bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of phytochemicals in sepsis: A mechanistic and therapeutic perspective
Authors: Alikiaii Babak , Bagherniya Mohammad , Askari Gholamreza , Johnston Thomas P. , Sahebkar Amirhossein
Published: November 2020

Sepsis and septic shock are still a leading cause of mortality and morbidity in intensive care units worldwide. Sepsis is an uncontrolled and excessive response of the innate immune system toward the invading infectious microbes, characterized by the hyper‐production of pro‐inflammatory mediators such as interleukin (IL)‐1β, IL‐6, tumor‐necrosis factor (TNF)‐α, and high‐mobility group box 1 (HMGB1). In severe sepsis, the overwhelming production of pro‐inflammatory cytokines and reactive oxygen species may compromise organ function and lead to the induction of abnormal apoptosis in different organs, resulting in multiple organ dysfunction syndrome and death. Hence, compounds that are able to attenuate inflammatory responses may have therapeutic potential for sepsis treatment. Understanding the pathophysiology and underlying molecular mechanisms of sepsis may provide useful insights in the discovery and development of new effective therapeutics. Therefore, numerous studies have invested much effort into elucidating the mechanisms involved with the onset and development of sepsis. The present review mainly focuses on the molecules and signaling pathways involved in the pathogenicity of sepsis. Additionally, several well‐known natural bioactive herbal compounds and phytochemicals, which have shown protective and therapeutic effects with regard to sepsis, as well as their mechanisms of action, are presented. This review suggests that these phytochemicals are able to attenuate the overwhelming inflammatory responses developed during sepsis by modulating different signaling pathways. Moreover, the anti‐inflammatory and cytoprotective activities of phytochemicals make them potent compounds to be included as complementary therapeutic agents in the diets of patients suffering from sepsis in an effort to alleviate sepsis and its life‐threatening complications, such as multi‐organ failure.
Experimental and theoretical rationalization for the base pairing abilities of inosine, guanosine, adenosine, and their corresponding 8‐oxo‐7,8‐dihydropurine, and 8‐bromopurine analogues within A‐form duplexes of RNA
Authors: Skinner Austin , Yang Chou‐Hsun , Hincks Kazuki , Wang Haobin , Resendiz Marino J. E.
Published: November 2020

Inosine is an important RNA modification, furthermore RNA oxidation has gained interest due, in part, to its potential role in the development/progression of disease as well as on its impact on RNA structure and function. In this report we established the base pairing abilities of purine nucleobases G, I, A, as well as their corresponding, 8‐oxo‐7,8‐dihydropurine (common products of oxidation at the C8‐position of purines), and 8‐bromopurine (as probes to explore conformational changes), derivatives, namely 8‐oxoG, 8‐oxoI, 8‐oxoA, 8‐BrG, and 8‐BrI. Dodecamers of RNA were obtained using standard phosphoramidite chemistry via solid‐phase synthesis, and used as models to establish the impact that each of these nucleobases have on the thermal stability of duplexes, when base pairing to canonical and noncanonical nucleobases. Thermal stabilities were obtained from thermal denaturation transition (Tm) measurements, via circular dichroism (CD). The results were then rationalized using models of base pairs between two monomers, via density functional theory (DFT), that allowed us to better understand potential contributions from H‐bonding patterns arising from distinct conformations. Overall, some of the important results indicate that: (a) an anti‐I:syn‐A base pair provides thermal stability, due to the absence of the exocyclic amine; (b) 8‐oxoG base pairs like U, and does not induce destabilization within the duplex when compared to the pyrimidine ring; (c) a U:G wobble‐pair is only stabilized by G; and (d) 8‐oxoA displays an inherited base pairing promiscuity in this sequence context. Gaining a better understanding of how this oxidatively generated lesions potentially base pair with other nucleobases will be useful to predict various biological outcomes, as well as in the design of biomaterials and/or nucleotide derivatives with biological potential.
Selective and reliable determination of obacunone in rat plasma using solid‐phase extraction by liquid chromatography tandem mass spectrometry: Application to a pharmacokinetic study
Authors: Li Qian , Gao Yong , Wang Maoyu
Published: November 2020

This study aimed to develop a highly selective, sensitive and fast liquid chromatography tandem mass spectrometric (LC–MS/MS) method for the determination of obacunone in rat plasma. Sample preparation was accomplished by a simple solid‐phase extraction procedure. Chromatographic separation was carried out on an ACQUITY BEH C18 column using acetonitrile/methanol (1:1, v/v) and 0.1% formic acid in water as mobile phase at a flow rate of 0.4 mL/min. Quantification was performed with multiple reactions monitoring in positive ion mode with the precursor‐to‐product ion transitions at m/z 455.2 > 161.1 for obacunone and m/z 515.2 > 161.1 for nomilin (internal standard). The assay was demonstrated to be linear over the concentration range of 0.1–1,000 ng/mL with correlation coefficient >0.999 (r > 0.999). The intra‐ and inter‐day accuracy ranged from −8.33 to 10.40%, while the precision was <10.41%. The mean extraction recovery was >75.32%, and the assay was free of matrix effect. The validated LC–MS/MS method was successfully applied to the pharmacokinetic study of obacunone in rats after oral and intravenous administrations. The oral bioavailability of obacunone was 13.59%.
Fatherhood status in relation to prostate cancer risks in two large U.S.‐based prospective cohort studies
Authors: Geczik Ashley M. , Kelly Scott P. , Pfeiffer Ruth M. , Huang Wen‐Yi , Liao Linda M. , Zhou Cindy K. , Brinton Louise A. , Cook Michael B.
Published: November 2020

Background

Despite the high incidence and mortality of prostate cancer (PCa) in the Unites States, few risk factors have been consistently linked with these PCa outcomes. Assessing proxies of reproductive factors may offer insights into PCa pathogenesis. In this study, we examined fatherhood status as a proxy of fertility in relation to total, nonaggressive, aggressive, and fatal PCa.

Methods

We examined participants of two cohorts, the NIH‐AARP Diet and Health (NIH‐AARP) Study and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals of associations between fatherhood status and number of children sired in relation to PCa incidence.

Results

Fatherhood status (one or more children vs. childless) was positively associated with total PCa risk in NIH‐AARP or PLCO, but was not statistically significant (p = 0.06 and 0.55, respectively). Number of children sired indicated a slightly elevated risk of total PCa, but HRs were rarely significant and were of a fairly constant magnitude with no discernable trend relative to the childless referent group. Associations were similar for nonaggressive and aggressive PCa. The trend test for fatal PCa was statistically significant in NIH‐AARP (ptrend < 0.01), despite none of the individual categorical point estimates reaching this threshold.

Conclusion

This study provides tentative evidence that fathering children is associated with a slightly increased PCa risk. Future research should strive to assess better proxies of reproductive function in relation to aggressive and fatal PCa to provide more specific evidence for this putative relationship.
Q‐sort methodology: Bridging the divide between qualitative and quantitative. An introduction to an innovative method for psychotherapy research
Authors: Rost Felicitas
Published: November 2020

Q‐methodology offers unique opportunities for counselling and psychotherapy researchers and clinicians. It is an innovative technique capable of bridging the divide between clinical knowledge and the quantitative systematisation of it. It was initially developed by Stephenson as a data collection and data analytic method to empirically study human subjectivity. It was then extended by the British School to study shared viewpoints, thereby adopting a multi‐participant design and a highly unusual form of qualitative analysis. Finally, it was adapted by the Californian School for use as a standardised observer‐rated assessment tool. Its attractiveness stems from its aptitude to produce holistic data as it collects both quantitative and narrative data. This paper will provide an introduction to Q‐statistics and Q‐methodology (person‐centred) by contrasting it to R‐statistics and R‐methodology (variable‐centred). It will then provide an overview of the three schools of Q‐methodology and their various merits demonstrated with an example.
Quadruplex‐Templated and Catalyzed Ligation of Nucleic Acids
Authors: Kankia Besik
Published: November 2020

Template‐guided chemical reactions between nucleic acid strands are an important process in biomedical research. However, almost all of these reactions employ an oligonucleotide‐templated approach that is based on the double‐helix alignment. The moderate stability of the double helix makes this approach unsuitable for many chemical reactions, so alternative nucleic acid alignment mechanisms, demonstrating higher thermal and chemical stability, are desirable. Earlier, we described a noncovalent coupling mechanism between DNA strands through a quadruplex‐and‐Mg2+ connection (QMC). QMC is based on G‐quadruplexes and allows unusually stable and specific interactions. Herein, a novel catalytic nucleic acid reaction, based on QMC, is described. This approach uses G‐tetrads as a structural and recognition element without employing Watson‐Crick complementarity rules at any stage of substrate/catalyst formation or interaction between them. Quadruplex‐templated ligation can be achieved through the self‐ligation of two nucleic acid strands, or through a quadruplex catalyst, which forms a G‐triplex and specifically connects the strands. The process is extraordinarily robust and efficient. For instance, the ligation of carbodiimide‐activated substrates can proceed in boiling solutions, and complete ligation is demonstrated within a minute. The quadruplex‐templated and catalyzed reactions will create new opportunities for chemical reactions requiring harsh experimental conditions.
The multifaceted roles of nucleophagy in cancer development and therapy
Authors: Zhao Lili , Li Wenxi , Luo Xu , Sheng Surui
Published: November 2020

Autophagy is an evolutionarily conserved process in which the cell degrades its own components and recycles the biomolecules for survival and homeostasis. It is an important cellular process to eliminate pathogens or damaged organelles. Nucleophagy, also termed as nuclear autophagy, is a more recently described subtype of autophagy, in which nuclear components, such as nuclear lamina and DNA, are to be degraded. Nucleophagy plays a double‐facet role in the development of cancer. On one hand, the clearance of damaged DNA or nuclear structures via autophagic pathway is crucial to maintain nuclear integrity and prevent tumorigenesis. On the other hand, in later stages of tumor growth, nucleophagy may facilitate cancer cell survival and metastasis in the nutrient‐depleted microenvironment. In this review, we discuss the relationship between nucleophagy and cancer along with potential intervention methods to target cancer through manipulating nucleophagy. Given the known observations about nucleophagy, it could be promising to target different nuclear components during the processes of nucleophagy, especially nuclear lamina. Further research on investigating the role of nucleophagy in oncological context could focus on dissecting its remaining molecular pathways and their connection to known tumor suppressors.
A novel strategy to prevent contrast nephropathy: “Continuous hemodiafiltration”
Authors: McCullough Peter A. , Goldstein James A.
Published: November 2020

Key Points

Pre‐procedural “at risk” assessment for Contrast Induced Acute Kidney Injury (CI‐AKI).

Peri‐procedural volume expansion is essential.

Contrast Minimus: Practice “As Low as Reasonably Allowable”.

Fewer views, minimal contrast per‐injection and utilization of adjunctive direct coronary imaging.

No left ventriculography or aortography.

Optimize Renal Hemodynamics:

Pre‐procedural treatment of systemic venous‐renal congestion.

Avoidance of intra‐procedural hypotension.
Radial access and risk guided use of bivalirudin?
Authors: Ashley Kellan E. , Hillegass William B.
Published: November 2020

Key Points

In radial access percutaneous coronary intervention (PCI) for acute coronary syndromes, study‐level meta‐analysis suggests no long‐term benefit of bivalirudin over heparin.

Individual patient data meta‐analysis, however, suggests 28% lower cardiac mortality, 43% fewer serious bleeds, and 39% less non‐access site serious bleeds in ST‐elevation myocardial infarction (STEMI) patients with bivalirudin versus heparin adjusting for access site. Higher stent thrombosis risk with bivalirudin appears neutralized with post‐procedural infusion.

Risk‐guided bivalirudin use with radial access in high‐risk PCI patients with STEMI, increased bleeding risk (>2%), and/or clinical heart failure/left ventricular ejection fraction (LVEF) <35% might improve outcomes and cost, warranting further study.
Predicting post stent fractional flow reserve virtually from quantitative flow ratio – Can we really get there from here?
Authors: Kern Morton J. , Seto Arnold H.
Published: November 2020

Key Points

This study compared virtual (residual) post‐PCI QFR and actual post‐PCI QFR from pre‐ and post‐stent angiograms in predicting post‐PCI FFR.

While there was no difference in mean values, compared with post‐PCI FFR, the post‐PCI QFR correlated better than residual QFR.

As the CFD algorithms improve, post‐PCI QFR can potentially serve as a quality control after PCI to reduce post‐PCI angina and adverse outcomes.
It's not shocking that the SCAI shock classification works
Authors: Grines Cindy L. , Marshall J Jeffrey
Published: November 2020

Key Points

Cardiogenic shock mortality is extremely variable and likely is related to the heterogeneous population and hemodynamic differences in patients.

The National Cardiogenic Shock Initiative (NCSI) demonstrated that patients in SCAI shock class E had the worst prognosis, but mortality in all classes was better than expected, perhaps due to applying a vigorous treatment protocol.

Society for Cardiovascular Angiography and Interventions (SCAI) shock classification has now been validated in many studies and allows both clinicians and researchers to rapidly determine risk of mortality.
Percutaneous deep vein arterialization: An emerging technique for no‐option chronic limb‐threatening ischemia patients
Authors: N'Dandu Zola , Bonilla Jonathan , Yousef George M. , White Christopher J.
Published: November 2020

Chronic limb‐threatening ischemia (CLTI), with characteristic ischemic rest pain, non‐healing ulcers, or gangrene attributable to arterial occlusive disease, requires successful revascularization to minimize tissue loss. End‐stage CLTI in particular, with occlusion of the pedal arteries, results in a lack of suitable targets for bypass and can result in failure of endovascular revascularization procedures, leaving no option for treatment other than amputation. With limb salvage as the primary goal, nontraditional revascularization techniques such as percutaneous deep vein arterialization (pDVA) may help minimize incidence of amputation. We present a case of a patient with no‐option CLTI, at high risk of amputation who failed conventional endovascular revascularization attempts facing imminent major amputation. The limb was salvaged with a successful pDVA procedure.
Linac‐based STereotactic Arrhythmia Radioablation (STAR) of ventricular tachycardia: Case report and literature review
Authors: Fiorentino Alba , Di Monaco Antonio , Surgo Alessia , Vitulano Nicola , Gregucci Fabiana , Ludovico Elena , Carbonara Roberta , Quadrini Federico , Rubini Giuseppe , Bonaparte Ilaria , Grimaldi Massimo
Published: November 2020

Linac‐based STereotactic Arrhythmia Radioablation (STAR) is a safety and effective approach for selected patients with ventricular arrhythmias.
A tricky case of cardiogenic shock: Diagnostic challenges in the COVID‐19 era
Authors: Sachpekidis Vasileios , Adamopoulos Chris , Datsios Antonios , Mosialos Lampros , Stamatiadis Nikolaos , Gogos Christos , Poulianitis Vasileios , Galanos Othonas , Stratilati Sofia , Styliadis Ioannis , Nihoyannopoulos Petros
Published: November 2020

Myocardial wall rupture should be considered in patients presenting with hypotension and STEMI especially of delayed onset. Diagnosing this entity in the COVID‐19 era can be challenging—handheld echocardiography may aid toward this end.
A case of retropharyngeal emphysema as a complication of pneumothorax
Authors: Suda Tsuyoshi , Yoneda Tomoaki , Ichikawa Yukari
Published: November 2020

Retropharyngeal emphysema is a rare condition, and it is important to determine whether the patient presents with complications including pneumomediastinum or other severe clinical presentations such as an upper airway obstruction. In such cases, patients should undergo urgent tracheostomy and surgical neck drainage with concurrent administration of broad‐spectrum antibiotics.
Influence and Electrochemical Stability of Oxygen Groups and Edge Sites in Vanadium Redox Reactions
Authors: Radinger Hannes , Pfisterer Jessica , Scheiba Frieder , Ehrenberg Helmut
Published: November 2020

It is widely accepted that surface‐active oxygen functional groups (OFGs) effectively catalyze the vanadium redox reactions. Initial graphitic edge sites, OFGs and their electrochemical stability were examined using graphite felts, which were modified with multi‐walled carbon nanotubes and activated with KOH. It is demonstrated that OFGs cannot exclusively be responsible for the electrocatalysis since they did not correlate to the electrochemical activity. The surface composition after electrochemical cycling in the positive half‐cell was still different for all samples but did not reflect the performance either. However, a correlation was found between the activity and stable edge site defects. There was neither a correlation between the electrocatalytic activity and the amount of oxygen, nor for the kind of OFG in the negative half‐cell. The oxygen concentration after electrochemistry was very similar, even more highlighting the importance of edge sites in the VIII/VII redox reaction. The results of this work indicate that the major electrocatalytic effect for both half‐cell redox reactions is related to stable graphitic edge sites in sufficient quantity.
Experimental analysis of the mechanical properties of concrete using alternative binding agents
Authors: Quadflieg Till , Morozov Nikita , Karimova Albina , Gries Thomas , Stolyarov Oleg
Published: November 2020

Concrete is a building material that is widely used worldwide. The main ingredient in concrete is cement, which causes high CO2 emissions into the atmosphere. An alternative to conventional cement‐based concrete is geopolymer concrete. This material is inadequately researched to be used as a building material. In this work, mechanical properties of geopolymer‐based concrete are investigated to estimate its potential in construction industry.
Light‐Triggered Nitric Oxide Release by a Photosensitizer to Combat Bacterial Biofilm Infections
Authors: Zhao Zhennan , Li Huinan , Tao Xuan , Xie Yanxuan , Yang Liang , Mao Zong‐Wan , Xia Wei
Published: November 2020

Bacterial biofilms are a serious global health concern, often responsible for persistent infections. New strategies to prevent and treat bacterial infections by eradication of the biofilms are urgently needed. A novel ruthenium‐based compound is reported in this study that functions as both a boronic acid‐decorated photosensitizer (PS) and a light‐triggered nitric oxide (NO) releasing agent. The compound can selectively attach to the bacterial membrane and biofilms and it is highly potent at eradicatingPseudomonas aeruginosabiofilms through the simultaneous release of NO and reactive oxygen species (ROS). The compound, which is more effective than clinical antibiotic tobramycin, also has excellent bacterial specificity and shows no significant cytotoxicity to human cells. The results reveal potential applications of this innovative dual‐functional photoactivated ruthenium compound to combat bacterial biofilm infections.
Liquid Phase CO2‐Analytics for Standardized Mass Transfer Characterization in Packed Columns
Authors: Brinkmann Jost H. , Plate Dominik , Grünewald Marcus , Schultes Michael
Published: November 2020

Mass transfer parameters are necessary for the design of absorption and desorption processes in packed columns. To determine the effective interfacial area and liquid side mass transfer parameters, CO2 absorption and desorption are frequently used. Reliable analytics for concentration determination are essential to obtain correct results. In this work two methods of CO2 liquid phase analysis are compared: first, the back titration of unreacted NaOH after prior precipitation of the bound CO2; secondly, the inorganic carbon analysis with a commercial inorganic carbon analyzer.
Nachweismethoden von SARS‐CoV‐2
Authors: Witt Martin , Heuer Christopher , Miethke Lina , Preuß John‐Alexander , Rehfeld Johanna Sophie , Schüling Torsten , Blume Cornelia , Thoms Stefanie , Stahl Frank
Published: November 2020

Die COVID‐19‐Pandemie hält seit Anfang 2020 die Welt in Atem. Um die Ausbreitung von SARS‐CoV‐2 einzudämmen, haben die meisten Regierungen mit strengen Maßnahmen reagiert. Dazu gehören Grenzschließungen, Kontaktbeschränkungen und das Schließen von Schulen und Kitas. Des Weiteren wurden wie etwa in Deutschland die Krankenhaus‐ und Testkapazitäten ausgebaut. Der Ausdruck „Corona‐Krise“ verdeutlicht neben den gesundheitlich/medizinischen Aspekten auch die beispiellosen gesellschaftlichen und wirtschaftlichen Auswirkungen der COVID‐19‐Pandemie. Um die Eindämmung dieser Pandemie zu erreichen und die Rückkehr zu einem vergleichsweise normalen Alltagsleben zu ermöglichen, müssen unter anderem die Testkapazitäten weiter erhöht werden. Durch vorsorgliches und regelmäßiges Testen kann das Infektionsgeschehen früh erkannt und die Entstehung von „Corona‐Hotspots“ verhindert werden. Der Virusnachweis in einem Patienten erfolgt mittels Vervielfältigung der viralen Erbinformation durch PCR; mit dem Nachweis von Antikörpern lässt sich hingegen schlussfolgern, ob ein Patient bereits mit SARS‐CoV‐2 infiziert war. Ob die gebildeten Antikörper jedoch eine längerfristige Immunität bewirken, muss aufgrund der kurzen Zeit seit Auftreten von SARS‐CoV‐2 stetig geprüft werden und ist Gegenstand aktueller Forschung.
Effects of high oil viscosity on oil‐gas downward flow in deviated pipes. Part 2: Holdup and pressure gradient
Authors: Soto‐Cortes Gabriel , Pereyra Eduardo , Sarica Cem , Rivera‐Trejo Fabian , Torres Carlos
Published: November 2020

In Part 1 of this work, new experimental data on high viscosity oil‐gas flow in inclined downward flow were presented. Flow patterns transitions were identified and analyzed, and the performance of some flow pattern prediction models was validated. This study uses the same experimental data set generated for a mixture of air‐oil (with a viscosity of 213 mPa · s) flowing in a 50.8 mm internal diameter pipe with inclination angles of −45°, −60°, −70°, −80°, −85° for a ranges 0.05 m/s‐0.7 m/s and 0.7 m/s‐7 m/s of superficial liquid and gas velocities, respectively, to investigate holdup and pressure gradient behaviour. The holdup and pressure recovery effects are explained in terms of the predominant transport mechanism through phase slippage and the mechanical energy balance. For a constant superficial liquid velocity, the average‐liquid holdup results show a discernible behaviour dependent on the relative velocity between phases (slip velocity). Consistently, results show a switch between the gravity or shear forces transport mechanism, that coincides with the switch of a sign of the total pressure gradient (pressure recovery effect). Performance analysis of the available mechanistic models has been presented. The results are not satisfactory, which justifies the need for a detailed study of the effects of viscosity and the inclination of the pipe in liquid‐gas mixtures.
Fluoroscopy usage in contemporary interventional electrophysiology: Insights from a European registry
Authors: Kosiuk Jedrzej , Fiedler Lucas , Ernst Sabine , Duncker David , Pavlović Nikola , Guarguagli Silvia , Stegmann Clara , Miskowiec Dawid , Garcia Rodrigue , Russo Vincenzo , Yakushev Andriy , Szegedi Nándor , De Potter Tom
Published: November 2020

Background

Fluoroscopy has been an essential part of every electrophysiological procedure since its inception. However, till now no clear standards regarding acceptable x‐ray exposure nor recommendation how to achieve them have been proposed.

Hypothesis

Current norms and quality markers required for optimal clinical routine can be identified.

Methods

Centers participating in this Europe‐wide multicenter, prospective registry were requested to provide characteristics of the center, operators, technical equipment as well as procedural settings of consecutive cases.

Results

Twenty‐five centers (72% university clinics, with a mean volume of 526 ± 348 procedures yearly) from 14 European countries provided data on 1788 cases [9% diagnostic procedures (DP), 38% atrial fibrillation (AF) ablations, 44% other supraventricular (SVT) ablations, and 9% ventricular ablations (VT)] conducted by 95 operators (89% male, 41 ± 7 years old).

Mean dose area product (DAP) and time was 304 ± 608 cGy*cm2, 3.6 ± 4.8 minutes, 1937 ± 608 cGy*cm2, 15.3 ± 15.5 minutes, 805 ± 1442 cGy*cm2, 10.6 ± 10.7 minutes, and 1277 ± 1931 cGy*cm2, 10.4 ± 12.3 minutes for DP, AF, SVT, and VT ablations, respectively. Seven percent of all procedures were conducted without any use of fluoroscopy.

Procedures in the lower quartile of DAP were performed more frequently by female operators (OR 1.707, 95%CI 1.257‐2.318, P = .001), in higher‐volume center (OR 1.001 per one additional procedure, 95%CI 1.000‐1.001, P = .002), with the use of 3D‐mapping system (OR 2.622, 95%CI 2.053‐3.347, P < .001) and monoplane x‐ray system (OR 2.945, 95%CI 2.149‐4.037, P < .001).

Conclusion

Exposure to ionizing radiation varies widely in daily practice for all procedure. Significant opportunities for harmonization of exposure toward the lower range has been identified.
4,9‐Diaminoacridines and 4‐Aminoacridines as Dual‐Stage Antiplasmodial Hits
Authors: Fonte Mélanie , Tassi Natália , Fontinha Diana , Bouzón‐Arnáiz Inés , Ferraz Ricardo , Araújo Maria J. , Fernàndez‐Busquets Xavier , Prudêncio Miguel , Gomes Paula , Teixeira Cátia
Published: November 2020

Multi‐stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine‐based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine‐sensitive and ‐resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual‐stage antiplasmodial hits.
Semisynthetic Vitamin E Derivatives as Potent Antibacterial Agents against Resistant Gram‐Positive Pathogens
Authors: Viault Guillaume , Kempf Marie , Ville Alexia , Alsabil Khaled , Perrot Rodolphe , Richomme Pascal , Hélesbeux Jean‐Jacques , Séraphin Denis
Published: November 2020

New 5‐substituted vitamin E derivatives were semisynthesized, and their antibacterial activity against human Gram‐positive and Gram‐negative pathogens was evaluated. Several vitamin E analogues were active against methicillin‐resistant Staphylococcus aureus (MRSA) and/or methicillin‐resistant Staphylococcus epidermidis (MRSE); structure‐activity relationships (SARs) are discussed. As a result, it is shown that the presence of a carboxylic acid function at the C‐5 position and/or at the end of the side chain is crucial for the antibacterial activity. The bactericidal or bacteriostatic action of three compounds against MRSA and MRSE was confirmed in a time‐kill kinetics study, and the cytotoxicity on human cells was evaluated. The preliminary mechanism study by confocal microscopy indicated that those vitamin E analogues led to bacterial cell death through membrane disruption.
Novel Pyridine‐Based Hydroxamates and 2′‐Aminoanilides as Histone Deacetylase Inhibitors: Biochemical Profile and Anticancer Activity
Authors: Zwergel Clemens , Di Bello Elisabetta , Fioravanti Rossella , Conte Mariarosaria , Nebbioso Angela , Mazzone Roberta , Brosch Gerald , Mercurio Ciro , Varasi Mario , Altucci Lucia , Valente Sergio , Mai Antonello
Published: November 2020

Starting from the N‐hydroxy‐3‐(4‐(2‐phenylbutanoyl)amino)phenyl)acrylamide (5 b) previously described by us as a HDAC inhibitor, we prepared four aza‐analogues, 6–8, 9 b, as regioisomers containing the pyridine nucleus. Preliminary screening against mHDAC1 highlighted the N‐hydroxy‐5‐(2‐(2‐phenylbutanoyl)amino)pyridyl)acrylamide (9 b) as the most potent inhibitor. Thus, we further developed both pyridylacrylic‐ and nicotinic‐based hydroxamates (9 a, 9 c–f, and 11 a–f) and 2′‐aminoanilides (10 a–f and 12 a–f), related to 9 b, to be tested against HDACs. Among them, the nicotinic hydroxamate 11 d displayed sub‐nanomolar potency (IC50: 0.5 nM) and selectivity up to 34 000 times that of HDAC4 and from 100 to 1300 times that of all the other tested HDAC isoforms. The 2′‐aminoanilides were class I‐selective HDAC inhibitors, generally more potent against HDAC3, with the nicotinic anilide 12 d being the most effective (IC50HDAC3=0.113 μM). When tested in U937 leukemia cells, the hydroxamates 9 e, 11 c, and 11 d blocked over 80 % of cells in G2/M phase, whereas the anilides did not alter cell‐cycle progress. In the same cell line, the hydroxamate 11 c and the anilide 10 b induced about 30 % apoptosis, and the anilide 12 c displayed about 40 % cytodifferentiation. Finally, the most potent compounds in leukemia cells 9 b, 11 c, 10 b, 10 e, and 12 c were also tested in K562, HCT116, and A549 cancer cells, displaying antiproliferative IC50 values at single‐digit to sub‐micromolar level.
Reconstructing haemodynamics quantities of interest from Doppler ultrasound imaging
Authors: Galarce Felipe , Lombardi Damiano , Mula Olga
Published: November 2020

The present contribution deals with the estimation of haemodynamics Quantities of Interest by exploiting Ultrasound Doppler measurements. A fast method is proposed, based on the Parameterized Background Data‐Weak (PBDW) method. Several methodological contributions are described: a sub‐manifold partitioning is introduced to improve the reduced‐order approximation, two different ways to estimate the pressure drop are compared, and an error estimation is derived. A fully synthetic test‐case on a realistic common carotid geometry is presented, showing that the proposed approach is promising in view of realistic applications.
A comparative evaluation of similarity measurement algorithms within a colour palette
Authors: Ren Shuai , Chen Yun , Westland Stephen , Yu Luwen
Published: November 2020

Recently, there has been interest in the development of colour palettes from images. Colour palettes have long been used by designers to communicate colours and their relationships but increasingly palettes are being derived automatically from digital images, concepts, or from a plethora of digital design tools online. Methods to predict differences between palettes are growing in popularity. This study is concerned with the prediction of visual self‐similarity for colour palettes with large numbers of patches. A psychophysical experiment was carried out to collect the human judgments of similarity and then six different algorithms were introduced and evaluated in terms of their ability to predict the psychophysical data. Two methods to quantify the agreement between the visual data and algorithm predictions were used based on regression analysis with coefficient of determination for the goodness of fit and multidimensional scaling with loss function Kruskal's stress. Of the six algorithms, the Pearson correlation coefficient method was considered to give the best performance.
Subjective evaluation of colourized images with different colorization models
Authors: Teng Xiao , Li Zhijiang , Liu Qiang , Pointer Michael R. , Huang Zheng , Sun Hongguang
Published: November 2020

Two psychophysical experiments were conducted to evaluate the performance of grayscale image colorization models, and to verify the objective image quality metrics adopted in grayscale image colorization. Twenty representative grayscale images were colourized by four colorization models and three typical metrics, root mean square error (RMSE), peak signal‐to‐noise ratio (PSNR) and structural similarity index (SSIM), were used to characterize the objective quality of the colourized images. Forty observers were asked to evaluate those images based on their subjective preference in a pair‐comparison experiment, and to evaluate the perceived similarity between the generated and reference colour images using a seven‐point rating scale. The experimental results indicate that different colorization models and objective metrics exhibit different performance in different scenarios. Each colorization method has its own advantages and disadvantages while none of the tested models performed well for all images. For preference, the model proposed by Iizuka et al based on ImageNet performed better while for perceived similarity the models proposed by Zhang et al and Iizuka et al, also based on ImageNet, outperformed the models of Larsson et al and Iizuka et al which were based on the Places dataset. Due to the fact that many objects have instances of distinct colour, a colorization algorithm cannot correctly reconstruct ground truth image for most gray level images, although it was found that perceived similarity and preference ratings of observers were correlated. In addition, it was found that the tested objective metrics correlated poorly with the subjective judgments of the human observers and their performance varied significantly with image content. These findings demonstrate the limitations of current image colorization studies, and it is suggested that due consideration must be given to human visual perception when evaluating the performance of colorization models.
Efficient fault‐tolerant logical Hadamard gates implementation in Reed–Muller quantum codes
Authors: Quan DongXiao , Niu Li , Zhu LiLi , Pei ChangXing
Published: November 2020

We investigate the implementation of fault‐tolerant logical Hadamard gates in Reed–Muller quantum codes (RMQCs). During the realization, we consider the influences of random single‐qubit errors and some error‐detecting stabilizers are simplified by the existing syndromes. We first identify the errors and modify the gauge‐fixing syndromes, then refer to the modified syndromes to select the fix operations, and finally perform the error‐correcting and fix operations together. Furthermore, we establish a graph model for the RMQCs and exhibit a progress of finding the fix operations for the unsatisfied stabilizers. For the circuit design, we optimize the choice of gauge operators, the positions of the ancillary qubits and design a parallel circuit for implementing a fault‐tolerant logical Hadamard gate in 15‐qubit RMQC. We simulate the progress of finding corresponding fix operations for 31‐qubit and 63‐qubit RMQCs and the whole process of realizing logical Hadamard gate with random single‐qubit errors for 15‐qubit and 31‐qubit RMQCs. Results show that correct fix operations can be obtained and fault‐tolerant logical Hadamard gates can be realized as expected. The performance comparisons are also given and the results show that our method can achieve a higher success rate with a reasonable higher cost. With the implementation of the logical Hadamard gate, a universal fault‐tolerant gate set is achieved in single RMQC.
The Evidence REVEAL Study: Exploring the Use of Real‐World Evidence and Complex Clinical Trial Design by the European Pharmaceutical Industry
Authors: Varnai Peter , Davé Anoushka , Farla Kristine , Nooijen Anke , Petrosova Liana
Published: November 2020

The rapid evolution of science and technology allows innovative approaches to generate new types of evidence about the effectiveness of medical product development so as to speed up patients’ access to better diagnostics and treatment. Our study explored how two emerging approaches, the use of real‐world evidence (RWE) and complex clinical trial (CCT) design, are currently being used by the pharmaceutical industry to support premarketing authorization of medical product development and reviewed the international landscape for regulatory acceptance of such novel approaches. Combining evidence from a literature review, company survey, and interviews with international regulators and experts, we found that 80% of Europe‐based pharmaceutical companies have used RWE and 50% have used CCTs, in some capacity. Further, we present case examples of how companies are using these approaches and how international regulators are preparing for such developments. To conclude, we provide a set of recommendations for European industry and regulators to consider so that these novel approaches achieve their full potential within the EU regulatory system.
Sustainability stewardship: Does roundtable on sustainable palm oil certification create shareholder value?
Authors: Tey Yeong Sheng , Brindal Mark
Published: November 2020

The adoption of sustainability standards is often viewed as a profitability conundrum by palm oil firms and their shareholders. This study examines whether, considering the inherent risk, the Roundtable on Sustainable Palm Oil (RSPO) sustainability initiative creates shareholder value. Based on the panel information of plantation firms listed on the Indonesia and Kuala Lumpur Stock Exchanges, RSPO‐certified firms earned mixed risk‐adjusted performance results relative to non‐RSPO and total palm oil portfolios. They also demonstrated a limited probability for upside growth. Additionally, it is possible that institutionalized sustainability standards do not address all the environmental, social and governance pillars that should constitute sustainable investing. Consequently, business operators and investors seeking improved performance should focus on the fundamentals whilst incorporating sustainability standards.
OMIP 071: A 31‐Parameter Flow Cytometry Panel for In‐Depth Immunophenotyping of Human T‐Cell Subsets Using Surface Markers
Authors: Wang Song‐Rong , Zhong Na , Zhang Xin‐Mei , Zhao Zhi‐Bin , Balderas Robert , Li Liang , Lian Zhe‐Xiong
Published: November 2020

Dissecting the functional diversity of T cells is critical in elucidating mechanisms and in developing therapies for various diseases. Here, we designed a 31‐parameter (29‐color) panel to enable the characterization of T‐cell subsets and immunophenotyping of the human peripheral blood and lymph nodes using cell surface staining. In addition to adaptive T‐cell markers, TCR Vα24‐Jα18, TCR γδ, TCR Vɑ7.2, and CD161 were included to identify iNKT, γδ T, and MAIT cells, respectively, which are innate‐like T cells. C‐X‐C chemokine receptors (CXCR3, CXCR4, CXCR5, CXCR6) and C‐C motif chemokine receptors (CCR4, CCR6, CCR7) were included to enable the identification of Th cell subsets (Th1, Th2, Th17), Tfh cell subsets (Tfh1, Tfh2, Tfh17), and Th cells with specific homing capacities. Furthermore, in this panel, we also used markers for assessing cell differentiation (CD45RO, CD7), activation (CD57, CD95, HLA‐DR) and the expression of some cosignaling molecules (PD‐1, NKG2D, CD28). Particularly, CD69 and CD103 were included for the further analysis of tissue resident memory T (Trm) cells. This panel would enable the in‐depth immunophenotyping of human T‐cell subsets, and may be applied in the monitoring, prognosis, and mechanistic studies of various immune‐related diseases.
Endoscopic ultrasonography‐fine needle aspiration of solid pancreatic masses: Do we need the fourth pass? A prospective study
Authors: Teodorescu Casandra , Gheorghiu Marcel , Zaharie Teodor , Rusu Ioana , Pojoga Cristina , Bolboacă Sorana D. , Seicean Radu , Petrusel Livia , Seicean Andrada
Published: November 2020

Background

Endoscopic ultrasonography‐guided fine‐needle aspiration (EUS‐FNA) is important for the differential diagnosis of solid pancreatic lesions. Sample adequacy is related to the number of needle passes, and European guidelines recommend three to four needle passes with a standard EUS‐FNA needle.

We aimed to evaluate the optimal number of passes with standard EUS‐FNA needles in solid pancreatic lesions.

Methods

Patients with solid pancreatic masses without cystic component >20% on computed tomography scan, and without biliary metallic stents, or coagulation problems were included prospectively. Standard 22G needles were used (maximum four passes); each sample was paraffin‐embedded and analyzed separately. Final diagnosis was established by EUS‐FNA, repeat EUS‐FNA, surgery, or follow‐up.

Results

Sixty‐one of 65 patients were included. The final diagnoses were adenocarcinoma (n = 44, 72%), neuroendocrine tumor (NET) (n = 10, 16%), metastasis (n = 1, 4%) and nonmalignant lesion (n = 6, 10%). Immunohistochemical staining was possible in 17 cases. The diagnosis was established by the first pass in 62% of cases (n = 38), by the second in 15% (n = 9), by the third in 15% (n = 9), and by the fourth in 3% (n = 2). The diagnostic accuracy for all four passes compared to the first three passes was 95% vs 92% (P = .5). The contribution of the fourth pass was not different between adenocarcinoma and NET (2% vs 10%, respectively; P = .667).

Conclusion

Three passes with standard EUS‐FNA was optimal for a specific diagnosis of solid pancreatic masses, regardless of the histological type of the lesion.
A systematic review of MRI studies of language development from birth to 2 years of age
Authors: Silver Eero , Korja Riikka , Mainela‐Arnold Elina , Pulli Elmo P. , Saukko Ekaterina , Nolvi Saara , Kataja Eeva‐Leena , Karlsson Linnea , Karlsson Hasse , Tuulari Jetro J.
Published: November 2020

Neurocognitive functions supporting language development start to develop well before first words are spoken during the first years of life. This process coincides with the initial growth spurt of the brain. While the core components of the language network are well characterized in adults and children, the initial neural correlates of language skills are still relatively unknown. We reviewed 10 studies identified via a systematic search that combined magnetic resonance imaging and language‐related measures in healthy infants from birth to 2 years of age. We aimed to describe the current knowledge as well as point out viable future directions for similar studies. Expectedly, the implicated cerebral areas included many established components of the language networks, including frontal and temporal regions. A volumetric leftward asymmetry of the brain was suggested as a determinant of language skills, yet with marked interindividual variation. Overall, temporal and frontal brain volumes associated positively with language skills. Positive associations were described between the maturation of language related white matter tracts and language skills. The language networks showed adult‐like structural similarities already in neonates, with weaker asymmetry compared to adults. In summary, we found some evidence that the language circuit described in older age groups is also associated to language skills during the first 2 years of life. However, across the reviewed studies there were no systematic neural correlates of language skills, which is partly explained by a modest number of studies, scattered representation of ages in measurements and the variance in the used methods.
Spatial optimization of invasive species control informed by management practices
Authors: Nishimoto Makoto , Miyashita Tadashi , Yokomizo Hiroyuki , Matsuda Hiroyuki , Imazu Takeshi , Takahashi Hiroo , Hasegawa Masami , Fukasawa Keita
Published: November 2020

Optimization of spatial resource allocation is crucial for the successful control of invasive species under a limited budget but requires labor‐intensive surveys to estimate population parameters. In this study, we devised a novel framework for the spatially explicit optimization of capture effort allocation using state‐space population models from past capture records. We applied it to a control program for invasive snapping turtles to determine effort allocation strategies that minimize the population density over the whole area. We found that spatially heterogeneous density dependence and capture pressure limit the abundance of snapping turtles. Optimal effort allocation effectively improved the control effect, but the degree of improvement varied substantially depending on the total effort. The degree of improvement by the spatial optimization of allocation effort was only 3.21% when the total effort was maintained at the 2016 level. However, when the total effort was increased by two, four, and eight times, spatial optimization resulted in improvements of 4.65%, 8.33%, and 20.35%, respectively. To achieve the management goal for snapping turtles in our study area, increasing the current total effort by more than four times was necessary, in addition to optimizing the spatial effort. The snapping turtle population is expected to reach the target density one year after the optimal management strategy is implemented, and this rapid response can be explained by high population growth rate coupled with density‐dependent feedback regulation. Our results demonstrated that combining a state‐space model with optimization makes it possible to adaptively improve the management of invasive species and decision‐making. The method used in this study, based on removal records from an invasive management program, can be easily applied to monitoring data for wildlife and pest control management using traps in a variety of ecosystems.
Learning principles of evolution during a crisis: An exploratory analysis of student barriers one week and one month into the COVID‐19 pandemic
Authors: Driessen Emily , Beatty Abby , Stokes Alexis , Wood Sara , Ballen Cissy
Published: November 2020

The coronavirus disease (COVID‐19) outbreak forced an emergency transition to online classes across the world with little warning or instruction for faculty and students. The goal of this research was to document how this response impacted undergraduate students studying the principles of evolution in an introductory organismal biology class over time; specifically, how their study habits for exams differed (a) one week and (b) one month after a university's decision to transition to emergency remote instruction. We asked students about the extent to which COVID‐19 impacted their study habits, and we categorized students’ responses using open coding. We identified a number of consistent similarities—as well as dramatic differences—in their responses as the time away from campus increased. The report that follows is a summary of the documented barriers and recommendations based on literature concerning crises and equitable practices.