bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenicity analysis and splicing rescue of a classical splice site variant (c.1343+1G>T) of CNOT1 gene associated with neurodevelopmental disorders
Authors: Dong Yan , Li Weiran , Meng Jing , Wang Ping , Sun Mei , Zhou Feiyu , Li Dong , Shu Jianbo , Cai Chunquan
Published: July 2023

Mutations in the CNOT1 gene lead to an incurable rare neurological disorder mainly manifested as a clinical spectrum of intellectual disability, developmental delay, seizures, and behavioral problems. In this study, we investigated a classical splice site variant of CNOT1 (c.1343+1G>T) associated with neurodevelopmental disorders, which was a master regulator, orchestrating gene expression, RNA deadenylation, and protein ubiquitination. To link CNOT1 dysfunction with the neurodevelopmental phenotype observed in a patient, in vitro minigene assay was used to verify the effect of CNOT1 gene splice site variant c.1343+1G>T on mRNA splicing. We also explored the impact of transient transfection introducing modified U1 snRNA on correcting the splicing variant. Through minigene expression in mammalian cells, we demonstrated that the variant induced complete exon 12 skipping, which explained the patient's clinical condition and provided additional genetic diagnosis evidence for the clinical significance of the variant. Moreover, we confirmed that the aberrant splice pattern could be partially corrected by the modified U1 snRNA at the mRNA level, which provided strong evidence for the therapeutic potential of modified U1 snRNA in neutralizing the hazardous effect of incorrect splicing patterns.
Light‐Induced Metal‐Free Generation of Cyanocarbenes from Alkynyl Triazenes for the Synthesis of Nitrile Derivatives
Authors: Michel Elena , Grieser Fabian F. , Mackenroth Alexandra V. , Schukin Michael , Krämer Petra , Tahir Shaista , Rominger Frank , Rudolph Matthias , Hashmi A. Stephen K.
Published: July 2023

The chemistry of alkynyl triazenes is an emerging field for organic chemists and especially acid‐induced nucleophilic functionalizations, either directly, or after a prior reaction towards aromatic triazenes under extrusion of nitrogen, paved the way for fruitful strategies. In contrast, the chemical behavior of alkynyl triazenes upon irradiation with light is still unknown. Herein we present the first photoactivation of alkynyl triazenes that triggers an uncommon reactivity pattern involving the cleavage of the N1−N2 bond of the triazene moiety resulting in a unique approach to cyanocarbenes from a readily available, stable, and insensitive precursor. This allows to access various nitrile compounds without the use of a toxic cyanating agent by exploiting the reactivity pattern of carbenes. By variation of the reaction conditions and light sources, different substitution patterns can be obtained selectively in good yields under mild and metal‐free conditions, thus introducing the alkynyl triazene unit as a photo accessible methylene nitrile synthon. Using this synthon, subclasses like α‐alkoxynitriles, α‐aminonitriles and α‐cyanohydrazones become easily available. These exhibit synthetically valuable substitution patterns for the synthesis of pharmaceuticals, intermediates for total synthesis and amino acid synthesis.
A critically endangered estuarine limpet’s only two populations are genomically and morphologically distinct
Authors: de Coito Paula M. , Emami‐Khoyi Arsalan , Hedderson Terry A. , Toonen Robert J. , Teske Peter R. , Branch George M.
Published: July 2023

Seagrass habitats are declining worldwide, placing several seagrass‐associated animals at risk of extinction. The Critically Endangered limpet Siphonaria compressa is one of the rarest molluscs in Africa, and has been reported from only two disjunctive lagoons in South Africa. Being a highly specialized grazer that lives exclusively on the narrow blades of Cape eelgrass, Zostera capensis, which is itself listed as Endangered in the South African Red List and has decreased in abundance, conservation initiatives are urgently needed to ensure the long‐term survival of S. compressa.

Molecular data (sequence data from the mitochondrial genome and single nucleotide polymorphism data of the nuclear genome) and morphological data were analysed to determine whether the two populations are conspecific, with implications for whether translocation between localities could be a viable management strategy to restore either population in the event of a collapse, or to maintain the genetic diversity of each population.

Strong evidence emerged for the distinctness of the two populations, including a lack of shared mtDNA haplotypes that indicate an absence of contemporary gene flow, a divergence time that dates to the late Pleistocene, and a number of morphological characters that distinguish their shells. These findings indicate that the two populations are distinct cryptic subspecies.

As the two populations occur in different temperature‐defined marine biogeographical regions, they are probably adapted to different thermal environments. Translocations are not recommended, as this management strategy has considerable potential to result in outbreeding depression and exacerbate the extinction risk. Instead, each population should be managed separately, and several alternative conservation measures are discussed, including the protection and restoration of seagrass beds.
Morphological variability in the inner ear of mice with osteogenesis imperfecta
Authors: Huston Lila A. , Husain Tooba S. , Moore Jacob C. , Organ Jason M. , Menegaz Rachel A. , Handler Emma K. , Gonzales Lauren A.
Published: July 2023

Osteogenesis imperfecta (OI) is known to cause hearing loss in ~60% of the affected human population. While OI‐related pathologies have been studied in the middle ear, the development of cochlear pathologies is less well understood. In this study, we examine OI‐related pathologies of the cochlea in a mouse model of OI to (1) document variation between OI and unaffected mice, and (2) assess the intrusion of the otic capsule onto the cochlea by analyzing differences in duct volumes. Juvenile and adult OIM C57BL/6mice were compared to unaffected wildtype (WT) mice using three‐dimensional models of the cochlea generated from high resolution micro‐CT scans. Two‐tailed Mann–Whitney U tests were then used to investigate duct volume differences both within and between the OI and WT samples. Areas of higher ossification were observed at the cochlear base in the OI sample. OI mice also had significant intraindividual differences in duct volume between right and left ears (4%–15%), an effect not observed in WT mice. WT and OI duct volumes showed a large degree of overlap, although the OIM volumes were more variable. Our findings indicate that OIM mice are likely to exhibit more asymmetry and variation in cochlear volume despite minor differences in sample cochlear volumes, possibly due to bony capsule intrusion. This suggests a potential mechanism of hearing loss, and a high potential for cochlear and otic capsule alteration in OIM mice.
Constructing Rechargeable Solid‐State Lithium‐Oxygen Batteries
Authors: Li Minghui , Pan Kecheng , Wang Weicheng , Xing Shuochao , Dou Yaying , Zhang Zhang , Zhou Zhen
Published: July 2023

Lithium‐oxygen batteries (LOBs) hold great potential for electrochemical energy storage due to their high theoretical energy density. However, the utilization of conventional liquid electrolytes raises safety concerns such as flammability and leakage, which are also problematic in lithium‐ion batteries. The development of practical open battery systems employing volatile liquid electrolytes, with the ultimate goal of lithium‐air batteries, presents particular challenges. Solid‐state electrolytes (SSEs) have emerged as a promising solution to tackle these issues. In the past two decades, SSEs have garnered significant attention and have been successfully implemented in LOBs. This review aims to highlight recent advancements in SSEs for LOBs, exploring the opportunities and challenges associated with developing SSEs possessing high ionic conductivity, interfacial compatibility, and stability. The objective is to enhance reversibility, promote an increase in stable triple‐phase boundaries, and safeguard the Li anode in open battery systems. Finally, we put forth future directions for the advancement of solid‐state Li‐air batteries.
Visual display size and shape impact the accuracy of US adults' health‐risk estimates
Authors: Fitzsimmons Charles J. , Woodbury Lauren , Taber Jennifer M. , Schiller Lauren K. , Mielicki Marta K. , Sidney Pooja G. , Coifman Karin G. , Thompson Clarissa A.
Published: July 2023

Health risks, when presented as ratios (e.g., two out of seven people), are challenging to understand, but visual displays can foster accurate understanding. We conducted three experiments to test how characteristics of numbers (Experiment 1), icon arrays (Experiments 1, 2, and 3), and number lines (Experiments 1 and 3) influenced people's ability to accurately estimate the risk of experiencing side effects. Participants in each experiment saw smaller‐ (e.g., 2 out of 7) and larger‐component (e.g., 264 out of 924) equivalent ratios in one of three conditions: with number lines only, with icon arrays only, or in the form of Arabic numerals with no accompanying visual. We found that risk estimates were more accurate when presented in 10 × 10 icon arrays, long horizontal 1 × 99 arrays, or number lines. We theorize that hypothetical risks can be estimated more accurately when the display affords easy translation to a percentage.
Made to escape: How the neoliberal rationality changed consumer escape
Authors: Scussel Fernanda
Published: July 2023

Current research on consumer escape is characterized by a paradox: when seeking to escape the structures, pressures, and obligations of modern life, consumers end up reinforcing the same structure that caused the desire to escape. We propose that this paradox can be explained by a connection between consumer escape and the neoliberal rationality, which is understood to focus on the creation of autonomous, ambitious, and aspiring individuals. Thus, in this article, we explain how the neoliberal rationality affects consumer escape. A three‐year ethnography in a community of long‐distance runners has enabled us to explain that the neoliberal rationality acts on consumer escape through three specific and interdependent dynamics: the community of performance, the entrepreneurial body, and the performance market. Together, those three dynamics change the nature of consumer escape experiences in our contemporary society, according to the main contribution of this research.
Exploring the role of augmented reality as a new brand advocate
Authors: Kumar Harish , Tuli Nikhita , Singh Rajesh Kumar , Arya Vikas , Srivastava Ritu
Published: July 2023

Augmented reality (AR) has proven to be a potential source of disruption in the marketing discipline. Abundant research has attested to AR's potential by exploring the impact of AR attributes on behavioral intentions and users' attitudes. However, AR's potential to spark customer interactions, co‐create value, and foster brand advocacy remains poorly understood. This study explores whether and how AR can turn users into brand advocates. Applying structural equation modeling to a sample of 502 AR users, the study finds that AR empowers users during their shopping experience, creating strong brand attachment and engagement and ultimately leading to brand advocacy. This brand‐focused study, which goes beyond the technical aspects of AR, is unique and has the potential to inform the strategic decision‐making of managers aiming to enhance the customer experience by means of AR implementation.
Intracellular calcium ion transients evoked by cell poking independently of released autocrine ATP in Madin–Darby canine kidney cells
Authors: Chang Minki , Montagne Kevin , Furukawa Katsuko S. , Ushida Takashi
Published: July 2023

The mechanical stimulation induced by poking cells with a glass needle activates Piezo1 receptors and the adenosine triphosphate (ATP) autocrine pathway, thus increasing intracellular Ca2+concentration. The differences between the increase in intracellular Ca2+concentration induced by cell poking and by ATP‐only stimulation have not been investigated. In this study, we investigated the Ca2+signaling mechanism induced by autocrine ATP release during Madin–Darby Canine Kidney cell membrane deformation by cell poking. The results suggest that the pathways for supplying Ca2+into the cytoplasm were not identical between cell poking and conventional ATP stimulation. The functions of the G protein‐coupled receptor (GPCR) subunits (Gq, G), ATP‐activated receptor and the upstream Ca2+release signal from the intracellular endoplasmic reticulum Ca2+store, were investigated. The results show that Gq plays a major role in the Ca2+response evoked by ATP‐only stimulation, while cell poking induces a Ca2+response requiring the involvement of both Gq and G units simultaneously. These results suggest that GPCR are not only activated by ATP‐only stimulation or autocrine ATP release during Ca2+signaling, but also activated by the mechanical effects of cell poking.
Dynamic Change of Rh Oxidation State During Lean‐Rich Perturbation and Light‐Off of Three‐Way Catalysis Analysed using In Situ Diffuse Reflectance UV‐vis Spectroscopy
Authors: Fujiwara Ayumi , Tsurunari Yutaro , Iwashita Shundai , Yoshida Hiroshi , Ohyama Junya , Machida Masato
Published: July 2023

This study investigated the redox behaviour of Rh in three‐way catalysts (TWC) using time‐resolved in situ diffuse reflectance UV‐vis spectroscopy in different modes with air‐to‐fuel ratio (A/F) step, A/F perturbation, and temperature ramping. When Rh/ZrO2−CeO2 (Rh/ZC) and Rh/ZrO2 (Rh/Z) containing fully oxidised Rh were treated at 400 °C under simulated TWC conditions with A/F stepping from 15.0 (fuel‐lean) to 14.1 (fuel‐rich), a steep increase in the metallic fraction (Rh0/Rh) and a simultaneous increase in Kubelka–Munk function (ΔKM) at λ=450 nm occurred near the stoichiometric point (A/F=14.6). Metallic Rh became abundant until A/F=14.1, where the largest ΔKM was attained. In the A/F perturbation mode, the Rh oxidation state fluctuated with repetitious switching of rich and lean gas feeds, but the ΔKM oscillation amplitude was lessened for Rh/ZC compared to Rh/Z because of the oxygen‐scavenging function of ZC. Furthermore, the changes in Rh oxidation state during TWC light‐off were analysed in the temperature‐ramping mode. Under rich conditions, Rh0/Rh and ΔKM increased after 200 °C, where the formation of Rh metal led to efficient conversions of CO and NO. However, metallic Rh did not appear during light‐off under the lean condition, where NO conversion was negligible.
Spin‐Injection in Graphene: An EPR and Raman Study
Authors: Fragkogiannis Christos , Belles Loukas , Gournis Dimitrios P. , Deligiannakis Yiannis , Georgakilas Vasilios
Published: July 2023

In this article, the enrichment of graphene and graphene oxide with free radicals through their functionalization with tyrosine is studied. In contrast with what is commonly observed in the functionalization of graphene with organic species the addition of tyrosine radicals on to the graphene substrate led to a remarkable increase of the aromatic character as indicated by the spectroscopic data. Similar behaviour was observed for the functionalization of graphene oxide. In addition, a brief analysis of the tyrosine functionalized graphene with EPR spectroscopy showed a remarkable enhancement of the spin density that could be useful in spintronics.
Unprecedented Direct Asymmetric Total Syntheses of 5,8’‐Naphthylisoquinoline Alkaloids from their Fully Substituted Precursors Employing a Novel Nickel/N,N‐ligand‐Catalyzed Atroposelective Cross‐Coupling Reaction
Authors: Berthold Dino , van Otterlo Willem A. L.
Published: July 2023

A general and concise synthetic pathway for the preparation of four different 5,8’‐coupled naphthylisoquinoline alkaloids, employing a specially developed nickel/N,N‐ligand‐catalyzed atroposelective Negishi coupling is reported. In the first reported direct atroposelective coupling of the fully substituted precursors, the naturally occurring cross‐coupled products were generally obtained directly in reasonable yields and high enantiomeric purities. For the synthesis of the cross‐coupling precursors, we employed a modification of Bringmann's known approach to the dihydroisoquinoline compounds and a newly developed route for the naphthalene building blocks. For the latter 1,8‐dioxynaphthalene precursors, our strategy utilized Hartwig's borylation/methylation approach and included the efficient installation of orthogonal protecting groups.
CNS sites controlling the gastric pyloric sphincter: Neuroanatomical and functional study in the rat
Authors: Richardson Janell , Dezfuli Ghazaul , Mangel Allen W. , Gillis Richard A. , Vicini Stefano , Sahibzada Niaz
Published: July 2023

The pyloric sphincter receives parasympathetic vagal innervation from the dorsal motor nucleus of the vagus (DMV). However, little is known about its higher‐order neurons and the nuclei that engage the DMV neurons controlling the pylorus. The purpose of the present study was twofold. First, to identify neuroanatomical connections between higher‐order neurons and the DMV. This was carried out by using the transneuronal pseudorabies virus PRV‐152 injected into rat pylorus torus and examining the brains of these animals for PRV labeling. Second, to identify the specific sites within the DMV that functionally control the motility and tone of the pyloric sphincter. For these studies, experiments were performed to assess the effect of DMV stimulation on pylorus activity in urethane‐anesthetized male rats. A strain gauge force transducer was sutured onto the pyloric tonus to monitor tone and motility. L‐glutamate (500 pmol/30 nL) was microinjected unilaterally into the rostral and caudal areas of the DMV. Data from the first study indicated that neurons labeled with PRV occurred in the DMV, hindbrain raphe nuclei, midbrain Edinger–Westphal nucleus, ventral tegmental area, lateral habenula, and arcuate nucleus. Data from the second study indicated that microinjected L‐glutamate into the rostral DMV results in contraction of the pylorus blocked by intravenously administered atropine and ipsilateral vagotomy. L‐glutamate injected into the caudal DMV relaxed the pylorus. This response was abolished by ipsilateral vagotomy but not by intravenously administered atropine or L‐NG‐nitroarginine methyl ester (L‐NAME). These findings identify the anatomical and functional brain neurocircuitry involved in controlling the pyloric sphincter. Our results also show that site‐specific stimulation of the DMV can differentially influence the activity of the pyloric sphincter by separate vagal nerve pathways.
Nuclei and tracts in the epithalamus of crocodiles
Authors: Pritz Michael B.
Published: July 2023

The epithalamus, an area of the dorsal diencephalon found in all vertebrates, consists of the habenula, the subhabenular nuclei, and associated tracts. The habenula is itself divisible into two parts—a medial and a lateral nucleus differing in their inputs, outputs, and cellular morphology. The medial component is related to the limbic system and serotonergic raphe, while the lateral nucleus is more interconnected with the basal ganglia and midbrain dopamine systems. These findings, which come from experiments mainly done on mammals, serve as a basis for comparison with other vertebrates. However, similar studies in other amniotes, such as reptiles, are few. To fill this gap in knowledge, two species of crocodiles were examined utilizing a variety of histological methods in various planes of section. The following results were obtained. First, the habenula was divided into medial and lateral parts based on its cytoarchitecture. Neurons in the medial habenula were small, were closely packed, and had a limited dendritic arbor characterized by unusual distal dendritic appendages, whereas neurons in the lateral habenula were larger, were more loosely packed, and had longer dendritic processes that were commonly beaded. Second, the stria medullaris, the major input to the habenula, was identified by its immunoreactivity to parvalbumin. Third, the fasciculus retroflexus (habenulointerpeduncular tract), the primary output of the habenula, was visualized by staining with acetylcholinesterase. Fourth, nuclei associated with the habenula, the subhabenular nuclei, have been identified and characterized. These features provide a means to recognize the major nuclei and tracts in the epithalamus in crocodiles and are likely applicable to other reptiles.
Effect of muscle pre‐tension and pre‐impact neck posture on the kinematic response of the cervical spine in simulated low‐speed rear impacts
Authors: Correia Matheus A. , Corrales Miguel A. , McLachlin Stewart D. , Cronin Duane S.
Published: July 2023

Computational human body models (HBMs) can identify potential injury pathways not easily accessible through experimental studies, such as whiplash induced injuries. However, previous computational studies investigating neck response to simulated impact conditions have neglected the effect of pre‐impact neck posture and muscle pre‐tension on the intervertebral kinematics and tissue‐level response. The purpose of the present study was addressing this knowledge gap using a detailed neck model subjected to simulated low‐acceleration rear impact conditions, towards improved intervertebral kinematics and soft tissue response for injury assessment. An improved muscle path implementation in the model enabled the modeling of muscle pre‐tension using experimental muscle pre‐stretch data determined from previous cadaver studies. Cadaveric neck impact tests and human volunteer tests with the corresponding cervical spine posture were simulated using a detailed neck model with the reported boundary conditions and no muscle activation. Computed intervertebral kinematics of the model with pre‐tension achieved, for the first time, the S‐shape behavior of the neck observed in low severity rear impacts of both cadaver and volunteer studies. The maximum first principal strain in the muscles for the model with pre‐tension was 27% higher than that without pre‐tension. Although, the pre‐impact neck posture was updated to match the average posture reported in the experimental tests, the change in posture was generally small with only small changes in vertebral kinematics and muscle strain. This study provides a method to incorporate muscle pre‐tension in HBM and quantifies the importance of pre‐tension in calculating tissue‐level distractions.
Assessing a heterogeneous model for accounting for endovascular devices in hemodynamic simulations of cerebral aneurysms
Authors: Bérod Alain , Mut Fernando , Cebral Juan , Mendez Simon , Chnafa Christophe , Nicoud Franck
Published: July 2023

The heterogeneous model developed by Berod et al [Int J Numer Method Biomed Eng 38, 2021] for representing the hemodynamic effects of endovascular prostheses is applied to a series of 10 patient specific cerebral aneurysms, 6 being treated by flow diverters, 4 being equipped with WEBs. Two markers correlated with the medical outcome of the treatment are used to assess the potential of the model, namely the saccular mean velocity and the inflow rate at the neck of the aneurysm. The comparison with the corresponding wire‐resolved simulations is very favorable in both cases, and the model‐based simulations also retrieve the jetting‐type flows generated downstream of the struts. Noteworthy, the very same model was used for representing the flow diverters and the WEBs, showing the versatility and robustness of the heterogeneous modeling of the devices.
Design of Silica@Au Hybrid Nanostars for Enhanced SERS and Photothermal Effect
Authors: Kaur Gagandeep , Kaur Vishaldeep , Kaur Navneet , Kaur Charanleen , Sood Kritika , Shanavas Asifkhan , Sen Tapasi
Published: July 2023

Core‐shell nanostructures of silicon oxide@noble metal have drawn a lot of interest due to their distinctive characteristics and minimal toxicity with remarkable biocompatibility. Due to the unique property of localized surface plasmon resonance (LSPR), plasmonic nanoparticles are being used as surface‐enhanced Raman scattering (SERS) based detection of pollutants and photothermal (PT) agents in cancer therapy. Herein, we demonstrate the synthesis of multifunctional silica core – Au nanostars shell (SiO2@Au NSs) nanostructures using surfactant free aqueous phase method. The SERS performance of the as‐synthesized anisotropic core‐shell NSs was examined using Rhodamine B (RhB) dye as a Raman probe and resulted in strong enhancement factor of 1.37×106. Furthermore, SiO2@Au NSs were also employed for PT killing of breast cancer cells and they exhibited a concentration‐dependent increase in the photothermal effect. The SiO2@Au NSs show remarkable photothermal conversion efficiency of up to 72 % which is unprecedented. As an outcome, our synthesized NIR active SiO2@Au NSs are of pivotal importance to have their dual applications in SERS enhancement and PT effect.
Complex‐order controller design examples and their implementation
Authors: Nako Julia , Psychalinos Costas , Elwakil Ahmed S.
Published: July 2023

A systematic method for approximating the complex‐order Laplacian operator by realizable integer‐order transfer functions is presented in this work. The realization is performed by a simple structure where only one active element is used. Thanks to the employment of complex‐order impedances, both integrators and differentiators can be readily implemented by the same core simply by interchanging the associated impedance locations. The validity of the presented concept is verified through simulation and experimental results, using the OrCAD PSpice suite and a Field Programmable Analog array device.
Detection and quantification of the metabolite Ac‐Tβ1–14 in in vitro experiments and urine of rats treated with Ac‐Tβ4: A potential biomarker of Ac‐Tβ4 for doping tests
Authors: Rahaman Khandoker Asiqur , Muresan Anca Raluca , Hasan Md Lemon , Joung Yoon Ki , Min Hophil , Son Junghyun , Kang Min‐Jung , Kwon Oh‐Seung
Published: July 2023

Thymosin β4 (Tβ4) was reported to exert various beneficial bioactivities such as tissue repair, anti‐inflammation, and reduced scar formation, and it is listed on the prohibited substances in sports by the World Anti‐Doping Agency. However, no metabolism studies of Tβ4 were reported yet. Previously, our lab reported in in vitro experiment that a total of 13 metabolites were found by using multiple enzymes, and six metabolites (Ac‐Tβ31–43, Ac‐Tβ17–43, Ac‐Tβ1–11, Ac‐Tβ1–14, Ac‐Tβ1–15, and Ac‐Tβ1–17) were confirmed by comparing with the synthetic standards. This study was aimed at identifying new metabolites of Tβ4 leucine aminopeptidase (LAP), human kidney microsomes (HKM), cultured huvec cells, and rats after administration of Tβ4 protein to develop biomarkers for detecting doping drugs in sports. A method for detecting and quantifying Ac‐Tβ1–14 was developed and validated using Q‐Exactive orbitrap mass spectrometry. The limit of detection (LOD) and limit of quantification (LOQ) of the Ac‐Tβ1–14 were 0.19 and 0.58 ng/mL, respectively, and showed a good linearity (r2 = 0.9998). As a result, among the six metabolites above, Ac‐Tβ1–14, as a common metabolite, was found in LAP, HKM, huvec cells exposed to Tβ4, and the urine of rats intraperitoneally treated with 20‐mg/kg Tβ4. And the metabolite Ac‐Tβ1–14 was quantitatively determined by 48 h in rats, with the highest concentration occurring between 0 and 6 h. Ac‐Tβ1–14 was not detected in non‐treated control groups, including human blank urine. These results suggest that Ac‐Tβ1–14 in urine is a potential biomarker for screening the parent Tβ4 in doping tests.
Insularity determines nestling sex ratio variation in Egyptian vulture populations
Authors: Gómez‐López Guillermo , Sanz‐Aguilar Ana , Carrete Martina , Arrondo Eneko , Benítez José Ramón , Ceballos Olga , Cortés‐Avizanda Ainara , de Pablo Félix , Donázar José Antonio , Frías Óscar , Gangoso Laura , García‐Alfonso Marina , González José Luis , Grande Juan Manuel , Serrano David , Tella José Luis , Blanco Guillermo
Published: July 2023

Variation in offspring sex ratio, particularly in birds, has been frequently studied over the last century, although seldom using long‐term monitoring data. In raptors, the cost of raising males and females is not equal, and several variables have been found to have significant effects on sex ratio, including food availability, parental age, and hatching order. Sex ratio differences between island populations and their mainland counterparts have been poorly documented, despite broad scientific literature on the island syndrome reporting substantial differences in population demography and ecology. Here, we assessed individual and environmental factors potentially affecting the secondary sex ratio of the long‐lived Egyptian vulture Neophron percnopterus. We used data collected from Spanish mainland and island populations over a ca. 30‐year period (1995–2021) to assess the effects of insularity, parental age, breeding phenology, brood size, hatching order, type of breeding unit (pairs vs. trios), and spatial and temporal variability on offspring sex ratio. No sex bias was found at the population level, but two opposite trends were observed between mainland and island populations consistent with the island syndrome. Offspring sex ratio was nonsignificantly female‐biased in mainland Spain (0.47, n = 1112) but significantly male‐biased in the Canary Islands (0.55, n = 499), where a male‐biased mortality among immatures could be compensating for offspring biases and maintaining a paired adult sex ratio. Temporal and spatial variation in food availability might also have some influence on sex ratio, although the difficulties in quantifying them preclude us from determining the magnitude of such influence. This study shows that insularity influences the offspring sex ratio of the Egyptian vulture through several processes that can affect island and mainland populations differentially. Our research contributes to improving our understanding of sex allocation theory by investigating whether sex ratio deviations from parity are possible as a response to changing environments comprised by multiple and complexly interrelated factors.
Metal‐Free Visible Light‐Promoted Synthesis of 1,2,2‐Triarylethanones and 2,2‐Diarylethanones: Route Towards Tamoxifen
Authors: Zhu Zhiqiang , Chen Shaoshuai , Qiu Dian , Li Bao Qiong
Published: July 2023

An efficient and straightforward methodology for the synthesis of 1,2,2‐triarylethanones and 2,2‐diarylethanones has been developed, via a visible light‐promoted/Brønsted acid‐catalyzed carbonyl‐alkyne metathesis/transfer hydrogenation one‐pot reaction of benzoquinone, arylalkyne, and Hantzsch ester. A series of synthetically useful triarylethanones and diarylethanones were achieved in excellent yield under mild reaction conditions. This protocol is operationally simple, photocatalyst‐free, and scalable and has a broad substrate scope. Moreover, this reaction involves the formation of three chemical bonds, namely C=O, C−C, and C−H bonds. This feature enables de novo synthesis of 1,2,2‐triarylethanones and 2,2‐diarylethanones. Additionally, this protocol provides a convenient and practical synthetic route for tamoxifen.
Synthesis and Chiroptical Properties of Binaphthyl‐Hinged [5]Helicenes
Authors: Hasegawa Masashi , Nojima Yuki , Nagata Yuya , Usui Kazuteru , Sugiura Ken‐ichi , Mazaki Yasuhiro
Published: July 2023

The synthesis, structure, and circularly polarized luminescence (CPL) of two types of shape‐persistent [5]helicenes, hinged by a tethered (−OCH2CH2O−) or untethered (−OCH3) binaphthyl, are reported. The binaphthyl tethering system facilitated an effective Wittig ring‐closure reaction in the synthesis of a macrocyclic precursor, which could be easily converted to the title compound via successive photocyclization. The tethered groups were replaced with untethered −OCH3 groups by treatment with BBr3 followed by methylation. Both compounds exhibited similar spectra, and their longest wavelength absorption band with a low intensity was attributed to the transition from HOMO to LUMO+1. These compounds exhibited CPL with higher dissymmetry factors glum values than unlocked helicenes.
Religious costly signal induces more trustworthiness than secular costly signal: A study of pilgrimage to Santiago de Compostela
Authors: Chvaja Radim , Chinchilla Juana , Goméz Ángel , Lang Martin
Published: July 2023

Research suggests that costly displays of commitment increase trust and cooperation. In five studies (total n > 1,700), we investigated whether costly behaviours are more effective in promoting trust when integrated within a religious rather than secular context using the pilgrimage to Santiago de Compostela as a costly display of commitment. First, we show that pilgrims base their pilgrim identity on physical effort (Studies 1A and 1B). Next, in three pre‐registered experiments (Studies 2–4) with the Spanish population, we compared the trustworthiness of people posting on Facebook about their participation in a religious pilgrimage and a secular pilgrimage/hike with various control posts. The results showed that pilgrims/hikers are perceived as more trustworthy than non‐pilgrims and that long‐distance pilgrims are perceived as more trustworthy than short‐distance pilgrims. Moreover, these effects are stronger when the pilgrimage is framed in a religious context compared to a secular context. Our research highlights the key role of religion in the costly signalling of commitment.
Control Strategy Analysis of Vehicle Thermal Management System Based on Motor Heat Utilization
Authors: He Liange , Gu Zihan , Zhang Yan , Jing Haodong , Li Pengpai
Published: July 2023

Waste heat recovery can not only reduce the heating energy consumption during heating, but also assist the positive temperature coefficient to improve the heating efficiency. Herein, a motor waste heat recovery system composed of two four‐way valves is proposed. Through simulation and test, the thermal management system model is established based on the parameters of each component. Experiments and simulations are also conducted at 0, 20, and 40 °C. Under the New European Driving Cycle, it is verified that the motor waste heat recovery system can meet the heating demand of the cabin. At the same time, the temperature rise of the battery increases by 2.9% from 0 to 15 °C compared to no heat recovery system. From 0 to 18 °C, the cabin temperature increases by 8.1%. The cooling rate of the battery increases by 5.8% from 40 to 30 °C and the cooling rate of the cabin increases by 9.7% from 40 to 23 °C.
Proactive and reactive language control in bilingual language production revealed by decoding sustained potentials and electroencephalography oscillations
Authors: Zhang Zhaoqi , Ma Fengyang , Guo Taomei
Published: July 2023

Adopting highly sensitive multivariate electroencephalography (EEG) and alpha‐band decoding analyses, the present study investigated proactive and reactive language control during bilingual language production. In a language‐switching task, Chinese–English bilinguals were asked to name pictures based on visually presented cues. EEG and alpha‐band decoding accuracy associated with switch and non‐switch trials were used as indicators for inhibition over the non‐target language. Multivariate EEG decoding analyses showed that the decoding accuracy in L1 but not in L2, was above chance level shortly after cue onset. In addition, alpha‐band decoding results showed that the decoding accuracy in L1 rose above chance level in an early time window and a late time window locked to the stimulus. Together, these asymmetric patterns of decoding accuracy indicate that both proactive and reactive attentional control over the dominant L1 are exerted during bilingual word production, with a possibility of overlap between two control mechanisms. We addressed theoretical implications based on these findings for bilingual language control models.
Web‐based comparative study of some national experiences of health care quality management
Authors: Dare Labante Outcha , Champagne François , Denis Jean‐Louis , Ste‐Marie Genevieve , Yordanov Yassen
Published: July 2023

Since the publication of study results on adverse events to health care in OECD countries, the importance of the national quality improvement strategies has been recognised. To examine how these strategies have been shaped in different jurisdictions, we carried out this study. We conducted a web‐based comparative study of international practices. We first defined seven key health care and services quality management functions. We then drew on the experience of authors to make a reasoned selection of 13 countries or states across the world. We determined the distance that separates each of these functions from a country's Ministry of Health (MoH); and examined whether these functions are concentrated in a single organisation or dispersed across several organisations. Afterwards, we correlated our results with the quality level of these countries based on the OECD's health care indicators. Overall, Netherlands, Québec (Canada), Korea, Germany, England (UK), and the United States had at least 50% of their quality management functions controlled by self‐regulated organisations. The Market Concentration Index ranged from 937 for the United States to 6800 for Russia. Graphical representation has shown us two health system models. Our results also clearly showed that countries had a better quality of care most often when they belong to model 1 of our taxonomy. These findings will help countries design and implement large‐scale health care and services quality strategies for better and safer health care and services.
Toward more accurate diagnosis of multiple sclerosis: Automated lesion segmentation in brain magnetic resonance image using modified U‐Net model
Authors: Amaludin Bakhtiar , Kadry Seifedine , Ting Fung Fung , Taniar David
Published: July 2023

Early diagnosis of multiple sclerosis (MS) through the delineation of lesions in the brain magnetic resonance imaging is important in preventing the deteriorating condition of MS. This study aims to develop a modified U‐Net model for automating lesions segmentation in MS more accurately. The proposed modified U‐Net uses residual dense blocks to replace the standard convolutional stacks and incorporates three axes (axial, sagittal, and coronal) of 2D slice images as input. Furthermore, a custom fusion method is also introduced for merging the predicted lesions from different axes. The model was implemented on ISBI2015 and OpenMS data sets. On ISBI2015, the proposed model achieves the best overall score of 93.090% and DSC of 0.857 on the OpenMS data set.
Impact of pharmacist‐provided medication therapy management service on reducing unplanned readmissions in adult patients in Singapore
Authors: Lee Elena Meishan , Toh Yue Feng , Lim Nathaniel Wei Xiong , See Qin Yong
Published: July 2023

Introduction

Older patients on polypharmacy are predisposed to drug‐related problems (DRPs). While medication therapy management (MTM) with pharmacist involvement can reduce DRP occurrence, few have examined its impact on reducing unplanned admissions. This study was designed to determine whether a pharmacist‐provided MTM service can reduce unplanned admissions through the comparison with patients receiving usual care.

Methods

A retrospective case–control study was conducted in Changi General Hospital. Patients enrolled to MTM service from January 2016 to December 2021 were included in the intervention arm (n = 96) while patients who were not enrolled were recruited as control (n = 96). Primary outcome was the incidence rate ratio (IRR) of unplanned admissions within 6 months postindex visit comparing between intervention arm and control arm. Secondary outcomes included number of DRPs identified, types of DRPs, and the potential risks avoided by resolving DRPs. The negative binomial mixed model was used to model the unplanned admissions data.

Results

MTM with pharmacists' involvement was associated with a 39% (IRRs 0.61, 95% confidence interval [CI] 0.37–0.99, p = 0.047) lower rate of admissions in the intervention compared with the control group. There were higher number of DRPs (144 vs. 2) found in the intervention arm compared with control arm, respectively. The most prevalent types of DRPs were “Nonadherence” (80.1%), “Drug omission” (5.6%), and “Inappropriate dose” (2.8%). The most common potential risks avoided were increased cardiovascular risk, n = 29 (22.1%), increased fall risk, n = 18 (13.7%), and increased fracture risk, n = 17 (13.0%).

Conclusion

The study suggests that pharmacist‐provided MTM service decreased unplanned admission. It has improved medication safety and quality of care by identifying and resolving more DRPs.
Evaluation of a pharmacist‐led smoking cessation service in a pulmonary clinic
Authors: Andras Sera , Sherwin Erin , Bodreau Charles , Schadler Aric , Kormelink Lauren
Published: July 2023

Introduction

Studies have demonstrated the positive effect that pharmacist‐led smoking cessation services have on smoking cessation rates, but data regarding pharmacists' impact on smoking cessation in a pulmonary clinic are lacking.

Objectives

To evaluate the effect of pharmacist‐led smoking cessation visits compared with routine smoking cessation counseling performed by other pulmonary practitioners on smoking cessation rates and outcomes in a population with significant pulmonary disease.

Methods

This was a single center, retrospective, observational cohort study comparing patients who were solely counseled on smoking cessation by a practitioner during their pulmonary clinic appointment to patients who received smoking cessation services from a pharmacist. The primary outcome was a comparison of the percentage of patients who self‐reported cessation at 1, 6, and at 12 months from their initial visit between both cohorts. Other outcomes included the rate of relapse, rate of asthma and chronic obstructive pulmonary disease exacerbations, and time spent counseling patients. Continuous variables were analyzed with an independent samples t‐test or Mann–Whitney U‐test as appropriate. Pearson's chi‐square or Fisher's exact test was used to analyze categorical data.

Results

In total, 149 patients counseled by a pharmacist met the inclusion criteria for the study. A matched cohort of 88 practitioner‐managed patients was used for comparison. Patients managed by the pharmacist achieved higher cessation rates at 1 and 6 months compared with those managed by practitioners, though results were not statistically significant. Patients managed by the pharmacist had significantly higher quit rates at 12 months compared with those managed by practitioners, with 21 patients (14.1%) quitting in the pharmacist‐managed group versus 5 patients (5.7%) in the practitioner‐managed group (p = 0.045).

Conclusion

Patients with significant pulmonary disease had higher rates of smoking cessation at 12 months when managed by a pharmacist compared with routine counseling provided during practitioner‐led visits.
Cellular consequences triggered by ketamine on exposure to human glioblastoma epithelial (LN‐229) cells
Authors: Megha Kizhakkepurakkal B. , Mohanan Parayanthala V.
Published: July 2023

Ketamine is generally a noncompetitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist that interrelates with various other receptors, contributing to a wide range of actions. They are mainly approved as a general anesthetic, but a low dose of ketamine is applied for pain management, depression, and as analgesics. However, there is a significant concern regarding the long‐term usage as antidepressants and as an abused drug. The study mainly aims to exhibit the possible long‐term side effects of ketamine as an antidepressant and in recreational users. The study explores the in vitro cytotoxicity revealed on LN‐229 cells in a dose‐dependent manner. According to the cell viability assays, there is a dose‐dependent response toward ketamine. Morphological and nuclear integrity was changed on exposure and assessed using Giemsa, Rhodamine phalloidin, 4’,6‐diamidino‐2‐phenylindole (DAPI), and Acridine orange staining. The apoptotic cell death marked by nuclear condensation, Lactate dehydrogenase leakage, pro‐inflammatory cytokine (interleukin [IL]‐β) release, and inhibition of cell migration was observed. The study highlights the importance of nonanesthetic usage of ketamine, which can lead to severe adverse side effects on long‐term exposure rather than a single exposure as an anesthetic agent.
Association between polymorphism rs2421943 of the insulin‐degrading enzyme and schizophrenia: Preliminary report
Authors: Ambrozová Laura , Zeman Tomáš , Janout Vladimír , Janoutová Jana , Lochman Jan , Šerý Omar
Published: July 2023

Background

Insulin‐degrading enzyme (IDE) is an important gene in studies of the pathophysiology of type 2 diabetes mellitus (T2DM). Recent studies have suggested a possible link between type 2 diabetes mellitus (T2DM) and the pathophysiology of schizophrenia (SZ). At the same time, significant changes in insulin‐degrading enzyme (IDE) gene expression have been found in the brains of people with schizophrenia. These findings highlight the need to further investigate the role of IDE in schizophrenia pathogenesis.

Methods

We enrolled 733 participants from the Czech Republic, including 383 patients with schizophrenia and 350 healthy controls. Our study focused on the single nucleotide polymorphism (SNP) rs2421943 in the IDE gene, which has previously been associated with the pathogenesis of Alzheimer's disease. The SNP was analyzed using the PCR‐RFLP method.

Results

The G allele of the rs2421943 polymorphism was found to significantly increase the risk of developing SZ (p < 0.01) when a gender‐based analysis showed that both AG and GG genotypes were associated with a more than 1.55 times increased risk of SZ in females (p < 0.03) but not in males. Besides, we identified a potential binding site at the G allele locus for has‐miR‐7110‐5p, providing a potential mechanism for the observed association.

Conclusion

Our results confirm the role of the IDE gene in schizophrenia pathogenesis and suggest that future research should investigate the relationship between miRNA and estrogen influence on IDE expression in schizophrenia pathogenesis.
CRISPR‐Cas12a assisted specific detection of mpox virus
Authors: Singh Mandeep , Misra Chitra Seetharam , Bindal Gargi , Rangu Shyam Sunder , Rath Devashish
Published: July 2023

Mpox virus, a member of genus Orthopoxvirus, causes rash and flu‐like symptoms in humans. In the recent global outbreak, it was reported from several geographical areas that have not historically reported mpox. Point of care, sensitive and specific mpox diagnostic assays are critical in checking the spread of the disease. We have developed a clustered regularly interspaced short palindromic repeats associated Cas12a nuclease‐based assay for detecting mpox virus. Mpox specific conserved sequences were identified in polA (E9L) gene which differ by a single nucleotide polymorphism (SNP) from all the viruses present in the genus Orthopoxvirus. This SNP was exploited in our assay to specifically distinguish mpox virus from other related orthopox viruses with a limit of detection of 1 copy/μl in 30 min. The assay exhibits a sensitive and specific detection of mpox virus which can prove to be of practical value for its surveillance in areas infected with multiple orthopox viruses, especially in hotspots of mpox virus infections.