bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Events of Cannabidiol Use in Patients With Epilepsy
Authors: Fazlollahi Asra , Zahmatyar Mahdi , ZareDini Mahta , Golabi Behnam , Nejadghaderi Seyed Aria , Sullman Mark J. M. , Gharagozli Koroush , Kolahi Ali-Asghar , Safiri Saeid
Published: April 2023

Importance

Epilepsy is one of the most common neurologic disorders globally. Cannabidiol (CBD) has been approved for the treatment of epilepsy, but its use has been associated with several different adverse events (AEs).

Objective

To investigate the frequency and risk of AEs developing in patients with epilepsy who are using CBD.

Data Sources

PubMed, Scopus, Web of Science, and Google Scholar were searched for relevant studies published from database inception up to August 4, 2022. The search strategy included a combination of the following keywords: (cannabidiol OR epidiolex) AND (epilepsy OR seizures).

Study Selection

The review included all randomized clinical trials that investigated at least 1 AE from the use of CBD in patients with epilepsy.

Data Extraction and Synthesis

Basic information about each study was extracted. I2 statistics were calculated using Q statistics to assess the statistical heterogeneity among the included studies. A random-effects model was used in cases of substantial heterogeneity, and a fixed-effects model was used if the I2 statistic for the AEs was lower than 40%. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.

Main Outcomes and Measures

Frequency of each AE and risk of developing each AE in patients with epilepsy using CBD.

Results

Nine studies were included. Overall incidences of 9.7% in the CBD group and 4.0% in the control group were found for any grade AEs. The overall risk ratios (RRs) for any grade and severe grade AEs were 1.12 (95% CI, 1.02-1.23) and 3.39 (95% CI, 1.42-8.09), respectively, for the CBD group compared with the control group. Compared with the control group, the CBD group had a greater risk for incidence of serious AEs (RR, 2.67; 95% CI, 1.83-3.88), AEs resulting in discontinuation (RR, 3.95; 95% CI, 1.86-8.37), and AEs resulting in dose reduction (RR, 9.87; 95% CI, 5.34-14.40). Because most of the included studies had some risk of bias (3 raised some concerns and 3 were at high risk of bias), these findings should be interpreted with some caution.

Conclusions and Relevance

In this systematic review and meta-analysis of clinical trials, the use of CBD to treat patients with epilepsy was associated with an increased risk of several AEs. Additional studies are needed to determine the safe and effective CBD dosage for treating epilepsy.
Association Between 5α-Reductase Inhibitors and Prostate Cancer Mortality
Authors: Baboudjian Michael , Gondran-Tellier Bastien , Dariane Charles , Fiard Gaëlle , Fromont Gaëlle , Rouprêt Morgan , Ploussard Guillaume
Published: April 2023

Importance

Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality.

Objective

To systematically evaluate the current evidence regarding 5-ARI use and PCa mortality.

Data Sources

A literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases.

Study Selection

Studies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies.

Data Extraction and Synthesis

This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022.

Main Outcomes and Measures

The primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline.

Results

Among 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen–adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08).

Conclusions and Relevance

This systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.
Morgagnian Cataract With Liquified Nuclear Cleft
Authors: Fan Jason , Goldhagen Brian Evan
Published: April 2023

This case report discusses a diagnosis of morgagnian cataract with liquified nuclear cleft in a patient in his 60s who presented with gradually decreasing visual acuity.
High Oxide‐Ion Conductivity through the Interstitial Oxygen Site in Sillén Oxychlorides
Authors: Yaguchi Hiroshi , Morikawa Daisuke , Saito Takashi , Tsuda Kenji , Yashima Masatomo
Published: April 2023

Oxide‐ion conductors are gaining attention as future materials in energy applications, such as solid oxide fuel cells. Many Bi‐containing compounds exhibit high oxide‐ion conductivity via conventional vacancy mechanism. However, interstitial oxide‐ion conduction is rare in Bi‐containing materials. Herein, high oxide‐ion conductivity is reported through interstitial oxygen sites in Sillén oxychlorides, LaBi2−xTexO4+x/2Cl (Bi2LaO4Cl‐based oxychlorides). Oxide‐ion conductivity of LaBi1.9Te0.1O4.05Cl is 20 mS cm−1 at 702 °C, and higher than best oxide‐ion conductors as Bi2V0.9Cu0.1O5.35 below 201 °C. Despite of the presence of Bi and Te species, LaBi1.9Te0.1O4.05Cl shows extremely high chemical and electrical stability at 400 °C from oxygen partial pressure 10−25 to 0.2 atm and high chemical stability under CO2 flow, wet 5% H2 in N2 flow, and air with natural humidity. Neutron scattering length density analysis, DFT calculations, and ab initio molecular dynamics simulations indicate that the extremely high oxide‐ion conduction is attributed to cooperative diffusion through interstitial oxygen sites (interstitialcy diffusion mechanism) in triple fluorite‐like layers. The present findings demonstrate the ability of LaBi2−xTexO4+x/2Cl as superior oxide‐ion conductors, which can open new horizons for oxide‐ion conductors.
Exploring Functional Photonic Devices made from a Chiral Metal–Organic Framework Material by a Multiscale Computational Method
Authors: Zerulla Benedikt , Li Chun , Beutel Dominik , Oßwald Simon , Holzer Christof , Bürck Jochen , Bräse Stefan , Wöll Christof , Fernandez‐Corbaton Ivan , Heinke Lars , Rockstuhl Carsten , Krstić Marjan
Published: April 2023

Electronic circular dichroism is an important optical phenomenon offering insights into chiral molecular materials. On the other hand, metal–organic frameworks (MOFs) are a novel group of crystalline porous thin‐film materials that provide tailor‐made chemical and physical properties by carefully selecting their building units. Combining these two aspects of contemporary material research and integrating chiral molecules into MOFs promises devices with unprecedented functionality. However, considering the nearly unlimited degrees of freedom concerning the choice of materials and the geometrical details of the possibly structured films, urgently it needs to complement advanced experimental methods with equally strong modeling techniques. Most notably, these modeling techniques must cope with the challenge that the material and devices thereof cover size scales from Ångströms to mm. In response to that need, a computational workflow is outlined that seamlessly combines quantum chemical methods to capture the properties of individual molecules with optical simulations to capture the properties of functional devices made from these molecular materials. The focus is on chiral properties and applying work to UiO‐67‐BINOL MOFs, for which experimental results are available to benchmark the results of the simulations and explore the optical properties of cavities and metasurfaces made from that chiral material.
Color‐Tunable Organic Light‐Emitting Displays for Interactive Multi‐Signal Visualization
Authors: Mu Ge , Rao Tianyu , Qi Yawei , Ma Su , Hao Qun , Chen Menglu , Tang Xin
Published: April 2023

Optoelectronic devices integrated with multiple functions for interactive signal visualization have become increasingly important in the intelligent era. Here, a color‐tunable organic light‐emitting diode (CTOLED) is developed to achieve a user‐interaction intelligent device that enables multicolor visualization of infrared light and temperature distribution via the modulation with a multi‐stimuli responsive silicon (Si) sensor for the first time. The key to the color‐tunable functionality of the CTOLED is an ultrathin exciton‐blocking layer between different emitting layers, which leads to the quantitative correlation of driving current and emitted visible color. As a result, the user can manipulate the silicon/color‐tunable organic light‐emitting diode (Si/CTOLED) device through the infrared pen, and the “writing” spatial information and the infrared intensity can influence the display patterns and colors. Besides, the temperature is sensed by the flexible Si/CTOLED device and is displayed in corresponding different colors, which is promising as a wearable temperature visualization monitor and directly interact with a user. The temperature monitor exhibits ultrasensitivity with a low minimum distinguishable temperature difference of only 65 mK. The Si/CTOLED devices open new possibilities for the development of intelligent devices and have promising multi‐disciplinary applications.
Review of Carbon Support Coordination Environments for Single Metal Atom Electrocatalysts (SACS)
Authors: Song Wanqing , Xiao Caixia , Ding Jia , Huang Zechuan , Yang Xinyi , Zhang Tao , Mitlin David , Hu Wenbin
Published: April 2023

This topical review focuses on the distinct role of carbon support coordination environment of single‐atom catalysts (SACs) for electrocatalysis. The article begins with an overview of atomic coordination configurations in SACs, including a discussion of the advanced characterization techniques and simulation used for understanding the active sites. A summary of key electrocatalysis applications is then provided. These processes are oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), nitrogen reduction reaction (NRR), and carbon dioxide reduction reaction (CO2RR). The review then shifts to modulation of the metal atom‐carbon coordination environments, focusing on nitrogen and other non‐metal coordination through modulation at the first coordination shell and modulation in the second and higher coordination shells. Representative case studies are provided, starting with the classic four‐nitrogen‐coordinated single metal atom (MN4) based SACs. Bimetallic coordination models including homo‐paired and hetero‐paired active sites are also discussed, being categorized as emerging approaches. The theme of the discussions is the correlation between synthesis methods for selective doping, the carbon structure–electron configuration changes associated with the doping, the analytical techniques used to ascertain these changes, and the resultant electrocatalysis performance. Critical unanswered questions as well as promising underexplored research directions are identified.
Enhanced Light Extraction of Nano‐Light‐Emitting Diodes with Metal‐Clad Structure Using Vertical GaAs/GaAsP Core–Multishell Nanowires on Si Platform
Authors: Tomioka Katsuhiro , Sugita Kazuharu , Motohisa Junichi
Published: April 2023

Nanometer‐scaled light sources using III–V compound semiconductor nanowires (NWs) on Si are expected as building blocks for next‐generation Si photonics, bioimaging, on‐chip microscopy, and light detection and ranging (LiDAR) techniques. This is, however, limited in a few materials systems due to complexity in integration of the vertical III–V NWs on Si and device process flow. Suppressing optical loss in the NW materials beyond the optical diffraction remains difficult in enhancing light extraction. Herein, the effect of the vertical metal‐clad architectures for the vertical nano‐light‐emitting diodes (LEDs) using GaAs/GaAsP‐related core–multishell NWs heterogeneously integrated on Si is investigated. The grown core–multishell NW is composed of a radial n‐GaAs/n‐GaAsP/p‐GaAs/p‐GaAsP double heterostructure. The vertical metal‐clad NW‐LEDs show suppression of carrier overflow effect and rapid enhancement of electrical luminescence.
In Situ Generation of Copper Nanoparticle‐Graphitic Carbon Nitride Composite for Stereoselective Transfer Semihydrogenation of Alkynes: Evaluation of Catalytic Activity Using Fluorescence‐Based High‐Throughput Screening
Authors: Yong Park Byoung , Su Han Min
Published: April 2023

Herein, we present the effective synthesis of a copper nanoparticle‐graphitic carbon nitride (g‐C3N4) composite for the efficient (Z)‐selective transfer semihydrogenation of alkynes. A fluorescence‐based high‐throughput screening method was applied to identify the most synergistic support for in situ‐generated copper nanoparticles. The derived Cu(OAc)2/g‐C3N4 system exhibited more than five‐fold increase in the turnover frequency compared to the copper nanoparticle catalyst in the absence of g‐C3N4. Various alkynes were selectively reduced to the corresponding (Z)‐alkenes under mild reactions conditions, affording up to 99% isolated yields. The present work demonstrates a simple and cost‐effective method for the synthesis of a copper nanoparticle‐g‐C3N4 composite for the efficient (Z)‐selective transfer semihydrogenation of alkynes.

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How Do Surface Polar Molecules Contribute to High Open‐Circuit Voltage in Perovskite Solar Cells?
Authors: Ma Yinyi , Zeng Chengsong , Zeng Peng , Hu Yuchao , Li Faming , Zheng Zhonghao , Qin Minchao , Lu Xinhui , Liu Mingzhen
Published: April 2023

To date, the improvement of open‐circuit voltage (VOC) offers a breakthrough for the performance of perovskite solar cells (PSCs) toward their theoretical limit. Surface modification through organic ammonium halide salts (e.g., phenethylammonium ions PEA+ and phenmethylammonium ions PMA+) is one of the most straightforward strategies to suppress defect density, thereby leading to improved VOC. However, the mechanism underlying the high voltage remains unclear. Here, polar molecular PMA+ is applied at the interface between perovskite and hole transporting layer and a remarkably high VOC of 1.175 V is obtained which corresponds to an increase of over 100 mV in comparison to the control device. It is revealed that the equivalent passivation effect of surface dipole effectively improves the splitting of the hole quasi‐Fermi level. Ultimately the combined effect of defect suppression and surface dipole equivalent passivation effect leads to an overall increase in significantly enhanced VOC. The resulted PSCs device reaches an efficiency of up to 24.10%. Contributions are identified here by the surface polar molecules to the high VOC in PSCs. A fundamental mechanism is suggested by use of polar molecules which enables further high voltage, leading ways to highly efficient perovskite‐based solar cells.
Hybrid Metasurfaces for Perfect Transmission and Customized Manipulation of Sound Across Water–Air Interface
Authors: Zhou Hong‐Tao , Zhang Shao‐Cong , Zhu Tong , Tian Yu‐Ze , Wang Yan‐Feng , Wang Yue‐Sheng
Published: April 2023

Extreme impedance mismatch causes sound insulation at water–air interfaces, limiting numerous cross‐media applications such as ocean‐air wireless acoustic communication. Although quarter‐wave impedance transformers can improve transmission, they are not readily available for acoustics and are restricted by the fixed phase shift at full transmission. Here, this limitation is broken through impedance‐matched hybrid metasurfaces assisted by topology optimization. Sound transmission enhancement and phase modulation across the water–air interface are achieved independently. Compared to the bare water–air interface, it is experimentally observed that the average transmitted amplitude through an impedance‐matched metasurface at the peak frequency is enhanced by ≈25.9 dB, close to the limit of the perfect transmission 30 dB. And nearly 42 dB amplitude enhancement is measured by the hybrid metasurfaces with axial focusing function. Various customized vortex beams are experimentally realized to promote applications in ocean‐air communication. The physical mechanisms of sound transmission enhancement for broadband and wide‐angle incidences are revealed. The proposed concept has potential applications in efficient transmission and free communication across dissimilar media.
Artificial Organelles with Digesting Characteristics: Imitating Simplified Lysosome‐ and Macrophage‐Like Functions by Trypsin‐Loaded Polymersomes
Authors: Xu Xiaoying , Moreno Silvia , Boye Susanne , Wang Peng , Voit Brigitte , Appelhans Dietmar
Published: April 2023

Defects in cellular protein/enzyme encoding or even in organelles are responsible for many diseases. For instance, dysfunctional lysosome or macrophage activity results in the unwanted accumulation of biomolecules and pathogens implicated in autoimmune, neurodegenerative, and metabolic disorders. Enzyme replacement therapy (ERT) is a medical treatment that replaces an enzyme that is deficient or absent in the body but suffers from short lifetime of the enzymes. Here, this work proposes the fabrication of two different pH‐responsive and crosslinked trypsin‐loaded polymersomes as protecting enzyme carriers mimicking artificial organelles (AOs). They allow the enzymatic degradation of biomolecules to mimic simplified lysosomal function at acidic pH and macrophage functions at physiological pH. For optimal working of digesting AOs in different environments, pH and salt composition are considered the key parameters, since they define the permeability of the membrane of the polymersomes and the access of model pathogens to the loaded trypsin. Thus, this work demonstrates environmentally controlled biomolecule digestion by trypsin‐loaded polymersomes also under simulated physiological fluids, allowing a prolonged therapeutic window due to protection of the enzyme in the AOs. This enables the application of AOs in the fields of biomimetic therapeutics, specifically in ERT for dysfunctional lysosomal diseases.
Characterization of unsteady flow in a 3D‐printed Schwarz Diamond monolith using magnetic resonance velocimetry
Authors: Clarke Daniel , Galvosas Petrik , Holland Daniel J.
Published: April 2023

Process engineering applications such as heat transfer, reactions, and separations involve passing fluid through a porous medium. Historically, random‐channel porous media have been used for these operations. Such systems do not represent optimal configurations for process performance because of poor flow distribution and high‐pressure drop. It is now possible to fabricate porous monoliths with tailored morphology and regular channel structure using 3D‐printing. In this work, we use magnetic resonance imaging to study flow through a Schwarz Diamond triply periodic minimal surface (TPMS) monolith for Reynolds numbers up to 350. A transition to unsteady flow was observed experimentally for the first time. The channel structure diverts flow such that free shear layers form in the channel centers that contribute to flow instability. These measurements serve to inform the design of novel transport processes with enhanced performance.
Morphology prediction for organic molecular crystals using various force fields in ADDICT
Authors: Zhao Yongsheng , Gee Robert , Doherty Michael F.
Published: April 2023

All‐atom force fields are important for calculating interaction energies between growth units to predict crystal morphology. Our group at UCSB developed the ADDICT morphology design software to predict crystal morphology using mechanistic growth models driven by the generalized Amber force field (GAFF). In this study, the universal force field (UFF), the consistent force field (CFF), and the Coulomb‐London‐Pauli (CLP) force field are incorporated into ADDICT. We systematically test the lattice energies and crystal morphologies of olanzapine, adipic acid, rubrene, biphenyl, and naphthalene using all these force fields. The unit cells for these crystals are represented by the original CSD experimental structure, as well as optimized structures. Considering the high accuracy of CLP, its wide range of applications, and the fact that ADDICT can automatically specify the atomic charge and type required for this force field, we find that CLP is the best all‐atom model to drive morphology calculations.
Navigating COVID‐19 and racial trauma as a Black student at predominantly White institutions
Authors: Francois Samantha , Blakey Joan , Stevenson Rae , Walker Timothy , Davis Curtis
Published: April 2023

Black students at predominantly White institutions (PWIs) contend with racial microaggressions that can lead to negative mental health and academic outcomes. The physical and mental health consequences of the novel coronavirus pandemic are well‐known. What remains unknown is how targeted racial hate during a pandemic might have a compounded effect on Black essential workers. The current study examines how future essential workers in helping professions cope with dual crises as they navigate mostly White universities. Study participants were Black university students attending PWIs in the United States enrolled in social work, public health, or psychology programs during the 2020–2021 academic year. Participants completed an online survey that measured racial microaggressions, COVID distress, sense of belonging, engagement in activism, and well‐being. Hierarchical regression models revealed COVID distress predicted poorer well‐being. Also, COVID distress interacted with racial microaggressions to predict well‐being. Findings have implications for developing decolonized learning communities with a liberation pedagogy in community psychology and other helping professions.
A Widespread Glycosidase Confers Lobophorin Resistance and Host‐Dependent Structural Diversity
Authors: Tan Bin , Zhang Liping , Zhang Qingbo , Chen Siqiang , Xiong Weiliang , Zhu Yiguang , Zhang Changsheng
Published: April 2023

Identifying new environmental resistance determinants is significant to combat rising antibiotic resistance. Herein we report the unexpected correlation of a lobophorin (LOB) resistance‐related glycosidase KijX with the host‐dependent chemical diversity of LOBs, by a process of glycosylation, deglycosylation and reglycosylation. KijX homologues are widespread among bacteria, archaea and fungi, and encode the same glycohydrolytic activity on LOBs. The crystal structure of AcvX (a KijX homologue) shows a similar fold to that of the glycoside hydrolase family 113 and a special negatively charged groove to accommodate and deglycosylate LOBs. Antagonistic assays indicate kijX as a defense weapon of actinomycetes to combat LOB producers in environment, reflecting an elegant coevolution relationship. Our study provides insight into the KijX‐related glycosidases as preexisting resistance determinants and represents an example of resistance genes accidentally integrated into natural product assembly.
Enzyme‐Triggered Chemodynamic Therapy via a Peptide‐H2S Donor Conjugate with Complexed Fe2+
Authors: Zhu Yumeng , Archer William R. , Morales Katlyn F. , Schulz Michael D. , Wang Yin , Matson John B.
Published: April 2023

Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe2+, CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide‐H2S donor conjugate, complexed with Fe2+, termed AAN‐PTC–Fe2+. The AAN tripeptide was specifically cleaved by legumain, an enzyme overexpressed in glioma cells, to release carbonyl sulfide (COS). Hydrolysis of COS by carbonic anhydrase formed H2S, an inhibitor of catalase, an enzyme that detoxifies H2O2. Fe2+ and H2S together increased intracellular ROS levels and decreased viability in C6 glioma cells compared with controls lacking either Fe2+, the AAN sequence, or the ability to generate H2S. AAN‐PTC–Fe2+ performed better than temezolimide while exhibiting no cytotoxicity toward H9C2 cardiomyocytes. This study provides an H2S‐amplified, enzyme‐responsive platform for synergistic cancer treatment.
Adaptive neural network fixed‐time control of p$$ p $$‐normal systems with asymmetric output constraints
Authors: Meng Yanting , Liu Yang , Wang Lijie , Xue Hong
Published: April 2023

This paper studies the problem of fixed‐time
control for a class of nonlinear
‐normal systems with asymmetric output constraints and external disturbances. Compared with the existing fixed‐time control schemes, the smooth switching functions are designed to avoid the singularity problem. Then, a time‐varying nonlinear transformation function (NTF) is introduced, blue and a unified tool to deal with the symmetric, asymmetric, and even unconstrained problems simultaneously. Moreover, by adding blue one power integration technology, the
controller is designed, which can inhibit the influence of external disturbances on the system. According to Lyapunov stability analysis, the presented fixed‐time
blue control method ensures that all signals are bounded in a fixed time. In the end, two simulation examples demonstrate the effectiveness of the proposed scheme.
Methods for analyzing infant heart rate variability: A preliminary study
Authors: Claiborne Alex , Williams Alexandra , Jolly Colby , Isler Christy , Newton Edward , May Linda , George Stephanie
Published: April 2023

Heart rate (HR) and heart rate variability (HRV) reflect autonomic development in infants. To better understand the autonomic response in infants, reliable HRV recordings are vital, yet no protocol exists. The purpose of this paper is to present reliability of a common procedure for analysis from two different file types. In the procedure, continuous electrocardiograph recordings of 5–10 min are obtained at rest in infants at 1 month of age by using a Hexoskin Shirt‐Junior's (Carre Technologies Inc., Montreal, QC, Canada). Electrocardiograph (ECG; .wav) and R–R interval (RRi; .csv) files are extracted. The RRi of the ECG signal is generated by VivoSense (Great Lakes NeuroTechnologies, Independence, OH). Two MATLAB (The MathWorks, Inc., Natick, MA) scripts converted files for analysis with Kubios HRV Premium (Kubios Oy, Kuopio, Finland). A comparison was made between RRi and ECG files for HR and HRV parameters, and then tested with t tests and correlations via SPSS. There are significant differences in root mean squared successive differences between recording types, with only HR and low‐frequency measures significantly correlated together. Recording with Hexoskin and analysis with MATLAB and Kubios enable infant HRV analysis. Differences in outcomes exist between procedures, and standard methodology for infant HR analysis is needed.
Towards a mechanism for expert policy advice in education
Authors: Skerritt Craig
Published: April 2023

There is a growing consensus that existing arrangements for policy making in education are far from optimal. This paper is about policy making and the roles of—and relationships between—elected officials, civil servants and academics in the making of policy. It aims to open up a conversation about new ways of making education policy that make better use of academic expertise by shedding light on policy making from the perspective of a former policy broker. With specific reference to England, experiences of the world of policy are drawn on to provide an account of the following: the disconnect between academic research and policy; what good policy advice looks like; and, most significantly, what an expert policy advice mechanism in education could look like. The mechanism put forward is one possibility for further discussion within the academic community in the first instance: an independent group of diverse academic experts to provide trustworthy and transparent policy advice to the education ministry. It is envisaged that by bringing a set of insights together here, understandings of the world of policy making will be enhanced and further thinking and conversations about mechanisms for expert policy advice in education will be induced, starting with this flagship journal's readership. The subsequent accumulation of these discussions may then, in time, lead us towards better policy making.
Green micellar spectrofluorimetric determination of α‐mangostin found in herbal products as antioxidant and other biological activities beneficial to human health
Authors: Salem Hesham , Mazen Dina Z. , Emad Nadeen , Hassan Hossam , Omran Bahaa , Abdelmajed Mahmoud A.
Published: April 2023

Pharmaceutical product quality control (QC) needs quick, sensitive and economical procedures to deliver high throughput at low cost, which is the key factor considered by such economic facilities. To lessen the risky effects of research laboratories, researchers must take into account the ecological impacts. α‐Mangostin (MAG) exhibit anti‐inflammatory, antioxidant, anticancer, anti‐allergic, antibacterial, antifungal, antiviral and antimalarial activities. Based on the spectrofluorimetric approach, a novel straightforward, sensitive and environmentally friendly method for MAG determination was developed and validated. Many variables were investigated to improve MAG native fluorescence, including solvent type, buffers, pH and additional surfactants. The best MAG fluorescence sensitivity was found in Britton–Robinson buffer (pH 4) at 450 nm after irradiation at 350 nm in the concentration range of 5–50 ng ml−1. The technique was successfully used to determine the presence of MAG in both its approved dose forms and in samples of spiked human plasma, as per FDA standards for validation. According to their evaluation on two recent greenness criteria (GAPI [Green Analytical Procedure Index] and AGREE [Analytical GREEnness]), the suggested approach has been shown to be environmentally beneficial because it normally uses biodegradable chemicals in solvent‐free aqueous phases.
Using quantitative magnetic resonance imaging to track cerebral alterations in multiple sclerosis brain: A longitudinal study
Authors: Vandeleene Nora , Guillemin Camille , Dauby Solène , Requier Florence , Charonitis Maëlle , Chylinski Daphne , Balteau Evelyne , Maquet Pierre , Lommers Emilie , Phillips Christophe
Published: April 2023

Introduction

Quantitative MRI quantifies tissue microstructural properties and supports the characterization of cerebral tissue damages. With an MPM protocol, 4 parameter maps are constructed: MTsat, PD, R1 and R2*, reflecting tissue physical properties associated with iron and myelin contents. Thus, qMRI is a good candidate for in vivo monitoring of cerebral damage and repair mechanisms related to MS. Here, we used qMRI to investigate the longitudinal microstructural changes in MS brain.

Methods

Seventeen MS patients (age 25–65, 11 RRMS) were scanned on a 3T MRI, in two sessions separated with a median of 30 months, and the parameters evolution was evaluated within several tissue classes: NAWM, NACGM and NADGM, as well as focal WM lesions. An individual annual rate of change for each qMRI parameter was computed, and its correlation to clinical status was evaluated. For WM plaques, three areas were defined, and a GLMM tested the effect of area, time points, and their interaction on each median qMRI parameter value.

Results

Patients with a better clinical evolution, that is, clinically stable or improving state, showed positive annual rate of change in MTsat and R2* within NAWM and NACGM, suggesting repair mechanisms in terms of increased myelin content and/or axonal density as well as edema/inflammation resorption. When examining WM lesions, qMRI parameters within surrounding NAWM showed microstructural modifications, even before any focal lesion is visible on conventional FLAIR MRI.

Conclusion

The results illustrate the benefit of multiple qMRI data in monitoring subtle changes within normal appearing brain tissues and plaque dynamics in relation with tissue repair or disease progression.
Relations between peer influence, perceived costs versus benefits, and sexual offending among adolescents aware of sex offender registration risk
Authors: Najdowski Cynthia J. , Cleary Hayley M. D. , Oja Paige M.
Published: April 2023

A policy's general deterrent effect requires would‐be offenders to be aware of the policy, yet many adolescents do not know they could be registered as sex offenders, and even adolescents who do know may still commit registerable sexual offenses. We tested whether peer influences shape the perceived costs/benefits of certain sexual offenses and, subsequently, registration policy's general deterrent potential in a sample of policy‐aware adolescents. The more adolescents believed their peers approve of sexting of nude images, the more likely they were to have sexted. For forcible touching, having more positive peer expectations about sex and perceiving forcible touching as more prevalent among peers related to adolescents' likelihood of engaging in that behavior. Perceiving registration as a possible consequence was unrelated to sexual offending. Findings highlight the nuanced roles peers play in adolescent sexual decision‐making and support emerging evidence that juvenile registration policy has limited general deterrent efficacy.
Communication: The shifts in messaging … and their meaning
Authors: Skipworth Stan
Published: April 2023

Recently, my wife and I were enjoying a mid‐morning walk while vacationing on the island of Kauai when we began to take note of a variety of news and current events. As we continued our conversation along the beach, we more fully recognized several changes that have taken shape over the last several years in the scope of communication — and communications.
Digital tool maps campus sexual assaults, underlines needs for training
Authors: Sutton Halley
Published: April 2023

End Rape on Campus, a nonprofit out of Washington, D.C., that seeks to end sexual violence on college campuses through direct resources, prevention programming, and policy measures has released the Campus Accountability Map & Tool as a way to track not only assault on campuses, but also campus response to sexual assault.
USP33 enhances cell survival and stemness by deubiquitinating CTNNB1 in BXPC‐3 and SW1990 cells
Authors: Zhong Bo , Zhu Qiaozhen , Wang Linpei , Wang Fuyu , Zheng Yongbin , Lin Shujun , Cheng Xinsheng
Published: April 2023

Ubiquitin‐specific protease 33 (USP33) has been implicated in various cancers, but its biological function and mechanism of action remain unknown in pancreatic cancer (PCa) as a deubiquitinating enzyme. Herein, we report that USP33 silencing inhibits PCa cell survival and self‐renewal. USPs highly expressed in spherical PCa cells were screened by comparing the levels of ubiquitin‐specific proteases in spherical PCa cells and adherent PCa cells. After silencing USP, the effect of USP on the proliferation of PCa cells was detected by CCK‐8 and colony formation assay, and the effect of USP on cell stemness was detected by tumor sphere formation assay, flow analysis, and western blot analysis. The interaction of USP with CTNNB1 and the effect of USP on the ubiquitination of CTNNB1 were verified by coimmunoprecipitation assay. After replenishing CTNNB1, cell proliferation and cell stemness were examined. USP33 is upregulated in spheric BXPC‐3, PCNA‐1, and SW1990, compared with adherent BXPC‐3, PCNA‐1, and SW1990. USP33 interacts with CTNNB1, and stabilizes CTNNB1 by suppressing its degradation. Furthermore, cell proliferation, colony‐forming, and self‐renewal abilities of PCa cells in vitro, and the expression of stem cell markers EpCAM and CD44, C‐myc, Nanog, and SOX2, were suppressed when USP33 was knocked down, which was reversed when CTNNB1 was ectopically expressed in PCa cells. Thus, USP33 promotes PCa cell proliferation and self‐renewal by inhibiting the degradation of CTNNB1. USP33 inhibition may be a new treatment option for PCa patients.
Synthesis and Characterization of a Rhenanaphthalene Isomer
Authors: Cheng Xu , Wang Ping , Zheng Shaohui , Cao Qiang , Hua Yuhui , He Guomei , Chen Jiangxi
Published: April 2023

Exploration of organometallic metallacycles has led to the development of various polycyclic compounds with fascinating structures, which could be used as functional materials. In this work, a new rhenanaphthalene isomer was isolated from the reaction of ReH5(PMe2Ph)3 with o‐ethynylphenyl alkyne in the presence of excess HCl. Its structure was then identified using the single‐crystal X‐ray diffraction and NMR spectroscopy. DFT studies suggest that its formation involves two protonation reactions and two migration reactions. This new rhenanaphthalene isomer enriches the family of metallacycles.
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Authors: Dabbiru Venkata A. S. , Manu Emmanuel , Biedenweg Doreen , Nestler Peter , Pires Ricardo H. , Otto Oliver
Published: April 2023

ON THE BACK COVER: Effect of surface interactions on F‐Actin levels and cell morphology. Confocal microscopy images of tethered HEK293T cells labeled for F‐Actin and the nucleus. The cover image is based on the Research Article “Cell‐surface contacts determine volume and mechanical properties of human embryonic kidney 293 T cells” by Dabbiru, V. A. S., Manu, E., Biedenweg, D., Nestler, P., Pires, R. H., & Otto, O., https://doi.org/10.1002/cm.21735

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A differential privacy trajectory data storage and publishing scheme based on radix tree
Authors: Tian Junfeng , Zhu Qi
Published: April 2023

With the rapid development of information technology, location‐based services (LBSs) are becoming more and more popular, and at the same time, the users' privacy issues are becoming more and more serious. Therefore, this article proposes a differential private trajectory data storage and publishing scheme based on radix tree (TPRT). Firstly, the original trajectory is preprocessed by considering semantic information and simplified by dividing the stay area to reduce the risk of privacy leakage. Then, differential privacy technology is used to add Laplace noise to sensitive locations to achieve generalization. Finally, a radix tree structure satisfying differential privacy is defined, which alleviates the problem of large space consumption caused by tree height. To protect privacy, Laplace noise is added to the sensitive counts of the radix tree and limited by the Markov chain and privacy degree. Compared with several existing methods, our method has better performance and higher data availability.
Exploratory Food Effect Assessment in Patients in Early Clinical Development of Oncology Drugs
Authors: Ji Yan , Tan Eugene , Hengelage Thomas , Quinlan Michelle , Hendriks Bart S.
Published: April 2023

Instructions for administration with regard to food are a key aspect of how patients experience oral drugs. Through potential effects on pharmacokinetics, the food condition can influence safety and efficacy, and thereby is one of many dimensions of dose optimization. Regulatory guidance from major health authorities advocates for the early investigation of food effect (FE) in clinical development. In oncology, exploratory FE (eFE) evaluation is often incorporated into the first‐in‐human (FIH) studies in patients to inform food condition of later clinical studies. However, the design aspects of such exploratory assessments are generally under‐reported and barely described, and yet complex, due to uniqueness of FIH study design and drug development process in oncology. Herein, we review literature of eFE assessment study design in oncology in patients, and present the Novartis experience in the design, execution, and impact of eFE in FIH oncology studies from 2014 to 2021. Based on this, we propose a roadmap for eFE assessment in early clinical drug development for oncology drugs in patients, including a framework for common study design options with a focus on study‐ and patient‐level timing for typical scenarios. We also provide a broad spectrum of decision‐making factors which should be evaluated to drive the design and implementation of eFE assessment, spanning from clinical development strategy, FIH study design, to compound‐specific features.
Physiologically Based Pharmacokinetic Modeling to Determine the Impact of CYP2B6 Genotype on Efavirenz Exposure in Children, Mothers and Breastfeeding Infants
Authors: Pan Xian , Rowland Yeo Karen
Published: April 2023

The antiretroviral drug efavirenz remains widely used in children and mothers during breastfeeding in tuberculosis‐endemic areas. Evaluating the safety of efavirenz during breastfeeding requires an understanding of its pharmacokinetics (PKs) in breast milk, its exposure in the breastfed infant, and the potential influence of polymorphisms in drug disposition genes. The interplay of these factors between the mother and the nursing infant is a complex scenario that can be readily investigated using physiologically‐based PK (PBPK) modeling. A verified PBPK model for efavirenz describing the CYP3A4‐ and CYP2B6‐mediated auto‐induction during multiple dosing was reported previously and was applied in this study to predict the exposure of efavirenz in vulnerable populations, including children (down to the age of 3 months), mothers, and breastfeeding infants, accounting for the various CYP2B6 genotypes. Predicted pharmacokinetic parameters for mothers, breastfeeding infants, and children aged ≥ 3 months were reasonably consistent with observed data, irrespective of CYP2B6 genotype. The clinically significant trend toward higher infant efavirenz exposure from GG/GG to TT/TT composite maternal/infant CYP2B6 genotypes was captured reasonably well by the PBPK model. Thereafter, simulations were performed to determine the adequacy of the current World Health Organization (WHO; ≥ 3 years) and the US Food and Drug Administration (FDA; ≥ 3 months) weight‐based dosing regimens for efavirenz in children according to CYP2B6 genotype. The findings of this study indicate that PBPK models can be used in designing studies in vulnerable populations and providing guidance on optimal doses based on developmental physiology and pharmacogenetics.
Effectively Leveraging RWD for External Controls: A Systematic Literature Review of Regulatory and HTA Decisions
Authors: Sola‐Morales Oriol , Curtis Lesley H. , Heidt Julien , Walsh Laura , Casso Deborah , Oliveria Susan , Saunders‐Hastings Patrick , Song Yufei , Mercado Tiffany , Zusterzeel Robbert , Mastey Vera , Harnett James , Quek Ruben G. W.
Published: April 2023

Real‐world data (RWD)‐derived external controls can be used to contextualize efficacy findings for investigational therapies evaluated in uncontrolled trials. As the number of submissions to regulatory and health technology assessment (HTA) bodies using external controls rises, and in light of recent regulatory and HTA guidance on the appropriate use of RWD, there is a need to address the operational and methodological challenges impeding the quality of real‐world evidence (RWE) generation and the consistency in evaluation of RWE across agencies. This systematic review summarizes publicly available information on the use of external controls to contextualize outcomes from uncontrolled trials for all indications from January 1, 2015, through August 20, 2021, that were submitted to the European Medicines Agency, the US Food and Drug Administration, and/or select major HTA bodies (National Institute for Health and Care Excellence (NICE), Haute Autorité de Santé (HAS), Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), and Gemeinsamer Bundesausschuss (G‐BA)). By systematically reviewing submissions to regulatory and HTA bodies in the context of recent guidance, this study provides quantitative and qualitative insights into how external control design and analytic choices may be viewed by different agencies in practice. The primary operational and methodological aspects identified for discussion include, but are not limited to, engagement of regulators and HTA bodies, approaches to handling missing data (a component of data quality), and selection of real‐world endpoints. Continued collaboration and guidance to address these and other aspects will inform and assist stakeholders attempting to generate evidence using external controls.
Aggregation‐Induced Structural Symmetry Breaking Promotes Charge Separation for Efficient Photocatalytic Hydrogen Production
Authors: He Tian , Zhang Ya , Zhang Hongxia , Zhao Jianghong , Shi Hu , Yang Hengquan , Yang Pengju
Published: April 2023

Recently, organic semiconductors have received much attention in the field of photocatalysis due to their tunable physicochemical properties. However, organic semiconductor photocatalysts typically suffer from severe charge recombination due to high exciton binding energy. Herein, we found that aggregation of pyrene results in a red‐shift of the light absorption from UV to visible light region. Importantly, the aggregation can induce dipole polarization by spontaneous structural symmetry breaking, thus significantly accelerating the separation and transfer of charge carriers. As a result, the pyrene aggregates display enhanced hydrogen photosynthesis activity. Furthermore, the noncovalent interactions allow rational design of physicochemical and electronic properties of pyrene aggregates, further strengthening the charge separation and photocatalytic activity of aggregates. The quantum yield of pyrene aggregates for hydrogen production highly reaches 20.77 % at 400 nm. Moreover, we have also observed pyrene analogues (1‐hydroxypyrene, 1‐nitropyrene and perylene) after aggregation all display large dipole moments induced by structural symmetry breaking and therefore accelerate the separation of charge carriers, confirming its general principle. This work highlights the achievement of using aggregation‐induced structural symmetry breaking to enable the separation and transfer of charge carriers.