bluuebunny/crossref_metadata_2025 huggingface dataset:
The anticancer/cytotoxic effect of a novel gallic acid derivative in non‐small cell lung carcinoma A549 cells and peripheral blood mononuclear cells from healthy individuals and lung cancer patients
Authors: Jafarinejad Shohreh , Martin William H. C. , Ras Bayan Abu , Isreb Mohammad , Jacob Badie , Aziz Abid , Adoul Zahra , Lagnado Ruby , Bowen Richard D. , Najafzadeh Mojgan
Published: September 2023

Gallic acid (GA) is a naturally occurring polyphenol with a strong antioxidant capacity. GA stimulates the apoptosis of cancer cells, thereby suppressing cancer cell invasion. However, the low oral permeability of GA limits its therapeutic use. In order to enhance the antioxidant capacity and oral permeability of GA, a series of compounds analogous to GA were synthesized: 4‐methoxybenzenesulfonamide (MBS), 3,4‐dimethoxybenzenesulfonamide (DMBS) and 3,4,5‐trimethoxybenzenesulfonamide (TMBS). In the new compounds, hydroxyl groups were replaced with various numbers of methoxy groups (stronger electron‐donating groups), to increase hydrophobicity and oral permeability compared to GA. In addition, the carboxylic group was replaced with a sulfonyl group (a stronger electron‐withdrawing group), to increase the molecular polarity and antioxidative activities of the compounds. The cell counting kit‐8 (CCK‐8) assay was used to detect the effect of GA, MBS, DMBS, and TMBS on cell proliferation and apoptosis in peripheral blood mononuclear cells (PBMCs) from healthy individuals and non‐small cell lung carcinoma A549 cells. Additionally, the comet assay was used to assess the genotoxicity of these compounds in PBMCs from healthy individuals, lung cancer patients, and A549 cells. Compared to untreated cells, TMBS reduced DNA damage more effectively than GA in PBMCs from lung cancer patients and healthy donors. Furthermore, in comparison to GA, TMBS was more cytotoxic in A549 cells. Moreover, TMBS was not cytotoxic in healthy PBMCs, suggesting that TMBS demonstrates therapeutic potential in cancer.
Government environmental concerns and corporate green innovation: Evidence from heavy‐polluting enterprises in China
Authors: Chen Jinyu , Zhu Dandan , Ding Shijie , Qu Jingxiao
Published: September 2023

The objective of this study is to examine the impact of government environmental concerns on green innovation and whether this has a “leverage effect” or a “crowding‐out effect.” This study employs a two‐way fixed‐effects model to conduct an empirical test using panel data from 2010 to 2020 on Chinese firms listed in heavy‐polluting industries. The results suggest that an increase in government environmental concerns can promote corporate green innovation. However, government environmental concerns primarily stimulate strategic innovation rather than substantive innovation. After a series of robustness and endogeneity tests, the conclusions of this paper still hold. Corporate green innovation induced by government environmental concerns is not the “leverage effect” superimposed on existing innovation activities but the “crowding‐out effect” of other technological innovation. The heterogeneity tests in this paper indicate that the impact is more pronounced for firms with poorer environmental conditions, stronger political connections, and richer executive backgrounds.
Unexpected discovery in the thyroid cartilage during voice deepening surgery
Authors: Larsen Dalia Gustaityte , Yelken Kursat
Published: September 2023

Key clinical message

Voice deepening surgery has en increasing interest among laryngologist worldwide and a case of surprising foreign body in the thyroid cartilage awakes alert thoughts of awareness to certain patient group.
Upcycling of Polypropylene Wastes via Catalytically C−H Modification with Polar Olefins
Authors: Zhou Shuangjing , Zhang Zongnan , Zeng Rong
Published: September 2023

While polypropylene (PP) is one of the most widely used polyolefin materials, its post‐functionalization has been a continuously researched topic in the polymer field since it could significantly improve physical and chemical properties by introducing polar groups, beneficial for development of the next generation of polyolefin materials. In this work, we describe the development of a visible‐light promoted, environmentally friendly iron‐catalyzed strategy and establishing of the reaction scope for C−H alkylated modification of polypropylene. Under our conditions, various polypropylenes could be functionalized with diverse polar alkenes with good levels of functionalization (LOF). The properties of the resulting polymers were investigated by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and tensile testing. Polypropylene wastes could also be upcycled. While the incorporation of the polyglycol groups enhanced hydrophilicity, the installation of the ester groups increased the miscibility with other polymers by acting as a compatibilizer for polystyrene and polyethylene.
Ammonium and Tartrate Salts as Alternatives to Neutral Aqueous Electrolytes for Supercapacitors
Authors: Heumann Johannes , Baltes Norman T. M. , Tübke Jens
Published: September 2023

Supercapacitors are promising energy storage devices in terms of power density and lifetime. Organic electrolytes are frequently applied in commercial supercapacitor devices. However, their water‐based counterparts are much safer, more sustainable and cost‐effective. In this study we therefore present, for the first time, aqueous tartrate‐based electrolytes (sodium tartrate / ammonium tartrate) for supercapacitor applications, and relate them to well‐known inorganic aqueous electrolytes like Na2SO4. Additionally, the influence of the cation on the electrochemical performance of supercapacitors is investigated using sodium and ammonium cations for comparison. We demonstrate the electrochemical performance and physicochemical properties of ammonium tartrate / sulfate and sodium tartrate / sulfate. An improvement of the conductivity in the range of 40–60 % was achieved by the exchange of sodium cation with ammonium cation. Carbon electrodes in newly introduced aqueous tartrate‐based electrolytes deliver high specific capacitances up to 117 Fg−1. Furthermore, electrical double layer capacitors (EDLCs) containing 1 M ammonium tartrate display a high energy density at 0.1 Ag−1 and at 10 Ag−1 (9.88 Whkg−1 and 1.14 Whkg−1, respectively). Floating tests show excellent long‐term performance. Tartrate‐based EDLCs retain >80 % of their initial capacitance at 1.6 V cell voltage (120 h floating time). In the case of ammonium tartrate electrolyte, a novel metal‐free and non‐toxic concept for an eco‐friendly supercapacitor device is proposed.
Electrochemical Nitrate Reduction to Ammonia – Recent Progress
Authors: Niu Shanshan , Yang Ji , Qian Leilei , Zhou Dan , Du Pan , Si Nan , Gu Xiaomin , Jiang Dawei , Feng Yan
Published: September 2023

The presence of nitrate in industrial, domestic and agricultural wastewater has a detrimental impact on both ecosystem and human health, as remediation and purification efforts are slow, challenging and difficult, given the high solubility and stability of this pollutant. Taking nitrate into high value‐added ammonia by electrochemical reduction can overcome high pollution and energy consumption limit of Haber‐Bosch process with long‐term significance of environmental protection and energy saving. This review summarized the research progress on the electrocatalytic reduction of nitrate to ammonia, with a focus on the reaction mechanisms, influencing factors, product detection methods, performance evaluation methods and the research status of electrocatalysts up to now. The review reported the latest strategies employed to design efficient electrocatalysts, such as pore structure regulation, alloying, heterostructure construction, defect and interface engineering, crystal surface regulation and microenvironment modulation of single‐atom catalysts. It highlights critical factors that determin the performance in terms of nitrate adsorption, exposed active sites, mass transfer rate, intermediates barrier and side reactions, as well as the stability of electrocatalysts and recovery of ammonia. In addition, the future direction of technology for electrocatalytic reduction of nitrate to ammonia has also been proposed.
Isolation, Characterization and Reactivity of Key Intermediates Relevant to Reductive (Electro)catalysis with Cp*Rh Complexes Containing Pyridyl‐MIC (MIC=Mesoionic Carbene) Ligands
Authors: Bens Tobias , Walter Robert R. M. , Beerhues Julia , Lücke Clemens , Gabler Julia , Sarkar Biprajit
Published: September 2023

In recent years, metal complexes of pyridyl‐mesoionic carbene (MIC) ligands have been reported as excellent homogeneous and molecular electrocatalysts. In combination with group 9 metals, such ligands form highly active catalysts for hydrogenation/transfer hydrogenation/hydrosilylation catalysis and electrocatalysts for dihydrogen production. Despite such progress, very little is known about the structural/electrochemical/spectroscopic properties of crucial intermediates for such catalytic reactions with these ligands: solvato complexes, reduced complexes and hydridic species. We present here a comprehensive study involving the isolation, crystallographic characterization, electrochemical/spectroelectrochemical/theoretical investigations, and in‐situ reactivity studies of all the aforementioned crucial intermediates involving Cp*Rh and pyridyl‐MIC ligands. A detailed mechanistic study of the precatalytic activation of [RhCp*] complexes with pyridyl‐MIC ligands is presented. Intriguingly, amphiphilicity of the [RhCp*]‐hydride complexes was observed, displaying the substrate dependent transfer of H+, H or H−. To the best of our knowledge, this study is the first of its kind targeting intermediates and reactive species involving metal complexes of pyridyl‐MIC ligands and investigating the interconversion amongst them.
Mechanistic Study on Selenium‐ and Sulfur‐Mediated Isomerization of Hydroxamic Acids
Authors: Meyrelles Ricardo , Schupp Manuel , Maryasin Boris
Published: September 2023

An in‐depth computational study reveals the intriguing mechanism of the recently reported isomerization of hydroxamic acids into para‐aminophenols catalyzed by phenylselenyl bromide under mild conditions. The computations not only align with the reported experimental data, effectively explaining observed phenomena such as para‐selectivity but also shed light on crucial aspects of the reaction mechanism that establish limitations on the scope of the studied rearrangement. Additionally, a joint theoretical/experimental study was performed to examine the potency of the phenylsulfenyl bromide to mediate the reaction under the same conditions.
Gold‐Catalyzed Cyclization of Yndiamides with Isoxazoles via α‐Imino Gold Fischer Carbenes
Authors: Tong Zixuan , Smith Philip J. , Pickford Helena D. , Christensen Kirsten E. , Anderson Edward A.
Published: September 2023

Gold catalysis is an important method for alkyne functionalization. Here we report the gold‐catalyzed formal [3+2] aminative cyclization of yndiamides and isoxazoles in a direct synthesis of polysubstituted diaminopyrroles, which are important motifs in drug discovery. Key to this process is the formation, and subsequent cyclization, of an α‐imino gold Fischer carbene, which represents a new type of gold carbene intermediate. The reaction proceeds rapidly under mild conditions, with high regioselectivity being achieved by introducing a subtle steric bias between the nitrogen substituents on the yndiamide. DFT calculations revealed that the key to this regioselectivity was the interconversion of isomeric gold keteniminiun ions via a low‐barrier π‐complex transition state, which establishes a Curtin‐Hammett scenario for isoxazole addition. By using benzisoxazoles as substrates, the reaction outcome could be switched to a formal [5+2] cyclization, leading to 1,4‐oxazepines.
Transformation of Highly Hydrophobic Triarylphosphines into Amphiphiles via Staudinger Reaction with Hydrophilic Trichlorophenyl Azide
Authors: Suzuki Hayate , Akiyama Yoshimori , Yamashina Masahiro , Tanaka Yuya , Toyota Shinji
Published: September 2023

Owing to its hydrophobic properties and reactivity, triarylphosphines (PAr3) are promising precursors for the development of new amphiphiles. However, an efficient and reliable synthetic method for amphiphiles based on highly hydrophobic PAr3 is still required. Herein, a straightforward transformation of highly hydrophobic PAr3 into amphiphiles via the Staudinger reaction is reported. By simply mixing PAr3 and a hydrophilic trichlorophenyl azide containing two hydrophilic chains, amphiphiles bearing a N=P bond (i. e., an azaylide moiety) were quantitatively formed. The obtained azaylide‐based amphiphiles were remarkably water‐soluble, enabling their spontaneous self‐assembly into 2 nm‐sized micelles composed of 4–5 molecules in water with a low critical micelle concentration (up to 0.05 mM or less) due to the effective intermolecular interactions among the hydrophobic surfaces. Although the azaylide moiety is easily hydrolyzed in the presence of water, the azaylide in the amphiphiles displayed notable stability in water even at 60 h, which stems from the LUMO modulation induced by the presence of three electron‐withdrawing chloro groups and two twisted alkoxycarbonyl groups, according to DFT calculations. An amphiphile having a large hydrophobic surface solubilized various hydrophobic organic dyes through efficient intermolecular interactions, resulting in the dyes exhibiting either monomer or excimer emissions in water.
Spectrum of random d‐regular graphs up to the edge
Authors: Huang Jiaoyang , Yau Horng‐Tzer
Published: September 2023

Consider the normalized adjacency matrices of random d‐regular graphs on N vertices with fixed degree . We prove that, with probability for any , the following two properties hold as provided that : (i) The eigenvalues are close to the classical eigenvalue locations given by the Kesten–McKay distribution. In particular, the extremal eigenvalues are concentrated with polynomial error bound in N, that is, . (ii) All eigenvectors of random d‐regular graphs are completely delocalized.
Equivalent circuit modeling and optimization design for a novel double‐stator linear‐rotary switched reluctance motor
Authors: Qi Ge , Bu Zhenfan , Xu Shuai , Jiang Xiaochang
Published: September 2023

The energy coupling behavior is propagated through the magnetic field and would seriously affect the operation performance of two‐degree‐of‐freedom motion system based on linear‐rotary motor. This paper proposes a novel double‐stator linear‐rotary switched reluctance motor (DSLR‐SRM) to suppress the energy coupling behavior. First, the structure and operation principles of DSLR‐SRM are presented. The two stators of DSLR‐SRM are radially arranged to perform the independent magnetic circuit and suppress the energy coupling behavior through the magnetic field. Then, an equivalent circuit model is established to shorten the modeling and calculation time. It could be found that the energy coupling behavior directly affects the torque and force performance. Next, the sensitivity of the DSLR‐SRM dimensions is developed. Meanwhile, the dimensions of DSLR‐SRM are optimized to enhance the torque and force output via TOPSIS decision‐making. Finally, the validity of equivalent circuit modeling analysis and optimization results are verified through three‐dimensional finite element model.
Fractional delay Newton structure for Lagrangian interpolation in PV integrated grid connected system
Authors: Arora Ankita , Singh Alka
Published: September 2023

This paper proposes a fractional delay (FD) Newton structure for Lagrangian interpolation in single phase grid integrated photovoltaic (PV) system. The structure has been designed for achieving shunt compensation and as a phase locked loop circuit for synchronization. The designed controller performs multiple tasks of feeding the active power to meet the load demand and simultaneously providing reactive power compensation, power factor improvement, and compensating other power quality voltage and load current harmonics. Further, synchronization poses a severe challenge in integrating the PV power electronic converters to the grid. The FD filter is used to discretize the continuous time signal at any time instant using interpolation algorithm employing the non‐integral value of the sampling rate delays. The FD delay filter is made adaptive and self‐learning by using least mean square algorithm. The designed synchronization technique meets the objective of faithfully tracking the phase of the grid voltage under all grid disturbances such as under voltage, overvoltage, frequency variations, and phase angle disturbances in a precise manner.
Early‐onset Alzheimer's disease explained by polygenic risk of late‐onset disease?
Authors: Mantyh William G. , Cochran J. Nicholas , Taylor Jared W. , Broce Iris J. , Geier Ethan G. , Bonham Luke W. , Anderson Ashlyn G. , Sirkis Daniel W. , Joie Renaud La , Iaccarino Leonardo , Chaudhary Kiran , Edwards Lauren , Strom Amelia , Grant Harli , Allen Isabel E. , Miller Zachary A. , Gorno‐Tempini Marilu L. , Kramer Joel H. , Miller Bruce L. , Desikan Rahul S. , Rabinovici Gil D. , Yokoyama Jennifer S.
Published: September 2023

Early‐onset Alzheimer's disease (AD) is highly heritable, yet only 10% of cases are associated with known pathogenic mutations. For early‐onset AD patients without an identified autosomal dominant cause, we hypothesized that their early‐onset disease reflects further enrichment of the common risk‐conferring single nucleotide polymorphisms associated with late‐onset AD.

We applied a previously validated polygenic hazard score for late‐onset AD to 193 consecutive patients diagnosed at our tertiary dementia referral center with symptomatic early‐onset AD. For comparison, we included 179 participants with late‐onset AD and 70 healthy controls. Polygenic hazard scores were similar in early‐ versus late‐onset AD. The polygenic hazard score was not associated with age‐of‐onset or disease biomarkers within early‐onset AD. Early‐onset AD does not represent an extreme enrichment of the common single nucleotide polymorphisms associated with late‐onset AD. Further exploration of novel genetic risk factors of this highly heritable disease is warranted.

Highlights

There is a unique genetic architecture of early‐ versus late‐onset Alzheimer's disease (AD).

Late‐onset AD polygenic risk is not an explanation for early‐onset AD.

Polygenic risk of late‐onset AD does not predict early‐onset AD biology.

Unique genetic architecture of early‐ versus late‐onset AD parallels AD heterogeneity.
Fluoxetine enhances the antitumor effect of olfactory ensheathing cell‐thymidine kinase/ganciclovir gene therapy in human glioblastoma multiforme cells through upregulation of Connexin43 levels
Authors: Hosseindoost Saereh , Dehpour Ahmad R. , Dehghan Samaneh , Javadi Seyed A. H. , Arjmand Babak , Fallah Ali , Hadjighassem Mahmoudreza
Published: September 2023

Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma, resulting in poor clinical outcomes. Herpes simplex virus thymidine kinase/ganciclovir (HSV‐TK/GCV) gene therapy is considered a promising strategy for GBM treatment. Since Connexin43 (Cx43) expression is reduced in GBM cells, increasing Cx43 levels could enhance the effectiveness of gene therapy. The present study aims to examine the impact of fluoxetine on HSV‐TK/GCV gene therapy in human GBM cells using human olfactory ensheathing cells (OECs) as vectors. The effect of fluoxetine on Cx43 levels was assessed using the western blot technique. GBM‐derived astrocytes and OECs‐TK were Cocultured, and the effect of fluoxetine on the Antitumor effect of OEC‐TK/GCV gene therapy was evaluated using MTT assay and flow cytometry. Our results showed that fluoxetine increased Cx43 levels in OECs and GBM cells and augmented the killing effect of OECs‐TK on GBM cells. Western blot data revealed that fluoxetine enhanced the Bax/Bcl2 ratio and the levels of cleaved caspase‐3 in the coculture of OECs‐TK and GBM cells. Moreover, flow cytometry data indicated that fluoxetine increased the percentage of apoptotic cells in the coculture system. This study suggests that fluoxetine, by upregulating Cx43 levels, could strengthen the Antitumor effect of OEC‐TK/GCV gene therapy on GBM cells.
Embryonic development in the bonnethead (Sphyrna tiburo), a viviparous hammerhead shark
Authors: Byrum Steven R. , Frazier Bryan S. , Grubbs R. Dean , Naylor Gavin J. P. , Fraser Gareth J.
Published: September 2023

Background

The hammerhead sharks (family Sphyrnidae) are an immediately recognizable group of sharks due to their unique head shape. Though there has long been an interest in hammerhead development, there are currently no explicit staging tables published for any members of the group. The bonnethead Sphyrna tiburo is the smallest member of Sphyrnidae and is abundant in estuarine and nearshore waters in the Gulf of Mexico and Western North Atlantic Ocean. Due to their relative abundance, close proximity to shore, and brief gestation period, it has been possible to collect and document multiple embryonic specimens at progressive stages of development.

Results

We present the first comprehensive embryonic staging series for the Bonnethead, a viviparous hammerhead shark. Our stage series covers a period of development from stages that match the vertebrate phylotypic period, from Stage 23, through stages of morphological divergence to complete development at birth—Stage 35). Notably, we use a variety of techniques to document crucial stages that lead to their extreme craniofacial diversity, resulting in the formation of one of the most distinctive characters of any shark species, the cephalofoil or hammer‐like head.

Conclusion

Documenting the development of hard‐to‐access vertebrates, like this viviparous shark species, offers important information about how new and diverse morphologies arise that otherwise may remain poorly studied. This work will serve as a platform for future comparative developmental research both within sharks and across the phylogeny of vertebrates, underpinning the extreme potential of craniofacial development and morphological diversity in vertebrate animals.
Sperm‐dependent asexual species and their role in ecology and evolution
Authors: Janko Karel , Mikulíček Peter , Hobza Roman , Schlupp Ingo
Published: September 2023

Sexual reproduction is the primary mode of reproduction in eukaryotes, but some organisms have evolved deviations from classical sex and switched to asexuality. These asexual lineages have sometimes been viewed as evolutionary dead ends, but recent research has revealed their importance in many areas of general biology. Our review explores the understudied, yet important mechanisms by which sperm‐dependent asexuals that produce non‐recombined gametes but rely on their fertilization, can have a significant impact on the evolution of coexisting sexual species and ecosystems. These impacts are concentrated around three major fields. Firstly, sperm‐dependent asexuals can potentially impact the gene pool of coexisting sexual species by either restricting their population sizes or by providing bridges for interspecific gene flow whose type and consequences substantially differ from gene flow mechanisms expected under sexual reproduction. Secondly, they may impact on sexuals' diversification rates either directly, by serving as stepping‐stones in speciation, or indirectly, by promoting the formation of pre‐ and postzygotic reproduction barriers among nascent species. Thirdly, they can potentially impact on spatial distribution of species, via direct or indirect (apparent) types of competition and Allee effects. For each such mechanism, we provide empirical examples of how natural sperm‐dependent asexuals impact the evolution of their sexual counterparts. In particular, we highlight that these broad effects may last beyond the tenure of the individual asexual lineages causing them, which challenges the traditional perception that asexual lineages are short‐lived evolutionary dead ends and minor sideshows. Our review also proposes new research directions to incorporate the aforementioned impacts of sperm‐dependent asexuals. These research directions will ultimately enhance our understanding of the evolution of genomes and biological interactions in general.
Variation in bill surface area is associated with local climatic factors across populations of the plain laughingthrush
Authors: Liu Pengfei , Lou Yingqiang , Yao Jingxiao , Wang Linghui , Møller Anders Pape , Sun Yuehua
Published: September 2023

Recent studies have found that avian bill and tarsus morphology may have evolved in response to climatic conditions, and these organs play important roles in thermoregulation and water retention in extreme environments. Here, we examined whether bill surface area and tarsus length were associated with climatic conditions in the plain laughingthrush, Garrulax davidi, which mainly occurs in north China and occupies several climatic zones from east to west. We measured bill surface area and tarsus length in 321 adults from 11 populations, almost encompassing all habitat types of the species. We analyzed the relationships among these morphological traits and local climatic factors. Bill surface area was positively correlated with maximum temperature, indicating that bill surface area tended to be larger in hotter environments. Furthermore, we found a negative relationship among bill surface area and winter precipitation, indicating that bill surface area tended to be larger in arid areas. However, we did not find any relationships between tarsus length and climatic factors. These results suggest that local climates may shape the evolution of bill morphology divergence, and summer seems to be the critical season for thermoregulation in this temperate zone passerine.
Effects of geo‐climate factors on phenotypic variation in cone and seed traits of Pinus yunnanensis
Authors: Gao Chengjie , Liu Fangyan , Miao Yingchun , Li Jin , Liu Zirui , Cui Kai
Published: September 2023

Evaluating variations in reproductive traits and the response of the variations to geo‐climate conditions are essential for understanding the persistence, evolution, and range dynamics of plant populations. However, there are insufficient studies to attempt to analyze the importance of geo‐climate factors in explaining within‐ or among‐population variation in reproductive traits. We examined 14 traits for 2671 cones of Pinus yunnanensis collected from nine populations in the mountains of Southwest China to characterize the patterns of phenotypic variation of traits and estimate environmental effects on these trait performances and trait variation. We found the contribution of intrapopulation variation to the overall variation was greater than the interpopulation variation and the larger coefficients of variation for the populations lying at the edge of northern and southern regions. Climatic variables are more important than geographical and tree size variables in their relationships to cone and seed traits. Populations in more humid and warmer climate expressed greater cone and seed weight and seed number but lower seed abortion rate, while the larger coefficients of variation in seed weight and number were detected in northern and southern marginal regions with drier or colder climate. Our study illustrates that intraspecific trait variation should be considered when examining plant species response to changing climate and suggests that the high variability rather than high quality of seed traits in the marginal regions with drier or colder climate might foster plant‐population persistence in stressful conditions.
Psychometric evaluation of the Pain Vigilance and Awareness Questionnaire (PVAQ) in fibromyalgia: Confirmatory factor analysis and the development of a Swedish 8‐item version
Authors: Hoffmann Alice Ahnlund , Frostell Elsa , Hedman‐Lagerlöf Maria , McCracken Lance M. , Axelsson Erland
Published: September 2023

Background

Excessive attention to pain, or hypervigilance, is associated with negative outcomes in chronic pain conditions such as fibromyalgia. The Pain Vigilance and Awareness Questionnaire (PVAQ) is a self‐report questionnaire to measure attention to pain. This study aimed to evaluate the psychometric properties of a Swedish version of the PVAQ.

Methods

Psychometric evaluation on cross‐sectional data derived from a clinical trial for fibromyalgia (N = 274). We evaluated item characteristics, factor structure in a confirmatory factor analytic framework, internal consistency, and construct validity in terms of correlations with other clinical variables.

Results

Though confirmatory factor analysis did not result in a satisfactory solution for the full 16‐item scale, acceptable two‐factor solutions could be based on either nine or eight items (the PVAQ‐9 and PVAQ‐8). Internal consistency for both the PVAQ‐9 and PVAQ‐8 were good to excellent, and associations with pain catastrophizing, anxiety, depression, disability, and overall fibromyalgia impact were largely supportive of construct validity. An unexpected result was that, contrary to previous findings, no version of the PVAQ correlated consistently with pain intensity.

Conclusions

The Swedish PVAQ‐9 and PVAQ‐8 appear to have acceptable psychometric properties when administered online to individuals with fibromyalgia. The PVAQ‐8 may be preferable due to being shorter and including an equal number of items per factor. Replication is warranted.

Significance

This study evaluated the psychometric properties of a Swedish translation of the PVAQ in individuals with fibromyalgia. No convincing factor structure was found for the 16‐item version. We could, however, confirm the factor structure of an established 9‐item version (the PVAQ‐9), and recommend further use of a new 8‐item version (the PVAQ‐8). In summary, the PVAQ exhibited more convincing psychometric properties when the number of items was roughly cut in half.
The identity‐attitude nexus in the representation of energy transition in a coal region (Sulcis, Italy): An exploration through the Structural Topic Model
Authors: Rizzoli Valentina , Biddau Fulvio , Sarrica Mauro
Published: September 2023

This article explores the contribution of the Structural Topic Model (STM) to study the intertwining of social representations, attitudes, and identities. We examine newspapers’ discourse on energy transition in a coal‐dependent region (Sulcis, Italy), whose identity and economy are built around mining and carbon‐intensive industry. Drawing upon Social Representations Theory, we combined STM and qualitative content analysis to examine how newspapers represented the energy issue in Sulcis, and how these representations (including denotative and connotative facets) differed according to the social identities’ salience. Results show that coal is legitimated by discourses making salient local identities and providing continuity in the place–identity link, with no alternative to extractivism. When the Sardinian superordinate identity becomes salient, new themes emerge (e.g., renewables) but energy transition retains ambivalent or negative connotations. Overall representations seem to replicate and reflect processes of domination and injustice hindering a just transition, potentially explaining negative attitudes and collective resistance to decarbonization.
Mandated checkups, knowledge of own health status, and chronic care utilization: The effect of HIV medical evaluation mandates on healthcare quality and expenditure in a US‐single payer system
Authors: Topal Senay , Richard Patrick , Young John , Ganesan Anuradha , Gleeson Todd , Blaylock Jason , Okulicz Jason F. , Chu Xiuping , Agan Brian K.
Published: September 2023

In an effort to improve military readiness, in 2014 the US Air Force reduced the frequency of mandated HIV medical evaluation visits from every 6 months to every 12 months. We employ this natural experiment using data for 2676 active‐duty Military Health System beneficiaries living with HIV with a difference‐in‐differences empirical strategy using the Army, Navy, and Marines as a control group to estimate the causal effect of reducing the frequency of mandated evaluation visits on the quality and cost of medical care for active‐duty military members living with HIV. We find that reducing the frequency of mandated HIV medical evaluation visits reduced the likelihood of regular HIV visits by 23 percentage points but did not affect the likelihood of receiving other preventive care, adhering to HIV therapy, or maintaining viral testing and suppression. The study finds evidence that the recommended level of regular HIV visits may be higher than necessary. The reduction in regular HIV visits was not associated with a similar reduction in the studied quality of care measures, therefore, the effect of alleviating the mandate was overall positive in terms of reducing healthcare utilization without adversely affecting preventive care, HIV therapy, or viral testing and suppression.
Optoα1AR activation in astrocytes modulates basal hippocampal synaptic excitation and inhibition in a stimulation‐specific manner
Authors: Courtney Connor D. , Sobieski Courtney , Ramakrishnan Charu , Ingram Robbie J. , Wojnowski Natalia M. , DeFazio R. Anthony , Deisseroth Karl , Christian‐Hinman Catherine A.
Published: September 2023

Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. While there is abundant evidence that astrocytes modulate excitatory transmission in the hippocampus, evidence for astrocytic modulation of hippocampal synaptic inhibition remains more limited. Furthermore, to better investigate roles for astrocytes in modulating synaptic transmission, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we utilized AAV8‐GFAP‐Optoα1AR‐eYFP (Optoα1AR), a viral vector that enables activation of Gq signaling in astrocytes via light‐sensitive α1‐adrenergic receptors. To determine if stimulating astrocytic Optoα1AR modulates hippocampal synaptic transmission, recordings were made in CA1 pyramidal cells with surrounding astrocytes expressing Optoα1AR, channelrhodopsin (ChR2), or GFP. Both high‐frequency (20 Hz, 45‐ms light pulses, 5 mW, 5 min) and low‐frequency (0.5 Hz, 1‐s pulses at increasing 1, 5, and 10 mW intensities, 90 s per intensity) blue light stimulation were tested. 20 Hz Optoα1AR stimulation increased both inhibitory and excitatory postsynaptic current (IPSC and EPSC) frequency, and the effect on miniature IPSCs (mIPSCs) was largely reversible within 20 min. However, low‐frequency stimulation of Optoα1AR did not modulate either IPSCs or EPSCs, suggesting that astrocytic Gq‐dependent modulation of basal synaptic transmission in the hippocampus is stimulation‐dependent. By contrast, low‐frequency stimulation of astrocytic ChR2 was effective in increasing both synaptic excitation and inhibition. Together, these data demonstrate that Optoα1AR activation in astrocytes changes basal GABAergic and glutamatergic transmission, but only following high‐frequency stimulation, highlighting the importance of temporal dynamics when using optical tools to manipulate astrocyte function.
The Honeysuckle and the Bindweed Revisited: Synthesis and Stereochemistry of Extended Helical Structures from Coordination Complexes
Authors: Downward Alan M. , Granelli Matteo , Besnard Celine , Guénée Laure , Williams Alan F.
Published: September 2023

We report structural studies of a chiral tridentate ligand which forms helical cubanes with cobalt(II) and manganese(II). A quadruple helicate with (P)‐chirality is obtained using a (S)‐ligand with cobalt(II) but the ligand binds manganese(II) in one of two possible orientations and either (P)‐ or (M)‐quadruple helicates may be observed for a given ligand enantiomer. The helicates may be linked into extended structures by p‐nitrobenzoate capping ligands which show stacking interactions with neighbouring complexes. With cobalt(II) we find an extended helical structure with (M)‐chirality linking helicates which themselves have (P)‐chirality. With manganese(II) we observe a remarkable structure with extended (M)‐helices coexisting with extended (P)‐helices.
Leukopenia and leukocytosis as strong predictors of COVID‐19 severity: A cross‐sectional study of the hematologic abnormalities and COVID‐19 severity in hospitalized patients
Authors: Sharafi Fateme , Jafarzadeh Esfehani Reza , Moodi Ghalibaf AmirAli , Jarahi Lida , Shamshirian Ali , Mozdourian Mahnaz
Published: September 2023

Background and Aims

Predicting severe disease is important in provocative decision‐making for the management of patients with the coronavirus disease 2019 (COVID‐19); However, there are still some controversies about the COVID‐19's severity predicting factors. This study aimed to investigate the relationships between clinical and laboratory findings regarding COVID‐19's severity in patients admitted to a tertiary hospital in Mashhad, Iran.

Methods

A cross‐sectional study was conducted on patients with documented COVID‐19 infection based on the reverse transcription‐polymerase chain reaction test. Clinical symptoms, vital signs, and medical history of the patients were recorded from their medical records. Laboratory findings and computed tomography (CT) study findings were documented. Disease severity was defined based on CT scan findings.

Results

A total of 564 patients (58.8 ± 16.8 years old) were evaluated. The frequency of severe disease was 70.4%. There was a significant difference in heart rate (p = 0.0001), fever (p = 0.002), dyspnea (p = 0.0001), chest pain (p = 0.0001), diarrhea (p = 0.021), arthralgia (p = 0.0001), and chills (p = 0.044) as well as lymphopenia (p = 0.014), white blood cell count (p = 0.001), neutrophil count (p < 0.0001), lymphocyte count (p < 0.0001), and prothrombin time (p = 0.001) between disease severity groups. Predictors of severe COVID‐19 were pulse rate (crude odds ratio [cOR] = 1.014, 95% confidence interval [CI] for cOR: 1.001, 1.027) and leukopenia (cOR = 3.910, 95% CI for cOR: 1.294, 11.809). Predictors for critical COVID‐19 were pulse rate (cOR = 1.075, 95% CI for cOR: 1.046, 1.104), fever (cOR = 2.516, 95%CI for cOR: 1.020, 6.203), dyspnea (cOR = 4.190, 95% CI for cOR: 1.227, 14.306), and leukocytosis (cOR = 3.866, 95% CI for cOR: 1.815, 8.236).

Conclusions

Leukopenia and leukocytosis have the strongest correlation with the COVID‐19 severity. These findings could be a valuable guild for clinicians in COVID‐19 patient management in the inpatient setting.
Histomic and transcriptomic features of MRI‐visible and invisible clinically significant prostate cancers are associated with prognosis
Authors: Lehto Timo‐Pekka K. , Pylväläinen Juho , Sandeman Kevin , Kenttämies Anu , Nordling Stig , Mills Ian G. , Tang Jing , Mirtti Tuomas , Rannikko Antti
Published: September 2023

Magnetic resonance imaging (MRI) is increasingly used to triage patients for prostate biopsy. However, 9% to 24% of clinically significant (cs) prostate cancers (PCas) are not visible in MRI. We aimed to identify histomic and transcriptomic determinants of MRI visibility and their association to metastasis, and PCa‐specific death (PCSD). We studied 45 radical prostatectomy‐treated patients with csPCa (grade group [GG]2‐3), including 30 with MRI‐visible and 15 with MRI‐invisible lesions, and 18 men without PCa. First, histological composition was quantified. Next, transcriptomic profiling was performed using NanoString technology. MRI visibility‐associated differentially expressed genes (DEGs) and Reactome pathways were identified. MRI visibility was classified using publicly available genes in MSK‐IMPACT and Decipher, Oncotype DX, and Prolaris. Finally, DEGs and clinical parameters were used to classify metastasis and PCSD in an external cohort, which included 76 patients with metastatic GG2‐4 PCa, and 84 baseline‐matched controls without progression. Luminal area was lower in MRI‐visible than invisible lesions and low luminal area was associated with short metastasis‐free and PCa‐specific survival. We identified 67 DEGs, eight of which were associated with survival. Cell division, inflammation and transcriptional regulation pathways were upregulated in MRI‐visible csPCas. Genes in Decipher, Oncotype DX and MSK‐IMPACT performed well in classifying MRI visibility (AUC = 0.86‐0.94). DEGs improved classification of metastasis (AUC = 0.69) and PCSD (AUC = 0.68) over clinical parameters. Our data reveals that MRI‐visible csPCas harbor more aggressive histomic and transcriptomic features than MRI‐invisible csPCas. Thus, targeted biopsy of visible lesions may be sufficient for risk stratification in patients with a positive MRI.
The Risk of Seizures Associated with Tramadol
Authors: Jick Hershel , Derby Laura E. , Vasilakis Catherine , Fife Daniel
Published: September 2023

We conducted a study of the risk of idiopathic incident seizures among users of tramadol derived from data present in the General Practice Research Database based in the United Kingdom for 1994–1996. We used a nested case‐control study design, comparing risks of idiopathic incident seizures during exposed and unexposed times among patients who had ever taken tramadol using a 90‐day follow‐up. Among the 10,916 subjects, we identified 17 cases of idiopathic seizures, 11 of which were definite and 6 possible. None of the patients was exposed to tramadol alone in the prior 90 days. Eight patients were exposed to opiates, five to both tramadol and opiates, three to other analgesics, and one to no analgesics. We found no increased risk of idiopathic incident seizures associated with exposure to tramadol alone. Thus seizures seem rarely attributable to the agent.
Influenza Vaccination and Warfarin Anticoagulation: A Comparison of Subcutaneous and Intramuscular Routes of Administration in Elderly Men
Authors: Delafuente Jeffrey C. , Davis Judith A. , Meuleman John R. , Jones Ronald A.
Published: September 2023

Study Objectives. To determine if subcutaneous administration of influenza vaccine is as immunogenic as the intramuscular route, and to evaluate the frequency of local adverse events associated with both routes in elderly anticoagulated men.

Design. Single‐blind, prospective study of consecutively enrolled subjects.

Setting. Ambulatory clinic at a university‐affiliated Veterans Affairs medical center.

Patients. Twenty‐six men age 60 years or older, receiving therapeutic dosages of warfarin.

Interventions. Subjects were randomized to receive either intramuscular or subcutaneous injection of a standard trivalent influenza vaccine.

Measurements and Main Results. Serum antibody titers to the vaccine's components were measured at baseline, and 6 weeks and 4 months after vaccination. Both routes of administration induced comparable serum antibody titers. There were no differences in adverse events at administration sites between routes of administration.

Conclusions. Elderly individuals are able to mount an immune response to influenza vaccine and produce antibody concentrations deemed protective. The routes of administration are similarly effective at inducing an immune response. The intramuscular route in anticoagulated elderly men does not commonly result in local bleeding complications.
Bioavailability of Phenytoin Acid and Phenytoin Sodium with Enteral Feedings
Authors: Doak Karen K. , Haas Curtis E. , Dunnigan Karin J. , Reiss Robert A. , Reiser Janet R. , Huntress Jeff , Altavela Jeanette L.
Published: September 2023

Study Objective. To compare the absolute bioavailability of phenytoin (PHT) sodium solution and PHT acid suspension in healthy volunteers receiving continuously infused enteral feedings.

Design. Randomized, open‐label, single‐dose, three‐period crossover study.

Setting. University clinical research center.

Subjects. Ten healthy volunteers age 23–43 years.

Interventions. The three phases of the study were separated by at least 7 days. During phase A, subjects received PHT sodium 435 mg intravenously over 30 minutes. During phases B and C, subjects had a nasogastric feeding tube placed through which PHT acid suspension 400 mg and PHT sodium solution 435 mg were administered, respectively. For phases B and C, continuous enteral feedings were given by feeding tube for 14 hours before and after the PHT dose. Blood samples were collected over 72 hours after each PHT dose, and the serum was analyzed for PHT.

Measurements and Main Results. The rate and extent of PHT absorption and PHT pharmacokinetics were determined using an empirical quadratic function of time method. Bioavailability, rate of absorption, maximum concentration (Cmax), and time to maximum concentration (Tmax) were compared for the two enteral doses by paired Student's t test. There were no significant differences in bioavailability for PHT acid suspension and PHT sodium solution (0.88 ± 0.15 vs 0.91 ± 0.7, p=0.57, 90% CI −0.14–0.071). The Cmax was greater (7.4 ± 0.9 mg/L vs 5.5 ± 1.7 mg/L, p=0.019) and Tmax was less (2.5 ± 3.8 vs. 14.8 ± 11.2 hrs, p=0.004) for the sodium solution. The time to 50% fractional absorption (0.33 ± 0.08 vs 3.2 ± 2.4 hrs, p=0.004) and 90% fractional absorption (7.9 ± 6.2 vs 22.3 ± 17.2 hrs, p=0.021) was also significantly shorter for the sodium solution.

Conclusion. The absolute bioavailability of the two dosage forms of PHT administered with concomitant enteral feedings were not significantly different, however, the absorption patterns were significantly different, with the sodium solution being more rapidly absorbed.
AOMadillo: A program for fitting angular overlap model parameters
Authors: Buchhorn Moritz , Krewald Vera
Published: September 2023

The angular overlap model (AOM) is an established parameterization scheme within ligand field theory (LFT). In principle, its application is fairly straightforward, but can be tedious and involve a trial‐and‐error approach to identify and judge the best set of parameters. With the availability of quantum chemical methods to predict d‐d transitions in transition metal complexes, a rich source of computational spectroscopic data with unambiguous assignments to electronic states is available. Herein, we present AOMadillo, a software package that is designed to interface the output of ab initio LFT calculations from the ORCA suite of programs and performs a least‐squares fit for a chosen AOM parameterization. Many steps of the AOM parameterization are automated, so that scans of geometric parameters and evaluations of sets of similar complexes are convenient. The fitting routine is highly configurable, allowing the efficient evaluation of different parameter sets.
Ap4s1 truncation leads to axonal defects in a zebrafish model of spastic paraplegia 52
Authors: Li Yiduo , Zhang Cuizhen , Peng Gang
Published: September 2023

Biallelic mutations in AP4S1, the σ4 subunit of the adaptor protein complex 4 (AP‐4), lead to autosomal recessive spastic paraplegia 52 (SPG52). It is a subtype of AP‐4‐associated hereditary spastic paraplegia (AP‐4‐HSP), a complex childhood‐onset neurogenetic disease characterized by progressive spastic paraplegia of the lower limbs. This disease has so far lacked effective treatment, in part due to a lack of suitable animal models. Here, we used CRISPR/Cas9 technology to generate a truncation mutation in the ap4s1 gene in zebrafish. The ap4s1 truncation led to motor impairment, delayed neurodevelopment, and distal axonal degeneration. This animal model is useful for further research into AP‐4 and AP‐4‐HSP.