bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-oxidant Effects of Chromatographic Fractions of Abrus precatorius (Linn.) Leaf Extract in Wistar Rats
Authors: C J Uzodike, , N Brambaifa, , I Ogbuehi,
Published: January 2025

Aims: Plant antioxidants are considered safe, nutritional, and therapeutic, offering promising solutions to oxidative stress-related health issues. This study explores the antioxidant potential of column fractions derived from the methanol extract of Abrus precatorius, a plant with limited prior evaluation of its bioactive fractions.
Study Design:  The study used an experimental design.
Place and Duration of Study: Orlu LGA, Imo State, Nigeria
Methodology: Plant materials were collected from Orlu LGA, Imo State, Nigeria. The dried, powdered leaves were screened for phytochemical constituents using standard methods. Methanol extract was obtained through cold maceration and further fractionated using column chromatography packed with silica gel (60–120 mesh), with elution performed using a gradient mixture of hexane, ethyl acetate, and methanol. The phytochemical analysis confirmed the presence of alkaloids, flavonoids, tannins, cardenolides, and saponins, compounds known for their antioxidative properties. Column chromatography yielded five fractions (F1–F5), which were assessed for antioxidant activity using both in vivo (rat models) and in vitro methods, including 2,2-diphenyl-1-picryl hydrazyl (DPPH) and nitric oxide assays.
Results: Notably, fraction F1 demonstrated a significant increase in glutathione and catalase activity, while F4 showed a marked elevation in superoxide dismutase activity in erythrocytes. In liver tissue, F1 and F5 showed exceptional catalase activity, with respective increases of 258 % and 290 %. Fraction F3 exhibited a 290 % increase in superoxide dismutase activity. Furthermore, F3 effectively reduced DPPH radical activity with an IC50 of 0.2 mg/mL, while F4 significantly lowered nitric oxide levels with an IC50 of 0.3 mg/ml.
Conclusion: This study highlights the novel identification of potent antioxidant fractions from Abrus precatorius methanol extract, offering valuable insights for developing plant-based therapies for oxidative stress-related disorders such as cardiovascular diseases, diabetes, and neurodegenerative conditions. It underscores the plant's potential as a safe, natural antioxidant source for further pharmacological exploration.
Revitalization of Old Rose (Rosa damascena Mill.) Garden for Agumenting Growth, Flower Yield and Essential Oil Quality by Pruning and Fertilizer Application
Authors: Ramanjineyulu M. , Rao M. Sainath , Vaishnavi V. , J Deepika , H.M Sowmya , Nagireddy L.
Published: January 2025

The flower quality and essential oil concentration plays a critical role in marketing in local and international market. To unfold yield potential of the plants in old garden, cultural practices and nutrition remain the only feasible option as a part of management to the farmer to provide congenial environment to the plant. The impact of pruning and fertilizer application on growth, flower yield, volatile oil composition, physiological and biochemical processes are still poorly investigated on damask rose. Hence, the field experiment was led-out with nine treatment conditions encompassing three pruning systems and three fertilizer dosages to standardize the best practice to rejuvenate the old rose garden. The results showed that the pruning at 60 cm from ground level and application of 200:100:100 N, P2O5 and K2O kg ha-1exhibited maximum increase in growth parameters and flowering parameters like bud length (13.17 cm), diameter (5.52 cm), number of flowers per plant (273.41), flower yield (66.54 q ha-1) and vase life (9.37 days) followed by pruning at 45 cm from ground level and application of 150:75:75 N, P2O5 and K2O kg ha-1. Essential oil characters like volatile oil percentage (0.051 %) and volatile oil productivity (0.973 l plant-1) were highest in treatments of pruning at 60 cm from ground level and application of 200:100:100 N, P2O5 and K2O kg ha-1. From the experiment it is suggested that the old rose gardens can be rejuvenated by pruning and fertilizer application for better growth, flower production and increase in essential oil.
Development of an IoT-based Traffic Signal Violation Detection System
Authors: OLORIEGBE David Ugwunushemi , IKHARO Braimoh Abdullahi
Published: January 2025

This study tackles the pressing issue of traffic signal stop-line violations, which poses significant threat to road safety, by designing and implementing an intelligent traffic signal violation system (Internet-of-things (IoT) based technology). The system utilizes infrared (IR) sensors for vehicular detection and an ESP32 Camera to capture images of violating vehicles, which are then sent to a server via notification bots for media platforms. Also, the IR sensors are embedded with the ESP32 Camera and programmed microcontroller to detect traffic stop-line signal violations, capture images, and transmit them to designated authorities. The system was implemented using a prototype build and the result showed a 98% accuracy rate in detecting violations. The system reduces response time for violation detection by 60% success rate. In conclusion, this project demonstrates a reliable and efficient traffic signal violation system, leveraging IoT and Artificial Intelligence (AI) technologies to enhance road safety. The real-world significance of this system entails an enabled rapid intervention, identifying and disciplining offenders, enhance resource allocation, repository of data generated and enforcing legal actions thereby contributing to enhanced road traffic operations and user safety.
Longer-Term Efficacy and Safety of Evinacumab in Patients With Refractory Hypercholesterolemia
Authors: Rosenson Robert S. , Burgess Lesley J. , Ebenbichler Christoph F. , Baum Seth J. , Stroes Erik S. G. , Ali Shazia , Khilla Nagwa , McGinniss Jennifer , Gaudet Daniel , Pordy Robert
Published: September 2023

Importance

Patients with refractory hypercholesterolemia who do not achieve their guideline-defined low-density lipoprotein cholesterol (LDL-C) thresholds despite treatment with maximally tolerated combinations of lipid-lowering therapies (LLTs) have an increased risk of atherosclerotic cardiovascular disease (ASCVD).

Objective

To evaluate longer-term efficacy and safety of evinacumab in patients with refractory hypercholesterolemia.

Design, Setting, and Participants

This randomized clinical trial included a 2-week screening period followed by a 16-week double-blind treatment period (DBTP) for subcutaneous regimens (evinacumab, 450 mg, once weekly [QW]; evinacumab, 300 mg, QW; evinacumab, 300 mg, every 2 weeks; or placebo QW) or a 24-week DBTP for intravenous regimens (evinacumab, 15 mg/kg, every 4 weeks [Q4W]; evinacumab, 5 mg/kg, Q4W; or placebo Q4W); a 48-week open-label treatment period (OLTP) for intravenous treatment only; and a 24-week follow-up period. Patients from 85 sites across 20 countries were recruited for the study; patients with primary hypercholesterolemia (defined as heterozygous familial hypercholesterolemia or established clinical ASCVD without familial hypercholesterolemia) who entered the 48-week OLTP were included. In addition, the patients’ hypercholesterolemia was refractory to maximally tolerated LLTs.

Interventions

All patients entering the OLTP received evinacumab, 15 mg/kg, intravenously Q4W.

Main Outcomes and Measures

Efficacy outcomes included change in LDL-C level and other lipid/lipoprotein parameters from baseline to week 72 (end of the OLTP). Safety outcomes included assessment of treatment-emergent adverse events (TEAEs).

Results

A total of 96 patients (mean [SD] age, 54.4 [11.3] years; 52 female [54.2%]) entered the OLTP, of whom 88 (91.7%) completed the OLTP. Mean (SD) baseline LDL-C level was 145.9 (55.2) mg/dL. At week 72, evinacumab, 15 mg/kg, reduced mean (SD) LDL-C level from baseline by 45.5% (28.7%) in the overall cohort. Evinacumab, 15 mg/kg, reduced mean (SD) apolipoprotein B (38.0% [22.1%]), non–high density lipoprotein cholesterol (48.4% [23.2%]), total cholesterol (42.6% [17.5%]), and median (IQR) fasting triglyceride (57.2% [65.4%-44.4%]) levels at week 72 from baseline in the overall cohort. TEAEs occurred in 78 of 96 patients (81.3%). Serious TEAEs occurred in 9 of 96 patients (9.4%); all were considered unrelated to study treatment.

Conclusions and Relevance

In patients with refractory hypercholesterolemia, evinacumab provided sustained reductions in LDL-C level and was generally well tolerated.

Trial Registration

ClinicalTrials.gov Identifier: NCT03175367
Transfused Red Blood Cell Characteristics and Kidney Transplant Outcomes Among Patients Receiving Early Posttransplant Transfusion
Authors: Gaiffe Emilie , Vernerey Dewi , Bardiaux Laurent , Leroux Franck , Meurisse Aurelia , Bamoulid Jamal , Courivaud Cecile , Saas Philippe , Hazzan Marc , Tiberghien Pierre , Ducloux Didier
Published: September 2023

Importance

Red blood cell transfusion (RBCT) is frequently required in the early post–kidney transplant period, but long-term outcomes associated with RBCT is controversial. Therefore, it may be relevant to investigate the association between RBCT characteristics and transplant outcomes.

Objective

To study the association between RBC storage duration and transplant outcomes.

Design, Setting, and Participants

This was a nationwide retrospective cohort study based on data linking between 2 prospective French nationwide registries. Clinical transplant parameters, outcomes, and RBCT characteristics were extracted from the CRISTAL registry of the Agence de la Biomédecine and the national database of the Etablissement Français du Sang. All 12 559 patients having received a first kidney transplant in France between January 1, 2002, and December 31, 2008, were included. Patients were followed up from transplant to graft loss, death with a functional graft, or data retrieval in June 2016. Data were analyzed from April 2019 to June 2022.

Exposures

Clinical outcomes of transplant recipients who underwent early RBCT were analyzed considering transfusion characteristics.

Main Outcomes and Measures

Cox proportional hazards regression models were fitted to evaluate transplant failure defined as graft loss or death with a functional graft.

Results

Among 12 559 patients who underwent kidney transplant, 3483 received an RBCT during the first 14 days posttransplant. The median (IQR) age of patients was 53.0 (41.5-61.2) years, and 1929 patients (55.4%) were male. Median (IQR) follow-up was 7.8 (7.6-8.0) years. In multivariable analysis, longer (vs shorter) storage duration of transfused RBC was associated with a decrease in risk of transplant failure (hazard ratio, 0.99; 95% CI, 0.98-1.00 for each additional storage day; P = .06). Patients transfused with at least 1 RBC unit stored for more than 20 days had a 5% absolute decrease in transplant failure at 3 years and 7% at 5 years compared with those who received RBC stored for less than 20 days.

Conclusions and Relevance

In this study, longer RBC storage duration was associated with a decreased risk of transplant failure among patients who received kidney transplants and RBC transfusions. Preferential use of RBC with longer storage duration might improve kidney graft survival following transplant and transfusion.
Care Pathways and Initial Engagement in Early Psychosis Intervention Services Among Youths and Young Adults
Authors: Polillo Alexia , Foussias George , Wang Wei , Voineskos Aristotle N. , Veras Jacqueline , Davis-Faroque Nicole , Wong Albert H.C. , Kozloff Nicole
Published: September 2023

Importance

Broad efforts to improve access to early psychosis intervention (EPI) services may not address health disparities in pathways to care and initial engagement in treatment.

Objective

To understand factors associated with referral from acute hospital-based settings and initial engagement in EPI services.

Design, Setting, and Participants

This retrospective cohort study used electronic medical record data from all patients aged 16 to 29 years who were referred to a large EPI program between January 2018 and December 2019. Statistical analysis was performed from March 2022 to February 2023.

Exposures

Patients self-reported demographic information in a structured questionnaire. The main outcome for the first research question (referral source) was an exposure for the second research question (initial attendance).

Main Outcomes and Measures

Rate of EPI referral from acute pathways compared with other referral sources, and rate of attendance at the consultation appointment.

Results

The final study population included 999 unique patient referrals. At referral, patients were a mean (SD) age of 22.5 (3.5) years; 654 (65.5%) identified as male, 323 (32.3%) female, and 22 (2.2%) transgender, 2-spirit, nonbinary, do not know, or prefer not to answer; 199 (19.9%) identified as Asian, 176 (17.6%) Black, 384 (38.4%) White, and 167 (16.7%) other racial or ethnic groups, do not know, or prefer not to answer. Participants more likely to be referred to EPI services from inpatient units included those who were older (relative risk ratio [RRR], 1.10; 95% CI, 1.05-1.15) and those who identified as Black (RRR, 2.11; 95% CI, 1.38-3.22) or belonging to other minoritized racial or ethnic groups (RRR, 1.79; 95% CI, 1.14-2.79) compared with White participants. Older patients (RRR, 1.16; 95% CI, 1.11-1.22) and those who identified as Black (RRR, 1.67; 95% CI, 1.04-2.70) or belonging to other minoritized racial or ethnic groups (RRR, 2.11; 95% CI, 1.33-3.36) were more likely to be referred from the emergency department (ED) compared with White participants, whereas participants who identified as female (RRR, 0.51 95% CI, 0.34-.74) had a lower risk of ED referral compared with male participants. Being older (odds ratio [OR], 0.95; 95% CI, 0.90-1.00) and referred from the ED (OR, 0.40; 95% CI, 0.27-0.58) were associated with decreased odds of attendance at the consultation appointment.

Conclusions and relevance

In this cohort study of patients referred to EPI services, disparities existed in referral pathways and initial engagement in services. Improving entry into EPI services may help facilitate a key step on the path to recovery among youths and young adults with psychosis.
Prevalence of Thromboembolic Events in Patients With Non–Small Cell Lung Cancer and RET Fusions
Authors: Aldea Mihaela , Marinello Arianna , Guyon David , Gazzah Anas , Barlesi Fabrice , Planchard David , Besse Benjamin
Published: September 2023

This cohort study examines the incidence, risks, and characteristics of deep vein thrombosis, pulmonary embolism, arterial thrombosis, and stroke among patients with non–small cell lung cancer (NSCLC) and RET fusions.
MXene‐Composite‐Enabled Ultra‐long‐Distance Detection and Highly Sensitive Self‐Powered Noncontact Triboelectric Sensors and Their Applications in Intelligent Vehicle Perception
Authors: Zhao Cong , Wang Zhaoyang , Wang Yawei , Qian Zian , Tan Zheng , Chen Qingyu , Pan Xinxiang , Xu Minyi , Lai Ying‐Chih
Published: September 2023

With the ongoing advancement in sensor technologies, the development of intelligent, secure, and low‐carbon vehicles will be possible in the near future. However, providing continuous power to numerous onboard sensors consumes substantial amounts of power from vehicle, resulting in the shortened running times. Herein, a self‐powered noncontact triboelectric nanogenerator (SNC‐TENG) with ultralong‐distance detection and a high sensitivity is proposed, which can be used as ambient perception sensors for smart vehicles. The SNC‐TENG is constructed from a MXene/silicone nanocomposite with a fully embedded conductive sponge, which significantly enriches the tribo‐charges and leads to an excellent capability and performance. This SNC‐TENG is capable of perceiving human activity from a distance of 2 m. To the best of authors knowledge, the perceiving distance per unit area of this SNC‐TENG is the highest among previously reported non‐contact TENGs. Furthermore, the applicability of the SNC‐TENG is explored for vehicle sentry mode and blind spot detection for the first time. The use of this technology in a real vehicle demonstrates its feasibility for use in practical applications. Overall, this study provides a new design scheme for contactless self‐powered sensors, and the presented SNC‐TENG is expected to be applicable in various fields where non‐contact sensing is required.
Ultra‐Stable 3D‐Printed Zn Powder‐Based Anode Coated with a Conformal Ion‐Conductive Layer
Authors: Yang Jiayu , Xu Xi , Gao Yong , Wang Yuxuan , Cao Qinghe , Pu Jie , Bu Fan , Meng Ting , Guan Cao
Published: September 2023

Zinc powder is promising for rechargeable zinc‐ion batteries due to its low cost and well tunability. However, the corrosion and the dendrite growth are much more serious in zinc powder than those in conventional zinc foils, which poses a significant obstacle to wide utilization. Herein, an ultra‐stable Zn powder‐based anode constructed by coating a conformal ion‐conductive hydrogel layer on 3D‐printed Zn scaffolds is reported. The interconnected hydrogel effectively redistributes the zinc ion flux and homogenizes the surface electric field, while the 3D architecture alleviates the stress from volume change at high current densities/capacities. As a result, the 3D Zn powder‐based symmetric cell steadily works for over 4700 h (>6 months) at a high current density/capacity of 5 mA cm−2/5 mAh cm−2, which is superior to previously reported Zn powder‐based anodes and bare Zn foil, providing a promising route for practical applications of low‐cost and large‐scale zinc‐ion batteries.
Microcystic lymphatic malformations in Turner syndrome are due to somatic mosaicism of PIK3CA
Authors: Nriagu Bede N. , Williams Lydia S. , Brewer Niambi , Surrey Lea F. , Srinivasan Abhay S. , Li Dong , Britt Allison , Treat James , Crowley T. Blaine , O'Connor Nora , Ganguly Arupa , Low David , Queenan Maria , Drivas Theodore G. , Zackai Elaine H. , Adams Denise M. , Hakonarson Hakon , Snyder Kristen M. , Sheppard Sarah E.
Published: September 2023

Turner syndrome (45,X) is caused by a complete or partial absence of a single X chromosome. Vascular malformations occur due to abnormal development of blood and/or lymphatic vessels. They arise from either somatic or germline pathogenic variants in the genes regulating growth and apoptosis of vascular channels. Aortic abnormalities are a common, known vascular anomaly of Turner syndrome. However, previous studies have described other vascular malformations as a rare feature of Turner syndrome and suggested that vascular abnormalities in individuals with Turner syndrome may be more generalized. In this study, we describe two individuals with co‐occurrence of Turner syndrome and vascular malformations with a lymphatic component. In these individuals, genetic testing of the lesional tissue revealed a somatic pathogenic variant in PIK3CA—a known and common cause of lymphatic malformations. Based on this finding, we conclude that the vascular malformations presented here and likely those previously in the literature are not a rare part of the clinical spectrum of Turner syndrome, but rather a separate clinical entity that may or may not co‐occur in individuals with Turner syndrome.
Convergence of Visual and Motor Awareness in Human Parietal Cortex
Authors: Monai Elena , Pini Lorenzo , Palacino Federica , Bisio Marta , Bernocchi Francesca , Salvalaggio Alessandro , Corbetta Maurizio
Published: September 2023

Objective

Brain lesions sometimes induce a failure of recognition of one's own deficits (anosognosia). Lack of deficit awareness may underlie damage of modality‐specific systems, for example, visual cortex for visual anosognosia or motor/premotor cortex for motor anosognosia. However, focal lesions induce widespread remote structural and functional disconnection, and anosognosia, independent of modality, may also involve common neural mechanisms.

Methods

Here, we study the neural correlates of Anton syndrome (AS), anosognosia of blindness, and compare them with anosognosia for hemiplegia to test whether they share different or common mechanisms. We measured both local damage and patterns of structural–functional disconnection as predicted from healthy normative atlases.

Results

AS depends on bilateral striate and extrastriate occipital damage, and disconnection of ventral and dorsal frontoparietal regions involved in attention control. Visual and motor anosognosia each share damage of modality‐specific regions, but also involve the disruption of white matter tracts, leading to functional disconnection within dorsal frontal–parietal regions that play critical roles in motor control, visuospatial attention, and multisensory integration.

Interpretation

These results reveal the unique shared combination of content‐specific and supramodal mechanisms in anosognosia. ANN NEUROL 2024;95:90–103
Insertion of (Bioactive) Equatorial Ligands into Platinum(IV) Complexes
Authors: Kastner Alexander , Schueffl Hemma , Yassemipour Patrick A. , Keppler Bernhard K. , Heffeter Petra , Kowol Christian R.
Published: September 2023

Platinum(IV) prodrugs are highly interesting alternatives to platinum(II) anticancer therapeutics due to their increased tumor selectivity and reduced side effects. In contrast to the established theory, we recently observed that the equatorial ligand(s) of e.g. oxaliplatin(IV) complexes can be hydrolyzed with formation of [(DACH)Pt(OHeq)2(OAcax)2]. In the work presented here, we investigated the reactivity and synthetic usability of this complex to be exploited as a precursor for the development of novel platinum(IV) complexes, not able to be synthesized by conventional protocols. Indeed, we could substitute the equatorial hydroxido ligand(s) e.g. by one or two monodentate biotin ligands (which would be oxidized under standard methods). The formed complexes turned out to be very stable with slow ligand release after reduction, ideal for long‐circulating tumor‐targeting strategies. Therefore, two platinum(IV) complexes with equatorial maleimides, capable of exploiting serum albumin as a natural nanocarrier, were synthesized as well. The complexes showed massively prolonged plasma half‐life and distinctly improved anticancer activity in vivo compared to oxaliplatin. Taken together, the newly developed synthetic platform allows the simple and specific insertion of equatorial ligands into platinum(IV) complexes. This will enable the attachment of three different (bioactive) moieties generating targeted triple‐action platinum(IV) prodrugs within one single platinum complex.
Mechanical properties of viscoelastic materials subjected to thermal‐oxidative aging: An experimental and theoretical study
Authors: Li Qiang‐Qiang , Xu Zhao‐Dong , Tong Quek‐Ser , Dong Yao‐Rong , Xu Ye‐Shou , Lu Yong
Published: September 2023

Viscoelastic materials (VEMs) made from rubber polymer will inevitably age due to the interactions with the harmful environment during service life, thus reducing the reliability of viscoelastic (VE) damping equipment installed in building structures. In order to understand and be able to predict the degradation of VE damping equipment, it is imperative to comprehensively study the influence of aging on the mechanical properties of VEMs. In this paper, a series of thermal‐oxidative (TO) aging tests and mechanical property tests are conducted on our previously developed VEMs to study effects of TO aging on the molecular chain structure and corresponding changes of macroscopic mechanical properties of VEMs. By classifying molecular chains of VEMS into elastic chains and free chains, the effects of different chemical reactions during TO aging on these two main chains and corresponding changes on macroscopic mechanical behaviors of VEMs are analyzed. This facilitates formulating a mathematical model that can characterize the mechanical behavior of TO aging VEMs. In conjunction with the experimental data, the accuracy and applicability of the proposed model are compared and verified. Sensitivity analyses of parameters involved in the proposed model are then performed. The experimental results demonstrate that the TO aging can degrade the deformation capability and harden the modulus of VEMs, which may adversely affect the performance of VE damping devices. The parameter analyses depict that the TO aging affects the macroscopic mechanical behavior of VEMs by altering the relative number and configuration of free chains and elastic chains as well as their respective contributions to the total stress of VEMs. The results point to the high accuracy of the proposed model in representing the strain–stress behavior of VEMs under different aging conditions.
A matter of alignment? Effects of product types and environmental claim framing on consumer evaluation of sustainable foods
Authors: Weisstein Fei L. , Meyer Jeffrey , Kershaw Jonathan
Published: September 2023

Despite a growing interest in environmentally sustainable practices, consumers continue to prioritize taste, quality, and price above environmental concerns when purchasing food products. Previous studies have shown that environmental claims or messages may not uniformly enhance product perceptions. This research examines strategic approaches to framing substantively identical environmental benefit claims differently across product types to enhance consumers' sensory and quality evaluations as well as their willingness‐to‐pay for sustainable foods. Results from two experiments show that consumers' assessments of sustainable utilitarian and hedonic food products can be enhanced if environmental claims are strategically framed in accordance with the nature of product types. The alignment of utilitarian food products with an environment‐focus frame that emphasizes environmental benefits and hedonic food products with a self‐focus frame that stresses the personal relevance of these protections and benefits can enhance consumers' experienced tastiness, quality evaluations, and willingness‐to‐pay for sustainable foods.
The interplay of community resilience potential, trust in the future and social well‐being
Authors: Rochira Alessia , Marinaci Tiziana , De Simone Evelyn , Mannarini Terri , Valentino Cosima , Ciavolino Enrico , Verbena Serena , Pasca Paola
Published: September 2023

Community resilience (CR) has been mainly investigated as the ability of the community to respond to far‐reaching circumstances. Relatively less attention has been given to the understanding of CR as the ability of the community to deal with everyday problems, that is, community resilience potential (CRP). Using partial least squares path modelling, this study aims to elucidate how communities deal with issues that trouble their everyday functioning by investigating how this is related to social well‐being and trust in the future in a sample of 1278 subjects across 10 Italian communities with different population size and density. Results revealed that CRP was significantly associated with both social well‐being and trust in the future. Furthermore, in the more densely and heavily populated territorial communities, the link between CRP and social well‐being was stronger than in smaller and less dense communities. The findings suggested that social well‐being can be taken as a reliable community psychological resilient outcome. Moreover, CRP enables communities to respond positively to a wide range of phenomena, both large‐scale crises and everyday problems with variability across diverse contexts. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.
Multicomponent Synthesis Strategies, Catalytic Activities, and Potential Therapeutic Applications of Pyranocoumarins: A Comprehensive Review
Authors: M Jayalakshmi , Joy Francis , Nizam Aatika , Naidu Krishna Suresh Babu
Published: September 2023

Fused coumarins, because of their remarkable biological and therapeutic properties, particularly pyranocoumarins, have caught the interest of synthetic organic chemists, leading to the development of more efficient and environmentally friendly protocols for synthesizing pyranocoumarin derivatives. These compounds are the most promising heterocycles discovered in both natural and synthetic sources, with anti‐inflammatory, anti‐HIV, antitubercular, antihyperglycemic, and antibacterial properties. This review employed the leading scientific databases Scopus, Web of Science, Google Scholar, and PubMed up to the end of 2022, as well as the combining terms pyranocoumarins, synthesis, isolation, structural elucidation, and biological activity. Among the catalysts employed, acidic magnetic nanocatalysts, transition metal catalysts, and carbon‐based catalysts have all demonstrated improved reaction yields and facilitated reactions under milder conditions. Herein, the present review discusses the various multicomponent synthetic strategies for pyranocoumarins catalyzed by transition metal‐based catalysts, transition metal‐based nanocatalysts, transition metal‐free catalysts, carbon‐based nanocatalysts, and their potential pharmacological activities.
Anchoring (fullerol‐)Ru‐based‐complex onto TiO2 for Efficient Water Oxidation Catalysis
Authors: Wu Zhen‐Yi , Wang Wen‐Wen , Zhang Qian‐Xin , Wu Ni , Wu Ying , Tang Ding‐Liang
Published: September 2023

Ruthenium polypyridine complexes are the most effective catalysts for the water oxidation reaction (WOR), but the catalytic activity still has a large room for improvement. Herein, a fullerol‐based ruthenium complex was prepared by the covalent grafting of the polypyridyl ruthenium complex of water oxidation catalyst (WOC) with fullerol, and the (fullerol)‐Ru‐based WOCs anchored on the surface of nano‐TiO2 were prepared through a sensitization strategy. The synthesized heterogeneous nano‐catalysts are fully characterized by X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), infrared spectroscopy (IR), Brunauer–Emmett–Teller (BET) specific surface area and pore size distribution, and diffusion reflection ultraviolet‐visible spectrum (DRS). The chemical oxygen evolution experiments reveal that the WOR catalyzed by the catalyst is a first‐order reaction with respect to Ce (NH4)2(NO3)6 (denoted as CAN) concentration when using CAN as the sacrificial oxidant under acidic conditions. The anchoring of Ru‐based WOC to TiO2 result in a decrease in the redox potentials of RuIV/III couples, which decrease the barrier of the crucial O−O bond‐forming step, and the heterogeneous nano‐catalyst exhibit a high catalytic activity with a turnover frequency of 13.4 s−1 and more excellent stability with a 15‐min‐turn over number of 1054 for TiO2‐fullerol‐based ruthenium complex WOC.
Molecular Recognition Process in Resorcinarene‐based Coordination Capsules
Authors: Harada Kentaro , Sekiya Ryo , Haino Takeharu
Published: September 2023

Cu and Ag capsules can take up various organic molecules. Their molecular recognition possibly involves partial dissociation and slippage. We investigated molecular recognition processes in the Cu and Ag capsules by CD and 1H NMR spectroscopy and employed 4,4’‐diacetoxy biphenyl carrying two benzothiadiazole groups as a probe. CD and 1H NMR measurements reveal that the host‐guest complexation proceeds under second‐order reactions and that these capsules undergo the partial dissociation to take up the probe in [D1]chloroform and [D8]THF. The slippage also contributes to host‐guest complexation for a Cu capsule that carries p‐methoxyphenyl groups on the 2,2’‐bipyridiyl arms. DFT calculations suggest that π/π stacking interactions between the electron‐rich p‐methoxyphenyl group and the electron‐poor 2,2’‐bipyridyl arm elongate the capsule, allowing the guest to access the cavity without the partial dissociation.
Machine Learning‐Aided Data Analysis in Single‐Protein Conductance Measurement with Electron Tunneling Probes†
Authors: Yang Yuxin , Jiang Tao , Tian Ye , Zeng Biaofeng , Tang Longhua
Published: September 2023

Comprehensive Summary

The electrical tunneling sensors have excellent potential in the next generation of single‐molecule measurement and sequencing technologies due to their high sensitivity and spatial resolution capabilities. Electrical tunneling signals that have been measured at a high sampling rate may provide detailed molecular information. Despite the extraordinarily large amount of data that has been gathered, it is still difficult to correlate signal transformations with molecular processes, which creates great obstacles for signal analysis. Machine learning is an effective tool for data analysis that is currently gaining more significance. It has demonstrated promising results when used to analyze data from single‐molecule electrical measurements. In order to extract meaningful information from raw measurement data, we have combined intelligent machine learning with tunneling electrical signals. For the purpose of analyzing tunneling electrical signals, we investigated the clustering approach, which is a classic algorithm in machine learning. A clustering model was built that combines the advantages of hierarchical clustering and Gaussian mixture model clustering. Additionally, customized statistical algorithms were designed. It has been proven to efficiently gather molecular information and enhance the effectiveness of data analysis.
Photo‐Modulation of Gene‐Editing Enzymes CRISPR/Cas9 with Bifunctional Small‐Molecule Ligands†
Authors: Zhang Yidan , Zhang Yixin , Han Lili , Che Qiaoling , Tan Jiawei , Zou Peng , Chen Yiyun
Published: September 2023

Comprehensive Summary

The control of protein functions with light is valuable for spatiotemporal probing of biological systems. Current small‐molecule photo‐ modulation methods include the light‐induced uncaging of inhibitors and chromophore‐assisted light inactivation with reactive oxygen species (ROS). However, the constant target protein expression results in inadequate photo‐modulation efficiency, particularly for less potent inhibitors and chromophores. Herein, we report a novel bifunctional small‐molecule ligands strategy to photo‐modulate gene‐editing enzymes CRISPR/Cas9. A coumarin‐derived small‐molecule ligand Bhc‐BRD0539 is developed to uncage the active inhibitor upon light irradiation and to generate ROS in the Cas9 proximity for the dual inhibition of Cas9 activity. Our results highlight the synergistic photo‐modulation with bifunctional small‐molecule ligands, which offers a valuable addition to current CRISPR/Cas9 photo‐modulation technologies and may extend to other protein classes.
A predictive scoring model to select suitable patients for surgery on primary tumor in metastatic esophageal cancer
Authors: Wei Laiming , Xu Jing , Hu Xueyou , Xie Yu , Lyu Gang
Published: September 2023

Background

Surgery on primary tumor (SPT) has been a common treatment strategy for many types of cancer.

Aims

This study aimed to investigate whether SPT could be considered a treatment option for metastatic esophageal cancer and to identify the patient population that would benefit the most from SPT.

Methods

Data from 18 registration sites in the Surveillance, Epidemiology, and End Results Program database (SEER database) were analyzed to select patients with metastatic esophageal cancer. Multivariate Cox regression analysis was used to identify potential risk factors for pre‐treatment survival. Variables with a p‐value of less than 0.05 were used to construct a pre‐treatment nomogram. A pre‐surgery predictive model was then developed using the pre‐surgery factors to score patients, called the “pre‐surgery score”. The optimal cut‐off value for the “pre‐surgery score” was determined using X‐tile analysis, and patients were divided into high‐risk and low‐risk subsets. It was hypothesized that patients with a low “pre‐surgery score” risk would benefit the most from SPT.

Results

A total of 3793 patients were included in the analysis. SPT was found to be an independent risk factor for the survival of metastatic esophageal cancer patients. Subgroup analyses showed that patients with liver or lung metastases derived more benefit from SPT compared to those with bone or brain metastases. A pre‐treatment predictive model was constructed to estimate the survival rates at one, two, and three years, which showed good accuracy (C‐index: 0.705 for the training set and 0.701 for the validation set). Patients with a “pre‐surgery score” below 4.9 were considered to have a low mortality risk and benefitted from SPT (SPT vs. non‐surgery: median overall survival (OS): 24 months vs. 4 months, HR = 0.386, 95% CI: 0.303–0.491, p < 0.001).

Conclusion

This study demonstrated that SPT could improve the OS of patients with metastatic esophageal cancer. The pre‐treatment scoring model developed in this study might be useful in identifying suitable candidates for SPT. The strengths of this study include the large patient sample size and rigorous statistical analyses. However, limitations should be noted due to the retrospective study design, and prospective studies are needed to validate the findings in the future.
Missed opportunities in the diagnosis of heart failure: a real‐world assessment
Authors: Ferreira João Pedro , Taveira‐Gomes Tiago , Canelas‐Pais Mariana , Phan Phillip , Bernardo Filipa , Andersson Sundell Karolina , Almeida Mário , Martinho Hugo , Gavina Cristina
Published: September 2023

Aims

Heart failure (HF) is a leading cause of hospitalization worldwide. An early HF diagnosis is key to reducing hospitalizations. We used electronic health records (EHRs) to characterize HF pathways at the primary care physician (PCP) level prior to a first HF hospitalization (hHF). This study aimed to identify missed opportunities for HF diagnosis and management at the PCP level before a first hHF.

Methods and results

This cohort study used EHRs of a large health care organization in Portugal. Patients with incident hHF between 2017 and 2020 were identified. Missed opportunities were defined by the absence of any of the following work‐up in the 6 months after signs or symptoms had been recorded: lab results and electrocardiogram, natriuretic peptides, echocardiogram, referral to HF specialist, or HF medication initiation. A total of 2436 patients with a first hHF were identified. The median (interquartile range) age at the time of hospitalization was 81 (14) years, and 1361 (56%) were women. Most patients were treated with cardiovascular drugs prior or at index event. A total of 720 (30%) patients had records of HF signs or symptoms, 94% (n = 674) within 6 months prior to hHF. Among patients with recorded HF signs or symptoms, 410 (57%) had clinical management considered adequate before signs and symptoms were recorded. Of the 310 remaining patients, 155 (50%) had a follow‐up that was considered inadequate.

Conclusions

Relatively few patients with a first hHF had primary care records of signs or symptoms prior to admission. Of these, nearly half had inadequate management considering diagnosis and treatment. These data suggest the need to improve PCP HF awareness.
Genotoxicity assessment in HepaRG™ cells as a new approach methodology follow up to a positive response in the human TK6 cell micronucleus assay: Naphthalene case study
Authors: Recio Leslie , Fowler Jasmine , Martin Lincoln , Swartz Carol
Published: September 2023

We are evaluating the use of metabolically competent HepaRG™ cells combined with CometChip® for DNA damage and the micronucleus (MN) assay as a New Approach Methodology (NAM) alternative to animals for follow up genotoxicity assessment to in vitro positive genotoxic response. Naphthalene is genotoxic in human TK6 cells inducing a nonlinear dose–response for the induction of micronuclei in the presence of rat liver S9. of naphthalene. In HepaRG™ cells, naphthalene genotoxicity was assessed using either 6 (CometChip™) or 12 concentrations of naphthalene (MN assay) with the top dose used for assessment of genotoxicity for the Comet and MN assay was 1.25 and 1.74 mM respectively, corresponding to approximately 45% cell survival. In contrast to human TK6 cell with S9, naphthalene was not genotoxic in either the HepaRG™ MN assay or the Comet assay using CometChip®. The lack of genotoxicity in both the MN and comet assays in HepaRG™ cells is likely due to Phase II enzymes removing phenols preventing further bioactivation to quinones and efficient detoxication of naphthalene quinones or epoxides by glutathione conjugation. In contrast to CYP450 mediated metabolism, these Phase II enzymes are inactive in rat liver S9 due to lack of appropriate cofactors causing a positive genotoxic response. Rat liver S9‐derived BMD10 over‐predicts naphthalene genotoxicity when compared to the negative genotoxic response observed in HepaRG™ cells. Metabolically competent hepatocyte models like HepaRG™ cells should be considered as human‐relevant NAMs for use genotoxicity assessments to reduce reliance on rodents.
Estimation of change with partially overlapping and spatially balanced samples
Authors: Zhao Xin , Grafström Anton
Published: September 2023

Spatially balanced samples are samples that are well‐spread in some available auxiliary variables. Selecting such samples has been proven to be very efficient in estimation of the current state (total or mean) of target variables related to the auxiliary variables. As time goes, or when new auxiliary variables become available, such samples need to be updated to stay well‐spread and produce good estimates of the current state. In such an update, we want to keep some overlap between successive samples to improve the estimation of change. With this approach, we end up with partially overlapping and spatially balanced samples. To estimate the variance of an estimator of change, we need to be able to estimate the covariance between successive estimators of the current state. We introduce an approximate estimator of such covariance based on local means. By simulation studies, we show that the proposed estimator can reduce the bias compared to a commonly used estimator. Also, the new estimator tends to become less biased when reducing the local neighborhood size.
Airport Expansions and Public Protests—The Democratic Dilemma of Vertically Asymmetric Policies
Authors: Hornig Eike‐Christian
Published: September 2023

The concept of Vertically Asymmetric Policies (VAPs) offers a new explanation specified for the emergence and persistence of public protests against major infrastructure projects. In VAPs, the benefits, costs, and political competences are distributed asymmetrically among the different levels of the political system. The gap of those units (negatively) affected and those units involved in deciding, causes a democratic dilemma and likely public protests. The analysis of aviation as a policy and the protests against the expansion of Frankfurt Airport in Germany proves this explanation. Here, vertical linkage channels are blocked for the demands of local areas around the airport and a long‐lasting protest movement accompanies every step of airport expansion. Original data from a 2013 poll among ant‐expansion protesters reveal a growing loss of confidence in elections and the preference for protest measures.
Municipal Infrastructure Policies in the Federal Republic—In Between Growing Disparities and Losing Political Autonomy?
Authors: Scheller Henrik , Walker Benedikt
Published: September 2023

Drawing from Scharpf's joint decision making approach and his concept of the joint decision trap, the following paper researches the development of municipal infrastructure investment in relation to the overall financial situation. The analyzed data are being provided by a representative panel survey among 4,000 German municipalities conducted in 2016 by the German Institute of Urban Affairs. The starting point of the analysis is the description of a dilemma: growing financial disparities between the municipalities and a loss‐making infrastructure of many cities and towns leads to an institutionalization of a growing number of grant programmes and forms of mixed financing. These programmes—so the analysis guiding thesis—do not provide adequate solutions for the heterogeneity of municipal needs. By neglecting their individual needs they cannot take into account the growing disparities of municipal financial situations. Rather, they produce an institutional setting, which fosters sub‐optimal policy‐outcomes and is resilient to changes.
Scalp high‐frequency oscillations differentiate neonates with seizures from healthy neonates
Authors: Cserpan Dorottya , Guidi Greta , Alessandri Beatrice , Fedele Tommaso , Rüegger Andrea , Pisani Francesco , Sarnthein Johannes , Ramantani Georgia
Published: September 2023

Objective

We aimed to investigate (1) whether an automated detector can capture scalp high‐frequency oscillations (HFO) in neonates and (2) whether scalp HFO rates can differentiate neonates with seizures from healthy neonates.

Methods

We considered 20 neonates with EEG‐confirmed seizures and four healthy neonates. We applied a previously validated automated HFO detector to determine scalp HFO rates in quiet sleep.

Results

Etiology in neonates with seizures included hypoxic‐ischemic encephalopathy in 11 cases, structural vascular lesions in 6, and genetic causes in 3. The HFO rates were significantly higher in neonates with seizures (0.098 ± 0.091 HFO/min) than in healthy neonates (0.038 ± 0.025 HFO/min; P = 0.02) with a Hedge's g value of 0.68 indicating a medium effect size. The HFO rate of 0.1 HFO/min/ch yielded the highest Youden index in discriminating neonates with seizures from healthy neonates. In neonates with seizures, etiology, status epilepticus, EEG background activity, and seizure patterns did not significantly impact HFO rates.

Significance

Neonatal scalp HFO can be detected automatically and differentiate neonates with seizures from healthy neonates. Our observations have significant implications for neuromonitoring in neonates. This is the first step in establishing neonatal HFO as a biomarker for neonatal seizures.
Empirical dietary inflammatory index and lifestyle inflammation score relationship with obesity: A population‐based cross‐sectional study
Authors: Saber Niloufar , Hosseinzadeh Mahdieh , Shab‐Bidar Sakineh , Mirzaei Masoud , Najarzadeh Azadeh , Rahideh Seyedeh Tayebeh
Published: September 2023

The present study aimed to investigate the association between the empirical dietary inflammatory index (EDII) and lifestyle inflammatory score (LIS) with general and abdominal obesity in Iranian adults using data from the Yazd Health study (YaHS). This cross‐sectional study was conducted using the information of participants of the YaHS study. The dietary assessment was conducted using a validated food frequency questionnaire (FFQ) and anthropometric measurements assessed by standard protocols. The inflammatory potential of diet and lifestyle were calculated using EDII and LIS scores. We also created a combinational index of EDII and LIS as an EDII‐LIS score. General and abdominal obesity were defined based on body mass index (BMI), waist circumference (WC), and waist‐to‐hip ratio (WHR) cut points, respectively. The odds ratio (OR) and 95% confidence interval (CI) of general and abdominal obesity across tertiles of EDII and LIS were estimated using logistic regression analyses, adjusted for potential confounders. A significant association was found between a higher EDII score and general obesity (OR: 1.21, 95% CI: 1.04–1.41, p trend: .016), however, there was no significant association between EDII and both definitions of abdominal obesity. Participants in the highest versus lowest tertile of LIS had higher odds of increased abdominal obesity (ORWC: 37.0, 95% CI: 28.8–47.5, p trend <.001, ORWHR: 3.30, 95% CI: 2.65–4.11, p trend <.001). In addition, there was also a direct relationship between the higher score of EDII‐LIS and the increased likelihood of abdominal obesity (ORWC: 15.0, 95% CI: 12.3–18.3, p trend <.001, ORWHR: 2.68, 95% CI: 2.18–3.29, p trend <.001). Greater adherence to the EDII score was associated with a higher odds of general obesity, but not abdominal obesity. Also, individuals with a higher score of LIS and EDII‐LIS are more prone to abdominal obesity.