bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Role of Bimetal‐Doped BaCoO3−𝛿 Perovskites as Highly Active Oxygen Electrodes of Protonic Ceramic Electrochemical Cells
Authors: Kim Dongyeon , Jeong Incheol , Ahn Sejong , Oh Seeun , Im Ha‐Ni , Bae Hohan , Song Sun‐Ju , Lee Chan‐Woo , Jung WooChul , Lee Kang Taek
Published: February 2024

Protonic ceramic electrochemical cells (PCECs) hold great promise as an energy conversion and storage technology at lower temperatures (400–650 °C). However, the sluggish reaction kinetics at the oxygen electrode hinder the electrochemical activity of PCECs. Herein, a series of bifunctional oxygen electrodes based on bimetal‐doped BaCoO3‐𝛿 (BCO) are reported. Doping hampers hexagonal perovskite formation and transforms BCO into cubic perovskite, improving water uptake and hydration abilities. Density functional theory calculations highlight the effects of phase transformation on the proton transport properties of oxygen electrodes. Notably, PCECs incorporating the bimetal‐doped electrodes exhibit maximum power densities of 3.15 W cm−2 (650 °C) and 2.25 W cm−2 (600 °C) in fuel cell mode, as well as a current density of 4.21 A cm−2 at 1.3 V (650 °C) in electrolysis cell mode, setting record‐high values. The findings provide insights into the rational design of bifunctional oxygen electrodes for high‐performance PCECs.
Flexible antibacterial degradable bioelastomer nanocomposites for ultrasensitive human–machine interaction sensing enabled by machine learning
Authors: Fu Zihong , Wang Mingcheng , Huang Chenlin , Li Zehui , Yuan Yue , Hu Shikai , Zhang Liqun , Wan Pengbo
Published: February 2024

Flexible wearables have attracted extensive interests for personal human motion sensing, intelligent disease diagnosis, and multifunctional electronic skins. However, the reported flexible sensors, mostly exhibited narrow detection range, low sensitivity, limited degradability to aggravate environmental pollution from vast electronic wastes, and poor antibacterial performance to hardly improve skin discomfort and skin inflammation from bacterial growth under long‐term wearing. Herein, bioinspired from human skin featuring highly sensitive tactile sensation with spinous microstructures for amplifying sensing sensitivity between epidermis and dermis, a wearable antibacterial degradable electronics is prepared from degradable elastomeric substrate with MXene‐coated spinous microstructures templated from lotus leaf assembled with the interdigitated electrode. The degradable elastomer is facilely obtained with tunable modulus to match the modulus of human skin with improved hydrophilicity for rapid degradation. The as‐obtained sensor displays ultra‐low detection limit (0.2 Pa), higher sensitivity (up to 540.2 kPa−1), outstanding cycling stability (>23,000 cycles), a wide detection range, robust degradability, and excellent antibacterial capability. Facilitated by machine learning, the collected sensing signals from the integrated sensors on volunteer's fingers to the related American Sign Language are effectively recognized with an accuracy up to 99%, showing excellent potential in wireless human movement sensing and smart machine learning‐enabled human–machine interaction.
Identification of novel MYH14 variants in families with autosomal dominant sensorineural hearing loss
Authors: Duman Duygu , Ramzan Memoona , Subasioglu Asli , Mutlu Ahmet , Peart LéShon , Seyhan Serhat , Guo Shengru , Ila Kadri , Balta Burhan , Kalcioglu Mahmut Tayyar , Bademci Guney , Tekin Mustafa
Published: February 2024

Autosomal dominant sensorineural hearing loss (ADSNHL) is a genetically heterogeneous disorder caused by pathogenic variants in various genes, including MYH14. However, the interpretation of pathogenicity for MYH14 variants remains a challenge due to incomplete penetrance and the lack of functional studies and large families. In this study, we performed exome sequencing in six unrelated families with ADSNHL and identified five MYH14 variants, including three novel variants. Two of the novel variants, c.571G > C (p.Asp191His) and c.571G > A (p.Asp191Asn), were classified as likely pathogenic using ACMG and Hearing Loss Expert panel guidelines. In silico modeling demonstrated that these variants, along with p.Gly1794Arg, can alter protein stability and interactions among neighboring molecules. Our findings suggest that MYH14 causative variants may be more contributory and emphasize the importance of considering this gene in patients with nonsyndromic mainly post‐lingual severe form of hearing loss. However, further functional studies are needed to confirm the pathogenicity of these variants.
Severe unilateral refractory epistaxis arising from the septal branch of the anterior ethmoid artery
Authors: Nguyen Theodore V. , Bitner Benjamin F. , Hong Ellen M. , Pang Jonathan C. , Meller Leo Li Tang , Nguyen Cecilia , Kuan Edward C.
Published: February 2024

Key Points

The septal branch of the anterior ethmoid artery (sbAEA) is an underrecognized source of severe refractory epistaxis.

Herein, we describe the presentation, predisposing factors, treatment strategies, and outcomes of a series of patients with this condition.
Surface Reconstruction on Metal Nitride during Photo‐oxidation
Authors: Liu Siqi , Qi Weiliang , Yang Xuhui , Guo Xuyun , Liu Jue , Zhu Ye , Yang Min‐Quan , Yang Minghui
Published: February 2024

The efficient conversion and storage of solar energy for chemical fuel production presents a challenge in sustainable energy technologies. Metal nitrides (MNs) possess unique structures that make them multi‐functional catalysts for water splitting. However, the thermodynamic instability of MNs often results in the formation of surface oxide layers and ambiguous reaction mechanisms. Herein, we present on the photo‐induced reconstruction of a Mo‐rich@Co‐rich bi‐layer on ternary cobalt‐molybdenum nitride (Co3Mo3N) surfaces, resulting in improved effectiveness for solar water splitting. During a photo‐oxidation process, the uniform initial surface oxide layer is reconstructed into an amorphous Co‐rich oxide surface layer and a subsurface Mo−N layer. The Co‐rich outer layer provides active sites for photocatalytic oxygen evolution reaction (POER), while the Mo‐rich sublayer promotes charge transfer and enhances the oxidation resistance of Co3Mo3N. Additionally, the surface reconstruction yields a shortened Co−Mo bond length, weakening the adsorption of hydrogen and resulting in improved performance for both photocatalytic hydrogen evolution reaction (PHER) and POER. This work provides insight into the surface structure‐to‐activity relationships of MNs in solar energy conversion, and is expected to have significant implications for the design of metal nitride‐based catalysts in sustainable energy technologies.
Increasing the Accessibility of Internal Catalytic Sites in Covalent Organic Frameworks by Introducing a Bicontinuous Mesostructure
Authors: Liu Yamei , Zhou Qin , Yu Hongde , Yang Qiqi , Wang Mingchao , Huang Chuanhui , Xiang Luoxing , Li Chen , Heine Thomas , Hu Guoqing , Wang Shengyao , Feng Xinliang , Mai Yiyong
Published: February 2024

Introducing continuous mesochannels into covalent organic frameworks (COFs) to increase the accessibility of their inner active sites has remained a major challenge. Here, we report the synthesis of COFs with an ordered bicontinuous mesostructure, via a block copolymer self‐assembly‐guided nanocasting strategy. Three different mesostructured COFs are synthesized, including two covalent triazine frameworks and one vinylene‐linked COF. The new materials are endowed with a hierarchical meso/microporous architecture, in which the mesochannels exhibit an ordered shifted double diamond (SDD) topology. The hierarchically porous structure can enable efficient hole‐electron separation and smooth mass transport to the deep internal of the COFs and consequently high accessibility of their active catalytic sites. Benefiting from this hierarchical structure, these COFs exhibit excellent performance in visible‐light‐driven catalytic NO removal with a high conversion percentage of up to 51.4 %, placing them one of the top reported NO‐elimination photocatalysts. This study represents the first case of introducing a bicontinuous structure into COFs, which opens a new avenue for the synthesis of hierarchically porous COFs and for increasing the utilization degree of their internal active sites.
Understanding super‐partnerships in scientific collaboration: Evidence from the field of economics
Authors: Liu Junwan , Guo Xiaofei , Xu Shuo , Bu Yi , Sugimoto Cassidy R. , Larivière Vincent , Song Yinglu , Zhou Honghao
Published: February 2024

Super‐partnerships exist between scholars connected within densely‐knit collaboration networks. Understanding how such relationships affect scholars' careers is of great importance. In this paper, focusing on the longitudinal aspects of scientific collaboration, we analyze collaboration profiles from the egocentric perspective and use analytic extreme value thresholds to identify super‐partners. A total of 5722 pairs of super‐partners are found in the field of economics. The several interesting findings about super‐partners are summarized as follows. (1) The collaboration pattern of super‐partners can be divided into three types: the dual‐core, bridge, and triangle types. (2) Gender disparities are reflected in the collaboration among super‐partners, and the stability of super‐partnerships involving different combinations of genders displays different characteristics. The random‐effect model is constructed to explore the effect of a super‐partnership on both parties from the aspects of productivity and influence, which also shows gender disparities. (3) A super‐partnership contributes to above‐average productivity and citation impacts of the publication for three collaboration patterns, and the research improvement of the triangle type is the greatest among the three types. Overall, this paper explores the characteristics of super‐partners and the added value of a long‐term commitment, which provides quantitative insights into the effect on scientific collaboration associated with close collaboration.
Konzept eines Digitalen Zwillings für Brückenbauwerke in der Betriebsphase
Authors: Collin Fabian , Ulbrich Lisa , Jesse Frank
Published: February 2024

Das Konzept des Digitalen Zwillings hält auch im Brückenbau Einzug. Die während der Betriebsphase anfallenden Daten aus der Bauwerksprüfung, dem Bauwerksmonitoring und der Bauwerksdiagnostik sollen zukünftig in aggregierter Form die Grundlage bilden, um die derzeit reaktive Instandsetzung in eine prädiktive Instandhaltung zu überführen. Dieser Beitrag stellt ein Konzept für einen Objektzwilling mit dem Konnektivitätsgrad eines Digitalen Schattens im Reifegrad 2 vor. Es werden Kriterien für eine präzise Definition des Begriffs Digitaler Zwilling aufgeführt, BIM‐Anwendungsfälle für die Betriebsphase von Brücken definiert sowie notwendige Fachmodelle daraus abgeleitet. Mit Blick auf das Forschungsprojekt IDA‐KI werden Anforderungen an den Digitalen Zwilling aufgestellt und ein Softwarekonzept für deren prototypische Umsetzung erarbeitet. Dabei wird besonderer Fokus auf die Bereitstellung der IFC‐Fachmodelle in einer CDE als auch auf den Veredelungsprozess von Monitoringdaten gelegt.
Identifying chemical markers in wine‐processed Salvia miltiorrhiza using ultrahigh‐performance liquid chromatography‐quadrupole‐time‐of‐flight‐tandem mass spectrometry
Authors: Xu Tingting , Li Xiuwei , Sun Guodong , Wei Wenfeng , Huo Jinhai , Wang Weiming
Published: February 2024

To find the chemical markers of wine‐processed Salvia miltiorrhiza (WSM), 76 constituents, including diterpenoid quinones and phenolic acids in Salvia miltiorrhiza (SM) and WSM, were profiled using ultrahigh‐performance liquid chromatography‐quadrupole‐time‐of‐flight‐tandem mass spectrometry (UPLC‐Q‐TOF‐MS/MS) in positive‐ and the negative‐ion modes. Thirty compounds were screened out as candidate differential components using chemometrics analysis, and the concentration of most compounds increased after processing with wine. Seven compounds, namely tanshinone IIA, magnesium lithospermate B, salvianolic acid G, cryptotanshinone, isocryptotanshinone, salvianolic acid B, and rosmarinic acid, were selected as chemical markers of WSM using variable importance of the project. This study revealed the chemical markers of WSM and confirmed that WSM can improve the extraction and solubility effect of chemical constituents.
Values and diagnostic accuracy of sensory nerve action potentials in control participants and participants with diabetes with and without clinical diabetic neuropathy, based on neuropathy scale measurements
Authors: Abuzinadah Ahmad R. , Alrawaili Moafaq S. , Alshareef Aysha A. , Alkully Hussien S. , Milyani Haneen , Alamri Bashayr , Alshora Weam , Bamaga Ahmed K.
Published: February 2024

Background

The assessment of the normative values of sensory nerve action potentials (SNAP) and their diagnostic accuracies using validated neuropathy‐assessment tools to classify participants into groups with and without neuropathy was not previously described in the literature.

Methods

The Utah Early Neuropathy Scale (UENS), Michigan neuropathy‐screening instrument, and nerve conduction data were collected prospectively. We described and compared the values of the sural, superficial peroneal sensory (SPS), and superficial radial SNAP amplitude in different age groups for three groups. Group 1 (G1)—control participants (UENS <5), group 2 (G2)—participants with diabetes without clinical diabetic neuropathy (UENS <5), and group 3 (G3)—participants with clinical diabetic neuropathy (UENS ≥5). We also described the diagnostic accuracy of single‐nerve amplitude and a combined sensory polyneuropathy index (CSPNI) that consists of four total points (one point for each of the following nerves if their amplitude was <25% lower limit of normal: right sural, left sural, right SPS, and left SPS potentials).

Results

We assessed 135 participants, including 41, 37, and 57 participants in G1, G2, and G3, respectively, with age median (interquartile ranges) of 51 (45–56), 47 (38–56), and 54 (51–61) years, respectively, whereas 19 (46.3%), 18 (48.7%), and 32 (56.14%) of them were males, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) scores were 68.4%, 92.3%, 86.7%, and 80% for the sural amplitude; 86%, 58.3%, 62%, and 84% for the SPS amplitude; 66.7%, 94.4%, 90.5%, and 78.2% for the CSPNI of 3; and 54.4%, 98.6%, 96.9%, and 73.2% for the CSPNI of 4, respectively.

Conclusion

Sural nerve had a high specificity for neuropathy; however, the CSPNI had the highest specificity and PPV, whereas the SPS had the highest sensitivity and NPV.
Unraveling the impact of financial literacy on investment decisions in an emerging market
Authors: Shroff Sumita Jagdishprasad , Paliwal Udai Lal , Dewasiri Narayanage Jayantha
Published: February 2024

We examined the impact of financial literacy on investment decisions, taking a sample of 384 investors from India. A multi‐dimensional construct to measure financial literacy was developed basis the theory of planned behavior. Investment decisions were measured by taking six proxies on a five‐point Likert‐type scale. The causal link between financial literacy and investment decisions was examined using simple linear and binary logistic regression. The results exhibited moderate to high levels of financial literacy among investors. Results further confirm that investors' investment decisions are positively influenced by their financial literacy levels. It is concluded that financial literates have a greater likelihood of making informed investment decisions. These outcomes have practical implications for policymakers, managers, employers, and investors, especially in an emerging market context, making a case for relevant financial education programs to empower investors. The study adds to the theory of financial literacy developing a multi‐dimensional construct and introducing Macroeconomic Factors as a proxy for investment decisions.
Ultrasound clinical references of the healthy toenail unit
Authors: López Ripado Olga , Villar Rodríguez Julia , Mingorance Álvarez Esther , Pérez Pico Ana Mª. , García Nogales Agustín , Mayordomo Acevedo Raquel
Published: February 2024

The toenail unit, commonly called the nail, is one of the most frequently examined and treated structures in clinical podiatry. Ultrasound is a standard clinical technique because it is a noninvasive, painless, and rapid diagnostic tool. The main objective of this study was to obtain morphometric data of the healthy toenail unit by ultrasound for clinical application. The nails of 76 participants (152 hallux nails; 38 men, 38 women, average age 26.83 ± 12.20) were examined using a VINNO E35 ultrasound system and an X6‐16L linear probe with a frequency of 18 MHz. Five ultrasound measures of the healthy toenail unit were obtained, of which only the distance from the center of the distal phalange to the nail plate varied with age, sex, weight, and foot (p‐values ≤ 0.050). The other four parameters were less influenced by the variables analyzed, except sex, which influenced nearly all (p‐values ≤ 0.050). In one of these variables, indications of significance were observed (p‐values = 0.060), with greater distances in the men than in the women, except for nail plate curvature, which showed a higher value. The other variables studied did not influence the parameters analyzed. High‐frequency ultrasound can be used to examine the healthy toenail unit and define anthropometric reference measurements that can be used for more accurate and comparative diagnosis.
Did court dismiss Title IX retaliation claim?
Authors: Lyerly Eric
Published: February 2024

A member of the University of California‐San Diego rowing  team died by suicide, allegedly due to psychological  abuse from his coaches.
Cardiotoxicity and ROS Protection Assessment of three Structure‐Related N‐Acylhydrazones with Potential for the Treatment of Neurodegenerative Diseases
Authors: Helena Eduarda Santa , De Falco Anna , Cukierman Daphne S. , Gioda Adriana , Gioda Carolina Rosa , Rey Nicolás A.
Published: February 2024

The senescence process is associated with accumulated oxidative damage and increased metal concentration in the heart and brain. Besides, abnormal metal‐protein interactions have also been linked with the development of several conditions, including Alzheimer's and Parkinson's diseases. Over the years we have described a series of structure‐related compounds with different activities towards models of such diseases. In this work, we evaluated the potential of three N‐acylhydrazones (INHHQ: 8‐hydroxyquinoline‐2‐carboxaldehyde isonicotinoyl hydrazone, HPCIH: pyridine‐2‐carboxaldehyde isonicotinoyl hydrazone and X1INH: 1‐methyl‐1H‐imidazole‐2‐carboxaldehyde isonicotinoyl hydrazone) to prevent oxidative stress in cellular models, with the dual intent of being active on this pathway and also to confirm their lack of cardiotoxicity as an important step in the drug development process, especially considering that the target population often presents cardiovascular comorbidity. The 8‐hydroxyquinoline‐contaning compound, INHHQ, exhibits a significant cardioprotective effect against hydrogen peroxide and a robust antioxidant activity. However, this compound is the most toxic to the studied cell models and seems to induce oxidative damage on its own. Interestingly, although not possessing a phenol group in its structure, the new‐generation 1‐methylimidazole derivative X1INH showed a cardioprotective tendency towards H9c2 cells, demonstrating the importance of attaining a compromise between activity and intrinsic cytotoxicity when developing a drug candidate.
Tunable electrospun scaffolds of polyacrylonitrile loaded with carbon nanotubes: from synthesis to biological applications
Authors: Fromager Bénédicte , Cambedouzou Julien , Marhuenda Emilie , Iskratsch Thomas , Pinault Mathieu , Bakalara Norbert , Cornu David
Published: February 2024

Growing cells in a biomimetic environment is critical for tissue engineering as well as for studying the cell biology underlying disease mechanisms. To this aim a range of 3D matrices have been developed, from hydrogels to decellularized matrices. They need to mimic the extracellular matrix to ensure the optimal growth and function of cells. Electrospinning has gained in popularity due to its capacity to individually tune chemistry and mechanical properties and as such influence cell attachment, differentiation or maturation. Polyacrylonitrile (PAN) derived electrospun fibres scaffolds have shown exciting potential due to reports of mechanical tunability and biocompatibility. Building on previous work we fabricate here a range of PAN fibre scaffolds with different concentrations of carbon nanotubes. We characterize them in‐depth in respect to their structure, surface chemistry and mechanical properties, using scanning electron microscopy, image processing, ultramicrotomic transmission electron microscopy, x‐ray nanotomography, infrared spectroscopy, atomic force microscopy and nanoindentation. Together the data demonstrate this approach to enable finetuning the mechanical properties, while keeping the structure and chemistry unaltered and hence offering ideal properties for comparative studies of the cellular mechanobiology. Finally, we confirm the biocompatibility of the scaffolds using primary rat cardiomyocytes, vascular smooth muscle (A7r5) and myoblast (C2C12) cell lines.
Transcatheter tricuspid valve replacement for functional tricuspid regurgitation after left‐sided valve surgery: A single‐center experience
Authors: Wang Yiwei , Zhai Mengen , Mao Yu , Yang Tingting , Zhu Guangyu , Liu Yang , Yang Jian
Published: February 2024

Background

Functional tricuspid regurgitation (FTR) following left‐sided valve surgery (LSVS) is of clinical significance due to its high recurrence and mortality rates. Transcatheter therapy presents a potential solution to address this issue.

Aims

The study aimed to assess the safety and efficacy of transcatheter tricuspid valve replacement using the Lux‐Valve system in a single center for patients with FTR after LSVS.

Methods

From June 2020 to April 2023, 20 patients with symptomatic severe FTR after LSVS were referred to our center. A multidisciplinary cardiac team evaluated these patients for suitability for transcatheter tricuspid valve replacement with Lux‐Valve systems. Primary efficacy and safety endpoints were immediate postoperative tricuspid regurgitation severity ≤ moderate and major adverse events during follow‐up.

Results

Twenty patients (average age 65.7 ± 7.4 years; 65.0% women) successfully underwent Lux‐Valve system implantation after LSVS. All patients achieved ≤ moderate tricuspid regurgitation immediately after the procedure. Only one patient (5.0%) experienced a procedure‐related major adverse event, leading to in‐hospital mortality due to pulmonary infection. At the 6‐month follow‐up, 17 patients (89.5%) improved to New York Heart Association functional class I to II (p < 0.001). The overall Kansas City Cardiomyopathy Questionnaire score significantly improved (35.9 ± 6.7 points to 58.9 ± 5.8 points, p < 0.001).

Conclusion

The Lux‐Valve system was found to be safe and effective for treating FTR after LSVS. It resulted in positive early outcomes, including a significant reduction in FTR, improved functional status, and enhanced quality of life, especially in high‐risk patients.
Endodontic treatment of a C‐shaped mandibular second molar with narrow dentinal thickness: A case report
Authors: Mehrjouei Mina , Jafarzadeh Hamid , Esmaeelpour Pourya , Khorasanchi Maryam
Published: February 2024

Key Clinical Message

Formulating an effective root canal treatment plan necessitates clinician awareness of the complexities of the root canal system and possible anatomic challenges. The C‐shaped canal variation accompanying the radicular lingual groove makes the lingual dentinal wall so thin that cleaning and shaping of canals require accurate management. This report presents endodontic treatment of a C‐shaped mandibular second molar diagnosed with pulpal necrosis and asymptomatic apical periodontitis, that initial radiographic assessment revealed extremely thin (0.3 mm) width of the lingual wall of the canals prone to perforation. Mechanical preparation was performed through the anti‐curvature technique and basically by chemical irrigation rather than mechanical instrumentation. The C‐shaped isthmus was prepared up to 25/02 rotary system without dentinal defect while maintaining adequate dentin thickness so as to not significantly reduce the strength of the root. Follow‐up radiographs showed normal periodontal ligament and lamina dura indicating significant healing of the periapical lesion.
Enhancing Ammonia Synthesis on Co3Mo3N via Metal Support Interactions on a Single‐crystalline MgO Support
Authors: Rai Rohit K. , Maligal‐Ganesh Raghu , Maksoud Walid Al , Kim Seok‐Jin , Vaishnav Yuvraj , Yavuz Cafer T. , Kobayashi Yoji
Published: February 2024

Co3Mo3N has been reported to have activity for the synthesis of ammonia surpassing that of industrial Fe catalysts under certain conditions. However, so far the research has largely focused on unsupported Co3Mo3N. We report a comprehensive study on the catalytic activity of Co3Mo3N when supported on two distinct MgO substrates. Our findings reveal that the method of MgO preparation plays a crucial role in influencing surface basicity. Remarkably, Co3Mo3N supported on single‐crystalline MgO demonstrates significantly enhanced catalytic activity, achieving a 162.0 mmol g−1metal h−1 rate. This surpasses the performance on commercial MgO support (41.2 mmol g−1metal h−1) and unsupported Co3Mo3N (15.0 mmol g−1metal h−1). While kinetic analyses show no substantial differences between the two supported catalysts, spectroscopic studies employing CO2 and N2 temperature‐programmed desorption (TPD) reveal a richer array of basic sites and adsorption/desorption phenomena on the single‐crystalline MgO support. These catalysts exhibit exceptional stability. The drastically reduced Co/Mo loading amounts in comparison to the bulk form, make the commercialization of Co3Mo3N catalysts more practical.
Development of Pyridothiophene Compounds for PET Imaging of α‐Synuclein
Authors: Pees Anna , Tong Junchao , Birudaraju Saritha , Munot Yogeshkumar S. , Liang Steven H. , Saturnino Guarino Dinahlee , Mach Robert H. , Mathis Chester A. , Vasdev Neil
Published: February 2024

Aggregated α‐synuclein (α‐syn) protein is a pathological hallmark of Parkinson's disease (PD) and Lewy body dementia (LBD). Development of positron emission tomography (PET) radiotracers to image α‐syn aggregates has been a longstanding goal. This work explores the suitability of a pyridothiophene scaffold for α‐syn PET radiotracers, where 47 derivatives of a potent pyridothiophene (asyn‐44; Kd=1.85 nM) were synthesized and screened against [3H]asyn‐44 in competitive binding assays using post‐mortem PD brain homogenates. Equilibrium inhibition constant (Ki) values of the most potent compounds were determined, of which three had Ki′s in the lower nanomolar range (12–15 nM). An autoradiography study confirmed that [3H]asyn‐44 is promising for imaging brain sections from multiple system atrophy and PD donors. Fluorine‐18 labelled asyn‐44 was synthesized in 6±2 % radiochemical yield (decay‐corrected, n=5) with a molar activity of 263±121 GBq/μmol. Preliminary PET imaging of [18F]asyn‐44 in rats showed high initial brain uptake (>1.5 standardized uptake value (SUV)), moderate washout (~0.4 SUV at 60 min), and low variability. Radiometabolite analysis showed 60–80 % parent tracer in the brain after 30 and 60 mins. While [18F]asyn‐44 displayed good in vitro properties and acceptable brain uptake, troublesome radiometabolites precluded further PET imaging studies. The synthesis and in vitro evaluation of additional pyridothiophene derivatives are underway, with the goal of attaining improved affinity and metabolic stability.
Aggregate Removal by Responsive Electrospun Membrane based Hydrophobic Interaction Chromatography
Authors: Hao Xiaolei , Chen Shu-Ting , Chiao Yu-Hsuan , Matsuyama Hideto , Qian Xianghong , Wickramasinghe Ranil
Published: February 2024

Poly(N‐vinylcaprolactam) (PVCL), a salt responsive ligand, was grafted from electrospun cellulose nanofiber membranes by atom transfer radical polymerization (ATRP). The membranes were used for hydrophobic interaction chromatography. The modified PVCL‐cellulose membranes were used to separate BSA dimers from monomers as well as monoclonal antibody (mAb) aggregates. Fast protein liquid chromatography (FPLC) was used for protein separation and fraction collection. High performance liquid chromatography with a size exclusion column (HPLC‐SEC) analysis confirmed the separation of monomers and aggregates from both BSA and the mAb. The results suggest that use of a responsive ligand that changes its conformation with ionic strength could improve the performance of hydrophobic interaction chromatography enabling the separation of compounds based on slight differences in hydrophobicity.
Experimental and computational investigation of coaxial contra‐rotating impellers design in baffled‐free stirred reactors
Authors: Berestinas G. S. , Nunhez J. R.
Published: February 2024

Fluid mixing is a common topic in contemporary industry. The search for more efficient processes and reliable equipment is a constant challenge. In this work, numerical and experimental tests analyzed a 45° pitched blade turbine in a contra‐rotating coaxial impeller system (CRCIS) configuration mounted on baffles‐free reactors and compared it with conventional systems with one (CS1I) and two (CS2I) impellers mounted on tanks with baffles. Experimental tests were carried out using a pilot reactor with reduced scales of 1.0 m in diameter and 1.0 m in height (square batch). The behaviour of the physical variables was analyzed for mixing operations, solid particle suspension, and formation of vortices, and the power consumption was recorded through a torque transducer for different rotations. The acquired results helped in the validation of models and numerical simulations. The numerical simulation was carried out using the OpenFOAM® open‐source field operation and manipulation software. In addition, the velocity profile along with the height of the reactor, flow lines, pumping number, power consumption variations, and mixing time were compared. The conclusion of this study showed that CRCIS can be used in tanks without baffles. It also showed promising results for applications involving the suspension of solids, developing axial velocities at the bottom of the reactor higher than those of the CS1I and CS2I arrangements for the same rotation, with less energy consumption, proving to be a technically promising option for application on an industrial scale.
Promotion of hydrate formation by multi‐walled carbon nanotubes in ultrasonic compounding system
Authors: Du Xianghan , Jiang Husheng , Shang Liyan
Published: February 2024

Multi‐walled carbon nanotubes (MWCNTs) are an excellent hydrate promoter, with their own Brownian motion of nanoparticles effectively shortening hydrate nucleation and accelerating hydrate formation. In this work, the properties of methane hydrate formation in a complex system of MWCNTs, sodium dodecyl sulphate (SDS) and NaCl were investigated. It was shown that the compounding system effectively enhanced the kinetics of methane hydrate formation, and the gas consumption of the reaction reached 0.38 MPa at 100 ppm MWCNTs, an increase of 865.8% compared to the pure water system, effectively promoting methane hydrate. In the complexed system, NaCl significantly enhanced the dispersion of MWCNTs, with 1000 ppm NaCl showing the best kinetic promotion effect. SDS not only increases the gas–liquid contact area through the wall attachment effect, but also enhances the dispersion of MWCNTs by adsorbing on the surface of carbon nanotubes and forming an electronic layer with NaCl. MWCNTs not only improve the mass transfer of the system through Brownian motion, but their large heat transfer coefficients can also effectively conduct the heat generated by the system. However, MWCNTs become agglomerated with increasing concentration, making the kinetic promotion effect weaker and the solution less stable, resulting in shorter shelf life. This study confirmed the effective promotion of hydrate formation by MWCNTs under the ultrasonic compounding system, and also provided a reference for related studies on the compounding of MWCNTs with NaCl.
The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance
Authors: Wright Jonathan L. , Schenk Jeannette M. , Gulati Roman , Beatty Sarah J. , VanDoren Matthew , Lin Daniel W. , Porter Michael P. , Morrissey Colm , Dash Atreya , Gore John L. , Etzioni Ruth , Plymate Stephen R. , Neuhouser Marian L.
Published: February 2024

Background

Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS.

Methods

Overweight/obese men (body mass index >25 kg/m2) diagnosed with PCa who elected AS were recruited. The intervention was a 6‐month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6‐month intervention, which was measured by fasting plasma glucose, C‐peptide, insulin, insulin‐like growth factor 1, insulin‐like growth factor binding protein‐3, adiponectin, and homeostatic model assessment for insulin resistance.

Results

Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between‐group mean difference, −6.0 kg; 95% confidence interval, −8.0, −4.0). Mean percentage changes from baseline for insulin, C‐peptide, and homeostatic model assessment for insulin resistance in the intervention arm were −23%, −16%, and −25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between‐arm differences were detected for the other biomarkers.

Conclusions

Overweight/obese men with PCa undergoing AS who participated in a lifestyle‐based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose‐regulation biomarkers associated with PCa progression.
Cumulative incidence and risk factors of brain metastases in metastatic non–small cell lung cancer without baseline brain metastasis: Pooled analysis of individualized patient data from IMpower130, IMpower131, and IMpower150
Authors: Zhou Yue , Guo Tiantian , Liang Fei , Wang Zezhou , Zhang Junhua , Ni Jianjiao , Zhu Zhengfei
Published: February 2024

Background

The objective of this study was to explore the abilities of atezolizumab plus chemotherapy in preventing brain metastases (BMs) among metastatic non–small cell lung cancer (NSCLC) without initial BMs, as well as the risk factors of BMs.

Methods

Individual patient data from three trials involving first‐line atezolizumab for metastatic NSCLC (IMpower130, IMpower131, and IMpower150) were pooled. Among patients without baseline BMs and without epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) mutations, those receiving atezolizumab + chemotherapy ± bevacizumab were classified as the atezolizumab plus chemotherapy group and those receiving placebo + chemotherapy ± bevacizumab were classified as the chemotherapy group. The cumulative incidences of BM (CI‐BMs) between the two groups were compared. Other factors associated with the CI‐BM were analyzed by Cox regression analyses.

Results

With a median follow‐up of 17.6 months (range, 0.03–33.64 months), 74 (3.1%) of the 2380 enrolled patients developed BMs, including 50 (3.1%) and 24 (3.0%) in the atezolizumab plus chemotherapy group (n = 1589) and the chemotherapy group (n = 791), respectively. The CI‐BMs at 6, 12, and 24 months were 1.7%, 2.8%, and 3.3%, respectively. After taking competing risk events into account, there was no significant difference in the CI‐BMs between the two groups (p = .888). Nevertheless, the use of bevacizumab and the histology of nonsquamous NSCLC were found to be independently associated with the risk of BMs.

Conclusions

In patients with metastatic EGFR/ALK wild‐type NSCLC without baseline BMs, adding atezolizumab in the first‐line treatment might not reduce the CI‐BM. However, the administration of bevacizumab may reduce the risk of BMs.
Assessment on the use of allopurinol to improve safety and efficacy of mercaptopurine in pediatric patients with Acute Lymphoblastic Leukemia and Lymphoma during maintenance therapy
Authors: Barone Tecca , Dandekar Smita , McKeone Daniel , Mulieri Kevin
Published: February 2024

Background

Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6‐thioguanine nucleosides (6‐TGN) are believed to be the primary contributor to myelosuppression and immunosuppressive effects, while 6‐methylmercaptopurine (6‐MMPN) is believed to be responsible for several toxicities including hepatotoxicity, pancreatitis, and hypoglycemia. Previous reports suggest the addition of allopurinol may reduce these toxicities.

Aims

To assess the use of allopurinol to improve both safety and efficacy of mercaptopurine in pediatric patients with ALL and LLy during maintenance therapy. Secondary objectives included evaluating patient tolerability and skewed metabolism. In addition, we also analyzed mercaptopurine daily dose reduction upon allopurinol initiation.

Methods and Results

The primary endpoint was time within goal ANC prior to and after initiation of allopurinol. Secondary endpoints included; improvement in selective toxicities (hepatotoxicity, pancreatitis, and hypoglycemia) and 6‐MMPN to 6‐TGN ratio prior to and after allopurinol initiation. In addition, an exploratory endpoint assessing mercaptopurine daily dose reduction prior to and after allopurinol initiation was included. Sixteen patients met inclusion criteria and 15 (94%) of which were included in this study. Median percent of maintenance days within goal ANC prior to and after initiation of allopurinol was 27.8 (IQR 22.6–44.9) and 41.6 (IQR 20.2–58.2) respectively. All patients experienced selective toxicities; 15 (100%) hepatotoxicity, 1 (7%) pancreatitis, and 3 (20%) hypoglycemia. Improvement of toxicities was seen in 13/15 (87%), 1/1 (100%), and 2/3 (67%) respectively. Average 6‐MMPN:6‐TGN ratio prior to allopurinol initiation was 304:1 and after, allopurinol initiation improved to 15:1, resulting in a 95% reduction. Average mercaptopurine dose prior to and after allopurinol initiation decreased by about 56% (63 to 28 mg/m2/day).

Conclusion

Results suggest that the use of allopurinol in pediatric patients with ALL and LLy receiving mercaptopurine during maintenance therapy is both safe and effective.
Shrinking Devices: Shape‐Memory Polymer Fabrication of Micro‐and Nanostructured Electrodes
Authors: González‐Martínez Eduardo , Moran‐Mirabal Jose
Published: February 2024

The front cover artwork is provided by Prof. Jose Moran‐Mirabal's group at McMaster University in Hamilton, Ontario, Canada. The image shows a 3D rendering and electron microscopy images of micro/nanostructured electrodes, fabricated through thermal shrinking of a shape memory polymer. Read the full text of the Review at 10.1002/cphc.202300535.
Sustainable Beckmann Rearrangement using Bead‐Milling Technology: The Route to Paracetamol
Authors: Geib Romain , Colacino Evelina , Gremaud Ludovic
Published: February 2024

To address the growing demand for more sustainable and greener chemistry, mechanochemical methodologies are emerging as key players. However, to date there has been little data highlighting the benefits of these rising mechanochemical technologies with regard to process scale‐up activities or implementation in commercial production scale. Herein, we report the first application of bead‐mill technology (Dyno®‐mill) for the sustainable mechanochemical synthesis of Acetaminophen, known under the brand name Paracetamol. Using the Beckmann rearrangement, the optimized solvent‐free methodology delivered a final product on a scale of several tens of grams. In comparison to current production solvent‐based process, the proposed process achieves a higher yield while also allowing the removal of solvents in the chemical reaction, hereby reducing one of the extensive drivers to waste generation. The mechanochemical approach was compared to solvent‐based process using a combination of green metrics and EcoScale score. The mechanochemical synthesis of paracetamol scores the highest for all the metrics over currently used solution‐based processes.
The last stage of development: The restructuring and plasticity of the cortex during adolescence especially at puberty
Authors: Juraska Janice M.
Published: February 2024

There is considerable evidence of reorganization in the prefrontal cortex during adolescence in humans, as well as in rodents, where the cellular basis can be explored. Studies from my laboratory in the rat medial prefrontal cortex are reviewed here. In general, growth predominates before puberty. Pruning mainly occurs at puberty and after with decreases in the number of synapses, dendrites, and neurons. Perineuronal nets, extracellular structures that control plasticity, are pruned peripubertally only in female rats, which may further open the adolescent prefrontal cortex to environmental influences. This is supported by our recent evidence that exposure to mild stress early, but not late, in adolescence decreases prepulse inhibition. Additionally, exposure to methamphetamine in females early in adolescence increases the number of a major class of inhibitory interneurons, parvalbumin neurons, while the opposite occurs late in adolescence. In females, even estrogen receptor beta mRNA decreases at puberty in the prefrontal cortex. Interestingly, rats of both sexes perform better after puberty on a test of cognitive flexibility in the water maze. Thus, evidence is accruing that adolescence is not a single entity but rather an ongoing set of processes, and environmental effects will differ depending on timing and sex.
Effects of leaf herbivory and autumn seasonality on plant secondary metabolites: A meta‐analysis
Authors: Skovmand Lota , O'Dea Rose E. , Greig Keri A. , Amato Katherine R. , Hendry Andrew P.
Published: February 2024

Plant secondary metabolites (PSMs) are produced by plants to overcome environmental challenges, both biotic and abiotic. We were interested in characterizing how autumn seasonality in temperate and subtropical climates affects overall PSM production in comparison to herbivory. Herbivory is commonly measured between spring to summer when plants have high resource availability and prioritize growth and reproduction. However, autumn seasonality also challenges plants as they cope with limited resources and prepare survival for winter. This suggests a potential gap in our understanding of how herbivory affects PSM production in autumn compared to spring/summer. Using meta‐analysis, we recorded overall production of 22 different PSM subgroups from 58 published papers to calculate effect sizes from herbivory studies (absence to presence) and temperate to subtropical seasonal studies (summer to autumn), while considering other variables (e.g., plant type, increase in time since herbivory, temperature, and precipitation). We also compared production of five phenolic PSM subgroups – hydroxybenzoic acids, flavan‐3‐ols, flavonols, hydrolysable tannins, and condensed tannins. We wanted to detect a shared response across all PSMs and found that herbivory increased overall PSM production in herbaceous plants. Herbivory was also found to have a positive effect on individual PSM subgroups, such as flavonol production, while autumn seasonality was found to have a positive effect on flavan‐3‐ol and condensed tannin production. We discuss how these responses might stem from plants producing some PSMs constitutively, whereas others are induced only after herbivory, and how plants produce metabolites with higher costs only during seasons when other resources for growth and reproduction are less available, while other phenolic PSM subgroups serve more than one function for plants and such functions can be season dependent. The outcome of our meta‐analysis is that autumn seasonality changes some PSM production differently from herbivory, and we see value in further investigating seasonality–herbivory interactions with plant chemical defense.
Lactic acid bacteria in Swedish honey bees during outbreaks of American foulbrood
Authors: Nilsson Anna , D'Alvise Paul , Milbrath Meghan O. , Forsgren Eva
Published: February 2024

The honey bee microbiota is involved in several important functions, and alterations in the composition could have a severe effect on honey bee health. Among the bacteria identified in the honey bee microbiome are a group of non‐pathogenic honey bee‐specific lactic acid bacteria (hbs‐LAB) that have been shown to inhibit the growth of bacterial pathogens such as Paenibacillus larvae, the causative agent of American foulbrood (AFB). While P. larvae only causes disease in larvae and not in adult honey bees, there are reports of the pathogen causing changes in the microbiota composition of the adults. The aim of this study was to investigate how AFB in the colony affect the hbs‐LAB composition in adult honey bees. Adult bees were collected from colonies with and without AFB during three outbreaks of AFB in Sweden. The hbs‐LAB was analyzed using qPCR to detect and quantify the number of ten hbs‐LAB (five Lactobacilli, two Apilactobacilli, one Bombilactobacilli, and two Bifidobacterium). The hbs‐LAB composition was compared between AFB outbreaks and depending on the AFB status of the honeybee colony at the time of sampling. The data analyses revealed differences in the abundance of individual hbs‐LAB between outbreaks and an overall difference in bacterial community composition depending on AFB status. Also, a higher hbs‐LAB diversity was observed in samples that were P. larvae culture positive.