bluuebunny/crossref_metadata_2025 huggingface dataset:
Incremental Value of Polygenic Risk Scores in Primary Prevention of Coronary Heart Disease
Authors: Groenendyk Jacob William , Greenland Philip , Khan Sadiya S.
Published: August 2022

Importance

Risk prediction for coronary heart disease (CHD) is a cornerstone of primary prevention strategies. Polygenic risk scores (PRSs) have emerged as a new approach to predict risk in asymptomatic people. Polygenic risk scores for CHD have been studied in several populations, but there is lack of agreement about the incremental value of PRS beyond traditional risk factor scores in the primary prevention of CHD.

Observations

This narrative review critically appraised the 5 most highly cited studies published through 2021 that also included a large number (>45 000) of single-nucleotide variations (formerly single-nucleotide polymorphisms) and evaluated the incremental value of PRS in CHD risk prediction according to published PRS reporting standards. The cohorts studied included the Atherosclerosis Risk in Communities Study, FINRISK, the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the UK Biobank. All of the studies focused predominantly on populations of European ancestry. The hazard ratio per standard deviation of PRS ranged from 1.24 (95% CI, 1.15-1.34) to 1.74 (95% CI, 1.61-1.86). The C statistic for PRS alone ranged from 0.549 to 0.623. The change in C statistic when PRS was added to a standard risk factor model ranged between −0.001 to +0.021. Net reclassification index was reported in 4 of the 5 studies and varied from 0.001 to 0.097. At a sensitivity (true-positive rate) of 90%, positive predictive values ranged from 1.8% to 16.6%, and false-positive rates ranged from 77.1% to 85.7%.

Conclusions and Relevance

In this review, PRS was significantly associated with CHD risk in all studies. The degree of improvement in C statistic and the net reclassification indexes when PRS was added to traditional risk scores ranged from negligible to modest. Based on established metrics to assess risk prediction scores, the addition of PRS to traditional risk scores does not appear to provide meaningful improvements in clinical decision-making in primary prevention populations.
A 31-Year-Old Man With Bilaterally Limited Mobility of Joints
Authors: Wang Zhiqin , Wang Chunrong , Zhou Yafang
Published: August 2022

A 31-year-old man with limited mobility of joints in his hands, feet, and ankles presented for evaluation with no noted erythema, edema, or Raynaud phenomenon. What is your diagnosis?
Scientific Misinformation Is Criminalizing the Standard of Care for Transgender Youth
Authors: Lepore Christina , Alstott Anne , McNamara Meredithe
Published: August 2022

This Viewpoint challenges new laws that criminalize gender-affirming care for transgender and nonbinary youth in the US.
A Novel Pentanary Metal Oxide Cathode with P2/O3 Biphasic Structure for High‐Performance Sodium‐Ion Batteries
Authors: Liang Xinghui , Sun Yang‐Kook
Published: August 2022

The rapid capacity loss suffered by P2‐type Mn‐based layered oxide cathode materials, caused by deleterious high‐voltage phase transformations and the dissolution of active materials, greatly limits their application in large‐scale sodium‐ion battery installations. In this study, a novel P2/O3 biphasic cathode is developed using a multi‐element (Fe, Mg, and Li) co‐substitution strategy. The results of ex situ X‐ray diffraction analyses and the absence of significant voltage plateaus in the charge–discharge profiles of cells featuring the proposed cathode indicate that deleterious phase transformations and concomitant lattice mismatch in the high‐voltage region are effectively suppressed because of the topotactic intergrown structure of the resulting cathode. The optimized cathode also demonstrates improved structural stability and enhanced Na+ diffusion kinetics, owing to the incorporation of stabilizing dopant pillars and suppressed metal‐ion dissolution. Hence, the resulting Na half cell demonstrates a high initial capacity of 170.5 mA h g−1 at 0.1 C and excellent rate capability (106.6 mA h g−1 at 10 C). Furthermore, the resulting Na full cell, featuring a hard carbon anode, displays excellent cycling stability (72.1% capacity retention after 400 cycles), demonstrating its practical viability. This study presents the design and optimization of high‐performance Mn‐based cathodes.
Reinforced Hyaluronic Acid‐Based Matrices Promote 3D Neuronal Network Formation
Authors: Janzen Dieter , Bakirci Ezgi , Faber Jessica , Andrade Mier Mateo , Hauptstein Julia , Pal Arindam , Forster Leonard , Hazur Jonas , Boccaccini Aldo R. , Detsch Rainer , Teßmar Jörg , Budday Silvia , Blunk Torsten , Dalton Paul D. , Villmann Carmen
Published: August 2022

3D neuronal cultures attempt to better replicate the in vivo environment to study neurological/neurodegenerative diseases compared to 2D models. A challenge to establish 3D neuron culture models is the low elastic modulus (30–500 Pa) of the native brain. Here, an ultra‐soft matrix based on thiolated hyaluronic acid (HA‐SH) reinforced with a microfiber frame is formulated and used. Hyaluronic acid represents an essential component of the brain extracellular matrix (ECM). Box‐shaped frames with a microfiber spacing of 200 µm composed of 10‐layers of poly(ɛ‐caprolactone) (PCL) microfibers (9.7 ± 0.2 µm) made via melt electrowriting (MEW) are used to reinforce the HA‐SH matrix which has an elastic modulus of 95 Pa. The neuronal viability is low in pure HA‐SH matrix, however, when astrocytes are pre‐seeded below this reinforced construct, they significantly support neuronal survival, network formation quantified by neurite length, and neuronal firing shown by Ca2+ imaging. The astrocyte‐seeded HA‐SH matrix is able to match the neuronal viability to the level of Matrigel, a gold standard matrix for neuronal culture for over two decades. Thus, this 3D MEW frame reinforced HA‐SH composite with neurons and astrocytes constitutes a reliable and reproducible system to further study brain diseases.
Helical Polariton Lasing from Topological Valleys in an Organic Crystalline Microcavity
Authors: Long Teng , Ma Xuekai , Ren Jiahuan , Li Feng , Liao Qing , Schumacher Stefan , Malpuech Guillaume , Solnyshkov Dmitry , Fu Hongbing
Published: August 2022

Topological photonics provides an important platform for the development of photonic devices with robust disorder‐immune light transport and controllable helicity. Mixing photons with excitons (or polaritons) gives rise to nontrivial polaritonic bands with chiral modes, allowing the manipulation of helical lasers in strongly coupled light‐matter systems. In this work, helical polariton lasing from topological valleys of an organic anisotropic microcrystalline cavity based on tailored local nontrivial band geometry is demonstrated. This polariton laser emits light of different helicity along different angular directions. The significantly enhanced chiral characteristics are achieved by the nonlinear relaxation process. Helical topological polariton lasers may provide a perfect platform for the exploration of novel topological phenomena that involve light‐matter interaction and the development of polariton‐based spintronic devices.
CRISPR/Cas9 screen in human iPSC‐derived cortical neurons identifies NEK6 as a novel disease modifier of C9orf72 poly(PR) toxicity
Authors: Guo Wenting , Wang Haibo , Kumar Tharkeshwar Arun , Couthouis Julien , Braems Elke , Masrori Pegah , Van Schoor Evelien , Fan Yannan , Ahuja Karan , Moisse Matthieu , Jacquemyn Maarten , Furtado Madeiro da Costa Rodrigo , Gajjar Madhavsai , Balusu Sriram , Tricot Tine , Fumagalli Laura , Hersmus Nicole , Janky Rekin's , Impens Francis , Vanden Berghe Pieter , Ho Ritchie , Thal Dietmar Rudolf , Vandenberghe Rik , Hegde Muralidhar L. , Chandran Siddharthan , De Strooper Bart , Daelemans Dirk , Van Damme Philip , Van Den Bosch Ludo , Verfaillie Catherine
Published: August 2022

Introduction

The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are hexanucleotide repeats in chromosome 9 open reading frame 72 (C9orf72). These repeats produce dipeptide repeat proteins with poly(PR) being the most toxic one.

Methods

We performed a kinome‐wide CRISPR/Cas9 knock‐out screen in human induced pluripotent stem cell (iPSC) ‐derived cortical neurons to identify modifiers of poly(PR) toxicity, and validated the role of candidate modifiers using in vitro, in vivo, and ex‐vivo studies.

Results

Knock‐down of NIMA‐related kinase 6 (NEK6) prevented neuronal toxicity caused by poly(PR). Knock‐down of nek6 also ameliorated the poly(PR)‐induced axonopathy in zebrafish and NEK6 was aberrantly expressed in C9orf72 patients. Suppression of NEK6 expression and NEK6 activity inhibition rescued axonal transport defects in cortical neurons from C9orf72 patient iPSCs, at least partially by reversing p53‐related DNA damage.

Discussion

We identified NEK6, which regulates poly(PR)‐mediated p53‐related DNA damage, as a novel therapeutic target for C9orf72 FTD/ALS.
Enzyme‐Activatable Chemokine Conjugates for In Vivo Targeting of Tumor‐Associated Macrophages
Authors: Barth Nicole D. , Van Dalen Floris J. , Karmakar Utsa , Bertolini Marco , Mendive‐Tapia Lorena , Kitamura Takanori , Verdoes Martijn , Vendrell Marc
Published: August 2022

Increased levels of tumor‐associated macrophages (TAMs) are indicators of poor prognosis in most cancers. Although antibodies and small molecules blocking the recruitment of macrophages to tumors are under evaluation as anticancer therapies, these strategies are not specific for macrophage subpopulations. Herein we report the first enzyme‐activatable chemokine conjugates for effective targeting of defined macrophage subsets in live tumors. Our constructs exploit the high expression of chemokine receptors (e.g., CCR2) and the activity of cysteine cathepsins in TAMs to target these cells selectively over other macrophages and immune cells (e.g., neutrophils, T cells, B cells). Furthermore, we demonstrate that cathepsin‐activatable chemokines are compatible with both fluorescent and therapeutic cargos, opening new avenues in the design of targeted theranostic probes for immune cells in the tumor microenvironment.
Synthetic Reagents for Enzyme‐Catalyzed Methylation
Authors: Wen Xiaojin , Leisinger Florian , Leopold Viviane , Seebeck Florian P.
Published: August 2022

Late‐stage methylation is a key technology in the development of pharmaceutical compounds. Methyltransferase biocatalysis may provide powerful options to insert methyl groups into complex molecules with high regio‐ and chemoselectivity. The challenge of a large‐scale application of methyltransferases is their dependence on S‐adenosylmethionine (SAM) as a stoichiometric, and thus exceedingly expensive co‐substrate. As a solution to this problem, we and others have explored the use of methyl halides as reagents for the in situ regeneration of SAM. However, the need to handle volatile electrophiles, such as methyl iodide (MeI), may also hamper applications at scale. As a more practical solution, we have now developed an enzyme‐catalyzed process for the regeneration of SAM with methyl toluene sulfonate. Herein, we describe enzymes from the thiopurine methyltransferase family that accept sulfate‐ and sulfonate‐based methyl donors to convert S‐adenosylhomocysteine into SAM with efficiencies that rival MeI‐based reactions.
Photocatalytic Direct Decarboxylation of Carboxylic Acids to Derivatize or Degrade Polymers
Authors: Adili Alafate , Korpusik Angie B. , Seidel Daniel , Sumerlin Brent S.
Published: August 2022

Visible light‐mediated direct decarboxylation of carboxylic acids with an acridine photocatalyst is a convenient and powerful method to generate carbon‐centered radicals in polymer chains. Advantageously, this process proceeds under mild conditions, without preactivation of the acid groups. We utilize decarboxylation in the presence of a hydrogen atom donor to form statistical acrylate‐ethylene and acrylate‐propylene copolymers, which are challenging to obtain by direct polymerization. We additionally show that decarboxylation of methacrylic acid units within polymethacrylates can trigger degradation of the polymer backbones. Moreover, a dual catalytic approach, which combines the function of an acridine photocatalyst with that of a cobaloxime catalyst, is leveraged to furnish unique copolymers with pendent alkenes. Our work indicates that direct decarboxylation is a versatile technique for the synthesis of functional materials with tailored compositions and properties.
Reconstruction of Highly Dense Cu−N4Active Sites in Electrocatalytic Oxygen Reduction Characterized by Operando Synchrotron Radiation
Authors: Xing Gengyu , Tong Miaomiao , Yu Peng , Wang Lei , Zhang Guangying , Tian Chungui , Fu Honggang
Published: August 2022

The emerging star of single atomic site (SAS) catalyst has been regarded as the most promising Pt‐substituted electrocatalyst for oxygen reduction reaction (ORR) in anion‐exchange membrane fuel cells (AEMFCs). However, the metal loading in SAS directly affects the whole device performance. Herein, we report a dual nitrogen source coordinated strategy to realize high dense Cu−N4SAS with a metal loading of 5.61 wt% supported on 3D N‐doped carbon nanotubes/graphene structure wherein simultaneously performs superior ORR activity and stability in alkaline media. When applied in H2/O2AEMFC, it could reach an open‐circuit voltage of 0.90 V and a peak power density of 324 mW cm−2. Operando synchrotron radiation analyses identify the reconstruction from initial Cu−N4to Cu−N4/Cu‐nanoclusters (NC) and the subsequent Cu−N3/Cu−NC under working conditions, which gradually regulate the d‐band center of central metal and balance the Gibbs free energy of *OOH and *O intermediates, benefiting to ORR activity.
Regulating Crystal Packing by Terminal tert‐Butylation for Enhanced Solid‐State Emission and Efficacious Charge Transport in an Anthracene‐Based Molecular Crystal
Authors: Li Jie , Qin Zhengsheng , Sun Yajing , Zhen Yonggang , Liu Jie , Zou Ye , Li Chunlei , Lu Xueying , Jiang Lang , Zhang Xiaotao , Ji Deyang , Li Liqiang , Dong Huanli , Hu Wenping
Published: August 2022

Organic semiconductors with combinative high carrier mobility and efficient solid‐state emission are full of challenges but urgently pursued for developing new emerging optoelectronics. Herein, by delicately regulating the crystal packing of an anthracene‐based molecular crystal via terminal tert‐butylation, we developed a superior high mobility emissive molecule, 2,6‐di(6‐tert‐butylnaphthyl)anthracene (TBU‐DNA). The unique “slipped herringbone” packing motif of TBU‐DNA enables its appropriate exciton‐exciton coupling and electron‐phonon coupling, thus resulting in remarkably high solid‐state emission (photoluminescence quantum yield, ΦF≈74.9 %) and efficacious charge transport (carrier mobility, μ=5.0 cm2 V−1 s−1). Furthermore, OLETs based on TBU‐DNA show an external quantum efficiency (EQE) of 1.8 %, which is among the highest EQE values for single component OLETs reported till now. This work presents a crystal engineering strategy via exquisite molecular design to realize high mobility emissive organic semiconductors.
Probing for peptidic drugs (2–10 kDa) in doping control blood samples
Authors: Thomas Andreas , Thilmany Sam , Hofmann Amelie , Thevis Mario
Published: August 2022

Bioactive peptides with a molecular mass between 2 and 10 kDa represent an important class of substances banned in elite sports, which has been recognized with an increasing number and variety of substances by anti‐doping organizations. Also, the annually renewed list of prohibited substances of the World Anti‐Doping Agency (WADA) explicitly mentions more and more of these peptides, and efficient testing procedures are required. Even under simplified sample preparation conditions, liquid chromatography coupled to high‐resolution mass spectrometry (with resolution properties > 100,000 full width at half maximum) offers suitable conditions for this task and can therefore be used as an initial testing procedure. In contrast to urine, blood analysis essentially relies on the detection of intact peptide hormones, and the expected concentrations are commonly higher in blood samples than in urine. This facilitates the analysis, and a generic sample preparation by means of mixed‐mode solid‐phase extraction could be realized in this study. Co‐extraction and analysis of several different peptides such as insulins (human, lispro, aspart, glulisine, tresiba, detemir, glargine, bovine insulin and porcine insulin), growth hormone releasing hormones (sermorelin, CJC‐1295 and tesamorelin), insulin‐like growth factors (long‐R3‐IGF‐I, R3‐IGF‐I and Des1‐3‐IGF‐I) and mechano growth factors (human MGF and MGF‐Goldspink) with criteria that fulfil the requirements of the WADA documents (TD2022 MRPL) for doping controls. The proof of principle was shown by the analysis of post administration samples after treatment with synthetic insulin analogues.
Multi‐scale study of the structuration of candle blends with a high content of vegetable fats to replace paraffins: Effect of 12‐hydroxystearic acid content
Authors: Agogué Marie Caroline , Loisel Catherine , Gonçalves Olivier , Legrand Jack , Saint‐Jalmes Sylvaine , Arhaliass Abdellah
Published: August 2022

The aim is to replace mineral waxes with vegetable fats as an organogel for candle manufacturing while keeping the same texture. The physico‐chemical characteristics of renewable vegetable raw materials differ from those of mineral waxes and consequently the structure of the blends in which they are used is modified. Their properties are measured at different scales using FT‐IR analysis, polarized light microscopy, calorimetry and rheology. The addition of 12‐hydroxystearic acid (12‐HSA) promotes the creation of hydrogen bonds within the rapeseed oil that makes possible its incorporation to form an organogel. The addition of 12‐HSA also results in a modification of the crystal microstructure of blends made of 90% vegetable raw materials. Hence, the crystal lattice is denser and the crystal size is reduced compared to blends including mineral waxes. At a macroscopic scale, the physical properties of blends with 12‐HSA are modified compared to the reference one, mainly made of mineral waxes. A modification of crystallization and melting temperatures as measured by differential scanning calorimetry as well as the rheological behavior and the hardness assessed by penetrometer are observed. This results in a higher stability against exudation for blends with a high content of 12‐HSA. Mineral waxes can thus be substituted in the formulation of candles by renewable materials for the use of organogel, via the incorporation of an organogelator, 12‐HSA.
Ligamentum arteriosum: Muscular and contractile
Authors: Mensah Benedicta
Published: August 2022

Ductus arteriosus is a muscular artery in fetal circulation, spanning from the bifurcation of the pulmonary trunk to the aortic arch, shunting blood directly from pulmonary circulation into systemic circulation thus by‐passing the fluid‐filled lungs. Postnatally, it changes name to the ligamentum arteriosum (LA), when a cascade of anatomical and physiological processes leads to its closure. Though the LA has generally been considered as a fibrosed remnant of the ductus arteriosus, anecdotal and contradictory reports still describe the LA as a small muscular artery. We hypothesized the likelihood of contractile muscular elements retainment in this so‐called ligament. To investigate this, mediastinum of wild‐type mouse, pig, and human LA were subjected to routine and special histological staining, single‐immunolabeling, electron microscopy (mouse and pig only), and tension recording of explanted pig LA in organ bath experiments. Contrary to a canonical ligament, the LA was mainly made up of α‐smooth muscle actin‐positive cells in all three species, confirmed by routine and special histological staining as well as transmission electron microscopy. Myocytes within the LA contracted in response to exogenous noradrenalin (NA). NA‐induced precontracted LA relaxed upon administration of the α1‐adrenergic blockers (prazosin and tamsulosin). Though the LA does not function in its original capacity as fetal shunt, it is clearly not a passive structure, and may be described as muscular and contractile. The contractile abilities of LA myocytes may act on the two great vessels to which it is attached causing a change in their distensibility.
Perspective on Nanofluidic Memristors: From Mechanism to Application
Authors: Xie Boyang , Xiong Tianyi , Li Weiqi , Gao Tienan , Zong Jianwei , Liu Ying , Yu Ping
Published: August 2022

Nanofluidic memristors are memory resistors based on nanoconfined fluidic systems exhibiting history‐dependent ion conductivity. Toward establishing powerful computing systems beyond the Harvard architecture, these ion‐based neuromorphic devices attracted enormous research attention owing to the unique characteristics of ion‐based conductors. However, the design of nanofluidic memristor is still at a primary state and a systematic guidance on the rational design of nanofluidic system is desperately required for the development of nanofluidic‐based neuromorphic devices. Herein, we proposed a systematic review on the history, main mechanism and potential application of nanofluidic memristors in order to give a prospective view on the design principle of memristors based on nanofluidic systems. Furthermore, based on the present status of these devices, some fundamental challenges for this promising area were further discussed to show the possible application of these ion‐based devices.
Resilient control of cyber‐physical systems using adaptive super‐twisting observer
Authors: Nateghi Shamila , Shtessel Yuri , Edwards Christopher , Barbot Jean‐Pierre
Published: August 2022

In this work, the problem of online secure state estimation and attack reconstruction in the face of offensives that corrupt the sensor measurements and modify the actuator commands of cyber–physical systems is investigated for designing a resilient controller for the system. The states of cyber–physical system and its actuator attacks are estimated/reconstructed online using a novel adaptive line‐by‐line super‐twisting observer, whereas sparse stealth attacks on unprotected sensors are reconstructed using a sparse recovery algorithm. The estimated attacks are used for attack compensation by a resilient controller. The efficacy of the proposed technique is illustrated via simulation on a real electric power system under deception actuator attack and stealth sensor attack.
Side‐chain engineering of regioregular copolymers for high‐performance polymer solar cells processed with nonhalogenated solvents
Authors: Jung Hyeonwoo , Kim Honggi , Kim Jongyoun , Jang Soyeong , Lee Youngu
Published: August 2022

Conjugated polymers for bulk heterojunction polymer solar cells (BHJ PSCs) should be processed with nonhalogenated solvents because of environmental concerns. Here, we report novel regioregular copolymers for high‐performance PSCs processed with nonhalogenated solvents. The regioregular copolymers (i.e., rr‐PfBT2f4T‐2OD and rr‐PfBT2f4T‐2DT) consist of 3″,4′‐difluoro‐2,2′:5′,2″:5″,2‴‐quaterthiophene (2f4T) with different side chains (2‐octadodecyl (OD) and 2‐decyltetradecyl (DT)) and 5‐fluorobenzo[c][1,2,5]thiadiazole (fBT). The regioregular copolymers with controlled fBT orientation show high solubility in nonhalogenated solvents. Both regioregular copolymers possess suitable energy levels, leading to sufficient energy offsets with a nonfullerene acceptor, BTP‐eC11. An rr‐PfBT2f4T‐2DT:BTP‐eC11‐blended film exhibited predominant face‐on orientation compared to the rr‐PfBT2f4T‐2OD:BTP‐eC11‐blended film. In addition, the rr‐PfBT2f4T‐2DT:BTP‐eC11‐blended film showed much more balanced hole/electron mobility (μh/μe ~ 4.73) than rr‐PfBT2f4T‐2OD:BTP‐eC11‐blended film (μh/μe ~ 45.86). Therefore, rr‐PfBT2f4T‐2DT:BTP‐eC11‐based PSCs, processed with 1,2,4‐trimethylbenzene, showed a power conversion efficiency of 13.21% which is 60% higher than rr‐PfBT2f4T‐2OD:BTP‐eC11‐based PSCs.
An exploratory study on functional connectivity after mild traumatic brain injury: Preserved global but altered local organization
Authors: Kim Eunkyung , Seo Han Gil , Seong Min Yong , Kang Min‐Gu , Kim Heejae , Lee Min Yong , Yoo Roh‐Eul , Hwang Inpyeong , Choi Seung Hong , Oh Byung‐Mo
Published: August 2022

Introduction

This study aimed to investigate alterations in whole‐brain functional connectivity after a concussion using graph‐theory analysis from global and local perspectives and explore the association between changes in the functional network properties and cognitive performance.

Methods

Individuals with mild traumatic brain injury (mTBI, n = 29) within a month after injury, and age‐ and sex‐matched healthy controls (n = 29) were included. Graph‐theory measures on functional connectivity assessed using resting state functional magnetic resonance imaging data were acquired from each participant. These included betweenness centrality, strength, clustering coefficient, local efficiency, and global efficiency. Multi‐domain cognitive functions were correlated with the graph‐theory measures.

Results

In comparison to the controls, the mTBI group showed preserved network characteristics at a global level. However, in the local network, we observed decreased betweenness centrality, clustering coefficient, and local efficiency in several brain areas, including the fronto‐parietal attention network. Network strength at the local level showed mixed‐results in different areas. The betweenness centrality of the right parahippocampus showed a significant positive correlation with the cognitive scores of the verbal learning test only in the mTBI group.

Conclusion

The intrinsic functional connectivity after mTBI is preserved globally, but is suboptimally organized locally in several areas. This possibly reflects the neurophysiological sequelae of a concussion. The present results may imply that the network property could be used as a potential indicator for clinical outcomes after mTBI.
Improvement of sleep and melatonin in children with autism spectrum disorder after β‐1,3/1,6‐glucan consumption: An open‐label prospective pilot clinical study
Authors: Raghavan Kadalraja , Dedeepiya Vidyasagar Devaprasad , Kandaswamy Ramesh Shankar , Balamurugan Mangaleswaran , Ikewaki Nobunao , Sonoda Tohru , Kurosawa Gene , Iwasaki Masaru , Preethy Senthilkumar , Abraham Samuel JK
Published: August 2022

Introduction

Poor sleep quality is a major problem in patients with autism spectrum disorder (ASD), and is attributed to low melatonin levels. Melatonin supplementation is recommended; however, its effectiveness varies. β‐Glucans have previously been shown to improve melatonin levels in animal studies. Herein, we examined the effectiveness of Aureobasidium pullulans (Nichi Glucan), a species of black yeast that contains beta‐1,3/1,6‐glucan, in a pilot study of children with ASD.

Methods

Thirteen children (age, 2.5–13 years) with ASD were recruited for the study. The control group consisted of four patients (Gr. 1), while nine patients were classified into the treatment group (Gr. 2). Gr. 2 received 1 g of Nichi Glucan along with conventional therapy, whereas the Gr. 1 (control) patients received conventional therapy alone for 90 days. Serum melatonin levels and sleep patterns, assessed using a subjective questionnaire, were evaluated before and after treatment.

Results

In Gr. 2, the average serum melatonin level increased from 238.85 ng/L preintervention to 394.72 ng/L postintervention. Eight of nine participants (88%) in Gr. 2 showed improvements in sleep pattern and quality, while no improvement was observed in the participants in Gr. 1.

Conclusion

The consumption of Nichi Glucan for 90 days resulted in visible improvement in sleep quality, sleep pattern, and serum melatonin levels, which was reported for the first time by our study. A larger multicenter study is required to validate our findings.
The impact of internal company dynamics on sustainable circular business development: Insights from circular startups
Authors: von Kolpinski Charleen , Yazan Devrim Murat , Fraccascia Luca
Published: August 2022

The circular economy is commonly acknowledged as a solution to ecological problems such as resource depletion and waste emissions. New economic opportunities emerge by transitioning from a linear to a circular economy and innovative business models are needed to translate these opportunities into business reality. In recent years, researchers have investigated a variety of approaches to circular business models, but few studies have been conducted associating internal company dynamics with sustainable circular business approaches. Consequently, the purpose of this study is to investigate the internal dynamics of young and small‐scale companies in Germany that adopt a sustainable circular business model. This study focuses on internal barriers, enablers, competences and drivers to sustainable circular business model implementation. A case‐based research design was applied, drawing on semi‐structured interviews with 12 founders of businesses and organisations with a sustainable circular business model. The study develops four strategies to overcome barriers to sustainable circular business model adoption in young and small‐scale companies: (1) human‐centeredness in all activities affected by circular business model adoption, (2) high commitment for circularity on the managerial level, (3) requirement of special skills and competences and (4) consideration of cultural aspects inside and outside the company. Further empirical research about established and international incumbents with a sustainable circular business model is needed to be able to compare the internal dynamics of big and small companies in international contexts.
Diving into the business strategy: The strategy tripod's influence on supply chain sustainability orientation
Authors: Ponte Roselene C. Del Vecchio , Viana Fernando Luiz E. , Silva Minelle E.
Published: August 2022

Firm orientation is a key factor in the implementation of sustainability in supply chains (SCs). Although firms recognize the need to define strategies for success, they often overlook whatever strategies they do develop in their decision‐making process. To address this gap, we argue that the strategy tripod comprising the industry‐based view (IBV), resource‐based view (RBV), and institutional‐based view (INSBV) can influence SC orientation toward sustainability. This paper describes an investigation into this strategy tripod's impact on the cashew industry's SC sustainability orientation. Multiple case studies were conducted by gathering data from various cashew SC stakeholders. A deductive content analysis showed that, despite the existing influences from the three legs of the strategy tripod, emphasis was placed on the firm perspective (i.e., RBV), which affected SC sustainability orientation in that the industry‐ (i.e., IBV) and institutional‐ (i.e., INSBV) level views received less consideration in the creation of SC strategies. This research contributes to theory and practice by shedding light on under‐explored relations between business strategy and SC sustainability. Our results show that firms should move from pressure responsiveness to strategy management to implement sustainability‐oriented initiatives.
Development of a Novel Airlift Photobioreactor: Modeling, Particle Image Velocimetry Measurements, and Cultures
Authors: Feng Aiguo , Zhang Ting , Zhu Qiangui , Ye Xinyi , Liu Chunjiang
Published: August 2022

Microalgae are commonly cultivated using photobioreactors (PBRs). To investigate Chlorella vulgaris productivity, a 2.5‐L airlift photobioreactor (AL‐PBR) with vertical and incline baffles was newly developed using computational fluid dynamics (CFD), particle image velocimetry (PIV) methods, and dark/light cultures. A significant increase in cell density and lipid accumulation rate (LAR) in the AL‐PBR was observed. Hydrodynamic stresses including velocity fluctuation, pressure drop, looped bubble swarm, and vorticity magnitude were quantified in algae cultures, suggesting that microvortices induced light and CO2 distribution regulated the algae plastid metabolism in the exponential phase of growth. This study provides a fundamental practice to the scale‐up of bioreactors.
Numerical Investigation of the Cooling Behavior of Molded Chocolate Products
Authors: Lörcher Marc , Behrens Stefan , Böttger Arne , Lange Claudia , Schräer Christian , Luo Xing , Kabelac Stephan
Published: August 2022

In addition to taste and melting behavior, the gloss is an important quality criterion of chocolate products. Differences considering the gloss on products can be attributed to different causes in the production process. The chocolate which has been precrystallized by shearing and supercooling is further cooled, crystallized, and transported as a solid chocolate out of the cooling process. The cooling of the chocolate is largely unexplored in a paternoster refrigerator. Therefore, the resulting flow profile and temperature profile are numerically studied in this work.
Graphene Quantum Dot‐Doped PEDOT for Simultaneous Determination of Ascorbic Acid, Dopamine, and Uric Acid
Authors: Chul Lim Hong , Jang Seung‐Joo , Cho Yujin , Cho Hyunju , Venkata Prasad Gajapaneni , Venkatachalam Vinothkumar , Shin Ik‐Soo , Hyun Kim Tae
Published: August 2022

Invited for this issue's Front Cover is the group of Prof. Dr. Tae Hyun Kim from Soonchunhyang University (South Korea). The cover picture illustrates poly(3,4‐ethylenedioxythiophene) (PEDOT) electrodeposited thin films (PEDOT‐GQD) doped with graphene quantum dots (GQD) as an electrode active material that has a high electrochemically active area and interfacial electron transport rate. As a result, PEDOT‐GQD will simultaneously detect ascorbic acid, dopamine, and uric acid with high selectivity and high sensitivity. Read the full text of the Research Article at 10.1002/celc.202200557.
A review of precision management for golf course turfgrass
Authors: Carlson Michael G. , Gaussoin Roch E. , Puntel Laila A.
Published: August 2022

Precision turfgrass management (PTM) is a combination of methods and technologies proposed to increase the resiliency of golf courses by improving input efficiency while maintaining the function and aesthetics of the playing surface. However, there is no recent review describing the status of precision management in turfgrass. The objectives of this review were to (a) summarize peer reviewed research on precision technology for turfgrass management, (b) describe adoption of PTM‐based tools, and (c) propose an agenda of research priorities to advance and promote PTM adoption. Of the articles reviewed, 94% documented the accuracy of sensors to detect turfgrass performance and stressors before or during visual symptoms. Only 6% of the research reviewed focused on developing models or decision support systems to quantify the relationship among reflectance, nitrogen uptake, visual quality, biomass production, and irrigation which are required for precision management by golf course superintendents. Efficacy or value of using PTM methods and technologies have not been reported. Golf course superintendents lack of knowledge about PTM, and lack of quantification of benefits of PTM pose limitations to promote adoption. Increasing the adoption of PTM will require research to focus additionally on automating sensor data processing; quantifying costs, benefits, and value of adopting PTM; and simplifying input applications in a PTM system. This review described the status of precision management in golf course turfgrass and shed light into the need for research to develop models and decision support tools for precision management of golf course turfgrass.
Detection of Reactive Oxygen and Nitrogen Species by Upconversion Nanoparticle‐Based Near‐Infrared Nanoprobes: Recent Progress and Perspectives
Authors: Yu Xiaokan , Ouyang Wenao , Qiu Hao , Zhang Zhijun , Wang Zhimin , Xing Bengang
Published: August 2022

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are essential oxidative metabolites of organisms, which are closely related to physiological, pathological and pharmacological processes. The accurate detection of ROS/RNS is important for the understanding of biological processes, monitoring of pharmacological effects, and predicting the course of disease. The recently developed NIR nanoprobes based on upconversion nanoparticles (UCNPs) hold great prospects in sensitive and deep‐tissue detection of ROS/RNS, and considerable progress has been achieved so far. In this review, we systematically summarize the up‐to‐date advances of UCNPs‐based near‐infrared (NIR) probes for ROS/RNS sensing, and the potential challenges and perspectives for further research are also highlighted. We envision that such a research field will have a bright future for modern biomedical applications.
Thiazole Boron Difluoride Dyes with Large Stokes Shift, Solid State Emission and Room‐Temperature Phosphorescence
Authors: Wang Wei , Tong Shuo , Wang Qi‐Qiang , Ao Yu‐Fei , Wang De‐Xian , Zhu Jieping
Published: August 2022

The small Stokes shift and weak emission in the solid state are two main shortcomings associated with the boron‐dipyrromethene (BODIPY) family of dyes. This study presents the design, synthesis and luminescent properties of boron difluoro complexes of 2‐aryl‐5‐alkylamino‐4‐alkylaminocarbonylthiazoles. These dyes display Stokes shifts (Δλ, 77–101 nm) with quantum yields (ϕFL) up to 64.9 and 34.7 % in toluene solution and in solid state, respectively. Some of these compounds exhibit dual fluorescence and room‐temperature phosphorescence (RTP) emission properties with modulable phosphorescence quantum yields (ϕPL) and lifetime (τp up to 251 μs). The presence of intramolecular H‐bonds and negligible π‐π stacking revealed by X‐ray crystal structure might account for the observed large Stokes shift and significant solid‐state emission of these fluorophores, while the enhanced spin‐orbit coupling (SOC) of iodine and the self‐assembly driven by halogen bonding, π‐π and C−H…π interactions could be responsible for the observed RTP of iodine containing phosphors.
Synthesis, Design, and Structure‐Activity Relationship of a Benzenesulfonylpiperazine Series againstTrypanosoma cruzi
Authors: Cassiano Martinho Ana Clara , de Melo Resende Daniela , Landin Emanuelly Silva , Dit Lapierre Thibault Joseph William Jacques , Bernardes Talita Cristina Diniz , Martins Luan Carvalho , Ferreira Rafaela Salgado , Murta Silvane Maria Fonseca , de Oliveira Rezende Júnior Celso
Published: August 2022

Chagas disease is a neglected tropical disease, endemic in Latin America and caused by the protozoan parasiteTrypanosoma cruzi. Available treatments show low cure efficacy during the chronic phase of the disease and cause a series of side effects, reinforcing the need to develop new drugs against Chagas disease. In this work, we describe the optimization of a trypanocidal hit compound recently reported in phenotypic high‐throughput screening studies againstTrypanosoma cruzi. A hit‐to‐lead process was initiated and a structure‐activity relationship againstTrypanosoma cruziwas obtained after the synthesis and biological evaluation of 22 new benzenesulfonylpiperazine derivatives. From this structure‐activity relationship study, we identified three compounds with a promising predicted ADMET profile and potency comparable to the reference drug benznidazole, which are candidates for further development towards therapies for Chagas disease.
Boat‐, Cuboid‐, and Dumbbell‐Shaped Hierarchical Morphology of Cerium (IV) Hydroxidophosphate Materials for Oxidative Coupling Reaction
Authors: Sarkar Sunny , Sarkar Soumita , Patra Astam K.
Published: August 2022

A simple hydrothermal approach was used to obtain boat‐, cuboid‐, and dumbbell‐shaped hierarchical morphology of cerium (IV) hydroxidophosphate materials. The period of the reactions, pH, and types of bases play crucial roles in tuning the morphology of the material. PXRD, FE‐SEM, HR‐TEM, FT‐IR, XPS, EDX, and EPR spectroscopies were used to analyze the materials. FE‐SEM and HR‐TEM analysis show that the materials have hierarchical morphology. According to XPS and EPR analysis, the materials comprise a redox‐active Ce3+/Ce4+ couple. The thiol to disulfide oxidative coupling reaction is synergistically boosted by the hierarchical morphology and redox‐active Ce3+/Ce4+ couple. The catalyst has excellent catalytic activity both in aqueous as well as protic organic solvents. However, the catalyst exhibited no reactivity in common organic solvents such as CH3CN, DCM, and THF. The catalytic reaction was thoroughly investigated in the presence of various solvents, catalyst amounts, oxidising agents, and substrates. In the presence of H2O2, the yield is 99%, whereas in the presence of air, it is 79%. We found high yields for several aromatic thiols but aliphatic thiols exhibited relatively poor yields under identical conditions.
PreF: Predicting job failure on supercomputers with job path and user behavior
Authors: Xian Gang , Zhang Xiaorong , Yu Jie , Wang Guijuan , Yang Wenxiang , Zhou Longfang , Wu Yadong , Li Xuejun , He Xin
Published: August 2022

Large numbers of jobs are executed on supercomputers almost every day. Unfortunately, many jobs would fail for various reasons, resulting in the waste of resources and the prolonged waiting time for queuing jobs. Job failure prediction can guide adjustment measures in advance, which is vital to the system's overall execution efficiency and reliability. Aiming at the problem that the existing job failure prediction methods are single, the collection of job features is complex and challenging to apply. This article strives to study whether these failed jobs can be predicted with known and synthetic features. We perform a comprehensive analysis of large amounts of historical data and various features and find that two novel features (running path and retry count) can predict job failure well. The running path indicates the application type a job belongs to, and the retry count reflects the user's behavior when the job fails. We propose a job failure prediction framework called PreF on supercomputers using machine learning based on the novel features. The experimental results show that PreF can correctly identify over 89% of jobs, outperforming the latest related methods on the comprehensive evaluation indicator (S_score) by around 4%.
Synthesis of Scyllatoxin‐Based BH3 Domain Mimetics with Diverse Patterns of Native Disulfide Bonds
Authors: Vince Matthew J. K. , Holub Justin M.
Published: August 2022

This article outlines the design and development of scyllatoxin (ScTx)–based BH3 domain mimetics with diverse patterns of native disulfide bonds. More specifically, this method summarizes the total chemical synthesis of ScTx‐based peptides that contain zero, one, two, or three disulfide linkages, including techniques to generate variants with any combination of native disulfides. Each peptide reported herein is generated on solid‐phase support using microwave‐assisted coupling procedures, and all reaction parameters related to the peptide synthesis are described in detail. The various disulfide patterns of the ScTx‐based constructs are established during peptide synthesis and are ultimately verified by mass analysis of trypsin‐digested fragments. The BH3 domain mimetics developed herein were generated by transposing residues from the helical BH3 domain of the pro‐apoptotic BCL2 protein Bax to the α‐helix of wild‐type ScTx. Interestingly, we found that the relative binding affinities of ScTx‐Bax peptides for the anti‐apoptotic BCL2 protein Bcl‐2 (proper) were heavily influenced by the number and position of disulfide linkages within the ScTx‐Bax sequence. As a consequence, we were able to utilize ScTx‐Bax BH3 domain mimetics with varied patterns of disulfide bonds to survey how structural rigidity within the helical Bax BH3 domain affects binding to promiscuous anti‐apoptotic BCL2 proteins. More broadly, the ability to generate ScTx‐based molecules that contain any combination of native disulfide bonds expands the utility of such constructs as tools to study the molecular nature of protein‐protein interactions. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Synthesis and characterization of ScTx‐based Bax BH3 domain mimetics

Basic Protocol 2: Oxidation of ScTx‐Bax BH3 domain mimetics containing one, two, or three disulfide linkages

Support Protocol: Mapping of disulfide linkages in oxidized ScTx‐Bax BH3 domain mimetics
FFPE‐ATAC: A Highly Sensitive Method for Profiling Chromatin Accessibility in Formalin‐Fixed Paraffin‐Embedded Samples
Authors: Yadav Ram Prakash , Polavarapu Vamsi Krishna , Xing Pengwei , Chen Xingqi
Published: August 2022

In basic and translational cancer research, the majority of biopsies are stored in formalin‐fixed paraffin‐embedded (FFPE) samples. Chromatin accessibility reflects the degree to which nuclear macromolecules can physically interact with chromatinized DNA and plays a key role in gene regulation in different physiological conditions. As such, the profiling of chromatin accessibility in archived FFPE tissue can be critical to understanding gene regulation in health and disease. Due to the high degree of DNA damage in FFPE samples, accurate mapping of chromatin accessibility in these specimens is extremely difficult. To address this issue, we recently established FFPE‐ATAC, a highly sensitive method based on T7‐Tn5‐mediated transposition followed by in vitro transcription (IVT), to generate high‐quality chromatin accessibility profiles with 500–50,000 nuclei from a single FFPE tissue section. In FFPE‐ATAC, which we describe here, the T7‐Tn5 adaptors are inserted into the genome after FFPE sample preparation and are unlikely to sustain the DNA breakage that occurs during reverse cross‐linking of these samples. It should, therefore, remain at the ends of broken accessible chromatin sites after reverse cross‐linking. IVT is then used to convert the two ends of the broken DNA fragments to RNA molecules before making sequencing libraries from the IVT RNAs and further decoding Tn5 adaptor insertion sites in the genome. Through this strategy, users can decode the flanking sequences of the accessible chromatin even if there are breaks between adjacent pairs of T7‐T5 adaptor insertion sites. This method is applicable to dissecting chromatin profiles of a small section of the tissue sample, characterizing stage and region‐specific gene regulation and disease‐associated chromatin regulation in FFPE tissues. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Nuclei isolation from FFPE tissue samples

Basic Protocol 2: T7‐Tn5 transposase tagmentation, reverse‐crosslinking, and in vitro transcription

Basic Protocol 3: Preparation of libraries for high‐throughput sequencing