bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of peripheral blood volume for in silico reconstitution of the human B‐cell receptor repertoire
Authors: Lee Hyunho , Yoo Duck Kyun , Han Jerome , Kim Ki Hyun , Noh Jinsung , Lee Yonghee , Lee Eunjae , Kwon Sunghoon , Chung Junho
Published: July 2022

B cells recognize antigens via membrane‐expressed B‐cell receptors (BCR) and antibodies. Similar human BCR sequences are frequently found at a significantly higher frequency than that theoretically calculated. Patients infected with SARS‐CoV2 and HIV or with autoimmune diseases share very similar BCRs. Therefore, in silico reconstitution of BCR repertoires and identification of stereotypical BCR sequences related to human pathology have diagnostic potential. Furthermore, monitoring changes of clinically significant BCR sequences and isotype conversion has prognostic potential. For BCR repertoire analysis, peripheral blood (PB) is the most convenient source. However, the optimal human PB volume for in silico reconstitution of the BCR repertoire has not been studied in detail. Here, we sampled 5, 10, and 20 mL PB from the left arm and 40 mL PB from the right arm of two volunteers, reconstituted in silico PB BCR repertoires, and compared their composition. In both volunteers, PB sampling over 20 mL resulted in slight increases in functional unique sequences (FUSs) or almost no increase in repertoire diversity. All FUSs with a frequency above 0.08% or 0.03% in the 40 mL PB BCR repertoire were detected even in the 5 mL PB BCR repertoire from each volunteer. FUSs with a higher frequency were more likely to be found in BCR repertoires from reduced PB volume, and those coexisting in two repertoires showed a statistically significant correlation in frequency irrespective of sampled anatomical site. The correlation was more significant in higher‐frequency FUSs. These observations support the potential of BCR repertoire analysis for diagnosis.
Rheumatoid Arthritis Disease Activity and Hospitalized Infection in a Large US Registry
Authors: Yun Huifeng , Chen Lang , Roy Jason A. , Greenberg Jeffrey , Harrold Leslie R. , George Michael D. , Curtis Jeffrey R.
Published: July 2022

Objectives

The association between disease activity and infection risk among patients with rheumatoid arthritis (RA) is not clear, and it is challenging to determine because of confounding due to the effects of RA treatments and comorbidities.

Methods

Using patients with RA in the CorEvitas registry with Medicare coverage in 2006–2019, we identified eligible patients who had at least 1 visit with moderate disease activity based on the Clinical Disease Activity Index (CDAI; CDAI >10 and ≤22). Follow‐up started at the subsequent CorEvitas visit. Hospitalized infection during follow‐up was assessed in linked Medicare data. We calculated the incidence rate of hospitalized infection for patients in remission, and low and moderate disease activity, and estimated the effect of time‐varying CDAI on hospitalized infection by controlling for baseline and time‐dependent confounders using marginal structural models (MSMs).

Results

A total of 3,254 patients with RA were eligible for analysis, among which 529 hospitalized infections were identified during follow‐up. The crude incidence of hospitalized infection was 3.8 per 100 person‐years for patients in remission, 6.6 for low disease activity, and 8.0 for moderate disease activity. Using MSMs and compared with being in remission, the hazard ratio of hospitalized infection associated with low disease activity was 1.60 (95% confidence interval [95% CI] 1.13–2.28) and with moderate disease activity was 1.83 (95% CI 1.30–2.64).

Conclusion

The risk of hospitalized infection was higher for patients with RA in low or moderate disease activity than for those in remission after accounting for the interplay of disease activity, RA treatments, treatment switching, and other potential confounders.
Realization of Multifunctional Bosonic Magnon Transistor via Thermal Phonon Gating
Authors: Xu Jiapeng , Jin Lichuan , Zhang Dainan , Tang Xiaoli , Zhong Zhiyong , Zhang Huaiwu
Published: July 2022

Magnons have demonstrated enormous potential for next‐generation information technology, namely the ability to build quasiparticle low‐power integrated circuits without the moving of electrons. An experimental bosonic magnon transistor with multifunction, low‐loss, and full‐wavelength control of propagating spin waves (magnon current) is developed in this work. Using a monolayer of graphene as the high‐efficiency thermal phonon source and a low‐loss electrically insulating ferrimagnetic single‐crystalline yttrium iron garnet film as the propagating spin‐wave channel, the presented transistor has three functioning regions of spin‐wave modulation at full wavelength: prominent amplification, complete cut‐off, and linear phase shift. The magnon‐phonon‐mediated nonequilibrium state created by the temperature gradient in this transistor works in two ways: when the thermal phonon flow is small, the positive thermal spin‐torque induced by the longitudinal spin‐Seebeck effect amplifies spin waves; when the thermal phonon flow is large, the magnon–magnon interaction due to nonequilibrium thermal magnon injection greatly contributes to spin‐wave cut‐off. Furthermore, linear adjustment of the spin‐wave phase by creating a thermal phonon bath is demonstrated. These findings reveal that the numerous magnon–phonon coupling mechanisms in magnetic insulators offer a promising platform for the implementation of reconfigurable magnonic transistors.
Halide Remixing under Device Operation Imparts Stability on Mixed‐Cation Mixed‐Halide Perovskite Solar Cells
Authors: Ruggeri Edoardo , Anaya Miguel , Gałkowski Krzysztof , Abfalterer Anna , Chiang Yu‐Hsien , Ji Kangyu , Andaji‐Garmaroudi Zahra , Stranks Samuel D.
Published: July 2022

Mixed‐halide mixed‐cation hybrid perovskites are among the most promising perovskite compositions for application in a variety of optoelectronic devices due to their high performance, low cost, and bandgap‐tuning capabilities. Instability pathways such as those driven by ionic migration, however, continue to hinder their further progress. Here, an operando variable‐pitch synchrotron grazing‐incidence wide‐angle X‐ray scattering technique is used to track the surface and bulk structural changes in mixed‐halide mixed‐cation perovskite solar cells under continuous load and illumination. By monitoring the evolution of the material structure, it is demonstrated that halide remixing along the electric field and illumination direction during operation hinders phase segregation and limits device instability. Correlating the evolution with directionality‐ and depth‐dependent analyses, it is proposed that this halide remixing is induced by an electrostrictive effect acting along the substrate out‐of‐plane direction. However, this stabilizing effect is overwhelmed by competing halide demixing processes in devices exposed to humid air or with poorer starting performance. The findings shed new light on understanding halide de‐ and re‐mixing competitions and their impact on device longevity. These operando techniques allow real‐time tracking of the structural evolution in full optoelectronic devices and unveil otherwise inaccessible insights into rapid structural evolution under external stress conditions.
The Promise of Soft‐Matter‐Enabled Quantum Materials
Authors: Thedford R. Paxton , Yu Fei , Tait William R. T. , Shastri Kunal , Monticone Francesco , Wiesner Ulrich
Published: July 2022

The field of quantum materials has experienced rapid growth over the past decade, driven by exciting new discoveries with immense transformative potential. Traditional synthetic methods to quantum materials have, however, limited the exploration of architectural control beyond the atomic scale. By contrast, soft matter self‐assembly can be used to tailor material structure over a large range of length scales, with a vast array of possible form factors, promising emerging quantum material properties at the mesoscale. This review explores opportunities for soft matter science to impact the synthesis of quantum materials with advanced properties. Existing work at the interface of these two fields is highlighted, and perspectives are provided on possible future directions by discussing the potential benefits and challenges which can arise from their bridging.
Large Spin Coherence Length and High Photovoltaic Efficiency of the Room Temperature Ferrimagnet Ca2FeOsO6 by Strain Engineering
Authors: Rout Paresh C. , Schwingenschlögl Udo
Published: July 2022

The influence of epitaxial strain on the electronic, magnetic, and optical properties of the distorted double perovskite Ca2FeOsO6 is studied. These calculations show that the compound realizes a monoclinic structure with P21/n space group from −6% to +6% strain. While it retains ferrimagnetic ordering with a net magnetic moment of 2 μB per formula unit at low strain, it undergoes transitions into E‐antiferromagnetic and C‐antiferromagnetic phases at −5% and +5% strain, respectively. It is shown that spin frustration reduces the critical temperature of the ferrimagnetic ordering from the mean field value of 600–350 K, in excellent agreement with the experimental value of 320 K. It is also shown that the critical temperature can be tuned efficiently through strain and that the spin coherence length surpasses that of Sr2FeMoO6 under tensile strain. An indirect‐to‐direct bandgap transition is observed at +5% strain. Localization of the valence and conduction states on different transition metal sublattices enables efficient electron–hole separation upon photoexcitation. The calculated spectroscopic limited maximum efficiency of up to 33% points to excellent potential of Ca2FeOsO6 in solar cell applications.
Sculpting Rupture‐Free Nuclear Shapes in Fibrous Environments
Authors: Jana Aniket , Tran Avery , Gill Amritpal , Kiepas Alexander , Kapania Rakesh K. , Konstantopoulos Konstantinos , Nain Amrinder S.
Published: July 2022

Cytoskeleton‐mediated force transmission regulates nucleus morphology. How nuclei shaping occurs in fibrous in vivo environments remains poorly understood. Here suspended nanofiber networks of precisely tunable (nm–µm) diameters are used to quantify nucleus plasticity in fibrous environments mimicking the natural extracellular matrix. Contrary to the apical cap over the nucleus in cells on 2‐dimensional surfaces, the cytoskeleton of cells on fibers displays a uniform actin network caging the nucleus. The role of contractility‐driven caging in sculpting nuclear shapes is investigated as cells spread on aligned single fibers, doublets, and multiple fibers of varying diameters. Cell contractility increases with fiber diameter due to increased focal adhesion clustering and density of actin stress fibers, which correlates with increased mechanosensitive transcription factor Yes‐associated protein (YAP) translocation to the nucleus. Unexpectedly, large‐ and small‐diameter fiber combinations lead to teardrop‐shaped nuclei due to stress fiber anisotropy across the cell. As cells spread on fibers, diameter‐dependent nuclear envelope invaginations that run the nucleus's length are formed at fiber contact sites. The sharpest invaginations enriched with heterochromatin clustering and sites of DNA repair are insufficient to trigger nucleus rupture. Overall, the authors quantitate the previously unknown sculpting and adaptability of nuclei to fibrous environments with pathophysiological implications.
A Universal Spinning‐Coordinating Strategy to Construct Continuous Metal–Nitrogen–Carbon Heterointerface with Boosted Lithium Polysulfides Immobilization for 3D‐Printed LiS Batteries
Authors: Ouyang Yue , Zong Wei , Zhu Xiaobo , Mo Lulu , Chao Guojie , Fan Wei , Lai Feili , Miao Yue‐E , Liu Tianxi , Yu Yan
Published: July 2022

Constructing intimate coupling between transition metal and carbon nanomaterials is an effective means to achieve strong immobilization of lithium polysulfides (LiPSs) in the applications of lithium–sulfur (LiS) batteries. Herein, a universal spinning‐coordinating strategy of constructing continuous metal–nitrogen–carbon (MNC, M = Co, Fe, Ni) heterointerface is reported to covalently bond metal nanoparticles with nitrogen‐doped porous carbon fibers (denoted as M/MN@NPCF). Guided by theoretical simulations, the Co/CoN@NPCF hybrid is synthesized as a proof of concept and used as an efficient sulfur host material. The polarized CoNC bridging bonds can induce rapid electron transfer from Co nanoparticles to the NPCF skeleton, promoting the chemical anchoring of LiPSs to improve sulfur utilization. Hence, the as‐assembled LiS battery presents a remarkable capacity of 781 mAh g−1 at 2.0 C and a prominent cycling lifespan with a low decay rate of only 0.032% per cycle. Additionally, a well‐designed Co/CoN@NPCF‐S electrode with a high sulfur loading of 7.1 mg cm−2 is further achieved by 3D printing technique, which demonstrates an excellent areal capacity of 6.4 mAh cm−2 at 0.2 C under a lean‐electrolyte condition. The acquired insights into strongly coupled continuous heterointerface in this work pave the way for rational designs of host materials in LiS systems.
Operando Decoding of Surface Strain in Anode‐Free Lithium Metal Batteries via Optical Fiber Sensor
Authors: Li Yanpeng , Zhang Yi , Li Zhen , Yan Zhijun , Xiao Xiangpeng , Liu Xueting , Chen Jie , Shen Yue , Sun Qizhen , Huang Yunhui
Published: July 2022

With zero excess lithium, anode‐free lithium metal batteries (AFLMBs) can deliver much higher energy density than that of traditional lithium metal batteries. However, AFLMBs are prone to suffer from rapid capacity loss and short life. Monitoring and analyzing the capacity decay of AFLMBs are of great importance for their future applications. It is known that the capacity fade mainly comes from the formation of solid electrolyte interphase species and dead lithium, which leads to irreversible volume expansion. Therefore, monitoring and distinguishing the irreversible volume expansion or reversible volume expansion are the key points to analyze the capacity fade of AFLMBs. Herein, an applicable technique based on optical fiber sensors to characterize and quantize the volume change of AFLMBs is developed. By attaching fiber Bragg grating (FBG) sensors onto the surface of the multilayered anode‐free pouch cells, the strain evolution of the cells is successfully monitored and correlated with their electrochemical properties. It is found that the decline of surface strain fluctuation amplitude caused by the loss of active lithium is the leading indicator of battery failure. The proposed sensing technique has excellent multiplexing capability that can be considered as an elementary unit for capacity fade analysis in next‐generation battery management system.
Bulk Restructure of Perovskite Films via Surface Passivation for High‐Performance Solar Cells
Authors: Xiong Jian , Liu Naihe , Hu Xiaotian , Qi Yifang , Liu Weizhi , Dai Junqian , Zhang Yongsong , Dai Zhongjun , Zhang Xiaowen , Huang Yu , Zhang Zheling , Dai Qilin , Zhang Jian
Published: July 2022

Defects in perovskite films and the suboptimal interface contact largely limit the performance and stability of inverted perovskite solar cells (PSCs). A simple surface post‐treatment with N‐benzyloxycarbonyl‐d‐valine (NBDV) is developed to overcome these problems. The device performance following NBDV treatment is systemically investigated. It is showed that NBDV surface post‐treatment results in the bulk restructure of the entire perovskite film and improves the film‐forming property of [6,6]‐phenyl‐C61‐butyric acid methyl ester. The grain sizes, crystallinity, trap states, cathode interfaces, as well as the built‐in field are also improved, which result in PSC performance and stability enhancement. A relatively higher power conversion efficiency (PCE) of 21.80% is reached, which is comparable to the PCE record based on single‐crystal MAPbI3. Meanwhile, the PCE of the NBDV devices can retain ≈77% and 84% of the initial value after storage for 768 h (32 days) in air and 8376 h (349 days) in N2, respectively, while the control devices only maintain ≈53% and 38% of their initial PCE values under the same exposure conditions. This work provides means to promote bulk, surface, and interface regulation toward high performance and stable inverted PSCs.
The OSSE: Development and validation of an “Objective Structured Supervision Evaluation”
Authors: Pokrajac Nicholas , Roszczynialski Kelly N. , Rider Ashley , Poffenberger Cori Mc Clure , Williams Sarah , Eakin Mc Kenzie , Sapp Richard W. , Jenkins Eric , Gisondi Michael A. , Schertzer Kimberly
Published: July 2022

Background

Trainee supervision and teaching are distinct skills that both require faculty physician competence to ensure patient safety. No standard approach exists to teach physician supervisory competence, resulting in variable trainee oversight and safety threats. The Objective Structured Teaching Evaluation (OSTE) does not adequately incorporate the specific skills required for effective supervision. To address this continuing medical education gap, the authors aimed to develop and identify validity evidence for an “Objective Structured Supervision Evaluation” (OSSE) for attending physicians, conceptually modeled on the historic OSTE.

Methods

An expert panel used an iterative process to create an OSSE instrument, which was a checklist of key supervision items to be evaluated during a simulated endotracheal intubation scenario. Three trained “standardized residents” scored faculty participants' performance using the instrument. Validity testing modeled a contemporary approach using Kane's framework. Participants underwent simulation‐based mastery learning (SBML) with deliberate practice until meeting a minimum passing standard (MPS).

Results

The final instrument contained 19 items, including three global rating measures. Testing domains included supervision climate, participant control of patient care, trainee evaluation, instructional skills, case‐specific measures, and overall supervisor rating. Reliability of the assessment tool was excellent (ICC range 0.84–0.89). The assessment tool had good internal consistency (Cronbach's α = 0.813). Out of 24 faculty participants, 17 (70.8%) met the MPS on initial assessment. All met the MPS after SBML and average score increased by 19.5% (95% CI of the difference 10.3%–28.8%, p = 0.002).

Conclusions

The OSSE is a promising tool to assess faculty supervision performance. Further study should evaluate the effect of OSSE training on supervision in the clinical environment, which may have measurable changes in patient‐centered outcomes and resident teaching.
Serum per‐ and polyfluoroalkyl substance concentrations in four municipal US fire departments
Authors: Burgess Jefferey L. , Fisher Julia M. , Nematollahi Amy , Jung Alesia M. , Calkins Miriam M. , Graber Judith M. , Grant Casey C. , Beitel Shawn C. , Littau Sally R. , Gulotta John J. , Wallentine Darin D. , Hughes R. Jeffrey , Popp Charles , Calafat Antonia M. , Botelho Julianne C. , Coleman Alissa D. , Schaefer‐Solle Natasha , Louzado‐Feliciano Paola , Oduwole Simi O. , Caban‐Martinez Alberto J.
Published: July 2022

Background

Firefighters have occupational and environmental exposures to per‐ and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants.

Methods

Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A–D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES.

Results

In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A–C, sum of branched perfluoromethylheptane sulfonate isomers (Sm‐PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n‐PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n‐PFOA) was elevated in Departments B–D, and perfluorononanoate (PFNA) was elevated in Departments B–D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2‐(N‐methyl‐perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B–D. In female firefighters compared with NHANES, PFHxS and Sm‐PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department.

Conclusions

Serum PFHxS, Sm‐PFOS, n‐PFOS, n‐PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.
Vitamin D intake and cognitive decline in Blacks and Whites: The role of diet and supplements
Authors: Dhana Klodian , Barnes Lisa L. , Agarwal Puja , Liu Xiaoran , Dhana Anisa , Desai Pankaja , Aggarwal Neelum , Evans Denis A. , Rajan Kumar B.
Published: July 2022

Introduction

To determine the role of vitamin D intake on cognitive decline among Blacks and Whites.

Methods

Using data from the population‐based Chicago Health and Aging Project, we studied 2061 Blacks and 1329 Whites with dietary vitamin D data and cognitive testing over 12 years of follow‐up. Multivariable linear mixed‐effects models were used to determine the association of vitamin D intake with cognitive decline.

Results

Vitamin D intake, particularly dietary vitamin D, was associated with a slower rate of decline in cognitive function among Blacks. In Blacks, comparing individuals in the lowest tertile of dietary intake, those in the highest tertile had a slower cognitive decline of 0.017 units/year (95% confidence interval 0.006, 0.027), independently of supplementation use. In Whites, vitamin D intake was not associated with cognitive decline.

Discussion

Dietary vitamin D may help to slow the decline in cognitive abilities among Blacks as they age.
Intact HIV Proviruses Persist in the Brain Despite Viral Suppression with ART
Authors: Cochrane Catherine R. , Angelovich Thomas A. , Byrnes Sarah J. , Waring Emily , Guanizo Aleks C. , Trollope Gemma S. , Zhou Jingling , Vue Judith , Senior Lachlan , Wanicek Emma , Eddine Janna Jamal , Gartner Matthew J. , Jenkins Trisha A. , Gorry Paul R. , Brew Bruce J. , Lewin Sharon R. , Estes Jacob D. , Roche Michael , Churchill Melissa J.
Published: July 2022

Objective

Human immunodeficiency virus (HIV) persistence in blood and tissue reservoirs, including the brain, is a major barrier to HIV cure and possible cause of comorbid disease. However, the size and replication competent nature of the central nervous system (CNS) reservoir is unclear. Here, we used the intact proviral DNA assay (IPDA) to provide the first quantitative assessment of the intact and defective HIV reservoir in the brain of people with HIV (PWH).

Methods

Total, intact, and defective HIV proviruses were measured in autopsy frontal lobe tissue from viremic (n = 18) or virologically suppressed (n = 12) PWH. Total or intact/defective proviruses were measured by detection of HIV pol or the IPDA, respectively, through use of droplet digital polymerase chain reaction (ddPCR). HIV‐seronegative individuals were included as controls (n = 6).

Results

Total HIV DNA was present at similar levels in brain tissues from untreated viremic and antiretroviral (ART)‐suppressed individuals (median = 22.3 vs 26.2 HIV pol copies/106 cells), reflecting a stable CNS reservoir of HIV that persists despite therapy. Furthermore, 8 of 10 viremic and 6 of 9 virally suppressed PWH also harbored intact proviruses in the CNS (4.63 vs 12.7 intact copies/106 cells). Viral reservoirs in CNS and matched lymphoid tissue were similar in the composition of intact and/or defective proviruses, albeit at lower levels in the brain. Importantly, CNS resident CD68+ myeloid cells in virally suppressed individuals harbored HIV DNA, directly showing the presence of a CNS resident HIV reservoir.

Interpretation

Our results demonstrate the first evidence for an intact, potentially replication competent HIV reservoir in the CNS of virally suppressed PWH. ANN NEUROL 2022;92:532–544
An Endoplasmic Reticulum (ER)‐Targeting DNA Nanodevice for Autophagy‐Dependent Degradation of Proteins in Membrane‐Bound Organelles
Authors: Liu Caixia X. , Wang Bin , Zhu Weiping P. , Xu Yufang F. , Yang Yangyang Y. , Qian Xuhong H.
Published: July 2022

Targeted protein degradation via proteasomal and lysosomal pathways is a promising therapeutic approach, and proteins in cytoplasm or on the cell membrane can be easily contacted and have become the major targets. However, degradation of disease‐related proteins that exist in membrane‐bound organelles (MBO) such as the endoplasmic reticulum (ER) remains unsolved due to the membrane limits. Here we describe a DNA nanodevice that shows ER targeting capacity and undergoes new intracellular degradation via the autophagy‐dependent pathway. Then the DNA nanostructure functionalized with specific ligands is used to selectively catch ER‐localized proteins and then transport them to the lysosome for degradation. Through this technique, the degradation of both exogenous ER‐resident protein (ER‐eGFP) and endogenous overexpressed molecular chaperone (glucose‐regulated protein 78) in cancer cells has been successfully executed with high efficiency.
A Modular Co‐assembly Strategy for Ordered Mesoporous Perovskite Oxides with Abundant Surface Active Sites
Authors: Zheng Yuenan , Wang Luoqi , Liu Hongyu , Yang Jiaqi , Zhang Rui , Zhang Ling , Qiao Zhen‐An
Published: July 2022

The ordered mesoporous perovskite oxides with well‐defined mesostrcture and versatile metal sites are attractive, but their successful synthesis faces challenges of complicated assembly dynamics and pore collapse in crystalline calcination. Here, we propose an energy balance concept to reveal interplay relationship in assembly process and realize regulation of porous structure for mesoporous perovskite oxides. A series of ordered mesoporous perovskite oxides with unique porous structure were prepared by a modular co‐assembly method. Mesoporous La2Zr2O7 shows 94 % conversion and 99 % selectivity for hydrogenation of 5‐hydroxymethylfurfural (HMF) to 2,5‐bis(hydroxymethyl)furan. Experiments reveal that rich Lewis acid sites, active Zr species, and favorable porous structure promote interaction between mesoporous La2Zr2O7 and HMF and reduce catalytic energy barrier. This work provides the insight into molecule co‐assembly and developing multiple component ordered mesoporous materials.
Chemical Investigations of Differentially Oxidized Polycylic Pyrroles from Bipolaris Fungi: Synthetic Entry Into the Bipolamine Alkaloids
Authors: Xuan Jun , Machicao Paulo A. , Haelsig Karl T. , Maimone Thomas J.
Published: July 2022

indolizidine alkaloids of unusual biosynthetic origin have recently been characterized from several species of fungi within the Pleosporaceae family. Possessing distinct polycyclic architectures with two embedded electron‐rich pyrroles as well as reported antibacterial activity against gram positive and negative pathogens, these natural products represent attractive targets for total synthesis. Herein we survey the differential functionalization of a chemically sensitive bispyrrole framework resulting in the preparation of multiple bipolamine alkaloids, work which sheds light on their innate chemical reactivity and potential biosynthetic relationships.
Leveraging Isothermal Titration Calorimetry to Explore Structure–Property Relationships of Protein Immobilization in Metal–Organic Frameworks
Authors: Tai Tzu‐Yi , Sha Fanrui , Wang Xiaoliang , Wang Xingjie , Ma Kaikai , Kirlikovali Kent O. , Su Shengyi , Islamoglu Timur , Kato Satoshi , Farha Omar K.
Published: July 2022

Proteins immobilized in metal–organic frameworks (MOFs) often show extraordinary stability. However, most efforts to immobilize proteins in MOFs have only been exploratory. Herein, we present the first systematic study on the thermodynamics of protein immobilization in MOFs. Using insulin as a probe, we leveraged isothermal titration calorimetry (ITC) to investigate how topology, pore size, and hydrophobicity of MOFs influence immobilization. ITC data obtained from the encapsulation of insulin in a series of Zr‐MOFs reveals that MOFs provide proteins with a hydrophobic stabilizing microenvironment, making the encapsulation entropically driven. In particular, the pyrene‐based NU‐1000 tightly encapsulates insulin in its ideally sized mesopores and stabilizes insulin through π‐π stacking interactions, resulting in the most enthalpically favored encapsulation process among this series. This study reveals critical insights into the structure–property relationships of protein immobilization.
Synergistic effect of polyphosphazene nanotubes and graphene on enhancing ablative resistance of ethylene propylene diene monomer insulation composites
Authors: Chen Junming , Huang Xiaobin , He Yongzhu , Liu Longquan , Sheng Haoqiang , Hu Wenbin , Zhao Zhengchuang , He Jinxuan
Published: July 2022

Many advanced fillers were used in ethylene propylene diene monomer (EPDM) insulation composites to enhance the ablative resistance by strengthening char layer. However, the structures of fillers and char layer were usually neglected. In this work, a new type of cross‐linked network‐like polyphosphazene nanotubes (PNTs) was added in EPDM composites in combination with graphene. The results showed that the ablation performance of EPDM composites was improved by 21.6% with the synergistic effect of PNTs and graphene. Moreover, the ablation mechanism was studied by analyzing ablated char layer using X‐ray diffraction (XRD), scanning electron microscopy (SEM), energy disperse spectroscopy (EDS) and Raman spectroscopy. PNTs served as skeleton to build the cross‐linked network char layer and graphene played a role in enhancing the properties of char layer. The findings of this work emphasize the synergistic effect of structures and properties of fillers when performing ablative modification, which provides a new idea to enhance the ablation properties of EPDM composites.
Delivery of bioactive albumin from multi‐functional polyampholyte hydrogels
Authors: Haag Stephanie L. , Martinez‐Alvarez Jacquelin , Schiele Nathan R. , Bernards Matthew T.
Published: July 2022

Tissue engineered scaffolds are currently being explored to aid in healing and regeneration of non‐union fractures in bone. Additionally, albumin has been demonstrated to provide benefits to healing when applied to injury sites. This article focuses on delivery of calcium modified, bioactive bovine serum albumin (BSA) from a multi‐functional polyampholyte polymer scaffold. First, the inherent nonfouling and conjugation properties of the polyampholyte hydrogel were verified to determine the impact of calcium exposure. The polyampholyte hydrogel delivery platform was then assessed with calcium titrations and osteoblast‐like cell (MC3T3‐E1) adhesion, proliferation, and viability evaluations. Finally, integrin inhibitors were used to identify the binding mechanisms that mediate cell adhesion to the calcium‐modified BSA‐conjugated hydrogels. An increase in cell adhesion was observed following calcium exposure up to 0.075 M, although this and higher calcium concentrations affected hydrogel stability and cell growth. BSA exposed to 0.05 M calcium and delivered from polyampholyte hydrogels promoted the most promising viable cell adhesion over 7 days. Cell adhesion to the calcium‐modified BSA‐conjugated hydrogels appeared to be regulated by arginine‐glycine‐aspartic acid (RGD) and collagen‐specific integrins. These results demonstrate that the delivery of calcium modified BSA from an implantable polymer scaffold is promising for bone tissue engineering applications.
Shear and elongational rheometry for determination of spinnability window of polymer solutions in solution blow spinning
Authors: Wojasiński Michał , Ciach Tomasz
Published: July 2022

Recently, processes for stable and efficient production of polymeric nano‐ and submicron fibrous materials, like solution blow spinning, have developed rapidly. However, the application of new polymers, synthetic or natural, for the fabrication of innovative fibrous materials still requires a trial‐and‐error approach to determine the spinnability window of polymer concentration in the solution. In this study, we investigated the use of shear and elongational rheometry to determine the spinnability window of polymer solutions of two synthetic polymers—poly‐L‐lactic acid (PLLA) and polyurethane (PU). Based on measured values of four polymer solution properties: density, surface tension, zero shear viscosity, and relaxation time, we calculated Ohnesorge (Oh) and Deborah (De) numbers corresponding to the polymer concentration ranges from 1 to 9%w/w for PLLA and 1–12%w/w for PU. After blow spinning each of the investigated solutions and using images from the scanning electron microscope and calculated values of Oh and De numbers, we determined the spinnability window for both polymers in the solution blow spinning process to be Oh >0.5, De/Oh >1, and Oh < 25.
Pulse Electromagnetic Field for Treating Postmenopausal Osteoporosis: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Lang Shuang , Ma Jianxiong , Gong Shuwei , Wang Yan , Dong Benchao , Ma Xinlong
Published: July 2022

Postmenopausal osteoporosis is a type of chronic disease with high morbidity and high economic burden. Due to the adverse effects of long‐term drug therapy, physical therapy, such as pulsed electromagnetic fields (PEMF), is widely implemented in clinical practice. Therefore, we first conducted the meta‐analysis on the efficacy and safety of PEMF in the treatment of postmenopausal osteoporosis. We searched eight databases to acquire potentially eligible studies. Outcome indicators include bone mineral density (BMD), visual analogue scale (VAS), biochemical markers of alkaline phosphatase (ALP), osteocalcin, bone‐specific alkaline phosphatase (BSAP), type I collagen carboxy‐terminal peptide (CTX), and adverse events. The results showed that a total of 19 studies (1303 patients) were retrieved from eight databases. Compared with conventional medications, PEMF combined with conventional medications significantly increased BMD of lumbar vertebra, femoral, Ward's triangle, bone‐specific biochemical indicators of ALP, BSAP, and osteocalcin, and relieved pain. However, The incidence of adverse events was not statistically significant between PEMF combined with conventional medications and conventional medications alone. Compared with conventional medications, PEMF significantly increased the BMD of the femur and reduced the degree of pain, but there was no statistical difference in the BMD of the lumbar spine between PEMF and placebo. Except osteocalcin, BSAP, CTX, and ALP showed no significant difference. In view of its efficacy and safety, PEMF intervention can be considered as a potentially effective complementary therapy for postmenopausal women with osteoporosis. © 2022 Bioelectromagnetics Society.
Dynamic alterations of metabolites revealed the vascularization progression of bioengineered liver
Authors: Zhou Qian , Guo Beibei , Chen Deying , Yao Heng , Liang Xi , Xin Jiaojiao , Shi Dongyan , Ren Keke , Yang Hui , Jiang Jing , Li Jun
Published: July 2022

Vascularization is a critical but challenging process in developing functional bioengineered livers with the decellularized liver scaffolds (DLSs) and the process is accompanied by cell‐specific metabolic alterations. To elucidate the dynamic alterations of metabolites during vascularization, rat DLSs were vascularized with human umbilical vein endothelial cells and liquid chromatography mass spectrometry‐based metabolomics was performed on culture supernatants collected at 0, 1, 3, 7, 14, and 21 days. Overall, 1698 peak pairs or metabolites were detected in the culture supernatants, with 309 metabolites being positively identified. The orthogonal partial least‐squares discriminant analysis and functional enrichment analysis revealed three phases that could be clearly discriminated, including Phase D1 (cell proliferation and migration), Phase D3D7 (vascular lumen formation), and Phase D14D21 (functional endothelial barrier formation). Seventy‐two common differentially abundant metabolites of known identity were detected in these three phases when compared with Day 0. Of these metabolites, a high level of β‐Alanine indicated a better degree of vascularization and 14 days of in vitro dynamic culture is required to develop a functionalized vascular structure. These results enriched our understanding of the metabolic mechanism of DLS vascularization and indicated that β‐Alanine could function as a potential predictor of the patency of vascularized bioengineered livers.
Synthesis of New Cinnamoyl‐Amino Acid Conjugates and in Vitro Cytotoxicity and Genotoxicity Studies
Authors: Çalışkan Eray , Öztürk Dilara Altay , Koran Kenan , Tekin Suat , Sandal Süleyman , Erkan Sultan , Görgülü Ahmet Orhan , Çetin Ahmet
Published: July 2022

Amino acid conjugates are described by the reaction of amino acids with bioactive organic groups such as vitamins, hormones, flavonoids, steroids, and sugars. In this study, 12 new conjugates were synthesized by reaction of cinnamic acid derivatives with various amino acids. Cytotoxic studies against four different human cancer cells (MCF7, PC‐3, Caco‐2, and A2780) were carried out by MTT assay method at five different concentrations. The structure‐activity relationships based on the cell viability rates were evaluated. To compare the anticancer activities of the compounds using computational chemistry methods, they were docked against A2780 human ovarian cancer, Michigan Cancer Foundation‐7 (MCF7), human prostate cancer (PC‐3) and human colon epidermal adenocarcinoma (Caco‐2) cell lines and compared with the standard 5‐Fluorouracil. The results indicate that the efficacy of cinnamic acid derivatives increases with the presence of amino acids. Comet assay was conducted to understand whether the cell deaths occur through DNA damage mechanism and the results exhibit that the changes in the specified parameters were statistically significant (p<0.05). Our study demonstrated that the compounds cause cell death through the formation of DNA damage mechanism.
Post‐Synthetic Modification of a Porous Hydrocarbon Cage to Give a Discrete Co24 Organometallic Complex**
Authors: Thomas Chriso M. , Liang Weibin , Preston Dan , Doonan Christian J. , White Nicholas G.
Published: July 2022

A new alkyne‐based hydrocarbon cage was synthesized in high overall yield using alkyne‐alkyne coupling in the cage forming step. The cage is porous and displays a moderately high BET surface area (546 m2 g−1). The cage loses crystallinity on activation and thus is porous in its amorphous form, while very similar cages have been either non‐porous, or retained crystallinity on activation. Reaction of the cage with Co2(CO)8 results in exhaustive metalation of its 12 alkyne groups to give the Co24(CO)72 adduct of the cage in good yield.
Switching Chirophilic Self‐assembly: From meso‐structures to Conglomerates in Liquid and Liquid Crystalline Network Phases of Achiral Polycatenar Compounds
Authors: Alaasar Mohamed , Cao Yu , Liu Yan , Liu Feng , Tschierske Carsten
Published: July 2022

Spontaneous generation of chirality from achiral molecules is a contemporary research topic with numerous implications for technological applications and for the understanding of the development of homogeneous chirality in biosystems. Herein, a series of azobenzene based rod‐like molecules with an 3,4,5‐trialkylated end and a single n‐alkyl chain involving 5 to 20 aliphatic carbons at the opposite end is reported. Depending on the chain length and temperature these achiral molecules self‐assemble into a series of liquid and liquid crystalline (LC) helical network phases. A chiral isotropic liquid (Iso1[*]) and a cubic triple network phase with chiral I23 lattice were found for the short chain compounds, whereas non‐cubic and achiral cubic phases dominate for the long chain compounds. Among them a mesoscale conglomerate with I23 lattice, a tetragonal phase (Tetbi) containing one chirality synchronized and one non‐synchronized achiral network, an achiral double network meso‐structure with Ia
d space group and an achiral percolated isotropic liquid mesophase (Iso1) were found. This sequence is attributed to an increasing strength of chirality synchronization between the networks, combined with a change of the preferred mode of chirophilic self‐assembly between the networks, switching from enantiophilic to enantiophobic with decreasing chain length and lowering temperature. These nanostructured and mirror symmetry broken LC phases exist over wide temperature ranges which is of interest for potential applications in chiral and photosensitive functional materials derived from achiral compounds.
Chemically Laminated 2D Bis(terpyridine)metal Polymer Films: Formation Mechanism at the Liquid–Liquid Interface and Redox Rectification
Authors: Komeda Joe , Takada Kenji , Maeda Hiroaki , Fukui Naoya , Tsuji Takuya , Nishihara Hiroshi
Published: July 2022

Invited for the cover of this issue is the group of Hiroshi Nishihara at Tokyo University of Science. The image depicts the moment of the growth of the second layer at the liquid–liquid interface to form a heterolaminated film. Read the full text of the article at 10.1002/chem.202201316.
Goals of care documentation by medical oncologists and oncology patient end‐of‐life care outcomes
Authors: Epstein Andrew S. , Riley Michael , Nelson Judith E. , Bernal Camila , Martin Steven , Xiao Han
Published: July 2022

Background

Goals of care (GOC) documentation is important but underused. We aimed to improve oncologist GOC documentation and end‐of‐life (EOL) care.

Methods

In April 2020, our cancer center launched a GOC note template, including optional fields for documenting discussion with the patient about: cancer natural history, goals, and/or EOL (resuscitation preferences, hospice receptivity). Associations between GOC notes and EOL care were evaluated.

Results

Among 1721 patients dying between June 1, 2020 and June 30, 2021, median days from first GOC note (± with documentation of EOL discussion) to death was 92, whereas a GOC note including EOL discussion (“GOC EOL note”), specifically, was 31. Patients with a first GOC note >60 days before death spent fewer days inpatient (6.7 vs 10.6 days, p < .001). Among patients with GOC EOL notes, those with such documentation >30 days before death had fewer inpatient (5 vs 11, p < .001) and intensive care unit days (0.5 vs 1.5, p < .001), more hospice referrals (57% vs 44%, p = .003), and less chemotherapy ≤14 days before death (6% vs 11%, p = .010). Of 925 admissions of patients dying within ≤30 days, those with GOC EOL notes were shorter (7 vs 9 days, p = .013) but not associated with more hospice discharge (30% vs 25%, p = .163). Oncologist (vs nononcologist) GOC documentation and earlier documentation of EOL discussion were associated in subset analyses with less inpatient care and more hospice referrals.

Conclusions

Documentation of GOC, including EOL discussions, is associated with favorable performance on accepted indicators of quality EOL care.
High Mobility and ON/OFF Ratio of Solution‐Processable p‐Channel OFETs from Arylacetylene End‐Capped Alkoxyphenanthrenes
Authors: Balambiga Balu , Devibala Paneerselvam , Imran Predhanekar Mohamed , Bhuvanesh Nattamai S. P. , Nagarajan Samuthira
Published: July 2022

New arylacetylene end‐capped alkoxyphenanthrenes were synthesized and demonstrated as the best active layer for solution‐processable p‐channel organic field‐effect transistors. The alkoxy chain embedded compounds exhibited enhanced solubility and induced non‐covalent interactions resulting in effective molecular packing. The ′Lewis soft′ heteroatoms direct the most stable conformation with dihedral angles possible for molecular interactions, and energy levels. DFT studies supported the fine‐tuning of FMOs, with high HOMO levels ∼−5.2 eV ensuring a low barrier for charge injection. OFET devices exhibited a maximum charge carrier mobility up to 1.30 cm2/Vs with the highest ON/OFF ratio of 107. The strong π–π interactions and the crystallinity of the films are well supported by GIXRD and SEM analysis.
Thermally‐Activated Tunneling in the Two‐Water Bridge Catalyzed Tautomerization of Phosphinylidene Compounds**
Authors: Nandi Ashim , Martin Jan M. L.
Published: July 2022

Phosphinylidenes are an important class of organophosphorus compounds that can exhibit tautomerization between tricoordinated P(III) hydroxide (R1R2POH) and a pentacoordinated P(V) oxide (R1R2P(O)H) form. Herein we show, using the canonical variational transition state theory combined with multidimensional small‐curvature tunneling approximation, the dominance of proton tunneling in the two‐water‐bridged tautomerizations of phosphinous acid and model phosphinylidenes comprising phosphosphinates, H‐phosphonates, H‐phosphinates and secondary phosphine oxides. Based on the studied system, the contribution of thermally‐activated tunneling is predicted to speed up the semiclassical reaction rate by ca. threefold to as large as two orders of magnitude at 298.15 K in the gas phase. The large KIE and the concavity in the Arrhenius plots are further fingerprints of tunneling. The simulations also predicted that the rapid tunneling rate and short half‐life span for the forward reaction, as opposed to the reverse reaction in fluorinated secondary phosphine oxides, would result in P(V) being elusive and only P(III) being isolable, which agrees with previous experiments where only P(III) was detected by IR and NMR spectroscopy. We also explored the role of solvent and predicted tunneling to be substantial.
Hydrazine Energy Storage: Displacing N2H4 from the Metal Coordination Sphere
Authors: McNeece Andrew J. , Jaroš Adam , Batista Enrique R. , Yang Ping , Scott Brian L. , Davis Benjamin L.
Published: July 2022

Hydrogen carriers, such as hydrazine (N2H4), may facilitate long duration energy storage, a vital component for resilient grids by enabling more renewable energy generation. Lanthanide coordination chemistry with N2H4 as well as efforts to displace N2H4 from the metal coordination sphere to develop an efficient catalytic production cycle were detailed. Modeling the equilibrium of different ligand coordination, it was predicted that strong sigma donor molecules would be required to displace N2H4. Monitoring competition experiments with nuclear magnetic resonance confirmed that trimethyl phosphine oxide, dimethylformamide, and dimethyl sulfoxide displaced N2H4 in large or small lanthanide complexes.