bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomical and molecular analyses of the deltoid muscle in chimpanzees (Pan troglodytes) and modern humans (Homo sapiens): Similarities and differences due to the uses of the upper extremity
Authors: Gómez Mónica , Casado Aroa , de Diego Marina , Pastor Juan Francisco , Potau Josep Maria
Published: May 2022

In the deltoid muscles of Pan troglodytes and Homo sapiens, we have analyzed the muscle architecture and the expression of the myosin heavy chain (MHC) isoforms. Our aim was to identify differences between the two species that could be related to their different uses of the upper limb. The deltoid muscle of six adult Pan troglodytes and six adult Homo sapiens were dissected. The muscle fascicle length (MFL) and the physiological cross‐sectional area (PCSA) of each muscle were calculated in absolute and normalized values. The expression pattern of the MHC‐I, MHC‐IIa and MHC‐IIx isoforms was analyzed in the same muscles by real‐time polymerase chain reaction. Only the acromial deltoid (AD) presented significant architectural differences between the two species, with higher MFL values in humans and higher PCSA values in chimpanzees. No significant differences in the expression pattern of the MHC isoforms were identified. The higher PCSA values in the AD of Pan troglodytes indicate a greater capacity of force generation in chimpanzees than in humans, which may be related to a greater use of the upper limb in locomotion, specifically in arboreal locomotion like vertical climbing. The functional differences between chimpanzees and humans in the deltoid muscle are more related to muscle architecture than to a differential expression of MHC isoforms.
Asymmetric Radical Cyclization of Alkenes by Stereospecific Homolytic Substitution of Sulfinamides
Authors: Chen Yasu , Wu Xinxin , Yang Shan , Zhu Chen
Published: May 2022

We report a novel asymmetric radical cyclization of alkenes via stereospecific homolytic substitution of sulfinamides. This reaction produces a variety of cyclic sulfinamides with excellent stereocontrol. The protocol features broad functional group tolerance, high product diversity, and easy accessibility to feedstocks, and outlines a new pathway for the synthesis of chiral cyclic sulfinamides.
Evolution of the Dearomative Functionalization of Activated Quinolines and Isoquinolines: Expansion of the Electrophile Scope
Authors: Kischkewitz Marvin , Marinic Bruno , Kratena Nicolas , Lai Yonglin , Hepburn Hamish B. , Dow Mark , Christensen Kirsten E. , Donohoe Timothy J.
Published: May 2022

Herein we disclose a mild protocol for the reductive functionalisation of quinolinium and isoquinolinium salts. The reaction proceeds under transition‐metal‐free conditions as well as under rhodium catalysis with very low catalyst loadings (0.01 mol %) and uses inexpensive formic acid as the terminal reductant. A wide range of electrophiles, including enones, imides, unsaturated esters and sulfones, β‐nitro styrenes and aldehydes are intercepted by the in situ formed enamine species forming a large variety of substituted tetrahydro(iso)quinolines. Electrophiles are incorporated at the C‐3 and C‐4 position for quinolines and isoquinolines respectively, providing access to substitution patterns which are not favoured in electrophilic or nucleophilic aromatic substitution. Finally, this reactivity was exploited to facilitate three types of annulation reactions, giving rise to complex polycyclic products of a formal [3+3] or [4+2] cycloaddition.
Herstellung von funktionalisierten Amiden mit Dicarbamoylzink‐Reagenzien
Authors: Djukanovic Dimitrije , Ganiek Maximilian A. , Nishi Kohei , Karaghiosoff Konstantin , Mashima Kazushi , Knochel Paul
Published: May 2022

Wir beschreiben eine neue Methode zur Herstellung von Dicarbamoylzink‐Reagenzien des Typs (R1R2NCO)2Zn durch Behandlung von ZnCl2 und Formamiden R1R2NCHO mit LiTMP in THF (15 °C, 15 min), oder durch die Reaktion von Formamiden R1R2NCHO mit TMP2Zn (25 °C, 16 h). Die zweite Methode toleriert sensitive Gruppen wie Ester, Ketone oder Nitrofunktionen. Reaktion dieser Dicarbamoylzink‐Reagenzien mit allylischen, benzylischen, arylischen, alkenylischen Bromiden, Säurechloriden, Aldehyden oder Enonen lieferte verschiedene polyfunktionalisierte Amide in Ausbeuten von 47–97 %. Die Charakterisierung dieser neuen Carbamoylzink‐Derivate mittels 13C NMR wird beschrieben.
Controlling the Energy‐Transfer Processes in a Nanosized Molecular Upconverter to Tap into Luminescence Thermometry Application
Authors: Gálico Diogo A. , Murugesu Muralee
Published: May 2022

Photon upconversion (UC) in molecular species remains a highly sought‐after property with vast potential applications in many fields. Until now, a few reports on molecular upconverters are limited to demonstrating upconversion. The low UC quantum yields (QY) and nuclearities hindered the application capabilities for molecular upconverters. To overcome these limitations, we report the use of a molecular cluster‐aggregate (MCA) containing 20 lanthanide ions to target YbIII‐TbIII‐based cooperative UC. Upconversion quantum yield value of 1.04×10−4 %, among the highest value observed for a molecular cooperative UC, was attained for the{Gd11Tb2Yb7}composition. Substitution of GdIIIions for EuIIIcenters opens a YbIII→TbIII→EuIIIenergy‐transfer pathway, allowing the first proof‐of‐concept of potential application for molecular UC. This report on upconversion‐based luminescence thermometry in a molecular species endorses further development of upconversion properties of nanoscale MCAs.
Directionally Aligned Crown Ethers as Superactive Organocatalysts for Transition‐metal Ion‐free Arylation of Unactivated Arenes
Authors: Li Zhaojie , Shen Jie , Jiang Qing , Shen Sheng , Zhou Jing , Zeng Huaqiang
Published: May 2022

When one‐dimensionally aligned to the same side, multiple non‐covalently associated crown ether groups could act as a whole to yield a higher catalytic activity than an individual poorly active crown ether group, delivering the lowest catalyst loading of 1–2 mol % among all hitherto known organocatalysts for catalyzing direct arylation of unactivated arenes with haloarenes.
In vitro evaluation of copper sulfide nanoparticles decorated with folic acid/chitosan as a novel pH‐sensitive nanocarrier for the efficient controlled targeted delivery of cytarabine as an anticancer drug
Authors: Hamrang Roya , Moniri Elham , Heydarinasab Amir , Safaeijavan Raheleh
Published: May 2022

Nanoparticles (NPs) have gained more attention as drug delivery systems. Folic acid (FA)‐chitosan (CS) conjugates, because of their biodegradability, low toxicity, and better stability, offer a pharmaceutical drug delivery tool. The aim of this work was to fabricate CuS NPs modified by CS followed by grafting FA as a nanocarrier for the delivery of cytarabine (CYT) as an anticancer drug. In this work, CuS NPs modified by CS and FA were successfully synthesized. The structural properties of the nanocarrier were characterized by using scanning electron microscopy, Fourier transform infrared, X‐ray diffraction, thermogravimetric analysis, and Brunauer–Emmett–Teller. The adsorption mechanism of CYT by adsorption isotherms, kinetics, and thermodynamics was deliberated and modeled. The in vitro CYT release behavior for the nanocarrier was 99% and 61% at pH 5.6 and 7.4, respectively. The adsorption behavior of CYT by CuS NPs–CS–FA was well explored by pseudo–second‐order kinetic and Langmuir isotherm models by the coefficient of determination (R2 > 0.99). Thermodynamic results showed that the uptake of CYT by CuS NPs‐CS‐FA was endothermic and spontaneous. The experimental results showed that CYT/CuS NPs‐CS‐FA can be proposed as an efficient nanocarrier for the targeted delivery of anticancer drugs.
Scalable Fabrication of Silicon‐Graphite Microsphere by Mechanical Processing for Lithium‐Ion Battery Anode with Large Capacity and High Cycling Stability
Authors: Shen Qiuyan , Zheng Ruibing , Lv Yingying , Lou Yanyan , Shi Liyi , Yuan Shuai
Published: May 2022

In order to combine the high stability of graphite and the large theoretical capacity of silicon, silicon‐graphite composites attract tremendous attentions. However, the cycling stability is still a bottleneck hindering their commercialization due to the large volume expansion and poor interface compatibility. In this study, the bead grinding method is used to break micro‐sized silicon and graphite particles by strong shear force simultaneously, inducing the solid‐solid interface reaction between fresh silicon nanoparticles and graphite nanosheets. Subsequently, an evaporation induced self‐assembly happens in spray drying process, allow for scalable synthesis of Si‐graphite microsphere. The silicon‐graphite microsphere (Si−G microsphere) delivers an excellent cycling performance, with a reversible capacity of 1895 mAh g−1 at a current density of 0.5 A g−1 over 500 cycles and a capacity retention of 99.8 %. Moreover, the pouch‐type full battery of Si−G microsphere/graphite||LiNi0.5Co0.2Mn0.3O2 exhibits remarkable cycling stability with the capacity retention of 79.3 % after 800 cycles. The manufacture process using commercial raw materials and simple mechanical strategy demonstrates great potential for the low‐cost and scaled synthesis of high‐performance silicon‐graphite anodes.
Structural basis of the conformational and functional regulation of human SERCA2b, the ubiquitous endoplasmic reticulum calcium pump
Authors: Zhang Yuxia , Inaba Kenji
Published: May 2022

Sarco/endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b), a member of the SERCA family, is expressed ubiquitously and transports Ca2+ into the sarco/endoplasmic reticulum using the energy provided by ATP binding and hydrolysis. The crystal structure of SERCA2b in its Ca2+‐ and ATP‐bound (E1∙2Ca2+‐ATP) state and cryo‐electron microscopy (cryo‐EM) structures of the protein in its E1∙2Ca2+‐ATP and Ca2+‐unbound phosphorylated (E2P) states have provided essential insights into how the overall conformation and ATPase activity of SERCA2b is regulated by the transmembrane helix 11 and the subsequent luminal extension loop, both of which are specific to this isoform. More recently, our cryo‐EM analysis has revealed that SERCA2b likely adopts open and closed conformations of the cytosolic domains in the Ca2+‐bound but ATP‐free (E1∙2Ca2+) state, and that the closed conformation represents a state immediately prior to ATP binding. This review article summarizes the unique mechanisms underlying the conformational and functional regulation of SERCA2b.
Development, method validation and simultaneous quantification of eleven bioactive natural products from high‐altitude medicinal plant by high‐performance liquid chromatography
Authors: Dar Alamgir A. , Raina Arun , Kumar Anil
Published: May 2022

Herein, a novel, rapid, reliable, simple method validation and simultaneous quantification of 11 bioactive compounds (mostly xanthones) have been described. International Conference on Harmonization guidelines were used for the analytical method validation. Good linearity, repeatability, intra‐ and inter‐day precision, accuracy and reliability were well‐illuminated in the method validation procedure. The calibration curves showed a good linear relationship (r > 0.999) within test range. Precision was evaluated by intra‐ and inter‐day tests with relative standard deviation <2.79% and accuracy validation recovery of 74.16%–91.84%. On quantification study, the validated method described the high content of bioactive xanthone derivatives, including 1‐hydroxy‐3, 5‐dimethoxyxanthone (7), 2‐(allyloxy)‐8‐hydroxy‐1, 6‐dimethoxyxanthone (6) 1, 7, 8‐trihydroxy‐3‐methoxyxanthone (9) and Coxanthone E (5) in Codonopsis ovata, which is advantageous given the numerous pharmacological and biological effects associated with these compounds, which mostly exhibit anti‐cancerous, antioxidant, anti‐inflammatory, anti‐mutagenic and anti‐obesity effects. The bulk abundance of these compounds can also be used for further modification to produce better lead molecules for drug discovery with low toxicity and high potency. The proposed method makes it possible to simultaneously determine all bioactive compounds in one run and can be extended to marker‐based standardization of herbal formulations in medicinal and pharmaceutical industries.
Skeletonized mean diffusivity and neuropsychological performance in relapsing‐remitting multiple sclerosis
Authors: Chylińska Magdalena , Karaszewski Bartosz , Komendziński Jakub , Wyszomirski Adam , Sabisz Agnieszka , Halas Marek , Szurowska Edyta
Published: May 2022

Background

Peak width of Skeletonized Mean Diffusivity (PSMD), as a novel marker of white matter (WM) microstructure damage, is associated with cognitive decline in several WM pathologies (i.e., small vessel disorders). We hypothesized that markers combining alterations in whole WM could be associated with cognitive dysfunction in relapsing‐remitting multiple sclerosis (RRMS) patients.

Methods

We used PSMD based on tract‐based spatial statistics (TBSS) of diffusion tensor imaging (DTI) magnetic resonance (MR) scans. We investigated RRMS patients (n = 73) undergoing interferon beta (IFN‐β) therapy. In this cross‐sectional study, we investigated the association between neuropsychological data and clinical and MRI variables: PSMD, WM hypointensities, and normalized brain volume (NBV).

Results

In our cohort, 37 (50.7%) patients were recognized as cognitively impaired (CI) and 36 (49.3%) patients were cognitively normal (CN). In regression analysis, PSMD was a statistically significant contributor in the California Verbal Learning Test (CVLT) list A (p = 0.04) and semantic fluency (p = 0.036). PSMD (p < 0.001, r2 = 0.35), NBV (p = 0.002, r2 = 2.6) and WM hypointensities (p < 0.001, r2 = 0.40) were major contributors to upper extremity disability (9HPT) in the CN subgroup. A significant contributor in the majority of neuropsychological measures was education attainment.

Conclusion

We investigated PSMD as a new parameter of WM microstructure damage that is a contributor in complex cognitive tasks, CVLT performance, and semantic fluency. PSMD was a statistically significant contributor to upper extremity disability (9HPT) together with WM hypointensities and NBV. Education attainment proved to be relevant in the majority of cognitive domains. Further studies are needed to estimate PSMD relevance as a marker of CI in MS.
The versatile role of sustainable market entrepreneurs in market transformation: An intervention framework for institutional change
Authors: Argyrou Aikaterini , Chevrollier Nicolas , Nijhof Andre
Published: May 2022

This article investigates in which way sustainable entrepreneurship can generate institutional change that transforms markets towards sustainability. A transformation of models of economic organization and market structures through sustainable entrepreneurship fosters the path towards sustainability. Institutional change involves sustainable market entrepreneurs as institutional entrepreneurs that operate in an effectual manner in different market transformation phases. Sustainable market entrepreneurs while seeking entrepreneurial opportunities simultaneously shape existing market structures and market conditions in different sustainable market transformation phases thereby creating new opportunities. Accordingly, a framework that explains institutional change prompted by sustainable market entrepreneurs in market transformation phases is developed. In this framework, various interventions which encourage sustainable market entrepreneurs to co‐create with the stakeholders of their choice are strategized. The provided framework enhances the understanding of the versatile role of sustainable market entrepreneurs and potentially the leverage of their actions towards institutional impact over time.
Rh(III)‐Catalyzed One‐Step Synthesis of ortho‐Alkynylated Perylene Imide Dyes: Optical and Electrochemical Properties of New Derivatives
Authors: Chand Tapasi , Khamari Laxmikanta , Chopra Deepak , Mukherjee Saptarshi , Kapur Manmohan
Published: May 2022

A one‐step Rh‐catalyzed site‐selective ortho‐C−H alkynylation of perylene as well as naphthalene mono‐ and diimides is reported. A single step regioselective access to ortho‐C−H alkynylated derivatives of these ryleneimides not only increases the step economy of the ortho‐functionalization on these dyes but also provides a quick access route towards highly functionalized dyes that have potential optoelectronic applications. Increased solubility of tetra(triisopropylsilyl)acetylenyl PDIs in organic solvents greatly enhances their utility for further derivatization.
Relevance of Palladium to Radiopharmaceutical Development Considering Enhanced Coordination Properties of TE1PA
Authors: Pineau Julie , Lima Luís M. P. , Platas‐Iglesias Carlos , Zeevaart Jan Rijn , Driver Cathryn H. S. , Le Bris Nathalie , Tripier Raphaël
Published: May 2022

The limited use of palladium‐103 and ‐109 radionuclides for molecular radiotherapy is surely due to the lack of appropriate ligands capable of fulfilling all criteria required for application in nuclear medicine. Furthermore, the thermodynamic properties of these complexes in solution remain difficult to establish. The challenge is compounded when considering that radiolabeling of compounds for translation to clinical trials requires fast complexation. Thus, the coordination of Pd(II) and 103/109Pd‐nuclides is a huge challenge in terms of molecular design and physicochemical characterization. Herein, we report a comprehensive study highlighting TE1PA, a monopicolinate cyclam – already established in nuclear imaging with 64Cu‐PET (positron emission tomography) imaging tracers – as a highly relevant chelator for natural Pd and subsequently 109Pd‐nuclide. The structural, thermodynamic, kinetic and radiolabeling studies of Pd(II) with TE1PA, as well as the comparison of this complex with three structurally related derivatives, support palladium‐TE1PA radiopharmaceuticals as leading candidates for targeted nuclear medicine.
Experimental study of secondary and tertiary modes combined low salinity water and polymer flooding in sandstone porous media
Authors: Mokhtari Farzad , Riahi Siavash , Rostami Behzad
Published: May 2022

Combined low salinity water (LSW) and polymer (LSP) flooding is the most attractive method of enhanced oil recovery (EOR). Considerable research has investigated effective mechanisms of LSP flooding. In this study, 10 laboratory core flood tests were carried out to evaluate the effects of LSW injection into samples without any clay particles, the timing of LSW injection, and the advantages of adding polymer to the injection water for EOR. Secondary and tertiary LSW injections were performed on sandpack samples with different wettability states and water salinity. Tertiary LSW injection after secondary synthetic seawater (SSW) injection in oil‐wet samples resulted in 13% more oil recovery, while the water‐wet sample showed no effect on the oil recovery. Secondary LSW injection in oil‐wet porous media improved oil recovery by 8% of the original oil in place (OOIP) more than secondary SSW injection. Tertiary LSP flooding after secondary SSW injection in the oil‐wet sample provided a recovery of 67.3% of OOIP, while secondary LSW injection followed by tertiary LSP flooding yielded the maximum ultimate oil recovery of about 77% of OOIP. The findings showed that the positive EOR effects of LSW and LSP flooding were the results of wettability alteration, pH increase, improved mobility ratio, better sweep efficiency, and oil redistribution. In addition, results showed that wettability alteration is possible without the presence of clay particles. The findings of this study can help for a better understanding of fluid propagation through the porous media and an investigation of delays in reaching ultimate oil recovery.
Rigidity‐Activity Relationships of bisQPC Scaffolds against Pathogenic Bacteria
Authors: Spahr Aaron C. , Michaud Marina E. , Amoo Lauren E. , Sanchez Christian A. , Hogue Cody E. , Thierer Laura M. , Gau Michael R. , Wuest William M. , Minbiole Kevin P. C.
Published: May 2022

Biscationic quaternary phosphonium compounds (bisQPCs) represent a promising class of antimicrobials, displaying potent activity against both Gram‐negative and Gram‐positive bacteria. In this study, we explored the effects of structural rigidity on the antimicrobial activity of QPC structures bearing a two‐carbon linker between phosphonium groups, testing against a panel of six bacteria, including multiple strains harboring known disinfectant resistance mechanisms. Using simple alkylation reactions, 21 novel compounds were prepared, although alkene isomerization as well as an alkyne reduction were observed during the respective syntheses. The resulting bisQPC compounds showed strong biological activity, but were hampered by diminished solubility of their iodide salts. One compound (P2P‐10,10 I) showed single‐digit micromolar activity against the entire panel of bacteria. Overall, intriguing biological activity was observed, with less rigid structures displaying better efficacy against Gram‐negative strains and more rigid structures demonstrating slightly increased efficacy against S. aureus strains.
Cardiovascular disease risk in long‐term breast cancer survivors: A population‐based cohort study
Authors: Koric Alzina , Chang Chun‐Pin , Mark Bayarmaa , Rowe Kerry , Snyder John , Dodson Mark , Deshmukh Vikrant G. , Newman Michael G. , Fraser Alison M. , Smith Ken R. , Date Ankita P. , Gren Lisa H. , Porucznik Christina A. , Haaland Benjamin A. , Henry N. Lynn , Hashibe Mia
Published: May 2022

Background

Breast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long‐term survivors and to investigate possible risk factors for CVD.

Methods

A population‐based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer‐free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years.

Results

Long‐term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00‐1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08‐6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long‐term breast cancer survivors.

Conclusion

Risk of CVD compared to the general population was moderate among this cohort of long‐term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.
Effects of CYP3A Inhibition, CYP3A Induction, and Gastric Acid Reduction on the Pharmacokinetics of Ripretinib, a Switch Control KIT Tyrosine Kinase Inhibitor
Authors: Li Xiaoyan , Shelton Mark J , Wang Jing , Meade Julie , Ruiz‐Soto Rodrigo
Published: May 2022

Ripretinib is a switch control KIT kinase inhibitor approved for treatment of adults with advanced gastrointestinal stromal tumors who received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib and its active metabolite (DP‐5439) are cleared mainly via cytochrome P450 enzyme 3A4/5 (CYP3A4/5), and ripretinib solubility is pH‐dependent, thus the drug–drug interaction potentials of ripretinib with itraconazole (strong CYP3A inhibitor), rifampin (strong CYP3A inducer), and pantoprazole (proton pump inhibitor) were each evaluated in open‐label, fixed‐sequence study designs. Overall, 20 participants received ripretinib 50 mg alone and with itraconazole 200 mg once daily, 24 participants received ripretinib 100 mg alone and with rifampin 600 mg once daily, and 25 participants received ripretinib 50 mg alone and with pantoprazole 40 mg once daily. Ripretinib exposure increased with concomitant itraconazole, with geometric least‐squares (LS) mean ratios of ripretinib area under the concentration–time curve from 0 to ∞ (AUC0–∞) and maximum observed concentration (Cmax) of 199% and 136%. Ripretinib exposure decreased with concomitant rifampin: geometric LS mean ratios for ripretinib AUC0–∞ and Cmax were 39% and 82%. Pantoprazole coadministration had no effect on ripretinib pharmacokinetics. No unexpected safety signals occurred. No dose adjustment is required for ripretinib coadministered with gastric acid reducers and strong CYP3A inhibitors; patients also receiving strong CYP3A inhibitors should be monitored more frequently for adverse reactions. Concomitant ripretinib use with strong CYP3A inducers should be avoided. Prescribers should refer to approved labeling for specific dose recommendations with concomitant use of strong and moderate CYP3A inducers.
Non‐Globular Organic Ionic Plastic Crystal Containing a Crown‐Ether Moiety – Tuning Its Behaviour Using Sodium Salts
Authors: Casimiro Anna , Lugger Jody , Lub Johan , Nijmeijer Kitty
Published: May 2022

Organic ionic plastic crystals (OIPCs) are a class of soft materials showing positional order while still allowing orientational freedom. Due to their motional freedom in the solid state, they possess plasticity, non‐flammability and high ionic conductivity. OIPC behavior is typically exhibited by ‘simple’ globular molecules allowing molecular rotation, whereas the interactions that govern the formation of OIPC phases in complex non‐globular molecules are less understood. To better understand these interactions, a new family of non‐globular OIPCs containing a 15‐crown‐5 ether moiety was synthetized and characterized. The 15C5BA molecule prepared does not exhibit the sought‐after behavior because of its non‐globular nature and strong intermolecular H‐bonds that restrict orientational motion. However, the OIPC behavior was successfully obtained through complexation of the crown‐ether moiety with sodium salts containing chaotropic anions. Those anions weaken the interactions between the molecules, allowing rotational freedom and tuning of the thermal and morphological properties of the OIPC.
Conflict management in the indigenous community of Batad in the Philippines: A system dynamic perspective
Authors: Ilac Emerald Jay D. , Presbitero Alfred
Published: May 2022

Conflict management has been widely examined, with research focusing on different conflict management styles, strategies, and factors that influence effective conflict resolution. However, despite the significant research attention dedicated to this field, the search for new insights and discoveries continues to discover how best to resolve and manage conflicts. The present study contributes to the literature by applying a system dynamic perspective to gain understanding of conflict management and constructs a theorized leadership model based on the experiences of leaders in an indigenous community in the Philippines. We utilize a phenomenological approach to involve multiple indigenous leaders and obtain their experiences of the conflict management process and system dynamics in their indigenous communities. Our results achieve the following: (a) demonstrating the complex nature of conflict management, validating the utility of the system dynamic perspective; (b) demonstrating that conflict management occurs on and involves multiple levels; and (c) revealing the importance of the humility and unbiasedness of leaders in the conflict management process. These findings provide novel insights into alternative mechanisms for effective management of conflicts in modern workplaces and organizations.
Elevation of fatty acid desaturase 2 in esophageal adenocarcinoma increases polyunsaturated lipids and may exacerbate bile acid‐induced DNA damage
Authors: Molendijk Jeffrey , Kolka Cathryn M. , Cairns Henry , Brosda Sandra , Mohamed Ahmed , Shah Alok K. , Brown Ian , Hodson Mark P. , Hennessy Thomas , Liu Guanghao , Stoll Thomas , Richards Renee S. , Gartside Michael , Patel Kalpana , Clemons Nicholas J. , Phillips Wayne A. , Barbour Andrew , Westerhuis Johan A. , Hill Michelle M.
Published: May 2022

Background

The risk of esophageal adenocarcinoma (EAC) is associated with gastro‐esophageal reflux disease (GERD) and obesity. Lipid metabolism‐targeted therapies decrease the risk of progressing from Barrett's esophagus (BE) to EAC, but the precise lipid metabolic changes and their roles in genotoxicity during EAC development are yet to be established.

Methods

Esophageal biopsies from the normal epithelium (NE), BE, and EAC, were analyzed using concurrent lipidomics and proteomics (n = 30) followed by orthogonal validation on independent samples using RNAseq transcriptomics (n = 22) and immunohistochemistry (IHC, n = 80). The EAC cell line FLO‐1 was treated with FADS2 selective inhibitor SC26196, and/or bile acid cocktail, followed by immunofluorescence staining for γH2AX.

Results

Metabolism‐focused Reactome analysis of the proteomics data revealed enrichment of fatty acid metabolism, ketone body metabolism, and biosynthesis of specialized pro‐resolving mediators in EAC pathogenesis. Lipidomics revealed progressive alterations (NE‐BE‐EAC) in glycerophospholipid synthesis with decreasing triglycerides and increasing phosphatidylcholine and phosphatidylethanolamine, and sphingolipid synthesis with decreasing dihydroceramide and increasing ceramides. Furthermore, a progressive increase in lipids with C20 fatty acids and polyunsaturated lipids with ≥4 double bonds were also observed. Integration with transcriptome data identified candidate enzymes for IHC validation: Δ4‐Desaturase, Sphingolipid 1 (DEGS1) which desaturates dihydroceramide to ceramide, and Δ5 and Δ6‐Desaturases (fatty acid desaturases, FADS1 and FADS2), responsible for polyunsaturation. All three enzymes showed significant increases from BE through dysplasia to EAC, but transcript levels of DEGS1 were decreased suggesting post‐translational regulation. Finally, the FADS2 selective inhibitor SC26196 significantly reduced polyunsaturated lipids with three and four double bonds and reduced bile acid‐induced DNA double‐strand breaks in FLO‐1 cells in vitro.

Conclusions

Integrated multiomics revealed sphingolipid and phospholipid metabolism rewiring during EAC development. FADS2 inhibition and reduction of the high polyunsaturated lipids effectively protected EAC cells from bile acid‐induced DNA damage in vitro, potentially through reduced lipid peroxidation.
Evidence for serial founder events during the colonization of North America by the yellow fever mosquito, Aedes aegypti
Authors: Pless Evlyn , Powell Jeffrey R. , Seger Krystal R. , Ellis Brett , Gloria‐Soria Andrea
Published: May 2022

The Aedes aegypti mosquito first invaded the Americas about 500 years ago and today is a widely distributed invasive species and the primary vector for viruses causing dengue, chikungunya, Zika, and yellow fever. Here, we test the hypothesis that the North American colonization by Ae. aegypti occurred via a series of founder events. We present findings on genetic diversity, structure, and demographic history using data from 70 Ae. aegypti populations in North America that were genotyped at 12 microsatellite loci and/or ~20,000 single nucleotide polymorphisms, the largest genetic study of the region to date. We find evidence consistent with colonization driven by serial founder effect (SFE), with Florida as the putative source for a series of westward invasions. This scenario was supported by (1) a decrease in the genetic diversity of Ae. aegypti populations moving west, (2) a correlation between pairwise genetic and geographic distances, and (3) demographic analysis based on allele frequencies. A few Ae. aegypti populations on the west coast do not follow the general trend, likely due to a recent and distinct invasion history. We argue that SFE provides a helpful albeit simplified model for the movement of Ae. aegypti across North America, with outlier populations warranting further investigation.
Coexistence research requires more interdisciplinary communication
Authors: Hawlena Hadas
Published: May 2022

Coexistence theories develop rapidly at the ecology forefront, outpacing their experimental testing. I discuss the reasons for this gap, call on interdisciplinary researchers to construct a road map for coexistence research, and recommend the actions that should be implemented therein.
Explanation of beta diversity in European alpine grasslands changes with scale
Authors: Malanson George P. , Pansing Elizabeth R. , Testolin Riccardo , Abdulhak Sylvain , Bergamini Ariel , Ćušterevska Renata , Marcenò Corrado , Kuzmanović Nevena , Milanović Đorđije , Ruprecht Eszter , Šibík Jozef , Vassilev Kiril , Willner Wolfgang , Jiménez‐Alfaro Borja
Published: May 2022

The importance of environmental difference among sites and dispersal limitations of species to the explanation of diversity differs among biological systems and geographical regions. We hypothesized that climate and then dispersal limitation will predominantly explain the similarity of alpine vegetation at increasing distances between pairs of regions at subcontinental extent. We computed the similarity of all pairs of 23 European mountain regions below 50° N after dividing the species lists of each region by calcareous or siliceous substrates. Distance decay in similarity was better fitted by a cubic polynomial than a negative exponential function, and the fit was better on calcareous than on siliceous substrate. Commonality analysis revealed that the proportion of explanation of beta diversity by climatic difference had unimodal patterns on a gradient of increasing distance between regions, while explanation by dispersal limitation had consistently rising patterns on both substrates. On siliceous substrate, dispersal limitation explained more of the variation in beta diversity only at longer distances, but it was predominant at all distances on calcareous substrate. The steeper response to distance at <1600 km and >2600 km may indicate dispersal limitation at different temporal scales, and the uptick in the response to distance at the longest distances may reflect how isolated some regions have been before and since the last glacial maximum.
Gathering in an empty house: Arthropod assemblages overwintering in abandoned hornet nests
Authors: Furusawa Chiharu , Okamiya Hisanori
Published: May 2022

Although some species of hornets spend enormous amounts of time constructing their nests, they only utilize the nest for one season and abandon it to overwinter in other habitats. Abandoned nests may be attractive habitats for other organisms to avoid predators and bad weather, but our knowledge of the organisms that make use of hornet nests for overwintering is very limited. Here, we examined the secondary inhabitants of abandoned winter hornet nests in northern part of Japan. A total of 96 live arthropods (5 orders, 23 species) were collected from six nests and were dominated by Araneae (85.4%). Our finding suggests that hornet nests serve as overwintering sites for many other organisms and that hornets may act as physical ecosystem engineers by creating overwintering habitats for other arthropods (mostly spiders). We predict that abandoned nests indirectly affect the prey community structure on trees, by providing overwintering sites for predatory spiders. In addition, reduced snow cover due to global warming may prevent nest collapse and enhance the ecological functioning of hornet nests. We emphasize that hornet nests present an ideal system for assessing how climate change alters communities through its effect on engineered structures. Further studies are required to clarify the role of hornets as ecosystem engineers among tree communities in fluctuating environments.
Effect of pulmonary artery pressure‐guided therapy on heart failure readmission in a nationally representative cohort
Authors: Kishino Yoshikazu , Kuno Toshiki , Malik Aaqib H. , Lanier Gregg M. , Sims Daniel B. , Ruiz Duque Ernesto , Briasoulis Alexandros
Published: May 2022

Aims

Pulmonary artery pressure (PAP)‐guided therapy in patients with heart failure (HF) using the CardioMEMS (CMM) device, an implantable PAP sensor, has been shown to reduce HF hospitalizations in previous studies. We sought to evaluate the clinical benefit of the CMM device in regard to 30, 90, and 180 day readmission rates in real‐world usage.

Methods and results

We queried the Nationwide Readmissions Database (NRD) to identify patients who underwent CMM implantation (International Classification of Diseases 9 and 10 codes) between the years 2014 and 2019 and studied their HF readmissions. Moreover, we compared CMM patients and their readmissions with a matched cohort of patients with HF but without CMM. Multivariable Cox regression analysis was performed to adjust for other predictors of readmissions. Prior to matching, we identified 5 326 530 weighted HF patients without CMM and 1842 patients with CMM. After propensity score matching for several patients and hospital‐related characteristics, the cohort consisted of 1839 patients with CMM and 1924 with HF without CMM. Before matching, CMM patients were younger (67.0 ± 13.5 years vs. 72.3 ± 14.1 years, P < 0.001), more frequently male (62.7% vs. 51.5%, P < 0.001), with higher rates of prior percutaneous coronary intervention (16.9% vs. 13.2%, P = 0.002), peripheral vascular disease (29.6% vs. 17.8%, P < 0.001), pulmonary circulatory disorder (38.7% vs. 23.2%, P < 0.001), atrial fibrillation (51.2% vs. 45.3%, P = 0.002), prior left ventricular assist device (1.8% vs. 0.2%, P < 0.001), high income (32.2% vs. 16.4%, P < 0.001), and acute kidney disease (43.8% vs. 29.9%, P < 0.001). Readmission rates at 30 days were 17.3% vs. 20.9% for patients with vs. without CMM, respectively, and remained statistically significant after matching (17.3% vs. 21.5%, P = 0.002). The rates of 90 day (29.6% vs. 36.5%, P = 0.002) and 180 day (39.6% vs. 46.6%, P = 0.009) readmissions were lower in the CMM group. In a multivariable regression model, CMM was associated with lower risk of readmissions (hazard ratio 0.75, 95% confidence interval 0.63–0.89, P = 0.001).

Conclusions

The CMM device was associated with reduced HF rehospitalization rates in a nationally representative cohort of HF patients, validating the clinical trial that led to the approval of this device and its utilization in the treatment of HF.
Changes in cardiac biomarkers in association with alterations in cardiac structure and function, and health status in heart failure with reduced ejection fraction: the EVALUATE‐HF trial
Authors: Myhre Peder L. , Claggett Brian L. , Shah Amil M. , Prescott Margaret F. , Ward Jonathan H. , Fang James C. , Mitchell Gary F. , Solomon Scott D. , Desai Akshay S.
Published: May 2022

Aims

N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), cardiac troponin T (cTnT) and soluble ST2 (sST2) provide complementary prognostic information in heart failure with reduced ejection fraction (HFrEF). We aimed to assess the association between changes in these markers with changes in cardiac structure, function and health status.

Methods and results

Patients in the EVALUATE‐HF trial (n = 464) were randomized to sacubitril/valsartan or enalapril for 12 weeks, followed by 12‐week open‐label sacubitril/valsartan. Cardiac biomarkers, echocardiography, and Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed at baseline, and after 12 and 24 weeks. A total of 410 patients (88%) had serial biomarker measurements available (mean age 67 ± 9 years, 75% male and 75% white). After 24 weeks of treatment, NT‐proBNP, sST2 and cTnT decreased by median (Q1, Q3) −31% (−55%, +6%), −6% (−19%, +8%) and − 3% (−13%, +8%), respectively (all p < 0.001). Decreases in NT‐proBNP were associated with reductions in cardiac volumes and improvements in systolic and diastolic function and health status. Decreases in cTnT were associated with reductions in left ventricular mass, but not with changes in left ventricular function or KCCQ. Decreases in sST2 were consistently associated with improvements in health status, but not with measures of cardiac structure or function. There was no effect modification from treatment on the associations investigated (p for interaction >0.05)

Conclusion

In HFrEF, serial changes in NT‐proBNP correlate with changes in several key measures of cardiac structure and health status. cTnT changes correlate with changes in left ventricular mass and sST2 with changes in health status. These data highlight possible complementary pathophysiologic implications of changes in NT‐proBNP, cTnT and sST2.

Clinical Trial Registration:
ClinicalTrials.gov Identifier: NCT02874794.
Impact of bacterial infections and spontaneous bacterial peritonitis prophylaxis on phage‐bacterial dynamics in cirrhosis
Authors: Bajaj Jasmohan S. , Rodriguez Marcela Peňa , Fagan Andrew , McGeorge Sara , Sterling Richard K. , Lee Hannah , Luketic Velimir , Fuchs Michael , Davis Brian C. , Sikaroodi Masoumeh , Gillevet Patrick M.
Published: May 2022

Background and Aims

Gut microbiota, including bacteria and phages, are altered in cirrhosis, but their role during infections and spontaneous bacterial peritonitis (SBP) prophylaxis is unclear. Our aim was determine metagenomic changes in gut bacteria; phages and their linkages centered around Gram‐negative and Gram‐positive pathobionts in patients with cirrhosis with/without infections or SBP prophylaxis.

Approach and Results

We included uninfected (n = 231) and infected (n = 30, SBP n = 19 and urinary tract infection n = 11 before antibiotics) patients who gave stool for bacterial and phage metagenomics. We matched uninfected to infected patients 1:1 on a model for end‐stage liver disease (MELD). We also analyzed subgroups of patients with ascites matched on an MELD (n = 73) to patients on SBP prophylaxis (n = 7) and then to SBP infection. Phage and bacterial taxa differences (DESeq2) and correlation networks centered around Escherichia coli and Enterococcus faecium were analyzed. Infections were mostly due to Enterobacteriaceae and Enterococcus spp. On metagenomics, higher fold changes of Enterobacteriaceae members, Enterococcus and Streptococcus spp., and Escherichia phages were seen in infected patients. Correlation networks showed more complex bacteria‐phage linkages in infected patients compared with uninfected ones overall and centered around E. coli and E. faecium. SBP prophylaxis induced higher Gram‐positive bacteria. In SBP, Enterococcus and Escherichia were higher versus ascites. Correlation networks around E. coli were complex in ascites but sparse with SBP prophylaxis, whereas the reverse was seen with E. faecium. Lytic phages and those associated with antibiotic resistance were correlated with E. faecium.

Conclusion

In cirrhosis, there are significant changes in phage‐bacterial linkages in infected patients and those on SBP prophylaxis compared to the remaining patients. SBP prophylaxis enriches complexity of E. faecium–centered but induces a collapse in E. coli–centered phage‐bacterial correlations.
Reducing measurement error with ecologically valid testing methods
Authors: Gunther Kelley E. , Anaya Berenice , Pérez‐Edgar Koraly
Published: May 2022

‘Six solutions for more reliable infant research’ outlines important steps in improving research with the youngest of participants. Here, we suggest that a complimentary avenue for further improving reliability can be found in employing more ecologically valid tasks. Because laboratory tasks are often designed as simple, heavily controlled representations of a construct, they can be devoid of the necessary context in which the construct naturally unfolds. We posit that additional error is generated in translating laboratory task metrics back to the construct of interest. Thus, it may be necessary to supplement more traditional laboratory tasks with iterations that more closely match the research construct of interest and how it may unfold in the ‘real world’. We make suggestions for adjusting to the ‘noise’ incurred by moving research out of traditional laboratory environments, while also recognizing how these adjustments may improve the sociodemographic profiles within research studies.
Triple combination therapy for clinically nonmetastatic super‐high‐risk prostate cancer
Authors: Yoshimura Koji , Muraoka Kei , Fukasawa Michiko , Fukushima Mika , Kumagai Masatoshi , Yabusaki Ryo , Ueda Masakatsu , Shiraishi Yusuke , Imamura Masaaki
Published: May 2022

Introduction

Patients with nonmetastatic but exceptionally high‐risk prostate cancer are liable to have biochemical failure and may even die. Triple combination therapy, which consists of surgery, radiotherapy, and androgen‐deprivation therapy, as first‐line treatment, may control the disease for a long period.

Case presentation

We treated a patient with super‐high‐risk, nonmetastatic prostate cancer, with triple combination therapy. He was biochemical relapse free at 60 months after the initiation of treatment.

Conclusion

Triple combination therapy may be an option for super‐high‐risk, nonmetastatic prostate cancer.
The mechanism and effects of remdesivir‐induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations
Authors: Li Ji‐tong , Zhang Yao‐dong , Song Xiao‐rui , Li Rui‐jing , Yang Wei‐li , Tian Ming , Zhang Shu‐feng , Cao Guang‐hai , Song Lu‐lu , Chen Yu‐ming , Liu Cui‐hua
Published: May 2022

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID‐19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non‐target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 μM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose‐dependent increases in mortality and malformation were observed in remdesivir‐treated embryos. Moreover, 10–100 μM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir‐treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir‐induced ecotoxicity to aquatic environments.