bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial intelligence for dementia—Applied models and digital health
Authors: Lyall Donald M. , Kormilitzin Andrey , Lancaster Claire , Sousa Jose , Petermann‐Rocha Fanny , Buckley Christopher , Harshfield Eric L. , Iveson Matthew H. , Madan Christopher R. , McArdle Ríona , Newby Danielle , Orgeta Vasiliki , Tang Eugene , Tamburin Stefano , Thakur Lokendra S. , Lourida Ilianna ,   The Deep Dementia Phenotyping (DEMON) Network, Llewellyn David J. , Ranson Janice M.
Published: July 2023

INTRODUCTION

The use of applied modeling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefits, particularly as “deep phenotyping” cohorts with multi‐omics health data become available.

METHODS

This narrative review synthesizes understanding of applied models and digital health technologies, in terms of dementia risk prediction, diagnostic discrimination, prognosis, and progression. Machine learning approaches show evidence of improved predictive power compared to standard clinical risk scores in predicting dementia, and the potential to decompose large numbers of variables into relatively few critical predictors.

RESULTS

This review focuses on key areas of emerging promise including: emphasis on easier, more transparent data sharing and cohort access; integration of high‐throughput biomarker and electronic health record data into modeling; and progressing beyond the primary prediction of dementia to secondary outcomes, for example, treatment response and physical health.

DISCUSSION

Such approaches will benefit also from improvements in remote data measurement, whether cognitive (e.g., online), or naturalistic (e.g., watch‐based accelerometry).
Treatment Effect on Brain Atrophy Correlates with Treatment Effect on Cognition in Multiple Sclerosis
Authors: Sormani Maria Pia , Schiavetti Irene , Ponzano Marta , Colato Elisa , De Stefano Nicola
Published: July 2023

Objective

The purpose of this study was to evaluate the extent to which treatment effect on magnetic resonance imaging (MRI)‐derived measures of brain atrophy and focal lesions can mediate, at the trial level, the treatment effect on cognitive outcomes in multiple sclerosis (MS).

Methods

We collected all published randomized clinical trials in MS lasting at least 2 years and including as end points: active MRI lesions (defined as new/enlarging T2 lesions), brain atrophy (defined as a change in brain volume between month 12 and month 24), and change in cognitive performance (assessed by the Paced Auditory Serial Addition Test [PASAT]). Relative reductions were used to quantify the treatment effect on MRI markers (lesions and atrophy), whereas the standardized mean difference (Hedges g) between baseline and follow‐up cognitive assessment was used to quantify the treatment effects on cognition. A linear regression, weighted for trial size, was used to assess the relationship between the treatment effects on MRI markers and cognition.

Results

Fourteen trials including more than 8,813 patients with MS were included in the meta‐regression. Treatment effect on cognition was strongly associated with the treatment effect on brain atrophy (R2 = 0.79, p < 0.001), but was not correlated with the treatment effect on active MRI lesions (R2 = 0.16, p = 0.14).

Interpretation

Results reported here suggest that brain atrophy, a well‐established MRI marker in MS clinical trials, can be used as a main outcome for clinical trials with drugs targeting cognitive impairment and neurodegeneration. ANN NEUROL 2023;94:925–932
Manipulating Intermetallic Charge Transfer for Switchable External Stimulus‐Enhanced Water Oxidation Electrocatalysis
Authors: Chalil Oglou Ramadan , Ulusoy Ghobadi Turkan Gamze , Hegner Franziska Simone , Galán‐Mascarós José Ramón , López Núria , Ozbay Ekmel , Karadas Ferdi
Published: July 2023

Electrocatalytic processes involving the oxygen evolution reaction (OER) present a kinetic bottleneck due to the existence of linear‐scaling relationships, which bind the energies of the different intermediates in the mechanism limiting optimization. Here, we offer a way to break these scaling relationships and enhance the electrocatalytic activity of a Co−Fe Prussian blue modified electrode in OER by applying external stimuli. Improvements of ≈11 % and ≈57 % were achieved under magnetic field (0.2 T) and light irradiation (100 mW cm−2), respectively, when working at fixed overpotential, η=0.6 V at pH 7. The observed enhancements strongly tie in with the intermetallic charge transfer (IMCT) intensity between Fe and Co sites. Density Functional Theory simulations suggest that tuning the IMCT can lead to a change of the OER mechanism to an external stimuli‐sensitive spin crossover‐based pathway, which opens the way for switchable electrocatalytic devices.
Trace metal optimization in CHO cell culture through statistical design of experiments
Authors: Polanco Ashli , Liang George , Park SoYoung , Wang Yongdan , Graham Ryan J. , Yoon Seongkyu
Published: July 2023

A majority of the biotherapeutics industry today relies on the manufacturing of monoclonal antibodies from Chinese hamster ovary (CHO) cells, yet challenges remain with maintaining consistent product quality from high‐producing cell lines. Previous studies report the impact of individual trace metal supplemental on CHO cells, and thus, the combinatorial effects of these metals could be leveraged to improve bioprocesses further. A three‐level factorial experimental design was performed in fed‐batch shake flasks to evaluate the impact of time wise addition of individual or combined trace metals (zinc and copper) on CHO cell culture performance. Correlations among each factor (experimental parameters) and response variables (changes in cell culture performance) were examined based on their significance and goodness of fit to a partial least square's regression model. The model indicated that zinc concentration and time of addition counter‐influence peak viable cell density and antibody production. Meanwhile, early copper supplementation influenced late‐stage ROS activity in a dose‐dependent manner likely by alleviating cellular oxidative stress. Regression coefficients indicated that combined metal addition had less significant impact on titer and specific productivity compared to zinc addition alone, although titer increased the most under combined metal addition. Glycan analysis showed that combined metal addition reduced galactosylation to a greater extent than single metals when supplemented during the early growth phase. A validation experiment was performed to confirm the validity of the regression model by testing an optimized setpoint of metal supplement time and concentration to improve protein productivity.
Impact of the COVID‐19 pandemic on paediatric renal tumour presentation and management, a SIOP renal tumour study group study
Authors: Roy Prakriti , van Peer Sophie E. , Dandis Rana , Duncan Catriona , de Aguirre‐Neto Joaquim Caetano , Verschuur Arnauld , de Camargo Beatriz , Karim‐Kos Henrike E. , Boschetti Luna , Spreafico Filippo , Ramirez‐Villar Gema L. , Graf Norbert , van Tinteren Harm , Pritchard‐Jones Kathy , van den Heuvel‐Eibrink Marry M.
Published: July 2023

Background

The COVID‐19 pandemic had global catastrophic effects on the management of non‐communicable diseases including paediatric cancers. Restrictions during the start of 2020 complicated timely referrals of patients to specialized centres. We aimed to evaluate the pandemic’s impact on the number of new diagnoses, disease characteristics and management delay for paediatric renal tumour patients included in the SIOP‐RTSG‐UMBRELLA study, as compared with data from a historical SIOP‐RTSG trial (2005–2009).

Methods

The number of intensive care admissions, population mobility rates and national lockdown periods/restrictions were used as proxies of the pandemic’s severity and impact on societies. Clinical and tumour data were extracted from the SIOP‐RTSG‐UMBRELLA study and from historical SIOP‐RTSG trials.

Results

During the first lockdown in Europe, the number of newly diagnosed patients decreased following restrictions and population immobilisation. Additionally, there was a higher proportion of advanced disease (37% vs. 17% before and after COVID‐9, p < 0.001) and larger median tumour volume (559 cm3 vs. 328 and 434 cm3 before and after, p < 0.0001). Also in Brazil, the proportion of advanced disease was higher during the national decrease in mobilisation and start of restrictions (50% and 24% vs. 11% and 18% before and after, p < 0.01). Tumour volume in Brazil was also higher during the first months of COVID‐19 (599 cm3 vs. 459 and 514 cm3), although not significant (p = 0.17). We did not observe any delays in referral time nor in time to start treatment, even though COVID‐19 restrictions may have caused children to reach care later.

Conclusion

The COVID‐19 pandemic briefly changed the tumour characteristics of children presenting with renal tumours. The longer‐term impact on clinical outcomes will be kept under review.
ECT for adolescents: Effective for many indications
Authors: Knopf Alison
Published: July 2023

Lee Elizabeth Wachtel, M.D., professor of psychiatry at Johns Hopkins School of Medicine, who specializes in using electroconvulsive therapy (ECT) for adolescents, spoke at this year's annual meeting of the American Psychiatric Association (APA). She was the second of the two speakers at the APA session. Wachtel calls it convulsive therapy — “It's really the convulsion that brings about the benefit, as compared to the fashion in which it's elicited,” said Wachtel at the May 20 APA meeting, which CABL covered.
First‐Principles Microkinetic Study of the Catalytic Hydrodeoxygenation of Guaiacol on Transition Metal Surfaces
Authors: Morteo‐Flores Fabian , Quayle Max , Salom‐Català Antoni , Pera‐Titus Marc , Roldan Alberto
Published: July 2023

The mechanism behind the hydrodeoxygenation (HDO) of guaiacol on Co(0001), Ni(111), Cu(111), Pd(111), and Pt(111) was investigated by constructing a first‐principles microkinetic model from density functional theory (DFT) models for 68 possible intermediates over each surface. We report that the most energetically favorable pathway for this process is the demethylation of guaiacol to catechol over Ni(111), which exhibits highly desirable deoxygenation and hydrogenation kinetics at industrial temperatures. Guaiacol readily undergoes hydrogenation over Pt(111) and Pd(111), but the products exhibit slow desorption from the surfaces at standard operation temperatures. Furthermore, the deoxygenation pathway is hindered by the high energy barrier associated with the scission of the Calkyl−O bond.
Special Collection: Photocatalytic Synthesis
Authors: Næsborg Line , Pieber Bartholomäus , Wenger Oliver S.
Published: July 2023

This Special Collection is dedicated to the field of photocatalytic synthesis and contains a diverse selection of original research contributions. It includes studies on catalyst development, mechanistic investigations, method development and the use of enabling technologies, illustrating the many facets of state‐of‐the‐art research in photocatalytic synthesis. Further, emerging topics are surveyed and discussed in three reviews and a concept article.
Estimation of Lysozyme Concentration on a Membrane Surface Using a Membrane Crystallization Method
Authors: Ueda Saya , Hirasawa Izumi , Kohori Fukashi
Published: July 2023

High‐quality single crystals are necessary for structural analysis of proteins. However, it is difficult to obtain high‐quality single crystals in a short time. Therefore, a membrane crystallization method was applied in which lysozyme is concentrated on the membrane surface using an ultrafiltration membrane. Membrane surface concentrations, which cannot be measured, were calculated based on the measurable permeation flux. At all operating pressures, the measured and simulated permeation fluxes were in close agreement, allowing the membrane surface concentration to be estimated. The membrane surface concentration increased rapidly at all pressures during the initial pressurization, indicating that crystals were formed at an early stage.
Evolution of the porous structure for phosphoric acid etching carbon as cathodes in Li–O2 batteries: Pyrolysis temperature‐induced characteristics changes
Authors: Yang Feiyang , Yao Ying , Xu Yunkai , Wang Cong , Wang Meiling , Ren Jingjie , Zhang Cunzhong , Wu Feng , Lu Jun
Published: July 2023

Although biomass‐derived carbon (biochar) has been widely used in the energy field, the relation between the carbonization condition and the physical/chemical property of the product remains elusive. Here, we revealed the carbonization condition's effect on the morphology, surface property, and electrochemical performance of the obtained carbon. An open slit pore structure with shower‐puff‐like nanoparticles can be obtained by finely tuning the carbonization temperature, and its unique pore structure and surface properties enable the Li–O2 battery with cycling longevity (221 cycles with 99.8% Coulombic efficiency at 0.2 mA cm−2 and controlled discharge–charge depths of 500 mAh g−1) and high capacity (16,334 mAh g−1 at 0.02 mA cm−2). This work provides a greater understanding of the mechanism of the biochar carbonization procedure under various pyrolysis conditions, paving the way for future study of energy storage devices.
Reconsidering the Structures of C2Al4− and C2Al5−
Authors: Zhang Chao‐Jiang , Ortíz‐Chi Filiberto , Xu Xi‐Ling , Xu Hong‐Guang , Merino Gabriel , Zheng Wei‐Jun
Published: July 2023

The study of C2Al4−/0 and C2Al5−/0 was conducted using anion photoelectron spectroscopy and quantum chemical computations. The present findings reveal that C2Al4− has a boat‐like structure, with a single C2 unit surrounded by four aluminum atoms. In contrast, the neutral C2Al4 species adopts a D2h planar structure with two planar tetracoordinate carbon (ptC) units, consistent with previous reports. Furthermore, the global minimum isomer of C2Al5− adopts a D3h symmetry, where the C2 unit interacts with five aluminum atoms. It was also found that a lower symmetry structure of C2Al5−, where all five aluminum atoms are located on the same side of the C2 unit, albeit slightly higher in energy compared to the D3h structure. These computations show that the D3h structure of C2Al5− is highly stable, exhibiting a large HOMO‐LUMO gap.
Bismuth Infrared Star: Being at a Glance
Authors: Pozdeev Anton S. , Rublev Pavel , Boldyrev Alexander I.
Published: July 2023

Bismuth polycations have garnered significant attention from researchers due to their extraordinary and counter‐intuitive structures and stoichiometries. Despite extensive experimental and theoretical investigations, understanding of the bonding in such clusters remains insufficient. An AdNDP bonding analysis was conducted to elucidate the bonding characteristics using both homoatomic and heteroatomic bismuth clusters with various stoichiometries. Analysis of the calculated nucleus‐independent chemical shift data confirmed the aromatic nature of these species. Universal bonding patterns were identified that can be applied to a range of homoatomic and heteroatomic bismuth clusters. Additionally, calculations of absorbance and fluorescence spectra were performed to gain insights into the near‐infrared emission and establish a potential correlation between absorbance and the identified bonding patterns.
Titanium‐Catalyzed Polymerization of a Lewis Base‐Stabilized Phosphinoborane
Authors: Braese Jens , Lehnfeld Felix , Annibale Vincent T. , Oswald Tim , Beckhaus Rüdiger , Manners Ian , Scheer Manfred
Published: July 2023

The reaction of the Lewis base‐stabilized phosphinoborane monomer tBuHPBH2NMe3 (2 a) with catalytic amounts of bis(η5:η1‐adamantylidenepentafulvene)titanium (1) provides a convenient new route to the polyphosphinoborane [tBuPH‐BH2]n (3 a). This method offers access to high molar mass materials under mild conditions and with short reaction times (20 °C, 1 h in toluene). It represents an unprecedented example of a transition metal‐mediated polymerization of a Lewis base‐stabilized Group 13/15 compound. Preliminary studies of the substrate scope and a potential mechanism are reported.
Pharmacokinetic Properties of an FDA‐approved Intranasal Nalmefene Formulation for the Treatment of Opioid Overdose
Authors: Crystal Roger , Ellison Mark , Purdon Charlotte , Skolnick Phil
Published: July 2023

Nalmefene is a high‐affinity, long‐duration opioid antagonist that was approved in 1995 as an injection for the treatment of opiate overdose, but subsequently withdrawn (2008) for reasons other than safety or effectiveness. The dramatic rise in opioid overdose deaths over the past 7‐8 years catalyzed the development of an intranasal (IN) formulation of nalmefene for the emergency treatment of opioid overdose. The studies described here compare the pharmacokinetic properties and safety profiles of an IN formulation containing nalmefene (2.7 mg in 0.1 mL) to an approved 1 mg intramuscular (IM) dose. IN nalmefene produced maximum plasma concentrations that were significantly higher than observed following the IM dose (12.2 and 1.77 ng/mL, respectively). The time to reach maximum plasma concentrations was also faster following IN administration (0.25 and 0.33 hours, respectively) with significant differences in plasma concentrations manifested as early as 2.5 minutes after administration (NCT04759768). The plasma half‐life of nalmefene was similar following IM and IN administration (10.6‐11.4 hours). Furthermore, dose‐normalized nalmefene exposure was similar for both 1 spray in each nostril and 2 sprays in the same nostril compared to a single spray in each nostril (NCT05219669). There were no sex differences in the pharmacokinetic properties of either IN or IM nalmefene. In an era when almost 90% of opioid overdose deaths have been linked to high‐potency synthetic opioids, the ability to rapidly deliver high concentrations of nalmefene could represent an important tool for reducing both morbidity and mortality.
Transfer Hydrogenation of Furfural to Furfuryl Alcohol Under Microwave Irradiation Using Mixed Oxides
Authors: Nope Eliana , Sathicq Ángel G. , Martínez José J. , Romanelli Gustavo P. , Luque Rafael
Published: July 2023

The reaction to obtain furan alcohols is one of the most important in the upgrading of furan derivates. An attractive route is the transfer hydrogenation of furfural using acidic‐basic catalysts. In this work, mixed oxides derived from ternary hydrotalcites were employed to obtain furfuryl alcohol from furfural assisted by microwave irradiation. These materials were characterized via X‐ray diffraction (XRD), N2 adsorption‐desorption isotherms, Fourier‐transform infrared (FTIR) and the CO2 temperature‐programmed desorption (CO2‐TPD) analyses. The lamellar structure of hydrotalcite‐type materials collapses during the calcination process, resulting in the loss of carbonate anions and hydroxyl groups, present in the interlayer space. This leads to the formation of mixed oxides that exhibit larger surface areas. Furthermore, these changes alter the basic nature of these materials, giving rise to the formation of strong basic sites. The reaction was studied using containing Co2+ and Ni2+ in their structure and was then optimized using distinct primary and secondary alcohols as hydrogen donor sources, as well as distinct temperatures and initial concentrations of furfural. The yields to furfuryl alcohol are strongly dependent on the type of Me2+ in layered oxides mainly due to higher basicity and to the donor employed in the reaction. The mixed oxide containing Co2+ showed complete conversion of furfural and higher yields to furfuryl alcohol (>95 %) at short times of reaction (<1 h).
Solvent‐Free Aerobic Oxidative Cleavage of Methyl Oleate to Biobased Aldehydes over Mechanochemically Synthesized Supported AgAu Nanoparticles
Authors: da Silva Rafael T. P. , Silva Dagoberto O. , de Oliveira Paulo F. M. , Bellabarba Ronan , Johnston Peter , Smit Joost , Holt Jarle , Betham Michael , Rossi Liane M.
Published: July 2023

The performance of mechanochemically synthesized supported bimetallic AgAu nanoalloy catalysts was evaluated in the oxidative cleavage of methyl oleate, a commonly available unsaturated bio‐derived raw material. An extensive screening of supports (SiO2, C, ZrO2, Al2O3), metallic ratios (Ag : Au), reaction times, temperatures, and use of solvents was carried out. The performance was optimized towards productivity and selectivity for the primary cleavage products (aldehydes and oxoesters). The optimal conditions were achieved in the absence of solvent, using Ag8Au92/SiO2 as catalyst, at 80 °C, reaction time of 1 h, substrate to catalyst=555 and 10 bar of molecular oxygen. A strong support effect was observed: the selectivity to aldehydes was best with silica as support, and to esters was best using zirconia. This shows not only that mechanochemical preparation of bimetallic catalysts is a powerful tool to generate useful catalyst compositions, but also that a safe, green, solventless synthesis of bio‐derived products can be achieved by aerobic oxidative cleavage.
Green finance policy and enterprise green development: Evidence from China
Authors: Lyu Yanwei , Bai Yangyang , Zhang Jinning
Published: July 2023

Global environmental issues are becoming increasingly prominent, and green finance may play a key role in achieving sustainable development. This study takes the “Green Financial Reform and Innovation Pilot Zone” policy as a quasi‐natural experiment. The Difference‐in‐Difference model and Propensity Score Matching‐Difference in Difference model are applied to examine the direct effect of green finance policy on the green development of enterprises. A mechanism test model is used to investigate its indirect transmission mechanism. Then several heterogeneity analyses are performed from five perspectives. The results show that green finance policy considerably promotes enterprise green development and the conclusion is supported by a series of robustness tests. The mechanism analyses show that financing constraints and green innovation are the two transmission channels for green finance policy affecting enterprise green development. The heterogeneity analyses indicate that the policy effect is more significant among enterprises those are non‐state‐owned, have managers with a financial background, operate in regions with high marketization, belong to industries with low monopoly, and locate in poilt zones of Zhejiang, Guangdong, and Guizhou. Based on the above findings, policy suggestions are made to establish a win‐win scenario for the economy and the environment.
B(C6F5)3‐Catalyzed Aza‐Friedel–Crafts Reaction of Indolizines with 2‐Aryl‐3H‐indol‐3‐ones
Authors: Liu Lei , He Yonghui , Zou Chang‐Peng , Ma Tao , Qiao Xiu‐Xiu , Jiang Yuntao , Li Ganpeng , Zhao Xiao‐Jing
Published: July 2023

A Friedel–Crafts reaction of indolizines with 2‐aryl‐3H‐indol‐3‐ones catalyzed by B(C6F5)3 is described. This protocol gives access to indolizine derivatives that are valuable building blocks in synthetic and pharmaceutical chemistry. The reaction proceeds under mild conditions, affording various C2‐quaternary indolin‐3‐ones based on indolizine with high yields and regioselectivities. Moreover, the synthetic transformations of the target products were realized by N‐methylation and trifluoromethane sulfonation.
Practice these tips to get promoted
Authors: Hodges Dawn Z.
Published: July 2023

Next month I will have been retired for five years. It really seems unbelievable to me. Since I retired, the world has known a pandemic, and I have known quite a few never‐before experiences. I was hospitalized for COVID, and my brother‐in‐law was hospitalized with COVID and died of a brain bleed. My older sister fell in her home and shattered both ankles, both knees, and a femur. My mother had a heart attack, two days after my brother‐in‐law died, and was diagnosed with vascular dementia; she died a year later. My husband and I opened and closed a small business. He has had open‐heart surgery, an injury that resulted in spinal fusion, and two hand surgeries. My youngest granddaughter started middle school! We’ve endured an eight‐month renovation of our home. Whew! It's just hard to fathom all that in five years.
Financial time series classification method based on low‐frequency approximate representation
Authors: Liu Bing , Cheng Huanhuan
Published: July 2023

Aiming at the mode mixing problems of high frequency information caused by fluctuation agglomeration and pointed peak thick tail of financial time series, a time series classification method based on low frequency approximate representation is proposed. The steps are as follows. Firstly, complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) was used to decompose the time series into a series of modal components and residual terms, and the permutation entropy of the modal components and residual terms was calculated. And the permutation entropy was clustered into two categories by Fisher's optimal segmentation method. Then, according to the clustering results of permutation entropy, the corresponding modal components and residual terms were integrated into high frequency information and low frequency information, so as to realize the adaptive extraction of low frequency information. Secondly, distance matrices were obtained by Euclidean distance (ED) or dynamic time warping (DTW) for low frequency information, and then the nearest neighbor 1‐NN algorithm was used to classify time series.
Modeling of a hybrid power system integrating solar radiation and syngas combustion energy
Authors: Cheng Chin‐Hsiang , Huang Shang‐Ting
Published: July 2023

This study aims to model a hybrid power system that can continuously generate power by switching between two possible thermal sources: solar radiation and combustion energy from synthesis gases. The system comprised a hybrid energy receiver, solar dish, Stirling generator, fluidized‐bed gasifier, boiler, and water tank. The solar dish was a dual‐reflection solar collector that used two mirrors, namely the main and subordinate concentrators, to concentrate a broad expanse of solar radiation onto a hybrid energy receiver. The fluidized‐bed gasifier was employed for the production of synthesis gases. The synthesis gases were combusted to provide an auxiliary heat source for the Stirling generator when solar radiation was insufficient. Solar radiation or combustion energy was alternatively introduced into the hybrid energy receiver and converted to power by a 1‐kW‐scale beta‐type Stirling engine. In this manner, the Stirling generator could serve as a base‐load power plant regardless of solar conditions. In this study, a complete quantitative model was developed for a demonstration plant by incorporating thermodynamic and dynamic models of the beta‐type Stirling engine, a ray‐tracing model for the dual‐reflection solar dish, an energy model of the hybrid energy receiver, and experimental data for the fluidized‐bed gasifier. The performance response of the system during switching between solar radiation and combustion energy was predicted. The modeling results indicated that switching can result in a continuous power output ranging from 600 to 1200 W. With synthesis gas combustion as the auxiliary heat source, the hybrid Stirling power system can be operated continuously, and the overall power output is increased by 109.82% compared to a conventional concentrated solar power system that only uses solar radiation.
Physicochemical understanding of biomineralization by molecular vibrational spectroscopy: From mechanism to nature
Authors: Liu Hao , Jiang Hui , Liu Xiaohui , Wang Xuemei
Published: July 2023

The process and mechanism of biomineralization and relevant physicochemical properties of mineral crystals are remarkably sophisticated multidisciplinary fields that include biology, chemistry, physics, and materials science. The components of the organic matter, structural construction of minerals, and related mechanical interaction, etc., could help to reveal the unique nature of the special mineralization process. Herein, the paper provides an overview of the biomineralization process from the perspective of molecular vibrational spectroscopy, including the physicochemical properties of biomineralized tissues, from physiological to applied mineralization. These physicochemical characteristics closely to the hierarchical mineralization process include biological crystal defects, chemical bonding, atomic doping, structural changes, and content changes in organic matter, along with the interface between biocrystals and organic matter as well as the specific mechanical effects for hardness and toughness. Based on those observations, the special physiological properties of mineralization for enamel and bone, as well as the possible mechanism of pathological mineralization and calcification such as atherosclerosis, tumor micro mineralization, and urolithiasis are also reviewed and discussed. Indeed, the clearly defined physicochemical properties of mineral crystals could pave the way for studies on the mechanisms and applications.
The correlation between Th17/Treg immune dysregulation and the disease severity in chronic spontaneous urticaria patients
Authors: Yang Xiaojing , Chen Leigang , Wang Shining , Wu Yuanhui , Zhou Xiangzhao , Meng Zhaoying
Published: July 2023

Objective

Chronic spontaneous urticaria (CSU) has a profound impact on the sleep quality, productivity and overall quality of life of affected individuals. This study aimed to investigate the correlation between serum Th17/Treg immune dysregulation and the severity of CSU in patients.

Methods

Clinical baseline data of 120 CSU patients and matched healthy controls were recorded. The pruritus level, disease severity, and quality of life of CSU patients were assessed using the visual analogue scale, weekly Urticaria Activity Score and chronic urticaria quality of life questionnaire, respectively. The Th17/Treg cell ratio was detected by flow cytometry. ELISA was used to measure the levels of serum Th17 cytokines (IL‐17, IL‐21) and Treg cytokines (TGF‐β1, IL‐35). Pearson's correlation analysis was conducted to examine the associations between these indicators.

Results

No significant differences were identified in terms of sex, age, and BMI between the two groups. However, CSU patients exhibited a significant increase in the Th17 cell ratio, as well as the elevated serum levels of TGF‐β1, IL‐17 and, IL‐21. Conversely, the proportion of Treg cells and the levels of IL‐35 were remarkably decreased in CSU patients. Peripheral blood Th17 cells were negatively correlated with Treg cells. The severity of pruritus, life quality, and disease severity in CSU patients were positively correlated to Th17 cell ratio, and inversely correlated with Treg cell proportion.

Conclusions

A positive correlation was found between the percentage of peripheral blood Th17 cell in CSU patients and the pruritus level, life quality, and disease severity. In constrast, there was a negative correlation between the proportion of peripheral blood Treg cells and these clinical parameters.
Expression of circulating angiotensin‐converting enzyme 2 in children with asthma and the effects of inhaled corticosteroids
Authors: Ma Xiang , Liu Lesen , Sun Jing , Zhang Yun , Liu Yanqin , Liu Miao , Wang Bing , Chang Yuna , Han Yuling , Gai Zhongtao
Published: July 2023

Background

The global spread of coronavirus disease 2019 (COVID‐19) has resulted in a significant disease burden, yet asthma patients do not have the expected high morbidity and mortality rates in the pandemics of COVID‐19.

Objective

To find the difference of angiotensin‐converting enzyme 2 (ACE2) in asthma and nonasthma children and evaluate the effect of inhaled corticosteroids (ICS) on its expression.

Methods

The ACE2, immunoglobulin E (IgE), and eosinophils were tested in different children.

Results

A total of 157 children aged 3–16 years were enrolled. The expression of ACE2 in asthma children were lower than nonasthma children (T = −2.512, p = .013). Allergic nonasthma children had a significant higher ACE2 expression than children with allergic asthma (p = .013) and nonallergic asthma (p = .029). The expression of ACE2 had no significant difference between first‐diagnosed asthma children and that had been treated with ICS for ≥6 months (F = 0.028, p = .598). The allergic asthma children showed a significantly higher eosinophils cells (EC) count than the allergic nonasthma (W = 200, p < .001) and nonallergic nonasthma children (W = 1089, p < .001). Nonallergic asthma children also had a significant higher EC count than the allergic non‐asthma (W = 182.5, p < .001) and nonallergic non‐asthma (W = 200.5, p < .001) children. There was no significant difference in IgE levels between asthmatic children and non‐asthmatic children (W = 2792.5, p = .18).

Conclusion

Circulating ACE2 levels in asthmatic children were lower than those in non‐asthmatic children and ICS treatment for ≥6 months did not affect the expression of ACE2 in peripheral blood in the asthma children.
Immunomodulatory role of spleen tyrosine kinase in chronic inflammatory and autoimmune diseases
Authors: Zhou Yaqi , Zhang Yaowen , Yu Wei , Qin Yufen , He Heng , Dai Fengxian , Wang Yibo , Zhu Fengqin , Zhou Guangxi
Published: July 2023

Background

The high prevalence of chronic inflammatory diseases or autoimmune reactions is a major source of concern and affects the quality of life of patients. Chronic inflammatory or autoimmune diseases are associated with many diseases in humans, including asthma, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and cancer. Splenic tyrosine kinase (SYK) is a non–receptor tyrosine kinase that plays an important role in immune receptor signalling in immune and inflammatory responses.

Methods

This is a review article in which we searched for keywords “splenic tyrosine kinase”, “inflammation” and “autoimmune diseases” in published literature such as Pubmed and Web of Science to collect relevant information and then conducted a study focusing on the latest findings on the involvement of SYK in chronic inflammatory or autoimmune diseases.

Results

This paper reviews the regulation of Fcγ, NF–κB, B cell and T cell–related signalling pathways by SYK, which contributes to disease progression in chronic inflammatory and autoimmune diseases such as airway fibrosis, inflammatory skin disease and inflammatory bowel disease.

Conclusion

This paper shows that SYK plays an important role in chronic inflammatory and autoimmune diseases. syk targets hematological, autoimmune and other inflammatory diseases and therefore, inhibition of SYK expression or blocking its related pathways may provide new ideas for clinical prevention and treatment of inflammatory or autoimmune diseases.
A study of the efficacy and safety of plaque psoriasis treatment by TNF‐α and IL‐17A inhibitor biologics in patients who received the inactivated SARS‐CoV‐2 vaccine
Authors: Ye Shuhong , Sun Hong , Xu Zining , Xu Bingyang , Wu Na , Wu Jiawen
Published: July 2023

Background

Vaccination is an important method for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission. There is currently a lack of real‐world clinical data regarding the safety and efficacy of coronavirus disease 2019 (COVID‐19) vaccines with respect to plaque psoriasis treatment involving tumor necrosis factor‐α (TNF‐α) and interleukin‐17A (IL‐17A) inhibitors.

Methods

We longitudinally analyzed 152 patients with plaque psoriasis, 86 of whom received two doses of inactivated COVID‐19 vaccine (either BBIBP‐CorV or CoronaVac). Comparisons were made between patients undergoing treatment with biologics (TNF‐ α inhibitors or IL‐17A inhibitors) or acitretin. Routine blood tests were used to assess safety; the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI) were used to assess efficacy.

Results

After inactivated COVID‐19 vaccination, biologics retained considerable advantages in terms of improving skin lesions (measured by PASI) and quality of life (measured by DLQI), compared with conventional treatment (p < 0.05 and p < 0.01, respectively). Routine blood tests and hepatorenal function analyses suggested that inactivated SARS‐CoV‐2 vaccines did not alter the safety of biologics treatment (p > 0.05).

Conclusions

Inactivated SARS‐CoV‐2 vaccines do not have significant impacts on the safety and efficacy of biologics (TNF‐α inhibitors or IL‐17A inhibitors) in patients with moderate to severe plaque psoriasis.
Transcription factor Krüppel‐like factor 4 upregulated G protein‐coupled receptor 30 alleviates intestinal inflammation and apoptosis, and protects intestinal integrity from intestinal ischemia–reperfusion injury
Authors: Yin Jie , Xie Xiaoli , Yao Jinfeng , Jin Xiaoxu , Jiang Huiqing , Ji Chenguang
Published: July 2023

Introduction

Intestinal ischemia/reperfusion (I/R) injury is a common clinical event occurring during multiple clinical pathological processes. Here, we designed this paper to discuss the role of G protein‐coupled receptor 30 (GPR30) playing in intestinal I/R injury.

Methods

An oxygen‐glucose deprivation/reoxygenation (OGD/R) cell model was established to simulate the pathological process of I/R injury. With the application of enzyme‐linked immunosorbent assay, TUNEL, and transepithelial electrical resistance (TEER) assays, the levels of inflammatory cytokines, cell apoptosis, and intestinal integrity were estimated. The corresponding proteins were estimated by applying western blot. Immunofluorescence was conducted to examine N‐terminal Gasdermin D (GSDMD‐N) expression. The interplay between KLF4 and GPR30 was demonstrated by dual‐luciferase reporter assay and chromatin immunoprecipitation.

Results

The results showed that GPR30 was downregulated in Caco‐2 cells exposed to OGD/R. GPR30 overexpression reduced the production of TNF‐α, IL‐6, IL‐1β, and IL‐18, the TUNEL‐positive cells, as well as the contents of p‐p65, Cox‐2, Inos, Bax, and cleaved‐PARP, but elevated the expression of Bcl‐2 in OGD/R‐induced Caco‐2 cells. In addition, OGD/R‐induced the reduction of TEER value and reduced expression of tight junction proteins in Caco‐2 cells, which was partially restored by GPR30 overexpression. Furthermore, GPR30 suppressed nod‐like receptor pyrin 3 inflammasome and GSDMD‐N expression. It was evidenced that Krüppel‐like factor 4 (KLF4) could directly bind to GPR30 promoter and positively regulate GPR30 expression. The regulation of GPR30 overexpression above was weakened by KLF4 knockdown.

Conclusion

Collectively, our findings suggested that KLF4 could transcriptionally upregulate GPR30, and GPR30 prevented intestine I/R injury by inhibiting inflammation and apoptosis, and maintaining intestinal integrity that provides potential targets for mitigating the I/R injury.
STK11 mutation impacts CD1E expression to regulate the differentiation of macrophages in lung adenocarcinoma
Authors: Zhang Qingfeng , Feng Juan , Liu Kui , Yang Xiaoyan , Huang Yun , Tang Bo
Published: July 2023

Background

The deficiency of serine/threonine protein kinase 11 (STK11), one of the most common tumor suppressor genes in non‐small‐cell lung cancer, is a crucial player in tumor immune microenvironment regulation. This study attempted to unveil how mutated STK11 impact the differentiation of macrophages in lung adenocarcinoma (LUAD).

Methods

STK11 and CD1E expression levels in different cell models were assessed by quantitative reverse transcription polymerase chain reaction. Western blot was utilized to detect the protein expression levels of STK11, CD1E, apoptosis markers, and AMPK signaling pathway markers after transfection treatment. Cell viability and macrophage differentiation were detected by CCK‐8 and flow cytometry. Immunohistochemistry and immunofluorescence were employed to detect the expression of related genes and macrophage markers, respectively.

Results

This study found that STK11 mutations promoted the proliferation of LUAD cells and inhibited the differentiation of M1 macrophages, apoptosis, and the AMPK signaling pathway. Mutated STK11 led to CD1E downregulation, which curbed the differentiation of M1 macrophages and hence promoted LUAD progression. It was further validated by the in vivo experimental results that STK11 mutation significantly decreased the immune infiltration of M1 macrophages and promoted LUAD progression.

Conclusion

It was revealed that STK11 mutation affected CD1E expression to regulate macrophage differentiation in LUAD and then promote tumor progression. In this way, CD1E could be a potential biological target for the therapeutic interventions of STK11‐mutant LUAD patients. These findings also threw new light on a new therapeutic strategy for STK11‐mutant tumor patients that assisted the macrophage polarization pathway.
A Hammett's analysis of the substituent effect in functionalized diketopyrrolopyrrole (DPP) systems: Optoelectronic properties and intramolecular charge transfer effects
Authors: Monteiro‐de‐Castro Gabriel , Borges Itamar
Published: July 2023

Diketopyrrolopyrrole (DPP) systems have promising applications in different organic electronic devices. In this work, we investigated the effect of 20 different substituent groups on the optoelectronic properties of DPP‐based derivatives as the donor ()‐material in an organic photovoltaic (OPV) device. For this purpose, we employed Hammett's theory (HT), which quantifies the electron‐donating or ‐withdrawing properties of a given substituent group. Machine learning (ML)‐based , , , , , , , and Hammett's constants previously determined were used. Mono‐ (DPP‐X1) and di‐functionalized (DPP‐X2) DPPs, where X is a substituent group, were investigated using density functional theory (DFT), time‐dependent DFT (TDDFT), and ab initio methods. Several properties were computed using CAM‐B3LYP and the second‐order algebraic diagrammatic construction, ADC(2), an ab initio wave function method, including the adiabatic ionization potential (), the electron affinity (), the HOMO‐LUMO gaps (), and the maximum absorption wavelengths (), the first excited state transition 1S0→ 1S1 energies () (the optical gap), and exciton binding energies. From the optoelectronic properties and employing typical acceptor systems, the power conversion efficiency (), open‐circuit voltage (), and fill factor () were predicted for a DPP‐based OPV device. These photovoltaic properties were also correlated with the machine learning (ML)‐based Hammett's constants. Overall, good correlations between all properties and the different types of constants were obtained, except for the constants, which are related to inductive effects. This scenario suggests that resonance is the main factor controlling electron donation and withdrawal effects. We found that substituent groups with large values can produce higher photovoltaic efficiencies. It was also found that electron‐withdrawing groups (EWGs) reduced and considerably compared to the unsubstituted DPP‐H. Moreover, for every decrease (increase) in the values of a given optoelectronic property of DPP‐X1 systems, a more significant decrease (increase) in the same values was observed for the DPP‐X2, thus showing that the addition of the second substituent results in a more extensive influence on all electronic properties. For the exciton binding energies, an unsupervised machine learning algorithm identified groups of substituents characterized by average values (centroids) of Hammett's constants that can drive the search for new DDP‐derived materials. Our work presents a promising approach by applying HT on molecular engineering DPP‐based molecules and other conjugated molecules for applications on organic optoelectronic devices.
Decision tree model for early use of semi‐elemental formula versus standard polymeric formula in critically ill Malaysian patients: A cost‐effectiveness study
Authors: Adam Aisha , Ibrahim Noor Airini , Tah Pei Chien , Liu Xin Yi , Dainelli Livia , Foo Chee Yoong
Published: July 2023

Background

Prevention of enteral feeding interruption (EFI) improves clinical outcomes of critically ill intensive care unit (ICU) patients. This leads to shorter ICU stays and thereby lowers healthcare costs. This study compared the cost of early use of semi‐elemental formula (SEF) in ICU vs standard polymeric formula (SPF) under the Ministry of Health (MOH) system in Malaysia.

Methods

A decision tree model was developed based on literature and expert inputs. An epidemiological projection model was then added to the decision tree to calculate the target population size. The budget impact of adapting the different enteral nutrition (EN) formulas was calculated by multiplying the population size with the costs of the formula and ICU length of stay (LOS). A one‐way sensitivity analysis (OWSA) was conducted to examine the effect each input parameter has on the calculated output.

Results

Replacing SPF with SEF would lower ICU cost by MYR 1059 (USD 216) per patient. The additional cost of increased LOS due to EFI was MYR 5460 (USD 1114) per patient. If the MOH replaces SPF with SEF for ICU patients with high EFI risk (estimated 7981 patients in 2022), an annual net cost reduction of MYR 8.4 million (USD 1.7 million) could potentially be realized in the MOH system. The cost‐reduction finding of replacing SPF with SEF remained unchanged despite the input uncertainties assessed via OWSA.

Conclusion

Early use of SEF in ICU patients with high EFI risk could potentially lower the cost of ICU care for the MOH system in Malaysia.
Effect of liposome composition on β‐blocker interactions studied by capillary electrokinetic chromatography
Authors: Ravald Henri , Moghaddam Amin Hedayati , Jaikishan Shishir , Lavainne Marine , Wiedmer Susanne K.
Published: July 2023

Liposome capillary electrokinetic chromatography was used to investigate the interactions between three β‐blockers of different hydrophobicity and various liposome solutions. The studied β‐blockers comprised alprenolol, propranolol, and carvedilol. The composition of the liposome solutions, containing 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine, 1,2‐dioleoyl‐sn‐glycero‐3‐phos‐phoethanolamine, 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phospho‐l‐serine, and cholesterol in various molar ratios, was designed by a response surface methodology‐central composite design approach. Subsequently, after conducting the liposome capillary electrokinetic chromatography experiments and determining the retention factors from the electrophoretic mobilities of the compounds, and further calculating the distribution coefficients, an analysis of variance was performed. After extracting the statistical models, optimal operational conditions were obtained based on the developed models. To further investigate the interactions between the β‐blockers and the liposomes, nanoplasmonic sensing experiments were carried out on two different liposome systems. The overall results demonstrate the strong influence of cholesterol and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phospho‐l‐serine on the distribution coefficients.