
Investigating Virus–Host Interactions in Cultured Primary Honey Bee Cells
Authors: McMenamin Alexander J. , Parekh Fenali , Lawrence Verena , Flenniken Michelle L.
Published: July 2021

Honey bee (Apis mellifera) health is impacted by viral infections at the colony, individual bee, and cellular levels. To investigate honey bee antiviral defense mechanisms at the cellular level we further developed the use of cultured primary cells, derived from either larvae or pupae, and demonstrated that these cells could be infected with a panel of viruses, including common honey bee infecting viruses (i.e., sacbrood virus (SBV) and deformed wing virus (DWV)) and an insect model virus, Flock House virus (FHV). Virus abundances were quantified over the course of infection. The production of infectious virions in cultured honey bee pupal cells was demonstrated by determining that naïve cells became infected after the transfer of deformed wing virus or Flock House virus from infected cell cultures. Initial characterization of the honey bee antiviral immune responses at the cellular level indicated that there were virus-specific responses, which included increased expression of bee antiviral protein-1 (GenBank: MF116383) in SBV-infected pupal cells and increased expression of argonaute-2 and dicer-like in FHV-infected hemocytes and pupal cells. Additional studies are required to further elucidate virus-specific honey bee antiviral defense mechanisms. The continued use of cultured primary honey bee cells for studies that involve multiple viruses will address this knowledge gap.
Intraguild Interactions between the Mealybug Predators Cryptolaemus montrouzieri and Chrysoperla carnea
Authors: Golsteyn Laura , Mertens Hana , Audenaert Joachim , Verhoeven Ruth , Gobin Bruno , De Clercq Patrick
Published: July 2021

The ladybird Cryptolaemus montrouzieri and the green lacewing Chrysoperla carnea have shown potential for use in augmentative biological control of mealybug pests in greenhouse crops. In the context of combining these predators within an integrated pest management system, the risk of negative intraguild interactions between both predators was evaluated in a laboratory setting. Different life stages of either predator were confronted in petri dish arenas containing a Ficus benjamina leaf, and after 24 h the incidence and direction of intraguild predation (IGP) was recorded for each combination. The effect of adding Planococcus citri nymphs or Ephestia kuehniella eggs as extraguild prey on the level of IGP was also studied. IGP was frequently observed between the two predator species and was asymmetrical in favour of C. carnea in most cases. The presence of extraguild prey reduced the number of IGP events between the predators to a similar extent. The relevance of the observed intraguild interactions for the combined use of these predators in protected cultivation is discussed.
Supraventricular Runs in 7-Day Holter Monitoring Are Related to Increased Incidence of Atrial Fibrillation in a 3-Year Follow-Up of Cryptogenic Stroke Patients Free from Arrhythmia in a 24 h-Holter
Authors: Kułach Andrzej , Dewerenda Milena , Majewski Michał , Lasek-Bal Anetta , Gąsior Zbigniew
Published: July 2021

Introduction: Silent atrial fibrillation (AF) is a common cause of cryptogenic ischemic stroke (CIS). The 24-h-Holter is insufficient to reveal an occult arrhythmic cause of stroke and the strategy to select the patients for long-term monitoring is missing. Objectives: The aim of the study was to evaluate 7-day-Holter monitoring to identify cases with the arrhythmic cause of stroke in CIS patients in whom 24-h-Holter was free from arrhythmia, and to assess the relation between supraventricular (SV) runs in baseline Holter and the incidence of AF in a 3-year follow-up period. Methods: 78 patients (aged 60 ± 9 years, 45 males) with CIS and no arrhythmic findings in 24-h-Holter were enrolled. All patients had 7-day-Holter monitoring after stroke and were followed up for 36 months, and then 7-day Holter was repeated. We assessed SV runs (≥5 QRS) in the initial 7-day Holter and analyzed the relation of the findings with clinical characteristics of novel AF episodes revealed early after stroke and during a 3-year follow-up. Results: Baseline 7-day-Holter revealed SV runs in 36% of patients and AF in 9% of cases. During a 3-year follow-up, 8 additional cases were confirmed, both in standard care and in repeated Holter (a total of 19% of AF cases). There was no difference with regard to CHADS2VASc score (3.6 ± 1.1 vs. 3.4 ± 1.5; p = NS) and left atrium parameters between patients with SV runs and the non-arrhythmic group. Patients with SV runs had a higher incidence of AF both after stroke and in a 3-year follow-up (46% vs. 4%, RR 11.6, p < 0.001). In 8 cases, patent foramen ovale was detected during follow-up. Conclusions: A strategy of baseline 7-day-Holter monitoring after stroke allows for disclosing SV runs in every third case and AF in 9% of stroke survivors. Patients with SV runs have a higher incidence of AF (RR 11.6, p < 0.001) and should be considered for extended continuous ECG monitoring.
Early Intervention of Pulmonary Rehabilitation for Fibrotic Interstitial Lung Disease Is a Favorable Factor for Short-Term Improvement in Health-Related Quality of Life
Authors: Matsuo Satoshi , Okamoto Masaki , Ikeuchi Tomoyuki , Zaizen Yoshiaki , Inomoto Atsushi , Haraguchi Remi , Mori Shunichiro , Sasaki Retsu , Nouno Takashi , Tanaka Tomohiro , Hoshino Tomoaki , Tsuda Toru
Published: July 2021

Patients with fibrosing interstitial lung disease (FILD) have poor health-related quality of life (HRQOL). We analyzed predictors of short-term improvement of HRQOL after starting pulmonary rehabilitation (PR) in moderate to severe FILD patients. This study involved 28 consecutive patients with FILD (20 males, median age of 77.5 years), who participated in PR program of our hospital for >6 weeks. The St. George’s Respiratory Questionnaire (SGRQ) score and the 6-min walk distance (6MWD) were evaluated before and after PR, and the predictors of efficacy of PR were analyzed. The duration from diagnosis of FILD to start of PR showed a positive correlation with the increase in the SGRQ score, and the baseline SGRQ score showed a negative correlation with increase in the 6MWD. The FILD subtype, modified Medical Research Council score, and treatment history were not associated with the endpoints. According to the receiver operating characteristic curve (ROC) analyses, starting PR within 514 days after diagnosis of FILD was a significant favorable predictor of improvement in the SGRQ total score more than a minimal clinically important difference of 4. In this study, early intervention of PR and lower SGRQ score were associated with the favorable response to PR. PR for FILD should be initiated early before the disease becomes severe.
Surgical Aortic Mitral Curtain Replacement: Systematic Review and Metanalysis of Early and Long-Term Results
Authors: Giambuzzi Ilaria , Bonalumi Giorgia , Di Mauro Michele , Roberto Maurizio , Corona Silvia , Alamanni Francesco , Zanobini Marco
Published: July 2021

The Commando procedure is challenging, and aims to replace the mitral valve, the aortic valve and the aortic mitral curtain, when the latter is severely affected by pathological processes (such as infective endocarditis or massive calcification). Given the high complexity, it is seldomly performed. We aim to review the literature on early (hospitalization and up to 30 days) and long-term (at least 3 years of follow-up) results. Bibliographical research was performed on PubMed and Cochrane with a dedicated string. Papers regarding double valve replacement or repair in the context of aortic mitral curtain disease were included. The metaprop function was used to assess early survival and complications (pacemaker implantation, stroke and bleeding). Nine papers (540 patients, median follow-up 41 (IQR 24.5–51.5) months) were included in the study. Pooled proportion of early mortality, stroke, pacemaker implant and REDO for bleeding were, respectively 16.2%, 7.8%, 25.1% and 13.1%. The long-term survival rate ranged from 50% to 92.2%. Freedom from re-intervention was as high as 90.9% when the endocarditis was not the first etiology and 78.6% in case of valvular infection (one author had 100%). Freedom from IE recurrences reached 85% at 10 years. Despite the high mortality, the rates of re-intervention and infective endocarditis recurrences following the Commando procedure are satisfactory and confirm the need for an aggressive strategy to improve long-term outcomes.
Vasopressor-Sparing Strategies in Patients with Shock: A Scoping-Review and an Evidence-Based Strategy Proposition
Authors: Guinot Pierre-Grégoire , Martin Audrey , Berthoud Vivien , Voizeux Pierre , Bartamian Loic , Santangelo Erminio , Bouhemad Belaid , Nguyen Maxime
Published: July 2021

Despite the abundant literature on vasopressor therapy, few studies have focused on vasopressor-sparing strategies in patients with shock. We performed a scoping-review of the published studies evaluating vasopressor-sparing strategies by analyzing the results from randomized controlled trials conducted in patients with shock, with a focus on vasopressor doses and/or duration reduction. We analyzed 143 studies, mainly performed in septic shock. Our analysis demonstrated that several pharmacological and non-pharmacological strategies are associated with a decrease in the duration of vasopressor therapy. These strategies are as follows: implementing a weaning strategy, vasopressin use, systemic glucocorticoid administration, beta-blockers, and normothermia. On the contrary, early goal directed therapies, including fluid therapy, oral vasopressors, vitamin C, and renal replacement therapy, are not associated with an increase in vasopressor-free days. Based on these results, we proposed an evidence-based vasopressor management strategy.
Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease
Authors: Cabrera Cesar Eva , Lopez-Lopez Lidia , Lara Estrella , Hidalgo-San Juan M. Victoria , Parrado Romero Concepcion , Palencia Jose Luis Royo Sánchez , Martín-Montañez Elisa , Garcia-Fernandez Maria
Published: July 2021

Introduction: The goal of this study is to determine whether Advanced glycosylated end-products (AGE), Advanced oxidation protein products (AOPP) and Matrix metalloproteinase 7 (MMP7) could be used as differential biomarkers for idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). Method: Seventy-three patients were enrolled: 29 with IPF, 14 with CTD-ILD, and 30 healthy controls. The study included a single visit by participants. A blood sample was drawn and serum was analysed for AGE using spectrofluorimetry, AOPP by spectrophotometry, and MMP7 using sandwich-type enzyme-linked immunosorbent assay. Results: AGE, AOPP and MMP7 serum levels were significantly higher in both IPF and CTD-ILD patients versus healthy controls; and AGE was also significantly elevated in CTD-ILD compared to the IPF group. AGE plasma levels clearly distinguished CTD-ILD patients from healthy participants (AUC = 0.95; 95% IC 0.86–1), whereas in IPF patients, the distinction was moderate (AUC = 0.78; 95% IC 0.60–0.97). Conclusion: In summary, our results provide support for the potential value of serum AGE, AOPP and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD to differentiate between ILD patients and healthy controls. Furthermore, this study provides evidence, for the first time, for the possible use of AGE as a differential diagnostic biomarker to distinguish between IPF and CTD-ILD. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF and CTD-ILD diagnosis needs to be considered and further explored. Multicentre studies are necessary to understand the role of AGE in differential diagnosis.
Improvement of the Quality of Life in Aging by Stimulating Autobiographical Memory
Authors: Villasán Rueda Alba , Sánchez Cabaco Antonio , Mejía-Ramírez Manuel , Justo-Henriques Susana I. , Carvalho Janessa O.
Published: July 2021

With notable increases in older adult populations, as well as with the associated cognitive impairments that can accompany aging, there is significant importance in identifying strategies to promote cognitive health. The current study explored the implementation of a positive reminiscence program (REMPOS), a non-pharmacological cognitive therapy that has been previously structured, defined, and tested in a Spanish sample. We sought to improve the quality of life of institutionalized older adults with healthy aging, mild cognitive impairment, and Alzheimer’s disease by utilizing this protocol in these samples. A randomized design with a pre-post measure was conducted over a three-month period. Two types of interventions were used: the experimental groups received REMPOS, and the control groups underwent their regular daily institutional programming with cognitive stimulation techniques. After the intervention, the three experimental groups showed higher cognitive functioning, decreased depressive symptomatology (except for the MCI group) and higher evocation of specific positive memories (except for the MCI group). This study supports the effectiveness of REMPOS and reminiscence therapy, with regard to both cognitive and mood factors in cognitively impaired older adults.
Localized Atrial Tachycardia and Dispersion Regions in Atrial Fibrillation: Evidence of Spatial Concordance
Authors: Gitenay Edouard , Bars Clément , Bremondy Michel , Ayari Anis , Maillot Nicolas , Baptiste Florian , Taormina Antonio , Fofana Aicha , Siame Sabrina , Kalifa Jérôme , Seitz Julien
Published: July 2021

Introduction: During atrial fibrillation (AF) ablation, it is generally considered that atrial tachycardia (AT) episodes are a consequence of ablation. Objective: To investigate the spatial relationship between localized AT episodes and dispersion/ablation regions during persistent AF ablation procedures. Methods: We analyzed 72 consecutive patients who presented for an index persistent AF ablation procedure guided by the presence of spatiotemporal dispersion of multipolar electrograms. We characterized spontaneous or post-ablation ATs’ mechanism and location in regard to dispersion regions and ablation lesions. Results: In 72 consecutive patients admitted for persistent AF ablation, 128 ATs occurred in 62 patients (1.9 ± 1.1/patient). Seventeen ATs were recorded before any ablation. In a total of 100 ATs with elucidated mechanism, there were 58 localized sources and 42 macro-reentries. A large number of localized ATs arose from regions exhibiting dispersion during AF (n = 49, 84%). Importantly, these ATs’ locations were generally remote from the closest ablation lesion (n = 42, 72%). Conclusions: In patients undergoing a persistent AF ablation procedure guided by the presence of spatiotemporal dispersion of multipolar electrograms, localized ATs originate within dispersion regions but remotely from the closest ablation lesion. These results suggest that ATs represent a stabilized manifestation of co-existing AF drivers rather than ablation-induced arrhythmias.
Relationship between Prognostic Stage in Breast Cancer and Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
Authors: Mori Mio , Fujioka Tomoyuki , Kubota Kazunori , Katsuta Leona , Yashima Yuka , Nomura Kyoko , Yamaga Emi , Tsuchiya Junichi , Hosoya Tokuko , Oda Goshi , Nakagawa Tsuyoshi , Onishi Iichiroh , Tateishi Ukihide
Published: July 2021

This retrospective study examined the relationship between the standardized uptake value max (SUVmax) of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the prognostic stage of breast cancer. We examined 358 breast cancers in 334 patients who underwent 18F-FDG PET/CT for initial staging between January 2016 and December 2019. We extracted data including SUVmax of 18F-FDG PET and pathological biomarkers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and nuclear grade. Anatomical and prognostic stages were determined per the American Joint Committee on Cancer (eighth edition). We examined whether there were statistical differences in SUVmax between each prognostic stage. The mean SUVmax values for clinical prognostic stages were as follow: stage 0, 2.2 ± 1.4; stage IA, 2.6 ± 2.1; stage IB, 4.2 ± 3.5; stage IIA, 5.2 ± 2.8; stage IIB, 7.7 ± 6.7; and stage III + IV, 7.0 ± 4.5. The SUVmax values for pathological prognostic stages were as follows: stage 0, 2.2 ± 1.4; stage IA, 2.8 ± 2.2; stage IB, 5.4 ± 3.6; stage IIA, 6.3 ± 3.1; stage IIB, 9.2 ± 7.5, and stage III + IV, 6.2 ± 5.2. There were significant differences in mean SUVmax between clinical prognostic stage 0 and ≥II (p < 0.001) and I and ≥II (p < 0.001). There were also significant differences in mean SUVmax between pathological prognostic stage 0 and ≥II (p < 0.001) and I and ≥II (p < 0.001). In conclusion, mean SUVmax increased with all stages up to prognostic stage IIB, and there were significant differences between several stages. The SUVmax of 18F-FDG PET/CT may contribute to prognostic stage stratification, particularly in early cases of breast cancers.
Disproportionate Vertebral Bodies and Their Impact on Lumbar Disc Herniation
Authors: Läubli Ralph , Brugger Robin , Pirvu Tatiana , Hoppe Sven , Sieroń Dominik , Szyluk Karol , Albers Christoph E. , Christe Andreas
Published: July 2021

Background: The aim of this study was to determine whether the presence of disproportionate vertebral bodies is a risk factor for disc herniation (DH). Methods: Sixty-seven consecutive patients (m: 31 f: 36) who underwent lumbar discectomy for symptomatic DH at one level between L3 and S1 were retrospectively included. The last three motion segments (3 × 67 = 201) were assessed on sagittal MRI scans. A disproportionate motion segment was defined as the difference of more than 10% of the antero-posterior diameter of two adjacent endplates. Results: DH was present in 6/67 (9%), 26/67 (38.8%), and 35/67 (52.2%) patients at L3/4, L4/5, and L5/S1, respectively. A total of 14 of 67 patients demonstrated a disproportionate motion segment at the discectomy level (20.9%). A total of 23 of the 201 (11.4%) investigated motion segments met our criteria for a disproportionate motion segment. In our study population, when one of the 201 segments was disproportionate, the positive predictive value (PPV) for DH increased toward the lower segments: the PPV at the L5/S1 level was 83.0%. The odds ratio of disproportion for DH was the highest at the L5/S1 level, with 6.0 ± 0.82 (p = 0.017). Conclusions: The presence of a disproportionate motion segment in the lower spine may lead to a significant higher risk for DH in patients undergoing discectomy.
Associates of Insomnia in People with Chronic Spinal Pain: A Systematic Review and Meta-Analysis
Authors: Bilterys Thomas , Siffain Carolie , De Maeyer Ina , Van Looveren Eveline , Mairesse Olivier , Nijs Jo , Meeus Mira , Ickmans Kelly , Cagnie Barbara , Goubert Dorien , Danneels Lieven , Moens Maarten , Malfliet Anneleen
Published: July 2021

Insomnia is a major problem in the chronic spinal pain (CSP) population and has a negative impact on health and well-being. While insomnia is commonly reported, underlying mechanisms explaining the relation between sleep and pain are still not fully understood. Additionally, no reviews regarding the prevention of insomnia and/or associated factors in people with CSP are currently available. To gain a better understanding of the occurrence of insomnia and associated factors in this population, we conducted a systematic review of the literature exploring associates for insomnia in people with CSP in PubMed, Web of Science and Embase. Three independent reviewers extracted the data and performed the quality assessment. A meta-analysis was conducted for every potential associate presented in at least two studies. A total of 13 studies were found eligible, which together identified 25 different potential associates of insomnia in 24,817 people with CSP. Twelve studies had a cross-sectional design. Moderate-quality evidence showed a significantly higher rate for insomnia when one of the following factors was present: high pain intensity, anxiety and depression. Low-quality evidence showed increased odds for insomnia when one of the following factors was present: female sex, performing no professional activities and physical/musculoskeletal comorbidities. Higher healthcare use was also significantly related to the presence of insomnia. One study showed a strong association between high levels of pain catastrophizing and insomnia in people with chronic neck pain. Last, reduced odds for insomnia were found in physically active people with chronic low back pain compared to inactive people with chronic low back pain. This review provides an overview of the available literature regarding potential associates of insomnia in people with CSP. Several significant associates of insomnia were identified. These findings can be helpful to gain a better understanding of the characteristics and potential origin of insomnia in people witch CSP, to identify people with CSP who are (less) likely to have insomnia and to determine directions of future research in this area.
Premedication Does Not Influence the Incidence of Infliximab Infusion Reactions in Pediatric Patients with Inflammatory Bowel Disease—A Single Center Case–Control Study
Authors: Szymanska Edyta , Dadalski Maciej , Sieczkowska-Golub Joanna , Jarzebicka Dorota , Meglicka Monika , Osiecki Marcin , Wiernicka Anna , Lebensztejn Dariusz , Korczowski Bartosz , Kierkus Jaroslaw
Published: July 2021

Background: Infusion reactions (IRs) are the most common adverse events (AEs) of infliximab (IFX) treatment in patients with inflammatory bowel disease (IBD). Prophylactic premedication (PM) with corticosteroids or antihistamines prior to IFX infusions has been used in clinical practice, but its efficacy is not known. The aim of this study was to assess the influence of steroid PM on IR incidence in pediatric patients with IBD receiving IFX. Methods: We performed a case–control study that included pediatric patients with IBD receiving IFX. Patients were divided into four subgroups according to the agent and PM they received: Remicade (original drug) + PM, and two biosimilars—Reshma +/− PM, and Flixabi—PM. At our site, until 2018, PM with steroids was used as a part of standard IFX infusion (PM+); however, since then, this method has no longer been administered (PM−). IRs were divided into mild/severe reactions. Differences between subgroups were assessed with the appropriate chi-square test. Multivariate logistic regression was used to assess associations between PM and IR incidence, correcting for co-medication usage. Results: There were 105 children (55 PM+, 44 male, mean age 15 years) included in the study who received 1276 infusions. There was no difference between the PM+ and PM− subgroups, either in incidence of IR (18.2% vs. 16.0% of patients, p > 0.05) or in percentage of infusions followed by IR (2.02% vs. 1.02% of infusions, p > 0.5). The OR of developing IR when using PM was 0.34, and the difference in IRs ratio in PM+ and PM− patients was not statistically significant (95% CI, 0.034–1.9). There were 11/18 (61.1%) severe IRs (anaphylactic shock) reported in all patients (both PM+ and PM−). Conclusion: At our site, the incidence of IR was low, and PM did not decrease the incidence of IR in pediatric patients with IBD receiving IFX. These results indicate that PM with steroids should not be a standard part of IFX infusion to prevent IR.
Antiphospholipid Antibodies and Heart Failure with Preserved Ejection Fraction. The Multicenter ATHERO-APS Study
Authors: Pastori Daniele , Ames Paul , Triggiani Massimo , Ciampa Antonio , Cammisotto Vittoria , Carnevale Roberto , Pignatelli Pasquale , Bucci Tommaso ,   on behalf of the ATHERO-APS Study Group
Published: July 2021

Background. The prevalence of heart failure with preserved ejection fraction (HFpEF) in patients with antiphospholipid syndrome (APS) is unknown. Methods. A prospective multicenter cohort study including 125 patients was conducted: 91 primary APS (PAPS), 18 APS-SLE, and 16 carriers. HFpEF was diagnosed according to the 2019 European Society of Cardiology criteria: patients with ≥5 points among major and minor functional and morphological criteria including NT-ProBNP > 220 pg/mL, left atrial (LA) enlargement, increased left ventricular filling pressure. Results. Overall, 18 (14.4%) patients were diagnosed with HFpEF; this prevalence increased from 6.3% in carriers to 13.2% in PAPS and 27.8% in APS-SLE. Patients with HFpEF were older and with a higher prevalence of hypertension and previous arterial events. At logistic regression analysis, age, arterial hypertension, anticardiolipin antibodies IgG > 40 GPL (odds ratio (OR) 3.43, 95% confidence interval (CI) 1.09–10.77, p = 0.035), anti β-2-glycoprotein-I IgG > 40 GPL (OR 5.28, 1.53–18.27, p = 0.009), lupus anticoagulants DRVVT > 1.25 (OR 5.20, 95% CI 1.10–24.68, p = 0.038), and triple positivity (OR 3.56, 95% CI 1.11–11.47, p = 0.033) were associated with HFpEF after adjustment for age and sex. By multivariate analysis, hypertension (OR 19.49, 95% CI 2.21–171.94, p = 0.008), age (OR 1.07, 95% CI 1.00–1.14, p = 0.044), and aβ2GPI IgG > 40 GPL (OR 8.62, 95% CI 1.23–60.44, p = 0.030) were associated with HFpEF. Conclusion. HFpEF is detectable in a relevant proportion of APS patients. The role of aPL in the pathogenesis and prognosis of HFpEF needs further investigation.
Effect of Twist Drill Geometry and Drilling Parameters on Hole Quality in Single-Shot Drilling of CFRP/Al7075-T6 Composite Stack
Authors: Hassan Muhammad Hafiz , Abdullah Jamaluddin , Franz Gérald , Shen Chim Yi , Mahmoodian Reza
Published: July 2021

Drilling two different materials in a layer, or stack-up, is being practiced widely in the aerospace industry to minimize critical dimension mismatch and error in the subsequent assembly process, but the compatibility of the drill to compensate the widely differing properties of composite is still a major challenge to the industry. In this paper, the effect of customized twist drill geometry and drilling parameters are being investigated based on the thrust force signature generated during the drilling of CFRP/Al7075-T6. Based on ANOVA, it is found that the maximum thrust force for both CFRP and Al7075-T6 are highly dependent on the feed rate. Through the analysis of maximum thrust force, supported by hole diameter error, hole surface roughness, and chip formation, it is found that the optimum tool parameters selection includes a helix angle of 30°, primary clearance angle of 6°, point angle of 130°, chisel edge angle of 30°, speed of 2600 rev/min and feed rate of 0.05 mm/rev. The optimum parameters obtained in this study are benchmarked against existing industry practice of the capability to produce higher hole quality and efficiency, which is set at 2600 rev/min for speed and 0.1 mm/rev for feed rate.
Enhanced Tensile Strength of Monolithic Epoxy with Highly Dispersed TiO2-Graphene Nanocomposites
Authors: Wang Yanshuai , Guo Siyao , Dong Biqin , Xing Feng
Published: July 2021

The functionalization of graphene has been reported widely, showing special physical and chemical properties. However, due to the lack of surface functional groups, the poor dispersibility of graphene in solvents strongly limits its engineering applications. This paper develops a novel green “in-situ titania intercalation” method to prepare a highly dispersed graphene, which is enabled by the generation of the titania precursor between the layer of graphene at room temperature to yield titania-graphene nanocomposites (TiO2-RGO). The precursor of titania will produce amounts of nano titania between the graphene interlayers, which can effectively resist the interfacial van der Waals force of the interlamination in graphene for improved dispersion state. Such highly dispersed TiO2-RGO nanocomposites were used to modify epoxy resin. Surprisingly, significant enhancement of the mechanical performance of epoxy resin was observed when incorporating the titania-graphene nanocomposites, especially the improvements in tensile strength and elongation at break, with 75.54% and 176.61% increases at optimal usage compared to the pure epoxy, respectively. The approach presented herein is easy and economical for industry production, which can be potentially applied to the research of high mechanical property graphene/epoxy composite system.
The Effects of High-Intensity Interval Exercise on Skeletal Muscle and Cerebral Oxygenation during Cycling and Isokinetic Concentric and Eccentric Exercise
Authors: Perentis Panagiotis A. , Cherouveim Evgenia D. , Malliou Vassiliki J. , Margaritelis Nikos V. , Chatzinikolaou Panagiotis N. , Koulouvaris Panayiotis , Tsolakis Charilaos , Nikolaidis Michalis G. , Geladas Nickos D. , Paschalis Vassilis
Published: July 2021

The aim of the present study was to study the effects of cycling and pure concentric and pure eccentric high-intensity interval exercise (HIIE) on skeletal muscle (i.e., vastus lateralis) and cerebral oxygenation. Twelve healthy males (n = 12, age 26 ± 1 yr, body mass 78 ± 2 kg, height 176 ± 2 cm, body fat 17 ± 1% of body mass) performed, in a random order, cycling exercise and isokinetic concentric and eccentric exercise. The isokinetic exercises were performed on each randomly selected leg. The muscle and the cerebral oxygenation were assessed by measuring oxyhemoglobin, deoxyhemoglobin, total hemoglobin, and tissue saturation index. During the cycling exercise, participants performed seven sets of seven seconds maximal intensity using a load equal to 7.5% of their body mass while, during isokinetic concentric and eccentric exercise, they were performed seven sets of five maximal muscle contractions. In all conditions, a 15 s rest was adopted between sets. The cycling HIIE caused greater fatigue (i.e., greater decline in fatigue index) compared to pure concentric and pure eccentric isokinetic exercise. Muscle oxygenation was significantly reduced during HIIE in the three exercise modes, with no difference between them. Cerebral oxygenation was affected only marginally during cycling exercise, while no difference was observed between conditions. It is concluded that a greater volume of either concentric or eccentric isokinetic maximal intensity exercise is needed to cause exhaustion which, in turn, may cause greater alterations in skeletal muscle and cerebral oxygenation.
Forgery Detection in Digital Images by Multi-Scale Noise Estimation
Authors: Gardella Marina , Musé Pablo , Morel Jean-Michel , Colom Miguel
Published: July 2021

A complex processing chain is applied from the moment a raw image is acquired until the final image is obtained. This process transforms the originally Poisson-distributed noise into a complex noise model. Noise inconsistency analysis is a rich source for forgery detection, as forged regions have likely undergone a different processing pipeline or out-camera processing. We propose a multi-scale approach, which is shown to be suitable for analyzing the highly correlated noise present in JPEG-compressed images. We estimate a noise curve for each image block, in each color channel and at each scale. We then compare each noise curve to its corresponding noise curve obtained from the whole image by counting the percentage of bins of the local noise curve that are below the global one. This procedure yields crucial detection cues since many forgeries create a local noise deficit. Our method is shown to be competitive with the state of the art. It outperforms all other methods when evaluated using the MCC score, or on forged regions large enough and for colorization attacks, regardless of the evaluation metric.
Liquid Biopsy Analysis in Clinical Practice: Focus on Lung Cancer
Authors: Pisapia Pasquale , Pepe Francesco , Iaccarino Antonino , Sgariglia Roberta , Nacchio Mariantonia , Russo Gianluca , Gragnano Gianluca , Mosaieby Elalah , Troncone Giancarlo , Malapelle Umberto
Published: July 2021

Lung cancer is the leading cause of cancer death worldwide. Despite the emergence of highly effective targeted therapies, up to 30% of advanced stage non-small cell lung cancer (NSCLC) patients do not undergo tissue molecular testing because of scarce tissue availability. Liquid biopsy, on the other hand, offers these patients a valuable opportunity to receive the best treatment options in a timely manner. Indeed, besides being much faster and less invasive than conventional tissue-based analysis, it can also yield specific information about the genetic make-up and evolution of patients’ tumors. However, several issues, including lack of standardized protocols for sample collection, processing, and interpretation, still need to be addressed before liquid biopsy can be fully incorporated into routine oncology practice. Here, we reviewed the most important challenges hindering the implementation of liquid biopsy in oncology practice, as well as the great advantages of this approach for the treatment of NSCLC patients.
Formation Control of Unmanned Vessels with Saturation Constraint and Extended State Observation
Authors: Fu Huixuan , Wang Shichuan , Ji Yan , Wang Yuchao
Published: July 2021

This paper addressed the formation control problem of surface unmanned vessels with model uncertainty, parameter perturbation, and unknown environmental disturbances. A formation control method based on the control force saturation constraint and the extended state observer (ESO) was proposed. Compared with the control methods which only consider the disturbances from external environment, the method proposed in this paper took model uncertainties, parameter perturbation, and external environment disturbances as the compound disturbances, and the ESO was used to estimate and compensate for the disturbances, which improved the anti-disturbance performance of the controller. The formation controller was designed with the virtual leader strategy, and backstepping technique was designed with saturation constraint (SC) function to avoid the lack of force of the actuator. The stability of the closed-loop system was analyzed with the Lyapunov method, and it was proved that the whole system is uniformly and ultimately bounded. The tracking error can converge to arbitrarily small by choosing reasonable controller parameters. The comparison and analysis of simulation experiments showed that the controller designed in this paper had strong anti-disturbance and anti-saturation performance to the compound disturbances of vessels and can effectively complete the formation control.
Application of Large Eddy Simulation to Predict Underwater Noise of Marine Propulsors. Part 2: Noise Generation
Authors: Kimmerl Julian , Mertes Paul , Abdel-Maksoud Moustafa
Published: July 2021

Methods to predict underwater acoustics are gaining increased significance, as the propulsion industry is required to confirm noise spectrum limits, for instance in compliance with classification society rules. Propeller–ship interaction is a main contributing factor to the underwater noise emissions by a vessel, demanding improved methods for both hydrodynamic and high-quality noise prediction. Implicit large eddy simulation applying volume-of-fluid phase modeling with the Schnerr-Sauer cavitation model is confirmed to be a capable tool for propeller cavitation simulation in part 1. In this part, the near field sound pressure of the hydrodynamic solution of the finite volume method is examined. The sound level spectra for free-running propeller test cases and pressure pulses on the hull for propellers under behind ship conditions are compared with the experimental measurements. For a propeller-free running case with priory mesh refinement in regions of high vorticity to improve the tip vortex cavity representation, good agreement is reached with respect to the spectral signature. For behind ship cases without additional refinements, partial agreement was achieved for the incompressible hull pressure fluctuations. Thus, meshing strategies require improvements for this approach to be widely applicable in an industrial environment, especially for non-uniform propeller inflow.
Time and Frequency Domain Dynamic Analysis of Offshore Mooring
Authors: He Shi , Wang Aijun
Published: July 2021

The numerical procedures for dynamic analysis of mooring lines in the time domain and frequency domain were developed in this work. The lumped mass method was used to model the mooring lines. In the time domain dynamic analysis, the modified Euler method was used to solve the motion equation of mooring lines. The dynamic analyses of mooring lines under horizontal, vertical, and combined harmonic excitations were carried out. The cases of single-component and multicomponent mooring lines under these excitations were studied, respectively. The case considering the seabed contact was also included. The program was validated by comparing with the results from commercial software, Orcaflex. For the frequency domain dynamic analysis, an improved frame invariant stochastic linearization method was applied to the nonlinear hydrodynamic drag term. The cases of single-component and multicomponent mooring lines were studied. The comparison of results shows that frequency domain results agree well with nonlinear time domain results.
Structurally Uncommon Secondary Metabolites Derived from Endophytic Fungi
Authors: Ortega Humberto , Torres-Mendoza Daniel , Caballero E. Zuleima , Cubilla-Rios Luis
Published: July 2021

Among microorganisms, endophytic fungi are the least studied, but they have attracted attention due to their high biological diversity and ability to produce novel and bioactive secondary metabolites to protect their host plant against biotic and abiotic stress. These compounds belong to different structural classes, such as alkaloids, peptides, terpenoids, polyketides, and steroids, which could present significant biological activities that are useful for pharmacological or medical applications. Recent reviews on endophytic fungi have mainly focused on the production of novel bioactive compounds. Here, we focus on compounds produced by endophytic fungi, reported with uncommon bioactive structures, establishing the neighbor net and diversity of endophytic fungi. The review includes compounds published from January 2015 to December 2020 that were catalogued as unprecedented, rare, uncommon, or possessing novel structural skeletons from more than 39 different genera, with Aspergillus and Penicillium being the most mentioned. They were reported as displaying cytotoxic, antitumor, antimicrobial, antiviral, or anti-inflammatory activity. The solid culture, using rice as a carbon source, was the most common medium utilized in the fermentation process when this type of compound was isolated.