bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual Variation in the Distribution of Apolipoprotein B Levels Across the Spectrum of LDL-C or Non–HDL-C Levels
Authors: Sayed Ahmed , Peterson Eric D. , Virani Salim S. , Sniderman Allan D. , Navar Ann Marie
Published: June 2024

Importance

Although apolipoprotein B (apoB) is a superior marker of lipid-related risk compared with low-density lipoprotein cholesterol (LDL-C), few data exist to translate the goals and thresholds from LDL-C to their apoB equivalent. In addition, although current American College of Cardiology/American Heart Association guidelines provide a relative indication for apoB measurement among individuals with hypertriglyceridemia, whether discordance is limited to those subgroups is unknown.

Objectives

To assess the variability in apoB level across the spectrum of LDL-C or non–high-density lipoprotein cholesterol (non–HDL-C) levels and evaluate whether discordance between apoB and LDL-C or non–HDL-C is limited to specifiable subgroups.

Design, Setting, and Participants

This cross-sectional study used data from a nationally representative sample of 12 688 adult participants not using statins in the National Health and Nutrition Examination Survey between 2005 and 2016. Statistical analysis was performed from April 2023 to February 2024.

Main Outcomes and Measures

Quantile regression was used to assess the population distribution of apoB across LDL-C or non–HDL-C levels. Discordance between apoB and LDL-C was the difference between measured apoB and median apoB levels for an individual’s LDL-C level. Discordance was evaluated by age, sex, race and ethnicity, obesity, diabetes, triglyceride level, hemoglobin A1c level, body mass index (BMI), statin use, and metabolic health (defined as a BMI between 18.5 and 24.9, triglyceride level <150 mg/dL, and no diabetes).

Results

Among the sample of 12 688 participants (median age, 41.0 years [IQR, 29.0-54.0 years]; 52.9% women) for LDL-C values of 55, 70, 100, and 190 mg/dL, the corresponding population median apoB levels were 49, 60, 80, and 140 mg/dL, respectively. For given levels of LDL-C, a range of apoB values was observed. At an LDL-C level of 100 mg/dL, the 95% population distribution of apoB ranged from 66 mg/dL to 99 mg/dL. ApoB variability was highest for LDL-C values estimated using the Friedewald equation, lower when using Sampson or Martin-Hopkins equations, and lowest for non–HDL-C. Although individuals with metabolic risk factors were more likely to have discordantly high apoB levels (ie, had higher median observed apoB levels relative to what was estimated based on LDL-C), significant variability in apoB levels was observed even among metabolically healthy individuals.

Conclusions and Relevance

This study suggests that even metabolically healthy individuals may have discordantly high apoB levels relative to LDL-C or non–HDL-C levels. The current guideline approach for apoB testing only for those with hypertriglyceridemia appears too narrow. Population percentile data can be used to translate LDL-C goals and thresholds to their apoB equivalent to facilitate clinical adoption.
Prevalence and Treatment Patterns in Patients With Lichen Planopilaris
Authors: Pelet del Toro Natalia , Strunk Andrew , Garg Amit , Han George
Published: June 2024

Importance

Lichen planopilaris (LPP) is a form of scarring alopecia associated with progressive, permanent hair loss. Symptoms range from burning pain to itching, also carrying substantial psychological morbidity. Yet, disease characteristics, pathophysiology, and effective treatment data are limited, making treatment a challenge.

Objective

To describe the prevalence and dermatologist-prescribed treatment patterns of LPP among US adults.

Design, Setting, and Participants

This cross-sectional study used the Explorys database. The prevalence analysis used a 15% random sample and identified US adults with LPP diagnoses between 2017 and 2019. The LPP treatment analysis included all patients with LPP diagnoses between 2016 and 2020 and a dermatologist encounter in the first year after diagnosis. Data were analyzed from January 2023 to April 2023.

Main Outcomes and Measures

The main outcomes of the prevalence analysis were the crude and standardized prevalence estimates of US adults with LPP across age, sex, and racial groups. The main outcomes of the treatment analysis were the frequency of LPP treatments within 1 year of diagnosis, and the number of patients who continued treatment beyond 1 year, switched treatments, and combined treatments.

Results

Among 1 466 832 eligible patients analyzed for prevalence, 241 patients had an LPP diagnosis (222 [92.1%] female; median [IQR] age, 64 [54-73] years). Standardized overall prevalence was 13.4 per 100 000 (95% CI, 11.7-15.1). In the treatment analysis, 991 patients had an LPP diagnosis (907 [91.5%] female; median (IQR) age, 60 [47-69] years). Most received at least 1 type of medication (635 [64.1%]), most frequently intralesional corticosteroids (370 [37.3%]) and topical corticosteroids (342 [34.5%]), followed by doxycycline (104 [10.5%]) and hydroxychloroquine (72 [7.3%]). Treatment continued beyond 1 year in 71 of 200 patients (35.5%) prescribed intralesional corticosteroids and 7 of 29 patients (24.1%) prescribed hydroxychloroquine. Treatment switching at 1 year occurred in 32 of 254 patients (12.6%) first prescribed an intralesional corticosteroid and in 44 of 194 (22.7%) first prescribed a topical corticosteroid. Combinations of 2 or 3 treatment types were given to 137 (13.8%) and 74 (7.5%) patients, respectively.

Conclusions and Relevance

This cross-sectional study reported prevalence and treatment patterns for US adults with LPP in a representative sample. Most patients with LPP received treatment, and many received multiple treatment types and switched treatments, suggesting further research into medication selection offers clinical benefit.
Worst Itch Numeric Rating Scale for Prurigo Nodularis
Authors: Kwatra Shawn G. , Yosipovitch Gil , Kim Brian , Stander Sonja , Rhoten Stephanie , Ivanescu Cristina , Haeusler Nadine , Brookes Ella , Msihid Jerome , Makhija Melanie , Bansal Ashish , Thomas Ryan B. , Bahloul Donia
Published: June 2024

Importance

Prurigo nodularis (PN) is a debilitating skin disease characterized by the hallmark symptom of chronic itch; the intensity of itch in PN was assessed using the Worst Itch Numeric Rating Scale (WI-NRS) to evaluate the primary efficacy end point of 2 recent phase 3 studies of dupilumab treatment for PN.

Objective

To validate the psychometric properties and to determine the clinically meaningful improvement threshold for WI-NRS in patients with moderate to severe PN.

Design, Setting, and Participants

In this secondary analysis of the PRIME and PRIME2 trials, content validity of WI-NRS was assessed through in-depth patient interviews. Psychometric assessments used pooled data from masked, intention-to-treat (ITT) patients with PN from randomized, double-masked, and placebo-controlled studies. Psychometric assessments included test-retest reliability, construct validity, known-groups validity, and sensitivity to change in adult patients with moderate-to-severe PN. Thresholds for meaningful within-patient improvement in the WI-NRS score were determined using anchor and distribution-based approaches. Data were analyzed after completion of each study, December 2019 to November 2021 for PRIME and January 2020 to August 2021 for PRIME2.

Exposures

Dupilumab (300 mg) or placebo subcutaneously every 2 weeks for 24 weeks.

Main outcomes and measures

WI-NRS score at specified time points up to 24 weeks after randomization.

Results

A total of 20 patients were included across the 2 studies (mean [SD] age, 49.3 [17.2] years; 11 female [55%]); 311 patients were included in the pooled intention-to-treat analysis (mean [SD] age, 49.5 [16.1] years; 203 female [65.3%]). The WI-NRS questions (20 of 20 patients), recall period (19 of 20 patients), and response scale (20 of 20 patients) were easy to understand and relevant for patients with PN. Adequate test-retest reliability was observed between screening and baseline (intraclass correlation coefficient = 0.72, using Patient Global Impression of Severity [PGIS] to define stable patients). Convergent and discriminant validity was supported by moderate to strong correlations (absolute r range = 0.34-0.73) with other conceptually related measures and weaker correlations (absolute r range = 0.06-0.32) with less-related measures, respectively. WI-NRS was sensitive to change, as demonstrated by differences in change from baseline among groups (per PGIS change and PGI of Change [PGIC]). Using anchor-based approach with PGIS and PGIC, the clinically meaningful improvement threshold was 4 points (range, 3.0-4.5), which was also supported by distribution-based methods.

Conclusion and Relevance

This study found that WI-NRS may be a fit-for-purpose instrument to support efficacy end points measuring the intensity of itching in adults with PN.

Trial Registration

NCT04183335 (PRIME) and NCT04202679 (PRIME2)
Racial Discrimination and Risk for Internalizing and Externalizing Symptoms Among Black Youths
Authors: Oshri Assaf , Reck Ava Jane , Carter Sierra E. , Uddin Lucina Q. , Geier Charles F. , Beach Steven R. H. , Brody Gene H. , Kogan Steven M. , Sweet Larry H.
Published: June 2024

Importance

Racial discrimination is a psychosocial stressor associated with youths’ risk for psychiatric symptoms. Scarce data exist on the moderating role of amygdalar activation patterns among Black youths in the US.

Objective

To investigate the association between racial discrimination and risk for psychopathology moderated by neuroaffective processing.

Design, Setting, and Participants

This cohort study used longitudinal self-report and functional magnetic resonance imaging (fMRI) data from Black youth participants in the US from the Adolescent Brain Cognitive Development (ABCD) study. Data were analyzed from January 2023 to May 2024.

Exposures

At time 1 of the current study (12 months after baseline), youths self-reported on their experiences of interpersonal racial discrimination and their feelings of marginalization. Amygdalar response was measured during an emotionally valenced task that included blocks of faces expressing either neutral or negative emotion.

Main Outcomes and Measures

At 24 and 36 months after baseline, youths reported their internalizing (anxiety and depressive symptoms) and externalizing symptoms (aggression and rule-breaking symptoms).

Results

A total of 1596 youths were a mean (SD) age of 10.92 (0.63) years, and 803 were female (50.3%). Families in the study had a mean annual income range of $25 000 to $34 999. Two factors were derived from factor analysis: interpersonal racial discrimination and feelings of marginalization (FoM). Using structural equation modeling in a linear regression, standardized β coefficients were obtained. Neural response to faces expressing negative emotion within the right amygdala significantly moderated the association between FoM and changes in internalizing symptoms (β = −0.20; 95% CI, −0.32 to −0.07; P < .001). The response to negative facial emotion within the right amygdala significantly moderated the association between FoM and changes in externalizing symptoms (β = 0.24; 95% CI, 0.04 to 0.43; P = .02). Left amygdala response to negative emotion significantly moderated the association between FoM and changes in externalizing symptoms (β = −0.16; 95% CI, −0.32 to −0.01; P = .04).

Conclusions and Relevance

In this cohort study of Black adolescents in the US, findings suggest that amygdala function in response to emotional stimuli can both protect and intensify the affective outcomes of feeling marginalized on risk for psychopathology, informing preventive interventions aimed at reducing the adverse effects of racism on internalizing and externalizing symptoms among Black youths.
Time to Rethink the Approach to Treating Obesity
Authors: Samuels Jason M. , Patel Mayur B. , Niswender Kevin D.
Published: June 2024

This Viewpoint describes potential benefits and hurdles to implementing a more personalized approach to obesity treatment through a comprehensive multidisciplinary evaluation that considers surgical, medical, and combined therapies.
The impact of the titanium cranial hardware in proton single‐field uniform dose plans
Authors: Wang Peng , O'Grady Fionnbarr Timothy , Janson Martin , Kim Daniel , Choe Kevin S. , Grayden MacLennan , Bamberger Caroline K. , Fan Jiajin
Published: June 2024

Background

Neurosurgical cranial titanium mesh and screws are commonly encountered in postoperative radiation therapy. However, only a limited number of reports are available in the context of proton therapy, resulting in a lack of consensus among the proton centers regarding the protocol for handling the hardware.

Purpose

This study is to examine the impact of the hardware in proton plans. The results serve as evidence for proton centers to generate standard operating procedures to manage the hardware in proton treatment.

Methods

Plans with different gantry angles and material overrides are generated on the CT images of a phantom made of the hardware. The dose distributions of the plans with and without material override, at different depths are compared. Films and ionization chambers are used to measure the plans and the measurements are compared to the treatment planning system (TPS) calculations by gamma analysis.

Results

There are some overdose and underdose regions downstream of the hardware. The overdose and underdose values are within a few percent of the prescribed dose when multiple fields with large hinge angles are used. The gamma analysis results show that the measurements agree with the TPS calculations within limits that are clinically relevant.

Conclusion

The study has demonstrated the influence of the hardware on proton plans. Based on the result of this study, a standard operating procedure of managing the hardware has been implemented in our clinic.
Development of a Mouse Cardiac Sarcoidosis Model Using Carbon Nanotubes
Authors: Van Remortel Sophie , Risha Yousef , Parent Sandrine , Nair Vidhya , Birnie David H. , Davis Darryl R.
Published: June 2024

Sarcoidosis, a granulomatous disorder of unknown etiology affecting multiple organs. It is often a benign disease but can have significant morbidity and mortality when the heart is involved (often presenting with clinical manifestations such as conduction irregularities and heart failure). This study addresses a critical gap in cardiac sarcoidosis (CS) research by developing a robust animal model. The absence of a reliable animal model for cardiac sarcoidosis is a significant obstacle in advancing understanding and treatment of this condition. The proposed model utilizes carbon nanotube injection and transverse aortic constriction as stressors. Intramyocardial injection of carbon nanotubes induces histiocytes typical of sarcoid granulomas in the heart but shows limited effects on fibrosis or cardiac function. Priming the immune system with transverse aortic constriction prior to intramyocardial injection of carbon nanotubes enhances cardiac fibrosis, diminishes cardiac function, and impairs cardiac conduction. This novel, easily executable model may serve as a valuable tool for disease profiling, biomarker identification, and therapeutic exploration.
Viscosity Calculation for Al–Si–Mg–Fe System through CALPHAD Method
Authors: Fu Yu , Luo Qun , Liu Bin , Li Qian
Published: June 2024

Viscosity is a crucial parameter affecting the fluidity of metal melts, which directly influences the founding properties of Al alloys. However, obtaining viscosity measurement data is difficult for metal melts, and the viscosity prediction for ternary and multicomponent alloys would provide the significant data for the selection of process parameters. This study compares the applicability of the Hirai model, SDS model, and R‐K function for viscosity calculations in the sub‐binary systems of Al–Si–Mg–Fe alloys. R‐K function shows the best agreement with experimental data. However, the SDS model shows lower relative error than Hirai model, which would play an important role in those systems lacking experimental data to predict the viscosities. Ultimately, a database capable of predicting viscosity values for the entire composition and temperature range of the Al–Si–Mg–Fe system is established using the CALPHAD method. Viscosity parameters for Al–Si, Al–Mg, Al–Fe, Mg–Si, and Mg–Fe are evaluated and optimized through the R‐K derivation, corroborated with existing experimental data. Using the R‐K function, successful extrapolation and prediction of viscosity for the Al–Si–Mg–Fe ternary and quaternary systems are achieved, with a mean square error between predicted and experimental values of only 0.7%, demonstrating the successful application of the Al–Si–Mg–Fe database for viscosity prediction.
Photoresponsive Drug Delivery Systems: Challenges and Progress
Authors: Yang Yang , Long Kaiqi , Chu Yuxiu , Lu Huiping , Wang Weiping , Zhan Changyou
Published: June 2024

Photoresponsive drug delivery systems (PDDSs) have emerged as a promising toolbox for drug delivery, offering precise control over the site, duration, and dosage of light‐triggered medication. It allows controlled drug release, photo‐triggered targeting, diagnosis, and treatment, improving the precision and efficacy of therapies for various diseases. Despite progress in designing different PDDSs, clinical translation has been limited due to various obstacles. Herein, this review article focuses on three critical challenges of PDDSs: 1) accumulation at diseased lesions, 2) precision of light irradiation, and 3) penetration of light in tissues. Also, this article summarizes and discusses current advancements and strategies to address these challenges. Overall, it emphasizes the need to clarify the current challenges from bench to bedside and develop strategies to enhance therapeutic outcomes, increase compatibility and patient compliance, and unlock the possibilities in different clinical therapies.
Biomimetic Stiff Nanocomposite for High‐Strength Structural Material
Authors: Liu Tanglong , Zhao Xuan , Zhong Linxin , Zhuo Hao , He Yingzi , Zhang Yuping , Peng Xinwen
Published: June 2024

The honeycomb structure stands out as an exemplary material, characterized by its remarkable combination of lightweight and superior mechanical strength. Drawing inspiration from the roles of cellulose nanofiber and lignin in natural wood, a novel high‐stiffness biomass honeycomb nanocomposite is developed. This composite is engineered by incorporating lignin into bacterial cellulose, followed by the self‐polycondensation of lignin at elevated temperature. The nanocomposite architecture features intricately interwoven nanofibers to provide a robust long‐range framework, while the self‐polymerized lignin through coniferyl alcohol radicals serves as a rigid binder that interlinks the nanofibers. The dual mechanisms endow the material with exceptional tensile strength and rigidity. Molding this nanocomposite into a honeycomb structure yields a material with outstanding mechanical properties that outperform commercial alternatives, including those derived from Nomex paper and aluminum alloys. Given its characteristics, this nanocomposite holds great promise as a substrate for the next generation of high‐performance structural materials.
Improving Generation Performance of 1O2 by Atomic Doping for Efficient Catalytic Advanced Oxidation Processes
Authors: Qi Defeng , Wang Jiaqi , Zhang Jian , Su Ke , Xu Jie , Lv Weiqiang , Wang Yong , Zhang Zhen , Xiao Yin
Published: June 2024

Singlet oxygen (1O2) has attracted great attention owing to its superior comprehensive oxidizing performance and extensive application in dealing with ever‐growing environmental pollution. However, the efficient catalytic generation of 1O2 is very challenging due to the low catalytic activity of most catalysts and the generation of oxygen‐containing radicals in the catalytic reaction. Herein, C‐doped Co nanoparticles (CoNPs) supported on porous carbon (C─Co/C) as highly reactive and selective 1O2‐producing catalysts are demonstrated for efficient catalytic oxidation of recalcitrant organics via activation of peroxymonosulfate (PMS). The doped C 2p orbitals can accept Co 3d electrons, thereby weakening the Co─O bonding between Co and PMS or other oxygen‐containing intermediates such as *SO4, *OH, *OOH, and *O. The adsorption and cleavage energy of PMS on Co nanoparticle is reduced from 8.09 to 4.64 eV by C doping. The energy barrier of the *OOH to 1O2 step is also lowered significantly, thereby kinetically improving the activity for the generation of 1O2. The C─Co/C catalysts promotes the efficient and 100% selective generation of 1O2 with high modified kinetic model (K) values of 457.0 and 94.5 µmol s−1 g−1 for rhodamine (RhB) and 2,4‐dichlorophenol (2,4‐DCP), respectively.
Highly Reversible Positive‐Valence Conversion of Sulfur Chemistry for High‐Voltage Zinc–Sulfur Batteries
Authors: Chen Ze , Huang Zhaodong , Zhu Jiaxiong , Li Dedi , Chen Ao , Wei Zhiquan , Wang Yiqiao , Li Nan , Zhi Chunyi
Published: June 2024

Sulfur is a promising conversion‐type cathode for zinc batteries (ZBs) due to its high discharge capacity and cost‐effectiveness. However, the redox conversion of multivalent S in ZBs is still limited, only having achieved S0/S2− redox conversion with low discharge voltage and poor reversibility. This study presents significant progress by demonstrating, for the first time, the reversible S2−/S4+ redox behavior in ZBs with up to six‐electron transfer (with an achieved discharge capacity of ≈1284 mAh g−1) using a highly concentrated ClO4−‐containing electrolyte. The developed succinonitrile–Zn(ClO4)2 eutectic electrolyte stabilizes the positive‐valence S compound and contributes to an ultra‐low polarization voltage. Notably, the achieved flat discharge plateaus demonstrate the highest operation voltage (1.54 V) achieved to date in Zn‖S batteries. Furthermore, the high‐voltage Zn‖S battery exhibits remarkable conversion dynamics, excellent cycling performance (85.7% capacity retention after 500 cycles), high efficiency (98.4%), and energy density (527 Wh kg S−1). This strategy of positive‐valence conversion of sulfur represents a significant advancement in understanding sulfur chemistry in batteries and holds promise for future high‐voltage sulfur‐based batteries.
Factors Impacting the Photostability of a Roll‐to‐Roll Processed PEDOT Derivative for Flexible Electrochromic Devices
Authors: Brändler Lisa , Niklaus Lukas , Schott Marco , Giffin Guinevere A. , Löbmann Peer
Published: June 2024

For the use of polymeric electrochromic devices (ECDs) in architectural or automotive applications, the photostability of the electrochromic (EC) polymer is crucial for long‐term durability. In this study, the photostability of the side‐chain modified poly(3,4‐ethylenedioxythiophene) (PEDOT‐EthC6)thin films deposited by roll‐to‐roll slot‐die coating on indium tin oxide coated polyethylene terephtalate (PET‐ITO) is investigated and characterized by UV–vis and IR spectroscopy. Residual iron salt on the EC polymer layer, necessary for the in situ polymerization, and the variation of storage times between processing steps have no influence on the degradation rate during light exposure. The photostability of the thin films is 30% better in an inert atmosphere than in ambient conditions. Different long‐pass filters are applied to enhance the photostability in the colored and the bleached state. The position of the absorption edge strongly affects the photostability and visual appearance/color of the PEDOT‐EthC6 electrodes. The analysis of the CIE L*a*b* color coordinates reveals that a trade‐off between stability and a desirable color is necessary. To prevent UV degradation of the EC polymer in flexible ECDs, sputtered nickel oxide is chosen as the counter electrode material. The hybrid ECD shows no sign of degradation and loss of electrochromic performance after 350 h of light exposure.
Effect of Gamma Irradiation on the Structure, Morphology, and Memristive Properties of CVD Grown ReS2 Thin Film
Authors: Aggarwal Pallavi , Bisht Prashant , Jana Subhajit , Mishra Ambuj , Ray Samit Kumar , Chang Edward Yi , Mehta Bodh Raj , Singh Rajendra
Published: June 2024

In this work, effect of gamma irradiation on chemical vapor deposition grown ReS2 thin films vis‐a‐vis change in its structure, morphology, chemical composition, and memristive behaviour is reported to assess its radiation hardness for space applications. High‐resolution transmission electron micrographs and selected area electron diffraction pattern infer polycrystalline to amorphous phase transition and increase in the number of grain boundaries (GBs) after exposure to 25 kGy of gamma radiation. X‐ray photoelectron spectroscopy and low‐temperature photoluminescence measurements reveal the formation of sulfur vacancies (SV) accompanied with partial oxidation of film. Memristors are then fabricated on the as‐grown film using different metal electrodes, which are Ag, Pt, and Ti in lateral geometry, and their resistive switching (RS) mechanism is studied along with the impact of gamma irradiation. RS is attributed to the formation of conducting filaments due to GB‐mediated migration of metal ions, SV, and oxygen ions from the partially oxidized film. Furthermore, irradiation is found to increase current in the high resistance state of the device, which subsequently reduces the memory window. This impact is observed to be consistent across all the devices which validates the effect of irradiation irrespective of the nature of the metal electrode used.
Biocatalytic Recycling Cascades Combining Aldolases and Transaminases for the Stereo‐Controlled Synthesis of γ‐Hydroxy‐α‐Amino Acids
Authors: Gourbeyre Léa , Perrard Jules , Bouzid Stephany , Matéos Alexandre , Hélaine Virgil , Guérard‐Hélaine Christine , Lemaire Marielle , Petit Jean‐Louis , de Berardinis Véronique , Gefflaut Thierry
Published: June 2024

Recycling cascades combining aldolases and transaminases from biodiversity were designed for the stereoselective synthesis of various isomers of γ‐hydroxy‐α‐amino acids. Aldolases with opposite enantioselectivities were combined with a d‐α‐transaminase to prepare in a single step, d‐syn or d‐anti‐4‐hydroxyglutamic acid with high yield and stereoselectivity. Bioactive (2S,3R,4S)‐4‐hydroxy‐isoleucine was also efficiently prepared via an aldolase‐transaminase recycling cascade. In that case, the unexpected high stereoselectivity was shown to result from the thermodynamically‐driven formation of a stable derivative of the product. This novel approach was applied to the synthesis of l‐syn and d‐syn‐4‐hydroxynorvaline as well as for 3 new β‐branched‐γ‐hydroxy‐α‐amino acids, analogues of 4‐hydroxyisoleucine.
NaSCN‐Induced Cyano‐Rich Porous Graphitic Carbon Nitride with Sodium Dopant and Nitrogen Vacancies for Enhanced Photosynthesis of Hydrogen Peroxide
Authors: Zhang Handong , Zhu Zhiqi , Sun Yanyan , Zuo Mingqing , Zhou Han , Chen Yaping , Han Lei
Published: June 2024

Defect engineering has been considered as an efficient and facile tactics to optimize the bandgap structure and improve the oxygen adsorption ability of graphitic carbon nitride (g‐C3N4). Herein porous g‐C3N4 with nitrogen vacancies and sodium dopant as well as cyano (─C≡N) groups has been successfully constructed by direct pyrolysis of melamine in the presence of cyano‐rich sodium thiocyanate (NaSCN). Moreover, the incorporation of NaSCN is interestingly found to induce the relative high content of ─C≡N groups compared to other inorganic sodium compounds (NaCl, NaOH, and Na2SO4), which has been experimentally demonstrated to be beneficial for extending the light absorption range and promoting the efficient separation of photo‐generated electron–hole pairs as well as improving the oxygen adsorption ability. Benefiting from the above features, the optimal photocatalyst exhibits high H2O2 yield of 438.2 µm within 4 h and excellent cyclic stability.
Exploiting the Mixed Entropy Strategy for the Design of Fast Ion Conductors
Authors: Wu Yanlong , Wang Limin , Wei Saiqi , Bi Xuanxuan , Zhuo Haoxiang , Xiao Wei , Yu Tianwei , Duan Yi , Zhao Changtai , Yang Rong , Liang Jianwen , Li Xiaona , Wang Jiantao , Sun Xueliang
Published: June 2024

The inorganic solid‐state electrolytes play a crucial role in all‐solid‐state batteries. The entropy of solid‐state electrolytes has a significant impact on ion transport. It has been reported that ionic conductivity can be enhanced by increasing the entropy by adding multiple atoms to the materials. However, there is a lack of understanding regarding the potential mechanism between entropy and ion transport in the atomic‐level microstructure of materials. Herein, a new point of view is brought up to understand the influence of entropy on lithium ionic conductivity at an atomic level only by adding one element at a time inspired by the diagonal relationship. A series of materials is designed, including Li1.75Zr0.75Ta0.25Cl6, Li1.75Zr0.75Nb0.25Cl6, Li1.75Zr0.75Mo0.25Cl6, and Li1.75Zr0.75W0.25Cl6, with various mixed entropy, directed by diagonal relationship. It reveals that the substitution increases the mixed entropy, alters the disorder degree of cations around lithium ions, and improves ionic conductivity. Highlighting the importance of mixed entropy in ion migration and establishing the close connection between mixed entropy and ion conduction could provide new insights into the design and development of solid‐state electrolytes.
Targeted proteomics involved in cardiovascular health and heart rate variability in children with overweight/obesity
Authors: Plaza‐Florido Abel , Olvera‐Rojas Marcos , Alcantara Juan M. A. , Radom‐Aizik Shlomit , Ortega Francisco B.
Published: June 2024

Background

Children with overweight/obesity often exhibit alterations in their plasma protein profiles and reduced heart rate variability (HRV). Plasma proteomics is at the forefront of identifying biomarkers for various clinical conditions. We aimed to examine the association between plasma‐targeted proteomics involved in cardiovascular health and resting vagal‐related HRV parameters in children with overweight/obesity.

Methods

Forty‐four children with overweight/obesity (10.2 ± 1.1 years old; 52% boys) participated in the study. Olink's technology was used to quantify 92 proteins involved in cardiovascular health. HRV was measured using a heart rate monitor (Polar RS800CX). Four resting vagal‐related HRV parameters were derived in time‐ and frequency‐domain.

Results

Eight proteins (KIM1, IgG Fc receptor II‐b, IDUA, BOC, IL1RL2, TNFRSF11A, VSIG2, and TF) were associated with at least one out of the four vagal‐related HRV parameters (β values ranging from −0.188 to 0.288; all p < .05), while KIM1, IDUA, and BOC associated with ≥ three vagal‐related HRV parameters. Multiple hypothesis testing corrections did not reach statistical significance (false discovery rate [FDR >0.05]).

Conclusion

Plasma‐targeted proteomics suggested novel biomarkers for resting vagal‐related HRV parameters in children with overweight/obesity. Future studies using larger cohorts and longitudinal designs should confirm our findings and their potential clinical implications.
Effects of family life cycle events on individual Body Mass Index trajectories: Evidence from China
Authors: Jiang Yicen , Zhu Qin
Published: June 2024

Purpose

Body mass index (BMI) is an important predictor of one's physiological health. China is a family‐centric nation compared to Western societies and has already entered an aged society. Exploring the characteristics and patterns of BMI changes during household events in China provides critical insights into the biological and social determinants of health, which can help enhance the scientific validity of health promotion measures and contribute to the realization of healthy aging goals in China.

Methods

Using data from the China Health and Nutrition Survey (CHNS) from 1993 to 2015, this article utilizes two‐level growth curve models with piecewise spline specifications for age to examine the effects of family life cycle events on BMI trajectories for age groups and gender differences.

Results

Compared to continuing status, experiencing transition in an individual's family life cycle could lead to more fluctuating variations in their BMI trajectories, generally, there is a faster increase in BMI during youth and a faster decline during old age. As for gender heterogeneity, males are more affected by divorce, widowhood, and empty nest, whereas females' BMI changes are influenced by entering/maintaining marriage and parenthood.

Conclusions

A long‐term perspective has revealed the significance of family events on BMI throughout the life course. Future research should focus on the nutrition and health of specific populations, especially elderly individuals in vulnerable groups.
Germline PTCH1: c.361_362insAlu alteration identified by comprehensive exome and RNA sequencing in a patient with Gorlin syndrome
Authors: Mochizuki Aaron Y. , Nagaraj Chinmayee B. , Depoorter Douglas , Schieffer Kathleen M. , Kim Sun Young
Published: June 2024

Gorlin syndrome can be caused by pathogenic/likely pathogenic (P/LP) variants in the tumor suppressor gene PTCH1 (9q22.1‐q31), which encodes the receptor for the sonic hedgehog (SHH) ligand. We present a 12‐month‐old boy clinically diagnosed with Gorlin syndrome who was found to have significantly delayed development, palmar pitting, palmar and plantar keratosis, short hands, frontal bossing, coarse face, hypertelorism, a bifid rib, misaligned and missing teeth, and SHH‐activated medulloblastoma. Genetic testing, including a pediatric cancer panel and genome sequencing with peripheral blood, failed to identify any P/LP variants in PTCH1. Paired tumor/normal exome sequencing was performed, which identified a germline NM_000264.5 (PTCH1): c.361_362ins? alteration through manual review of sequencing reads. Clinical RNA sequencing further demonstrated an Alu insertion at this region (PTCH1: c.361_362insAlu), providing molecular confirmation of Gorlin syndrome. This finding exemplifies a unique mechanism for PTCH1 disruption in the germline and highlights the importance of comprehensive analysis, including manual review of DNA sequencing reads and the utility of RNA analysis to detect variant types which may not be identified by routine genetic screening techniques.
Population differences in dental cementum growth rates: Implications for using cementum thickness as a method for age estimation
Authors: Cerrito Paola , Cherian Blessy E. , Hu Bin , Bromage Timothy G.
Published: June 2024

Objectives

Age at death estimation is a key element to many research questions in biological anthropology, archeology, and forensic science. Dental cementum is a tissue of choice for the estimation of age at death in adult individuals as it continues deposition for the entirety of an individual's life. Previous works have devised regression formulas correlating cementum thickness to age at death. However, interpopulation variances are unknown, and it is therefore not clear whether regressions based on a single population are applicable to individuals with different ancestries.

Materials and Methods

Here, we use a sample (n = 52) of teeth from individuals with known age at tooth extraction/death of European, African, and East Asian ancestry to assess whether there are interpopulations differences in cementum growth rate. We measured growth rate in four different areas (2nd and 5th decile of both the lingual and buccal aspect of the root) of each tooth and used nonparametric tests to evaluate population differences in growth rate between homologous regions of the teeth.

Results

The results of the analyses show that, even after controlling for tooth size, individuals of European ancestry have significantly lower growth rates than those of both African and East Asian ancestry across all four tooth areas.

Discussion

These results call into question the applicability of the regression formulas derived from European ancestry individuals to individuals of other ancestries.
Concurrent nutrient deficiencies are associated with dementia incidence
Authors: van Soest Annick P. M. , de Groot Lisette C. P. G. M. , Witkamp Renger F. , van Lent Debora Melo , Seshadri Sudha , van de Rest Ondine
Published: June 2024

INTRODUCTION

While observational research suggests a protective role for nutrition in brain aging, intervention studies remain inconclusive. This failing translation from observational to interventional research may result from overlooking nutrient interactions.

METHODS

We developed a nutrient status index capturing the number of suboptimal statuses of omega‐3 fatty acids, homocysteine, and vitamin D (range 0 to 3). We associated this index with dementia incidence in a subsample (age ≥ 50 years) of the Framingham Heart Study Offspring cohort.

RESULTS

Among 968 participants, 79 developed dementia over 15.5 years (median follow‐up). Each point increase in nutrient status index was associated with a 50% higher risk of dementia (hazard ratio [HR] = 1.50; 95% confidence interval [CI] = 1.16, 1.96). Participants with three high‐risk statuses had a four‐fold increased risk of dementia compared to participants without high‐risk status (HR = 4.68; 95% CI = 1.69, 12.94).

DISCUSSION

Concurrent nutrient deficiencies are associated with the risk of dementia. The potential of optimizing nutritional status to lower dementia risk warrants further study.

Highlights

Nutrition and dementia research calls for multiple‐nutrient approaches.

We studied combined suboptimal statuses of omega‐3 polyunsaturated fatty acids, homocysteine, and vitamin D.

Suboptimal status of the three nutrients was associated with dementia risk.

The risk estimate was larger than for other factors (ie, diabetes, apolipoprotein E ε4 carrier).

Future studies should assess the effect of improving nutrient status on dementia risk.
Herb pair of Huangqi‐Danggui exerts anti‐tumor immunity to breast cancer by upregulating PIK3R1
Authors: Liu Hai‐Xin , Lian Li , Hou Li‐Li , Liu Cai‐Xia , Ren Jin‐Hong , Qiao Yuan‐Biao , Wen Shi‐Yuan , Li Qing‐Shan
Published: June 2024

Background

According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti‐tumor activity associated with Qi‐supplementing herbs, specifically the paired use of Huangqi and Danggui.

Methods

Analysis of compatibility regularity was conducted to screen the combination of Qi‐supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti‐tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti‐tumor activity and the mechanism of the active ingredients were verified by molecular experiments.

Results

There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti‐tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti‐tumor effects of the extract.

Conclusions

The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.
Hybrid Paper/Polyester‐Based Laser‐Induced Graphene Electrodes for Electrochemical Detection of Tadalafil
Authors: Souza Shellyda G. G. , Silva‐Neto Habdias A. , Rocha Danielly S. , de Siervo Abner , Paixão Thiago R. L. C. , Coltro Wendell K. T.
Published: June 2024

Here, we describe for the first time the fabrication of laser‐induced graphene (LIG) electrodes on a hybrid substrate composed of sandpaper and polyester. As a proof of concept, the proposed device was used as a voltammetric sensor for tadalafil (TAD) quantification in authentic tablet samples. The electrochemical TAD sensing based on differential pulse voltammetry (DPV) revealed a linear behavior in the concentration range from 25 to 250 μmol L−1(R2=0.99), a limit of detection of ~9.6 μmol L−1, sensitivity of ~0.0048 μA(μmol L−1)−1 and acceptable reproducibility values (RSD≤5.8 %). The DPV responses involving the standard addition method in pharmaceutical samples presented recovery results of TAD ranging from 93 to 108 %. Also, the proposed analytical method offered a suitable green analytical chemistry profile. We successfully demonstrated the fabrication of graphene‐like sites and nanoparticles composed of alumina upon a hybrid substrate.
Solar Spectrum Light‐Driven Silicone‐Based Fluidic Actuators
Authors: Shahabi Ebrahim , Shabani Majid , Meder Fabian , Mazzolai Barbara
Published: June 2024

Soft materials that convert light into mechanical energy can create new untethered strategies for actuating soft robotics. Yet, the available light‐driven materials are often incompatible with standard fabrication in soft robotics and restricted to shapes (e.g., sheets) that have limited capability for 3D deformation; often laser or focused light is required for actuation. Here, to address these challenges, a straightforward method for synthesizing sunlight‐responsive fluidic actuators from off‐the‐shelf silicone precursors capable of expanding in 3D is developed. A liquid phase and activated carbon as photothermal elements are constrained in the elastomer. Solar spectral light triggers a liquid–gas phase transition creating sufficient pressure to overcome the internal elastic stress and actuate the material. The fluidic actuation is characterized under varying light conditions reaching expansion cycle times between ≈20–500 s, strains of 28%, and actuation stress of ≈1.3 MPa in different experiments. The materials were then used to exemplarily drive a mechanical switch, a liquid dispensing soft pump, a valve, and a bending actuator. As the described materials are easy to produce in a 5 min synthesis by standard molding techniques, it is believed that they are a promising opportunity for embodied energy converters in environmentally powered soft robots that respond to sunlight.
Development and validation of CYP26A1 inhibition assay for high‐throughput screening
Authors: Sakamuru Srilatha , Ma Dongping , Pierro Jocylin D. , Baker Nancy C. , Kleinstreuer Nicole , Cali James J. , Knudsen Thomas B. , Xia Menghang
Published: June 2024

All‐trans retinoic acid (atRA) is an endogenous ligand of the retinoic acid receptors, which heterodimerize with retinoid X receptors. AtRA is generated in tissues from vitamin A (retinol) metabolism to form a paracrine signal and is locally degraded by cytochrome P450 family 26 (CYP26) enzymes. The CYP26 family consists of three subtypes: A1, B1, and C1, which are differentially expressed during development. This study aims to develop and validate a high throughput screening assay to identify CYP26A1 inhibitors in a cell‐free system using a luminescent P450‐Glo assay technology. The assay performed well with a signal to background ratio of 25.7, a coefficient of variation of 8.9%, and a Z‐factor of 0.7. To validate the assay, we tested a subset of 39 compounds that included known CYP26 inhibitors and retinoids, as well as positive and negative control compounds selected from the literature and/or the ToxCast/Tox21 portfolio. Known CYP26A1 inhibitors were confirmed, and predicted CYP26A1 inhibitors, such as chlorothalonil, prochloraz, and SSR126768, were identified, demonstrating the reliability and robustness of the assay. Given the general importance of atRA as a morphogenetic signal and the localized expression of Cyp26a1 in embryonic tissues, a validated CYP26A1 assay has important implications for evaluating the potential developmental toxicity of chemicals.
Clioquinol rescues yeast cells from Aβ42 toxicity via the inhibition of oxidative damage
Authors: Zheng Qiaoqiao , Zhu Hongzheng , Lv Chunyi , Zhu Ziting , Cui Hanyue , Fan Zheyu , Sun Jing , Huang Zhiwei , Shi Ping
Published: June 2024

Alzheimer's disease (AD), the most common form of dementia, has gotten considerable attention. Previous studies have demonstrated that clioquinol (CQ) as a metal chelator is a potential drug for the treatment of AD. However, the mode of action of CQ in AD is still unclear. In our study, the antioxidant effects of CQ on yeast cells expressing Aβ42 were investigated. We found that CQ could reduce Aβ42 toxicity by alleviating reactive oxygen species (ROS) generation and lipid peroxidation level in yeast cells. These alterations were mainly attributable to the increased reduced glutathione (GSH) content and independent of activities of superoxide dismutase (SOD) and/or catalase (CAT). CQ could affect antioxidant enzyme activity by altering the transcription level of related genes. Interestingly, it was noted for the first time that CQ could combine with antioxidant enzymes to reduce their enzymatic activities by molecular docking and circular dichroism spectroscopy. In addition, CQ restored Aβ42‐mediated disruption of GSH homeostasis via regulating YAP1 expression to protect cells against oxidative stress. Our findings not only improve the current understanding of the mechanism of CQ as a potential drug for AD treatment but also provide ideas for subsequent drug research and development.
Ameliorative potential of rosmarinic acid in a rat model of polycystic ovary syndrome: Targeting MCP‐1 and VEGF: A histological, immunohistochemical, and biochemical study
Authors: Shalaby Amany Mohamed , Shalaby Rania H. , Elshamy Amira Mostafa , Alnasser Sulaiman Mohammed , Alorini Mohammed , Jaber Fatima A. , Alabiad Mohamed Ali , Alshaikh Ahmed Baker A. , Hassan Shaimaa Mohamed Abdelfattah , Aziz Seham Ahmed Mohammed Abdel , Safa Mohamed A. , Elkholy Mahmoud Ramadan
Published: June 2024

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole‐induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid‐PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle‐stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor‐α (TNF‐α), interleukin‐1β, monocyte chemotactic protein‐1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF‐α and caspase‐3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole‐induced PCOS through its anti‐inflammatory and antiangiogenesis effects.