bluuebunny/crossref_metadata_2025 huggingface dataset:
An open chat with… Laszlo Nagy
Authors: Wright Duncan E. , Nagy Laszlo
Published: January 2022

Laszlo Nagy has been on the Editorial Board of FEBS Open Bio since the journal’s inception and is a passionate supporter of FEBS Press and other society journals. Currently, he is also an editor of FEBS Letters and The Journal of Clinical Investigation (JCI). He studied medicine at the University Medical School of Debrecen in Hungary, where he graduated with an M.D. and later Ph.D., and then moved to the United States to conduct postdoctoral research at the University of Texas–Houston and subsequently the Salk Institute in San Diego. Laszlo is a Professor of Medicine and Biological Chemistry at John Hopkins School of Medicine, where he is Co‐Director of the Institute for Fundamental Biomedical Research and Associate Director of the Center for Metabolic Origins of Disease, and Adjunct Professor at the University of Debrecen. Formerly, he was a Professor and Founding Director of the Genomic Control of Metabolism Program at the Sanford Burnham Prebys Medical Discovery Institute. He is also a member of the European Molecular Biology Organisation (EMBO), Academia Europaea, the Hungarian Academy of Sciences and The Henry Kunkel Society, and recipient of several awards, including the Boehringer Ingelheim Research Award, Cheryl Whitlock/Pathology Prize, a Wellcome Trust Senior Research Fellowship in Biomedical Sciences, and three Howard Hughes Medical Institute International Research Scholar Awards. In this fascinating interview, Laszlo Nagy shares the advice that changed his career trajectory, relates his views on scientific publishing, discusses new developments at The Johns Hopkins Center for Metabolic Origins of Disease, and outlines the prospects for future development of research and technology infrastructures in eastern Europe.
Moderation vs. abstinence when it comes to well‐being in recovery: A continuum
Authors: Knopf Alison
Published: January 2022

People who have resolved substance use problems and go on to use substances at a low risk have greater self‐esteem, happiness, quality of life and functioning, and “recovery capital,” a recent study has found. The study, by David Eddie and colleagues at the Recovery Research Institute at Harvard Medical School, also found that these people had less psychological stress than those who used at higher risk.
New center to take personalized care to next level, embracing psychedelics
Authors: Enos Gary
Published: January 2022

Two professionals with experience in person‐centered treatment organizations that offered a stark alternative to the Minnesota Model have opened a new outpatient center with a similar approach and the additional component of a novel form of psychedelic‐assisted therapy.
Former SSA on MAT, communication and provider collaboration
Authors: Knopf Alison
Published: January 2022

Mark Stringer, former single state authority of Missouri and former president of the National Association of State Alcohol and Drug Abuse Directors (NASADAD), has some key advice for public officials involved in the substance use disorder (SUD) arena: Be better at explaining what addiction is.
FDA warns about buprenorphine and teeth: ASAM pushes back
Authors: Knopf Alison
Published: January 2022

The federal Food and Drug Administration (FDA) on Jan. 12 called for a dental warning on buprenorphine used to treat opioid use disorder, when dissolved in the mouth. According to the FDA, not taking care of teeth while being treated with buprenorphine, and not following certain steps to make sure the mouth is clean after absorbing the drug, can lead to serious dental problems in patients as young as 18 years old (for the FDA communication, see https://www.fda.gov/drugs/drug‐safety‐and‐availability/fda‐warns‐about‐dental‐problems‐buprenorphine‐medicines‐dissolved‐mouth‐treat‐opioid‐use‐disorder).
In Situ Investigation on Life‐Time Dynamic Structure–Performance Correlation Toward Electrocatalyst Service Behavior in Water Splitting
Authors: Xie Yong , Sun Yu , Tao Huibing , Wang Xin , Wu Jing , Ma Kaikai , Wang Li , Kang Zhuo , Zhang Yue
Published: January 2022

Electrocatalytic water splitting is recognized as quite a promising protocol for the renewable hydrogen energy production, and significant effort has been devoted to the design of high‐performance electrocatalysts that can efficiently alleviate the critical issue of fossil fuel scarcity. However, the vast majority of traditional design strategies restrictedly focus on the pristine electrocatalyst structure and ultimate performance results, which may lead to the incorrect or even opposite understanding of catalytic structure–performance correlations. With the burgeoning development of in situ techniques, the dynamic service behaviors of electrocatalysts during water splitting have been growingly investigated from enriched perspectives, only by which can the life‐time dynamic structure–performance correlations be established. Herein, to shed new light on the next‐stage development of in situ investigations for water splitting electrocatalysts, a series of dynamic service behavior that existed in water splitting process and highlight their key role for understanding the life‐time dynamic structure–performance correlations is comprehensively summarized. Besides, a wide variety of in situ techniques are systematically dissected in terms of their functional features, advantages, and limitations. Critical challenges and prospects are also discussed for establishing the life‐time dynamic structure–performance correlations of water splitting electrocatalysts.
Solution‐Deposited and Patternable Conductive Polymer Thin‐Film Electrodes for Microbial Bioelectronics
Authors: Tseng Chia‐Ping , Liu Fangxin , Zhang Xu , Huang Po‐Chun , Campbell Ian , Li Yilin , Atkinson Joshua T. , Terlier Tanguy , Ajo‐Franklin Caroline M. , Silberg Jonathan J. , Verduzco Rafael
Published: January 2022

Microbial bioelectronic devices integrate naturally occurring or synthetically engineered electroactive microbes with microelectronics. These devices have a broad range of potential applications, but engineering the biotic–abiotic interface for biocompatibility, adhesion, electron transfer, and maximum surface area remains a challenge. Prior approaches to interface modification lack simple processability, the ability to pattern the materials, and/or a significant enhancement in currents. Here, a novel conductive polymer coating that significantly enhances current densities relative to unmodified electrodes in microbial bioelectronics is reported. The coating is based on a blend of poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS) crosslinked with poly(2‐hydroxyethylacrylate) (PHEA) along with a thin polydopamine (PDA) layer for adhesion to an underlying indium tin oxide (ITO) electrode. When used as an interface layer with the current‐producing bacterium Shewanella oneidensis MR‐1, this material produces a 178‐fold increase in the current density compared to unmodified electrodes, a current gain that is higher than previously reported thin‐film 2D coatings and 3D conductive polymer coatings. The chemistry, morphology, and electronic properties of the coatings are characterized and the implementation of these coated electrodes for use in microbial fuel cells, multiplexed bioelectronic devices, and organic electrochemical transistor based microbial sensors are demonstrated. It is envisioned that this simple coating will advance the development of microbial bioelectronic devices.
Stimuli‐Responsive Liquid‐Crystal‐Infused Porous Surfaces for Manipulation of Underwater Gas Bubble Transport and Adhesion
Authors: Rather Adil Majeed , Xu Yang , Chang Yun , Dupont Robert Lewis , Borbora Angana , Kara Ufuoma Israel , Fang Jen‐Chun , Mamtani Rajdeep , Zhang Meng , Yao Yuxing , Adera Solomon , Bao Xiaoping , Manna Uttam , Wang Xiaoguang
Published: January 2022

Biomimetic artificial surfaces that enable the manipulation of gas bubble mobility have been explored in a wide range of applications in nanomaterial synthesis, surface defouling, biomedical diagnostics, and therapeutics. Although many superhydrophobic surfaces and isotropic‐lubricant‐infused porous surfaces have been developed to manipulate gas bubbles, the simultaneous control over the adhesion and transport of gas bubbles underwater remains a challenge. Thermotropic liquid crystals (LCs), a class of structured fluids, provide an opportunity to tune the behavior of gas bubbles through LC mesophase transitions using a variety of external stimuli. Using this central idea, the design and synthesis of LC‐infused porous surfaces (LCIPS) is reported and the effects of the LC mesophase on the transport and adhesion of gas bubbles on LCIPS immersed in water elucidated. LCIPS are demonstrated to be a promising class of surfaces with an unprecedented level of responsiveness and functionality, which enables the design of cyanobacteria‐inspired object movement, smart catalysts, and bubble gating devices to sense and sort volatile organic compounds and control oxygen levels in biomimetic cell cultures.
Construction of MXene/PDMS‐Based Triboelectric Nanogenerators for High‐Performance Cathodic Protection
Authors: Xu Hui , Wang Xiutong , Niu Jianmin , Nan Youbo , Pu Jiayan , Zhou Hui , Duan Jizhou , Huang Yanliang , Hou Baorong
Published: January 2022

A vertical contact‐separation mode triboelectric nanogenerator (TENG) to collect mechanical energy and protect stainless steel from corrosion is constructed by spraying to combine MXene powder and polydimethylsiloxane (PDMS). The output of TENG increases significantly by spraying a very small amount (1.2 mg) of MXene, which has excellent conductivity and electro‐negativity. The MXene/PDMS TENG (MP/PP‐TENG) shows the output performance with a short current circuit of 22 µA and output voltage of 900 V, and the output peak power increases by 2.6 times. Meanwhile, MP‐TENG is a reliable alternative to power supply for cathodic protection. The electrochemical measurement results show that the open circuit potential drop of the stainless steel coupled with the MP‐TENG is about 300 mV. Continuous motion of TENG can realize processive protection of metals, proving its potential practical application to all‐weather marine corrosion protection.
An In‐Depth Study of Regulable Zincophilic Alloy Matrix toward Stable Zinc Metal Batteries
Authors: Zhao Qiwen , Wang Yunyun , Liu Wen , Liu Xiaoyu , Wang Han , Yu Huaming , Chen Yuejiao , Chen Libao
Published: January 2022

Introducing 3D hosts is recognized as valid means to low the local current density for alleviating dendrite problems. However, the uncontrollable “top growth” behavior on some 3D hosts is still a serious issue. Although some strategies on the manipulation of Zn2+ ion flux by causing Zn‐alloying metals are reported, the covert details during cycles are still ignored. A tuned Cu‐Zn alloy interfacial layer on stainless‐steel mesh (SS) is proposed here as a fresh tactic. The zincophilic scaffold furnishes nucleation sites and lowers energy barriers for axipetally controllable Zn plating. In‐depth study reveals that CuxZny phase generated by variable Cu/Zn ratios preferentially forms into CuZn5 with Zn plating and then converts into metallic Zn in plating cycle, and no decomposition in a given voltage range in stripping process due to a negative Gibbs free energy of formation of zinc alloys. Thus, CuZn5 is the main zincophilic seed in the subsequent cycles, regardless of any CuxZny phases. As a result, the optimized SS in Zn//MnO2 full cell can render 70% retention after 350 cycles, while the bare SS only shows retention of 30%.
Elongated Focus Optoacoustic Microscopy with Matched Bessel Beam Illumination and Ultrabroadband Axicon Detection
Authors: Ali Zakiullah , Zakian Christian , Ntziachristos Vasilis
Published: January 2022

Current optoacoustic (OA) microscopy configurations often have narrow focal ranges that limit their use for fast volumetric imaging applications. Herein, the focal range of OA microscopes is extended by matching the elongated optical illumination profile of a Bessel beam with the pencil beam acoustic sensitivity profile of a broadband axicon detector. An inverted OA microscope is developed with interchangeable optical illumination and acoustic detection units to assess the working distance and resolutions retained with several combinations of illumination and detection profiles. Matching Bessel illumination with axicon detection extends the depth of focus 17‐fold over traditional configurations. Imaging a tilted mouse ear with the matched Bessel−axicon configuration reveals vasculature over a working distance exceeding 4.2 mm with optical resolution, while affording a sixfold increase in imaging volume over the same scanning duration compared with configurations using standard Gaussian illumination, demonstrating this approach's promise for increasing applications for OA microscopy in preclinical research.
Gaze‐Matched Pupil Steering Maxwellian‐View Augmented Reality Display with Large Angle Diffractive Liquid Crystal Lenses
Authors: Zou Junyu , Li Lingshan , Wu Shin-Tson
Published: January 2022

Maxwellian‐view structure exhibits several advantages in augmented reality (AR) displays, such as high efficiency, always‐in‐focus (no vergence‐accommodation conflict (VAC)), and simple optical structure. However, the bottleneck of Maxwellian‐view is its tiny eyebox. Extensive efforts have been devoted to enlarge the eyebox of the Maxwellian‐view system based on pupil duplication or pupil steering by creating multiple viewing points, however, the important gaze matching is neglected. Once the virtual image center deviates from the user's eye gaze, it will bring an unnatural viewing experience. Herein, a gaze‐matching Maxwellian‐view AR system with an enlarged eyebox is demonstrated. In the meantime, this AR system also maintains the properties of aberration‐free, high efficiency, highly transparent for ambient light, and relatively large field of view. Moreover, two layers of off‐axis cholesteric liquid crystal (CLC) lenses are applied as the optical combiner in the system, which is lightweight and compact. The off‐axis angle of such a CLC lens is as large as 60 degrees, which plays a vital role in future Maxwellian‐view AR headsets.
Organic Photoredox Catalyzed Direct Hydroamination of Ynamides with Azoles
Authors: Wang Ban , Mccabe Gavin E. , Parrish Mitchell J. , Singh Jujhar , Zeller Matthias , Deng Yongming
Published: January 2022

Disclosed herein is a photoinduced selective hydroamination of ynamides with nitrogen heteroaromatic nucleophiles. By using an organocatalytic photoredox system, a direct method to construct a diverse of (Z)‐α‐azole enamides from ynamides and pyrazoles, as well as triazoles, benzotriazoles, indazoles, and tetrazoles, is developed, thus providing a photocatalytically synthetic route to heterocyclic motifs common in medicinal agents. Based on the mechanistic studies, the hydroamination is postulated to operate via a mechanism in which the single‐electron oxidation of ynamide and the intermediacy of an alkyne radical cation, is responsible for the observed reactivity.

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Bleaching‐Resistant Super‐Resolution Fluorescence Microscopy
Authors: Kwon Jiwoong , Elgawish Mohamed Saleh , Shim Sang‐Hee
Published: January 2022

Photobleaching is the permanent loss of fluorescence after extended exposure to light and is a major limiting factor in super‐resolution microscopy (SRM) that restricts spatiotemporal resolution and observation time. Strategies for preventing or overcoming photobleaching in SRM are reviewed developing new probes and chemical environments. Photostabilization strategies are introduced first, which are borrowed from conventional fluorescence microscopy, that are employed in SRM. SRM‐specific strategies are then highlighted that exploit the on–off transitions of fluorescence, which is the key mechanism for achieving super‐resolution, which are becoming new routes to address photobleaching in SRM. Off states can serve as a shelter from excitation by light or an exit to release a damaged probe and replace it with a fresh one. Such efforts in overcoming the photobleaching limits are anticipated to enhance resolution to molecular scales and to extend the observation time to physiological lifespans.
Zoology of Multiple‐Q Spin Textures in a Centrosymmetric Tetragonal Magnet with Itinerant Electrons
Authors: Khanh Nguyen Duy , Nakajima Taro , Hayami Satoru , Gao Shang , Yamasaki Yuichi , Sagayama Hajime , Nakao Hironori , Takagi Rina , Motome Yukitoshi , Tokura Yoshinori , Arima Taka‐hisa , Seki Shinichiro
Published: January 2022

Magnetic skyrmion is a topologically stable particle‐like swirling spin texture potentially suitable for high‐density information bit, which was first observed in noncentrosymmetric magnets with Dzyaloshinskii–Moriya interaction. Recently, nanometric skyrmion has also been discovered in centrosymmetric rare‐earth compounds, and the identification of their skyrmion formation mechanism and further search of nontrivial spin textures are highly demanded. Here, magnetic structures in a prototypical skyrmion‐hosting centrosymmetric tetragonal magnet GdRu2Si2 is exhaustively studied by performing the resonant X‐ray scattering experiments. A rich variety of double‐Q magnetic structures, including the antiferroic order of meron(half‐skyrmion)/anti‐meron‐like textures with fractional local topological charges are identified. The observed intricate magnetic phase diagram is successfully reproduced by the theoretical framework considering the four‐spin interaction mediated by itinerant electrons and magnetic anisotropy. The present results will contribute to the better understanding of the novel skyrmion formation mechanism in this centrosymmetric rare‐earth compound, and suggest that itinerant electrons can ubiquitously host a variety of unique multiple‐Q spin orders in a simple crystal lattice system.
Ultrathick MoS2 Films with Exceptionally High Volumetric Capacitance
Authors: Bo Zheng , Cheng Xiangnan , Yang Huachao , Guo Xinzheng , Yan Jianhua , Cen Kefa , Han Zhaojun , Dai Liming
Published: January 2022

Manufacturing electrode films at an industrial‐level submillimeter thickness (≈100 µm) with superior volumetric performance is of practical significance for the commercialization of miniaturized supercapacitor systems. This work proposes a commercially scalable solvated‐ion‐intercalated hydrothermal strategy to demonstrate a record‐high volumetric capacitance (511.29 F cm−3) for supercapacitors based on an industrial‐level submillimeter MoS2 film electrode (94.2 µm). The intercalated solvated Li+ ions increase the amount of negative surface charge and reduce the formation energy of 1T MoS2, leading to a high metallic phase content of 82.7% with enhanced electrical conductivity. Together with the expanded interlayer distance (≈1.23 nm), this allows rapid electron transfer and ion transport in the excessively stacked ultrathick MoS2 film to be simultaneously realized. Thus, the as‐fabricated MoS2||graphene/carbon nanotube asymmetric supercapacitor presents both high energy and power densities, outperforms those of commercial devices, including supercapacitors with submillimeter‐thick electrodes and even micrometer‐thick electrodes.
Qualitative description of sexual harassment and discrimination of women in emergency medicine: Giving the numbers a voice
Authors: Maso Kristi , Theobald Jillian L.
Published: January 2022

Introduction

Gender disparities in medicine are well documented; however, little qualitative data exist. This study sought to provide a qualitative assessment of harassment and discrimination experienced by female physicians in emergency medicine (EM) specifically by colleagues or supervisors.

Methods

An electronic survey was distributed to female EM physicians on October 18, 2018, asking if they have felt harassed, diminished, uncomfortable, or discriminated against by a male colleague or supervisor at work based on a sexual comment or unwanted advance. Space for descriptive experiences was provided. A data abstraction tool was developed, and experiences were placed into thematic categories. The survey was closed on December 18, 2018, and data were analyzed.

Results

There were 1280 responses. Responses that were incomplete, not attributable to women, and outside of EM were excluded leaving 1144 to be analyzed. Respondents were primarily White (81%) and working in nonacademic environments (53.5%). The majority (57.3%) felt harassed, diminished, uncomfortable, or discriminated against by a male colleague or superior at work based on sexual comment or innuendo; 22.3% experienced an unwanted sexual act or advance. There were 482 descriptive experiences reported, most frequently focusing on patronizing behavior (16.5%), pregnancy/maternity leave (15.9%), and physical appearance (12.5%).

Conclusions

Women in EM experience sexual harassment and discrimination at work by their peers and supervisors. Exploring the themes of their shared experiences can guide and focus efforts on both prevention and intervention. Further studies are needed to determine if these experiences contribute to disparities in earnings, promotion, and leadership roles of women in medicine.
Grazing cover crops in a no‐till corn and soybean rotation
Authors: Dhakal Dhruba , Erwin Zachary L. , Nelson Kelly A.
Published: January 2022

Cover crop (CC) systems may offset expensive hay feeding in early spring. Field research evaluated the effect of CCs on forage mass, weed control, soil penetrometer resistance, and no‐till corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] grain yield (2003–2008) in upstate Missouri. The main plot was grazed and nongrazed CCs, corn and soybean were the subplots, and CCs [nonseeded control, cereal rye (CR, Secale cereale L.), wheat (Triticum aestivum L.), ‘King’ or ‘Marshall’ annual ryegrass (RG, Lolium multiflorum Lam.)] were the sub‐sub plot. Cover crops were grazed two to four times in the spring when the fastest growing species was 20–30 cm tall. Forage mass was collected from the nongrazed treatment. Cereal rye produced the greatest total forage mass in 3 and 4 of 6 yr following corn and soybean, respectively. Cereal rye forage mass (3,640 kg ha−1) was similar to wheat following corn and was 860 kg ha−1 greater than wheat following soybean. Winter annual weeds were controlled up to 92% with CCs. Cattle (Bos taurus) grazing CCs increased penetrometer resistance up to a 20‐cm soil depth compared with nongrazed CCs. Corn grain yield was reduced 0.4 Mg ha−1 following grazed CCs, while soybean yields following grazed CCs were similar to nongrazed treatments (4–6 yr). Corn yields following CCs were ranked nonseeded control = Marshall RG ≥ wheat ≥ King RG ≥ CR. Soybean yields following CCs were similar or less than the nonseeded control. Grazing CCs could add value over the absence of the CC and promote CCs in the U.S. Midwest.
Work‐related fatigue: A hazard for workers experiencing disproportionate occupational risks
Authors: Cunningham Thomas R. , Guerin Rebecca J. , Ferguson Jacqueline , Cavallari Jennifer
Published: January 2022

Background

Long working hours and fatigue are significant occupational safety and health (OSH) hazards for working populations who experience disproportionate risks of injury and illness. These groups include young or new workers, aging workers, contingent and temporary workers, immigrant and nonnative workers, female workers, minority workers, workers with low levels of education and lower socioeconomic status, and small business employees. An increasing focus on newer determinants of health in the workplace, such as health equity and work‐life conflict, in worker populations at greater risk for injury or illness, provides an opportunity for researchers to address the causes and consequences of work‐related fatigue in high‐risk populations.

Methods

Articles in the OSH literature that addressed fatigue in higher‐risk workers were identified by the authors or recommended by subject matter experts in workplace fatigue as part of a Working Hours, Sleep and Fatigue Forum. Additional articles were identified by searching for a combination of specific at‐risk worker group titles (e.g., female workers, temporary workers) with fatigue or working hours.

Results

There remains a paucity of research specifically addressing working hours and fatigue among disproportionately at‐risk worker populations. The literature reviewed in this paper suggests that several of these populations are at increased risk of fatigue due to multiple factors, such as irregular shifts, lack of access to fatigue management resources, and socioeconomic barriers.

Conclusions

More research is needed to identify solutions to address fatigue in working populations who may be at greater risk for its consequences by virtue of adverse socioeconomic and related factors. Interventions to address work‐related fatigue in specific at‐risk worker groups should also consider the multiple and overlapping categories of risk within these populations.
Whole exome sequencing studies in epilepsy: A deep analysis of the published literature
Authors: Shukralla Arif , Carton Robert , Benson Katherine A. , El Naggar Hany , Lacey Austin , Cavalleri Gianpiero , Delanty Norman
Published: January 2022

To evaluate the quality of whole‐exome sequencing (WES) reporting in the epilepsy literature. We aimed to assess the quality of reporting of WES in epilepsy. We compared studies based on journal type and if outcome reporting biases exist. We used a self‐constructed benchmark to quantitatively analyze studies. We included 451 publications. Reporting was heterogeneous with poor reporting of (1) ACMG guideline application 13% and (2) Human Phenotype Ontology (HPO) numbers in 3% of studies, 3) VUS in 19%. Predictors of reporting included journal type and journal impact factor. Date of publication and publication type were not predictors of poor reporting. Pairwise comparisons of genetics versus neurology journals using relative risks yielded significant differences in reporting of ACMG guideline application (RR 1.88, 95% CI 1.04–3.38); HPO numbers (RR 8.62, 95% CI 1.08–63.37) and deposition of findings to ClinVar (RR 2.50, 95% CI 1.03–6.1). Reporting of WES literature is heterogeneous in quality, and poor reporting hinders collaboration and accession of data into large databases like OMIM and OrphaNet. This study highlights reporting bias in this area and, formal structural guidelines like the CONSORT guidelines used in the reporting of clinical trials are needed to address the issue.
[3+2] Cycloaddition of Nitrile Imines with 3‐Benzylidene Succinimides: A Facile Access to Functionalized Spiropyrazolines
Authors: Yuan Cheng , Ning Xiaojun , Gao Tao , Zeng Zhigang , Lee Kevin , Xing Yalan , Sun Shaofa , Wang Gangqiang
Published: January 2022

A wide range of substituted spiro‐pyrazoline derivatives containing the pyrrolidinone core have been prepared by alkalic treatment of 3‐benzylidene succinimides and nitrile imines. All reactions proceeded under mild conditions and the products were isolated by column chromatography in good yields with high diastereoselectivity. Furthermore, this method featured several advantages such as good functional group tolerance and simple scalability.
Low untreated systolic blood pressure over 18 years is associated with survival free of dementia age 90+
Authors: Kuller Lewis H. , Snitz Beth E. , Hughes Timothy M. , Chang Yuefang , Cohen Ann D. , Mathis Chester A. , Aizenstein Howard J. , Lopez Oscar L.
Published: January 2022

Introduction

We hypothesized that lower untreated systolic blood pressure (SBP) would be associated with a lower risk of dementia and death up to age 95.

Methods

SBP measured between 2000 and 2006 was evaluated in relationship to dementia risk and brain biomarkers from 2009‐2020 (n = 177) in the Gingko Evaluation of Memory Study (GEMS), mean age 95 in 2020. Participants had measurements of brain amyloid beta (Aβ) and repeat clinical‐cognitive evaluations every 6 months.

Results

By 2020, only 9 of 177 patients (5%) were alive and cognitively unimpaired (CU). Mean SBP from 2000 to 2006 was 120 mm Hg for nine alive/CU, 125 mm Hg for alive/mild cognitive impairment (MCI), and 130 mm Hg for alive/dementia (P = .03). The amount of Aβ was directly related to SBP levels. In multivariate analysis, Aβ+ in 2009 and thinner cortex were significant predictors of dementia. Excluding Aβ, SBP became a significant predictor of dementia.

Discussion

Low SBP untreated by antihypertensive medications was associated with significant decreased risk of dementia and less Aβ.
Photoswitchable Molecular Communication between Programmable DNA‐Based Artificial Membraneless Organelles
Authors: Zhao Qi‐Hong , Cao Fang‐Hao , Luo Zhen‐Hong , Huck Wilhelm T. S. , Deng Nan‐Nan
Published: January 2022

Spatiotemporal organization of distinct biological processes in cytomimetic compartments is a crucial step towards engineering functional artificial cells. Mimicking controlled bi‐directional molecular communication inside artificial cells remains a considerable challenge. Here we present photoswitchable molecular transport between programmable membraneless organelle‐like DNA coacervates in a synthetic microcompartment. We use droplet microfluidics to fabricate membraneless non‐fusing DNA coacervates by liquid‐liquid phase separation in a water‐in‐oil droplet, and employ the interior DNA coacervates as artificial organelles to imitate intracellular communication via photo‐regulated uni‐ and bi‐directional transfer of biomolecules. Our results highlight a promising new route to assembly of multicompartment artificial cells with functional networks.
Oligo(N‐methylalanine) as a Peptide‐Based Molecular Scaffold with a Minimal Structure and High Density of Functionalizable Sites
Authors: Yokomine Marin , Morimoto Jumpei , Fukuda Yasuhiro , Shiratori Yota , Kuroda Daisuke , Ueda Takumi , Takeuchi Koh , Tsumoto Kouhei , Sando Shinsuke
Published: January 2022

Functionalizable synthetic molecules with nanometer sizes and defined shapes in water are useful as molecular scaffolds to mimic the functions of biomacromolecules and develop chemical tools for manipulating biomacromolecules. Herein, we propose oligo(N‐methylalanine) (oligo‐NMA) as a peptide‐based molecular scaffold with a minimal structure and a high density of functionalizable sites. Oligo‐NMA forms a defined shape in water without hydrogen‐bonding networks or ring constraints, which enables the molecule to act as a scaffold with minimal atomic composition. Furthermore, functional groups can be readily introduced on the nitrogens and α‐carbons of oligo‐NMA. Computational and NMR spectroscopic analysis suggested that the backbone structure of oligo‐NMA is not largely affected by functionalization. Moreover, the usefulness of oligo‐NMA was demonstrated by the design of protein ligands. The ease of synthesis, minimal structure, and high functionalization flexibility makes oligo‐NMA a useful scaffold for chemical and biological applications.
Hybrid Elastic Organic Crystals that Respond to Aerial Humidity
Authors: Lan Linfeng , Yang Xuesong , Tang Baolei , Yu Xu , Liu Xiaokong , Li Liang , Naumov Panče , Zhang Hongyu
Published: January 2022

Reshaping of elongated organic crystals that can be used as semiconductors, waveguides or soft robotic grippers by application of force or light is now a commonplace, however mechanical response of organic crystals to changes in humidity has not been accomplished yet. Here, we report a universal approach to instigating a humidity response into elastically bendable organic crystals that elicits controllable deformation with linear response to aerial humidity while retaining their physical integrity entirely intact. Hygroresponsive bilayer elements are designed by mechanically coupling a humidity‐responsive polymer with elastic molecular crystals that have been mechanically reinforced by a polymer coating. As an illustration of the application of these cladded crystalline actuators, they are tested as active optical transducers of visible light where the position of light output can be precisely controlled by variations in aerial humidity. Within a broader context, the approach described here provides access to a vast range of mechanically robust, lightweight hybrid hygroresponsive crystalline materials.
Fish acoustic community structure in Neptune seagrass meadows across the Mediterranean basin
Authors: Bolgan Marta , Di Iorio Lucia , Dailianis Thanos , Catalan Ignacio A. , Lejeune Pierre , Picciulin Marta , Parmentier Eric
Published: January 2022

Sound production represents an integral part of social communication in many teleost fish; however, few studies have investigated the structure, organization and variability of fish sounds at the community level.

Fish acoustic community structure was recorded simultaneously in three sites located along the Mediterranean basin within the endemic habitat of Posidonia oceanica seagrass beds. Acoustic diversity and species‐specific sound features were expected to differ between locations. We predicted that, in communities characterized by higher acoustic richness, fish species would specialize in their use of acoustic resources (i.e. realized acoustic niche compression), while the overall allocation of resources within the community signal space would expand.

The fish acoustic communities inhabiting Posidonia beds were characterized by the same main contributors (the /Kwa/, Ophidion rochei and Sciaena umbra sound types). However, their relative occurrence, abundances and use of acoustic resources were site‐specific. Acoustic diversity differed between geographic locations. The range of spectral and temporal resources exploited by the fish acoustic community was wider in sites where acoustic richness was at its highest score. Ophidion rochei was highly specialized in its use of temporal resources where acoustic richness was higher, whilst S. umbra appeared less efficient in specializing the use of spectral and temporal resources.

By showing that the same species can exploit different acoustic resources between locations, this study supports the concept of Acoustic Niche plasticity (i.e. plasticity of acoustic resources allocation within a species). The results suggest that the degree of acoustic niche plasticity might be determined by the species‐specific degree of sound‐producing system plasticity. In turn, different degrees of acoustic niche plasticity might determine different species‐specific levels of acoustic adaptability to changing biotic or environmental conditions.
Green synthesis of pregabalin‐stabilized gold nanoclusters and their applications in sensing and drug release
Authors: Ali Reham , Alfeneekh Bayader , Chigurupati Sridevi , Saleh Sayed M.
Published: January 2022

This is the first report on the simple preparation of gold nanoclusters stabilized with pregabalin (PREG) as a capping and reducing agent. PREG is an active pharmaceutical ingredient of the commercially available drug “Lyrica” used to treat different diseases like epilepsy and anxiety. PREG has never been used before in the synthesis of any nanoparticles or nanoclusters. The prepared gold nanoclusters (PREG‐stabilized gold nanoclusters [PREG‐AuNCs]) have blue fluorescence with excitation/emission at 365/425 nm, respectively. The reaction conditions were optimized for the synthesis of the as‐prepared AuNCs. Different tools were used for the characterization of the synthesized nanoclusters in terms of size and surface properties. The PREG‐AuNCs were exploited as a sensitive and selective fluorescent nanosensor for Cu2+ detection. The quenching of AuNC fluorescence intensity in the presence of Cu2+ is due to the aggregation‐induced fluorescence quenching mechanism. The detection limit of Cu2+ ions was found to be 1.11 × 10−7 M. The selectivity of the PREG‐AuNCs was studied and proved to be excellent. The drug entrapment efficacy and in vitro drug diffusion studies along with drug release kinetics helped to understand more about the pharmaceutical approaches of PREG‐AuNCs. Moreover, we think that PREG‐AuNCs open new opportunities as a promising candidate material for drug delivery systems and medical applications.
Risk assessment for nitrosated pharmaceuticals: A future perspective in drug development
Authors: Schmidtsdorff Sebastian , Neumann Jonas , Schmidt Alexander H. , Parr Maria K.
Published: January 2022

Since June 2018, thousands of drug products from around the world had to be recalled due to the unexpected presence of nitrosamines (NAs). Starting with the pharmaceutical group of sartans, antidiabetic drugs, antihistamines, and antibiotics also became the subject of investigation. The occurrence of NAs has shown that pharmaceutical companies and regulatory agencies did not focus on these substances in the past during drug development. In this study, we incorporated a nitrosation assay procedure into high‐resolution supercritical fluid chromatography (SFC)–mass spectrometry screening to test the potential of direct nitrosation of active pharmaceutical ingredients (APIs). The forced degradation study was performed with a four‐fold molar excess of sodium nitrite, relative to the drug substance, at pH 3–4 for 4 h at 37°C. Chromatographic separation was performed on a porous graphitic carbon column by SFC. The mass analysis then focused on direct N‐nitrosation or N‐nitroso compounds (NOCs) formed after dealkylation. Substances (n = 67) from various pharmaceutical classes were evaluated and 49.3% of them formed NOCs, of which 21.2% have not yet been reported in the literature. In addition, for two APIs, which are known to form an unidentified NOC, the structure could be identified. A few substances also showed multiple NOCs and even N,N’‐dinitroso‐species. As NAs are carcinogens, they have to be eliminated or at least limited to prevent cancer in patients, who rely on these drugs. This study contributes a procedure that can be implemented in preapproval drug development and postapproval risk assessment to prevent unexpected findings in the future.
Chemiluminescent Probes Based on 1,2‐Dioxetane Structures For Bioimaging
Authors: Wang Yaling , Bian Yongning , Chen Xueqian , Su Dongdong
Published: January 2022

Chemiluminescent probes based on 1,2‐dioxetane scaffold are one of the most sensitive imaging modalities for detecting disease‐related biomarkers and can obtain more accurate biological information in cells and in vivo. Due to the elimination of external light excitation, the background autofluorescence problem in fluorescence technology can be effectively avoided, providing ultrahigh sensitivity and signal‐to‐noise ratio for various applications. In this review, we highlight a comprehensive but concise overview of activatable 1,2‐dioxetane‐based chemiluminescent probes by reporting significant advances in accurate detection and bioimaging. The design principles and applications for reactive species, enzymes, and other disease‐related biomarkers are systematically discussed and summarized. The challenges and potential prospects of chemiluminescent probes are also discussed to further promote the development of new chemiluminescence methods for biological analysis and diagnosis.
LRFN5 locus structure is associated with autism and influenced by the sex of the individual and locus conversions
Authors: Lybæk Helle , Robson Michael , de Leeuw Nicole , Hehir‐Kwa Jayne Y. , Jeffries Aaron , Haukanes Bjørn Ivar , Berland Siren , de Bruijn Diederik , Mundlos Stefan , Spielmann Malte , Houge Gunnar
Published: January 2022

LRFN5 is a regulator of synaptic development and the only gene in a 5.4 Mb mammalian‐specific conserved topologically associating domain (TAD); the LRFN5 locus. An association between locus structural changes and developmental delay (DD) and/or autism was suggested by several cases in DECIPHER and own records. More significantly, we found that maternal inheritance of a specific LRFN5 locus haplotype segregated with an identical type of autism in distantly related males. This autism‐susceptibility haplotype had a specific TAD pattern. We also found a male/female quantitative difference in the amount histone‐3‐lysine‐9‐associated chromatin around the LRFN5 gene itself (p < 0.01), possibly related to the male‐restricted autism susceptibility. To better understand locus behavior, the prevalence of a 60 kb deletion polymorphism was investigated. Surprisingly, in three cohorts of individuals with DD (n = 8757), the number of deletion heterozygotes was 20%–26% lower than expected from Hardy–Weinberg equilibrium. This suggests allelic interaction, also because the conversions from heterozygosity to wild‐type or deletion homozygosity were of equal magnitudes. Remarkably, in a control group of medical students (n = 1416), such conversions were three times more common (p = 0.00001), suggesting a regulatory role of this allelic interaction. Taken together, LRFN5 regulation appears unusually complex, and LRFN5 dysregulation could be an epigenetic cause of autism.

Lay Summary

LRFN5 is involved with communication between brain cells. The gene sits alone in a huge genomic niche, called the LRFN5 locus, of complex structure and high mammalian conservation. We have found that a specific locus structure increases autism susceptibility in males, but we do not yet know how common this epigenetic cause of autism is. It is, however, a cause that potentially could explain why higher‐functioning autism is more common in males than females.
Febuxostat and its major acyl glucuronide metabolite are potent inhibitors of organic anion transporter 3: Implications for drug‐drug interactions with rivaroxaban
Authors: Tang Lloyd Wei Tat , Cheong Tino Woon Huai , Chan Eric Chun Yong
Published: January 2022

Febuxostat is a second‐line xanthine oxidase inhibitor that undergoes extensive hepatic metabolism to yield its major acyl‐β‐D‐glucuronide metabolite (febuxostat AG). It was recently reported that febuxostat inhibited organic anion transporter 3 (OAT3)‐mediated uptake of enalaprilat. Here, we investigated the inhibition of febuxostat and febuxostat AG on OAT3 in transfected human embryonic kidney 293 cells. Our transporter inhibition assays confirmed the potent noncompetitive and competitive inhibition of OAT3‐mediated estrone‐3‐sulfate transport by febuxostat and febuxostat AG with corresponding apparent Ki values of 0.55 and 6.11 μM respectively. After accounting for probe substrate‐dependency and protein binding effects, mechanistic static modelling with the direct factor Xa anticoagulant rivaroxaban estimated a 1.47‐fold increase in its systemic exposure when co‐administered with febuxostat based on OAT3 interaction which in turn exacerbates the bleeding risk from baseline for patients with atrial fibrillation by 1.51‐fold. Taken together, our results suggested that the concomitant usage of febuxostat with rivaroxaban may potentially culminate in a clinically‐significant drug‐drug interaction and result in an increased risk of bleeding as a result of its OAT3 inhibition.
A Hexameric Ribozyme Nanostructure Formed by Double‐Decker Assembly of a Pair of Triangular Ribozyme Trimers
Authors: Yu Kai , Hidaka Kumi , Sugiyama Hiroshi , Endo Masayuki , Matsumura Shigeyoshi , Ikawa Yoshiya
Published: January 2022

The modular architecture of naturally occurring ribozymes makes them a promising class of structural platform for the design and assembly of three‐dimensional (3D) RNA nanostructures, into which the catalytic ability of the platform ribozyme can be installed. We have constructed and analyzed RNA nanostructures with polygonal‐shaped (closed) ribozyme oligomers by assembling unit RNAs derived from the Tetrahymena group I intron with a typical modular architecture. In this study, we dimerized ribozyme trimers with a triangular shape by introducing three pillar units. The resulting double‐decker nanostructures containing six ribozyme units were characterized biochemically and their structures were observed by atomic force microscopy. The double‐decker hexamers exhibited higher catalytic activity than the parent ribozyme trimers.
Treatment with secukinumab for plaque psoriasis in patients with infectious comorbidities and latent tuberculosis: A multi‐case report analysis
Authors: Fiorella Carmen
Published: January 2022

Three patients affected by plaque psoriasis and presenting with multiple infectious comorbidities and latent tuberculosis infection (LTBI) were initially managed with conventional DMARD therapy. After showing unsuccessful results, treatment with secukinumab was initiated without prophylactic isoniazid and soon led to favorable dermatological outcomes without the reactivation of tuberculosis infection.
Presentation of Eagle syndrome following radiation therapy to carcinoma of the larynx
Authors: Cartwright Jake K. , Moreno Francisco G.
Published: January 2022

Eagle syndrome is a rare clinical condition that is characterized by either an elongated styloid process or a calcified stylohyoid ligament. This report describes the case of a 35‐year‐old woman who presented with Eagle syndrome following the treatment of recurrent laryngeal carcinoma with ionizing radiation.
Case of reversible Mobitz type II atrioventricular block after the use of injectable antipsychotics
Authors: Naono Hisao , Takeda Ryuichiro , Masuyama Hiroyuki , Kawano Jiro , Naono‐Nagatomo Keiko , Ishida Yasushi
Published: January 2022

Although Mobitz type II atrioventricular block is typically an arrhythmia arising from a permanent organic disorder of the His‐Purkinje system, reversible factors should also be considered. Here, we report the association between a rare reversible Mobitz type II atrioventricular block and antipsychotic medication in a 75‐year‐old patient with schizophrenia.
Puzzling hepatic tumor: Epithelioid angiomyolipoma
Authors: Limaiem Faten , Baccouch Seifeddine , Boujelbene Nadia , Atallah Aziz , Hajri Mohamed , Gabsi Sofiène , Ben Farhat Leila , Bouraoui Saâdia
Published: January 2022

Hepatic epithelioid angiomyolipomas are uncommon mesenchymal neoplasms. They are difficult to diagnose by imaging, especially when the fatty component is scant or absent. The gold standard for the diagnosis is histologic examination coupled with an immunohistochemical study. Positive HMB45 immunostaining of the myoid cells is a major diagnostic feature.
DMAP Immobilized on Porous Silica Particles and Monoliths for the Esterification of Phenylethanol in Continuous Flow
Authors: Schulze Julia S. , Brand Raoul D. , Hering Joachim G. C. , Riegger Luise M. , Schreiner Peter R. , Smarsly Bernd M.
Published: January 2022

We report the immobilization of 4‐dimethylaminopyridine (DMAP), a versatile organocatalyst for sterically demanding esterifications, on mesoporous silica particles and macro‐mesoporous silica monoliths, both possessing optimized properties for continuous flow synthesis. An alkyne‐functionalized DMAP derivative was immobilized via click chemistry; the materials were characterized by physisorption analysis, diffuse reflectance infrared Fourier transform spectroscopy (DRIFT) and elemental analysis. While silica particles were functionalized in batch and packed into a packed‐bed reactor, monoliths were cladded with a polyether ether ketone (PEEK) tube after sol‐gel synthesis and functionalized in a circulating flow process. Samples with three different catalyst loadings were prepared, in order to study the impact of the catalyst amount on the mesopore space as well as the catalytic performance. In continuous flow experiments, complete conversion of 1‐phenylethanol to phenylethylacetate was achieved with both materials and short contact times. Monoliths exhibited far lower pressures than packed bed reactors (7 bar at a flow rate of 1 mL min−1) and reached turnover rates up to 9.3x10−2 s−1, which is almost twice as high as a comparable batch experiment. The absence of diffusion limitations in monoliths made investigations on reaction kinetics with microkinetics‐dominated experiments possible. This study demonstrates that all properties needed for a successful transfer of immobilized organocatalysts to sophisticated flow syntheses with complex organocatalysts can be met with functionalized meso‐macroporous monoliths.