bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged requirements for mechanical ventilation and tube feeding support predicted 18‐month outcomes for neonatal encephalopathy
Authors: Tsuda Kennosuke , Shibasaki Jun , Takeuchi Akihito , Mukai Takeo , Sugiyama Yuichiro , Isayama Tetsuya , Ioroi Tomoaki , Takahashi Akihito , Yutaka Nanae , Iwata Osuke ,   the Baby Cooling Registry of Japan
Published: January 2023

Aim

We evaluated the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support for 18‐month composite outcomes in infants with hypoxic‐ischaemic encephalopathy treated with hypothermia.

Methods

This retrospective, nationwide, observational study focused on newborn infants registered in Japan's Baby Cooling Registry between 1 January 2012 and 31 December 2016. The adverse outcomes were defined as death or survival with cerebral palsy, visual or auditory impairment or the requirement for mechanical ventilation or tube feeding at 18 months of age.

Results

Adverse outcomes occurred in 165 (28%) of the 591 children in the final cohort. These were predicted by prolonged dependence on mechanical ventilation or tube feeding for more than seven and more than 14 days. The respective values were positive predictive value 0.34 (95% CI 0.33–0.34) and 0.60 (95% CI 0.56–0.62), negative predictive value 0.97 (95% CI 0.91–0.99) and 0.93 (95% CI 0.90–0.95) and area under the curve 0.59 (95% CI 0.54–0.64) and 0.81 (95% CI 0.77–0.85).

Conclusion

Prolonged dependence on mechanical ventilation or tube feeding for more than 14 days may be useful in predicting 18‐month outcomes in newborn infants who have received therapeutic hypothermia.
Striving for personal growth matters: The relationship between personal growth initiative, teacher engagement and instructional quality
Authors: Huang Xianhan , Lam Si Man , Wang Chan , Xu Peng
Published: January 2023

Background

Teachers' instructional quality is critical to student learning and development. However, the affordance of different aspects of instructional quality remains underexplored.

Aims

This study explores the relationship between teachers' personal growth initiative (PGI) and teacher engagement and instructional quality.

Sample

The data were collected from 998 teachers (82.9% female, average years of teaching experience = 15.25, SD = 10.29) from China.

Methods

The participants completed an anonymous online survey questionnaire that examined their PGI, work engagement and self‐reported instructional quality. Structural equation modelling and bootstrapping were performed to determine the differentiated associations between PGI and each aspect of the teachers' self‐reported instructional quality.

Results

The results confirmed the critical role of PGI in teacher engagement and self‐reported instructional quality. To varying degrees, the dimensions of teacher engagement, except for cognitive engagement, mediated the association between PGI and self‐reported instructional quality.

Conclusions

The teachers' self‐reported data showed that their motivation for personal growth played an important role in improving their instructional quality. The teachers' emotional engagement and social engagement with colleagues were positively related to classroom management, and their social engagement with students was associated with a supportive climate.
How living in economically unequal societies shapes our minds and our social lives
Authors: Peters Kim , Jetten Jolanda
Published: January 2023

In recent decades, the economies of many countries have produced increasingly unequal outcomes for the rich and poor. This economic trend has attracted interest from members of the media, public and political classes as well as researchers who are interested in its societal implications. While this research has traditionally been the purview of economists and sociologists, there has been a burgeoning growth in research that has sought to understand the psychology of economic inequality. In this review, we summarize this work, focusing on two major themes: (1) how people perceive the scale of economic inequality and appraise its significance, and (2) how living in an economically unequal environment shapes people's social lives. Together, this work affirms claims that economic inequality is ‘the defining issue of our time’ (Obama, 2013) with a great deal of destructive potential. We identify important questions that await further research attention.
Victims first? Examining the place of ‘child criminal exploitation’ within ‘child first’ youth justice
Authors: Marshall Hannah
Published: January 2023

‘Child first’ principles have become increasingly prevalent within youth justice policy in England and Wales. In parallel, the concept of ‘child criminal exploitation’ (CCE) has also emerged. On the surface, CCE compliments ‘child first’ principles by reconceptualising ‘young offenders’, who would previously have been criminalised, as children who are victims of exploitation. However, this article identifies two areas of conflict: rather than being diversionary, current responses to CCE further entrench children in the justice system; and, rather than responding holistically to unmet need among all children involved in offending, the concept of CCE functions to exclude some children from support.
Prevention of peri‐implant disease in edentulous patients with fixed implant rehabilitations
Authors: Revilla‐León Marta , Yilmaz Burak , Kois John C. , Att Wael
Published: January 2023

Objectives

To provide an overview about the current approaches to prevent peri‐implant diseases in edentulous patients with complete‐arch implant‐supported prostheses, and to review the clinical applications of the latest digital technologies for implant prosthodontics.

Methods

A review of the guidelines to prevent peri‐implant diseases in patient's receiving complete‐arch implant‐supported prostheses including facially driven treatment planning procedures using either conventional or digital methods, computer‐aided implant planning procedures, and prosthodontic design variables including the optimal number and distribution of dental implants, implant to abutment connection type, implant or abutment level design, screw‐ or cement‐retained alternatives, prostheses contours, and material selection is provided. Furthermore, an outline of the current therapeutic management approaches to address peri‐implant diseases is reviewed.

Conclusions

Clinicians should understand and know different planning and design‐related variables that can affect biological and mechanical complication rates of complete‐arch implant‐supported prostheses. Maintenance protocols are fundamental for minimizing biological and mechanical complications.
Marginal changes at bone‐level implants supporting fixed screw‐retained partial implant prostheses with or without intermediate standardised abutments: 1‐year results of a randomised controlled clinical trial
Authors: Maceiras Lucía , Liñares Antonio , Nóvoa Lourdes , Batalla Pilar , Mareque Santiago , Pérez Javier , Blanco Juan
Published: January 2023

Objective

To compare marginal changes at bone‐level implants restored with screw‐retained implant prosthesis with or without intermediate standardised abutments, after 1 year of follow‐up.

Materials and Methods

Thirty‐six partially edentulous patients received 72 implants. Each patient received 2 implants and a 2‐ to 4‐unit screw‐retained implant‐prosthesis. The test group received implants consisting of a screw‐retained prosthesis connected directly to the implant shoulder, while the prostheses in the control group were connected through a 3‐mm standardised intermediate abutment. Clinical and radiological data were recorded at baseline and at 3, 6 and 12 months in follow‐up visits.

Results

At 12 months, the marginal bone loss was 0.17 ± 0.24 mm for the test group (19 patients) and 0.09 ± 0.15 mm for the control group (17 patients), with no statistically significant differences (p > .05). The mean probing pocket depth was 2.96 mm ± 0.46 for the test group and 2.86 ± 0.62 mm for the control group. The test and control groups showed bleeding on probing levels of 18.86 ± 14.12% and 13.73 ± 17.66%, respectively. All patients scored below 25% on the plaque index levels.

Conclusions

Restoration of bone‐level implants with fixed screw‐retained partial prostheses with or without intermediate abutments presented similar radiographic and clinical outcomes after 1 year.
Apicidin attenuates memory deficits by reducing the Aβ load inAPP/PS1mice
Authors: Luo Biao , Chen Jian , Zhou Gui‐Feng , Xie Xiao‐Yong , Tang Jing , Wen Qi‐Xin , Song Li , Xie Shi‐Qi , Long Yan , Chen Guo‐Jun , Hu Xiao‐Tong
Published: January 2023

Aims

Amyloid beta (Aβ) is an important pathological feature of Alzheimer's disease (AD). A disintegrin and metalloproteinase 10 (ADAM10) can reduce the production of toxic Aβ by activating the nonamyloidogenic pathway of amyloid precursor protein (APP). We previously found that apicidin, which is a histone deacetylase (HDAC) inhibitor, can promote the expression of ADAM10 and reduce the production of Aβ in vitro. This study was designed to determine the potential of apicidin treatment to reverse learning and memory impairments in an AD mouse model and the possible correlation of these effects with ADAM10.

Methods

Nine‐month‐old APP/PS1 mice and C57 mice received intraperitoneal injections of apicidin or vehicle for 2 months. At 11 months of age, we evaluated the memory performance of mice with Morris water maze (MWM) and context fear conditioning tests. The Aβ levels were assessed in mouse brain using the immunohistochemical method and ELISA. The expression of corresponding protein involved in proteolytic processing of APP and the phosphorylation of tau were assessed by Western blotting.

Results

Apicidin reversed the deficits of spatial reference memory and contextual fear memory, attenuated the formation of Aβ‐enriched plaques, and decreased the levels of soluble and insoluble Aβ40/42 in APP/PS1 mice. Moreover, apicidin significantly increased the expression of ADAM10, improved the level of sAPPα, and reduced the production of sAPPβ, but did not affect the levels of phosphorylated tau in APP/PS1 mice.

Conclusion

Apicidin significantly improves the AD symptoms of APP/PS1 mice by regulating the expression of ADAM10, which may contribute to decreasing the levels of Aβ rather than decreasing the phosphorylation of tau.
STAT2/Caspase3 in the diagnosis and treatment of psoriasis
Authors: Fu Zhibing , He Yi , Gao Lihua , Tong Xiaoliang , Zhou Lu , Zeng Jinrong
Published: January 2023

Background

Psoriasis is a classic chronic recurrent inflammatory skin disease characterized by skin inflammation and abnormal biological behaviour of keratinocytes. Although Signal Transducer And Activator Of Transcription 2 (STAT2) was found to play an important role in the Janus kinase (JAK)‐STAT signalling pathway and contribute to the pathogenesis of psoriasis, its exact role in psoriasis remains unclear.

Methods

Using bioinformatics analysis, we identified the key pathways that significantly impacted psoriatic lesions. After identifying the critical molecule gene differentially expressed in multiple public databases using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, clinical samples were collected to validate the gene's significance. Its functions and underlying mechanism were also investigated in vitro. Lastly, we evaluated the diagnostic and therapeutic power of the target gene using the receiver operating characteristic curve (ROC), and gene association was assessed using Spearman correlation.

Results

A significant correlation was found between cysteine‐aspartic acid protease3 (Caspase3) and STAT2, and functional enrichment analysis revealed that they were both significantly up‐regulated in psoriatic skin lesions compared to non‐lesional tissues. Functional analysis revealed that Caspase3 functioned downstream of STAT2 in psoriasis. Lastly, we found that Caspase3 and STAT2 could be potential biomarkers for diagnosing and treating psoriasis.

Conclusions

In summary, STAT2 overexpression contributes to psoriasis progression by regulating Capase3 phosphorylation to induce excessive apoptosis of keratinocytes. Meanwhile, STAT2 and Capase3 were identified as promising biomarkers for the diagnosis and treatment of psoriasis and could be used for individualized treatments.
Lipid quantity and composition vary between three European house fly strains
Authors: Boatta F. , Jansen W. L. , Beukeboom L. W. , Ellers J.
Published: January 2023

Lipids are an important class of nutrients for insects, as they are the main energy source during metamorphosis and crucial for survival and reproduction. Lipid reserves in insects are mostly accumulated during larval development and can be influenced by environmental factors such as diet and temperature. Genetic factors can also affect larval lipid content and composition. Larvae of the house fly, Musca domestica L. (Diptera: Muscidae), are a valuable emerging resource for the insect feed sector, fueling a growing interest in the factors regulating larval lipid content. We investigated whether strains of three geographical origins vary in ontogeny, quantity, and composition of stored lipids in response to temperature. Italian, Spanish, and Dutch house fly larvae were reared on a similar diet at 25 and 35 °C. Larval dry weight and total lipid content were determined in early‐, mid‐, and late‐third instars by extraction of soluble lipids. The fatty acid composition was analyzed in late‐third instars using an improved extraction and derivatization protocol. We found that strain, larval stage, and temperature affected larval dry weight and absolute and relative lipid content, with significant interaction effects between these three factors. All flies were reared in a common environment, indicating a genetic component to lipid storage. Analysis of lipid composition identified 11 fatty acids, including some rarely reported in the literature. Five fatty acids accounted for 80 and 81% of the total fatty acid methyl esters detected at 25 and 35 °C, respectively. An effect of temperature but not strain was evident on the composition of the fatty acids. The observed differences in lipid content among strains and temperature conditions could be of interest for commercial rearing of the house fly.
Decreased serum levels of α‐synuclein in patients with schizophrenia and their unaffected siblings
Authors: Göverti Diğdem , Büyüklüoğlu Nihan , Nazik Yüksel Rabia , Kaya Hasan , Yücel Çiğdem , Göka Erol
Published: January 2023

Aim

The final common pathway in the etiopathogenesis of schizophrenia is suggested that there is a defect in the presynaptic terminal in dopaminergic transmission, in which α‐synuclein has an important role. Peripheral biomarker studies in schizophrenia have become crucial for better diagnoses, early interventions, and personalized therapies. This study aims to compare α‐synuclein levels in patients with schizophrenia and their unaffected siblings with healthy controls, as a potential peripheral biomarker for schizophrenia.

Methods

The quantifications of α‐synuclein serum concentrations were conducted by the ELISA method. PANSS and CGI‐S were used to analyse the severity of the symptoms of the subjects. Data were analysed by nonparametric tests and the Receiver Operating Curve (ROC) analysis.

Results

Sixty‐two patients with schizophrenia (mean age: 34,8 ± 9,9, %64,5 male), their 56 unaffected siblings (mean age: 39,4 ± 11,5, %55,4 male) and 56 healthy controls (mean age: 36,2 ± 9,8, %64,3 male) were included. α‐synuclein levels were significantly lower in the patient (27,65 (12,61‐46,09) pg/ml) and the unaffected sibling groups (24,62 (15,60‐57,87) pg/ml) compared with healthy controls (45,58 (11,25‐108,30) pg/ml) (p < .001). According to the ROC analysis, the optimal cut‐off value for α‐synuclein levels in distinguishing the schizophrenia group from the control group was 42.20. The sensitivity of the measurement of serum α‐synuclein at this point was 93.5%, and the specificity was 60.7%.

Conclusion

Our study demonstrates that decreased levels of serum α‐synuclein may be utilized as a possible peripheral biomarker of familial risk for schizophrenia in both patients and their siblings.
L‐DOPA functions as a plant pheromone for belowground anti‐herbivory communication
Authors: Cascone Pasquale , Vuts Jozsef , Birkett Michael A. , Dewhirst Sarah , Rasmann Sergio , Pickett John A. , Guerrieri Emilio
Published: January 2023

While mechanisms of plant–plant communication for alerting neighbouring plants of an imminent insect herbivore attack have been described aboveground via the production of volatile organic compounds (VOCs), we are yet to decipher the specific components of plant–plant signalling belowground. Using bioassay‐guided fractionation, we isolated and identified the non‐protein amino acid l‐DOPA, released from roots of Acyrtosiphon pisum aphid‐infested Vicia faba plants, as an active compound in triggering the production of VOCs released aboveground in uninfested plants. In behavioural assays, we show that after contact with l‐DOPA, healthy plants become highly attractive to the aphid parasitoid (Aphidius ervi), as if they were infested by aphids. We conclude that l‐DOPA, originally described as a brain neurotransmitter precursor, can also enhance immunity in plants.
Compensatory responses of vital rates attenuate impacts of competition on population growth and promote coexistence
Authors: Lyu Shengman , Alexander Jake M.
Published: January 2023

Competition is among the most important factors regulating plant population and community dynamics, but we know little about how different vital rates respond to competition and jointly determine population growth and species coexistence. We conducted a field experiment and parameterised integral projection models to model the population growth of 14 herbaceous plant species in the absence and presence of neighbours across an elevation gradient (284 interspecific pairs). We found that suppressed individual growth and seedling establishment contributed the most to competition‐induced declines in population growth, although vital rate contributions varied greatly between species and with elevation. In contrast, size‐specific survival and flowering probability and seed production were frequently enhanced under competition. These compensatory vital rate responses were nearly ubiquitous (occurred in 92% of species pairs) and significantly reduced niche overlap and stabilised coexistence. Our study highlights the importance of demographic processes for regulating population and community dynamics, which has often been neglected by classic coexistence theories.
Intermittent instability is widespread in plankton communities
Authors: Rogers Tanya L. , Munch Stephan B. , Matsuzaki Shin‐ichiro S. , Symons Celia C.
Published: January 2023

Chaotic dynamics appear to be prevalent in short‐lived organisms including plankton and may limit long‐term predictability. However, few studies have explored how dynamical stability varies through time, across space and at different taxonomic resolutions. Using plankton time series data from 17 lakes and 4 marine sites, we found seasonal patterns of local instability in many species, that short‐term predictability was related to local instability, and that local instability occurred most often in the spring, associated with periods of high growth. Taxonomic aggregates were more stable and more predictable than finer groupings. Across sites, higher latitude locations had higher Lyapunov exponents and greater seasonality in local instability, but only at coarser taxonomic resolution. Overall, these results suggest that prediction accuracy, sensitivity to change and management efficacy may be greater at certain times of year and that prediction will be more feasible for taxonomic aggregates.
Making sense of renouncing: A typology of types, motives, and approaches to renouncing at work
Authors: Bardon Thibaut , Frémeaux Sandrine , Letierce Clara , Roulet Thomas
Published: January 2023

In this paper, we provide an exploratory account of the experience of renouncing at work—giving up a work‐related aspiration. Despite the importance of the phenomenon, the conceptualization of renouncing has been overlooked by the literature. Taking a narrative sensemaking approach to renouncing, we document variance in individual experiences to renouncing, that is, how they subjectively understand what, why, and how they renounce at work. Through a qualitative approach, we investigate the case of 30 academics working in three French business schools characterized by an increasingly influential managerialist “publish or perish” regime, a context conducive to renouncing. Based on our findings identifying various experiences of renouncing, we inductively build a matrix and a model connecting six experiences of renouncing based on the type of renouncing (renouncing in order to succeed vs. renouncing success itself) and how people approach renouncing (suffered, accepted, or chosen renouncing).
Relationship between psychosocial and psychiatric risk factors and poor long‐term outcome following mild traumatic brain injury: A systematic review
Authors: de Neeling Martijn , Liessens Dirk , Depreitere Bart
Published: January 2023

Background and purpose

Mild traumatic brain injury (mTBI) has an estimated worldwide incidence of >60 million per year, and long‐term persistent postconcussion symptoms (PPCS) are increasingly recognized as being predicted by psychosocial variables. Patients at risk for PPCS may be amenable to closer follow‐up to treat modifiable symptoms and prevent chronicity. In this regard, similarities seem to exist with psychosocial risk factors for chronicity in other health‐related conditions. However, as opposed to other conditions, no screening instruments exist for mTBI.

Methods

A systematic search of the literature on psychological and psychiatric predictors of long‐term symptoms in mTBI was performed by two independent reviewers using PubMed, Embase, and Web of Science.

Results

Fifty papers were included in the systematic analysis. Anxiety, depressive symptoms, and emotional distress early after injury predict PPCS burden and functional outcome up to 1 year after injury. In addition, coping styles and preinjury psychiatric disorders and mental health also correlate with PPCS burden and functional outcome. Associations between PPCS and personality and beliefs were reported, but either these effects were small or evidence was limited.

Conclusions

Early psychological and psychiatric factors may negatively interact with recovery potential to increase the risk of chronicity of PPCS burden after mTBI. This opens opportunities for research on screening tools and early intervention in patients at risk.
Harboring Cnm‐expressing Streptococcus mutans in the oral cavity relates to both deep and lobar cerebral microbleeds
Authors: Ikeda Shuhei , Saito Satoshi , Hosoki Satoshi , Tonomura Shuichi , Yamamoto Yumi , Ikenouchi Hajime , Ishiyama Hiroyuki , Tanaka Tomotaka , Hattori Yorito , Friedland Robert P. , Carare Roxana O. , Kuriyama Nagato , Yakushiji Yusuke , Hara Hideo , Koga Masatoshi , Toyoda Kazunori , Nomura Ryota , Takegami Misa , Nakano Kazuhiko , Ihara Masafumi
Published: January 2023

Background

Cerebral microbleeds (CMBs) influence long‐term prognoses of stroke patients. Streptococcus mutans expressing the collagen‐binding protein Cnm induces cerebrovascular inflammation, impairing blood brain barrier integrity and causing cerebral bleeding. Here, we examine the association of Cnm‐positive S. mutans with CMBs.

Methods

Acute stroke patients were selected from a single‐center registry database. Oral carriage of Cnm‐positive or Cnm‐negative S. mutans was determined using polymerase chain reaction assays. The associations of Cnm‐positive S. mutans with CMB number and specifically the presence of >10 CMBs were examined using quasi‐Poisson and logistic regression models, respectively.

Results

This study included 3154 stroke patients, of which 428 patients (median [interquartile range] age, 73.0 [63.0–81.0] years; 269 men [62.9%]) underwent oral bacterial examinations. In total, 326 patients harbored S. mutans. After excluding four patients without imaging data, we compared patients with Cnm‐positive (n = 72) and Cnm‐negative (n = 250) S. mutans. Harboring Cnm‐positive S. mutans was independently associated with the presence of >10 CMBs (adjusted odds ratio 2.20 [1.18–4.10]) and higher numbers of deep and lobar CMBs (adjusted risk ratio 1.61 [1.14–2.27] for deep; 5.14 [2.78–9.51] for lobar), but not infratentorial CMBs, after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy.

Conclusions

Harboring Cnm‐positive S. mutans was independently associated with a higher number of CMBs in deep and lobar locations. Reducing Cnm‐positive S. mutans in the oral cavity may serve as a novel therapeutic approach for stroke.
A novel bioactive glass/graphene oxide composite coating for a polyether ether ketone‐based dental implant
Authors: Al‐Noaman Ahmed , Rawlinson Simon Charles Fielding
Published: January 2023

Polyether ether ketone (PEEK) is a biocompatible material that lacks antimicrobial activity and bioactivity; therefore, is not appropriate for use as a dental implant. To overcome these deficiencies, a novel composite coating of bioactive glass and graphene oxide was prepared. PEEK discs were polished, cleaned, and the surface treated with sulfuric acid for 15 min. The composite coating consisted of bioactive glass produced by the sol‐gel route and doped with 0.75 wt% graphene oxide. X‐ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy‐energy dispersive spectroscopy analyses were employed to characterize the composite coating, and the coating adhesion strength quantified using a pull‐off test. Cytotoxicity was assessed using osteoblast‐like cells and gingival fibroblasts. The wettability of the coated and non‐coated samples was determined by optical contact angle assessment, and bioactivity was assessed by immersion in simulated body fluid. The results revealed that the bioactive glass/graphene oxide composite coating, approximately 7 μm thick, was transparent, homogenous with few microcracks and microporosities, but adhered strongly and was not cytotoxic to either osteoblast‐like cells or gingival fibroblasts. The wettability of the PEEK sample was increased to <20° after coating with the composite, and apatite formation was detectable after 14 days of immersion in simulated body fluid.
History of familial adult myoclonus epilepsy/benign adult familial myoclonic epilepsy around the world
Authors: Berkovic Samuel F. , Striano Pasquale , Tsuji Shoji
Published: January 2023

Familial adult myoclonus epilepsy/benign adult familial myoclonic epilepsy (FAME/BAFME) has emerged as a specific and recognizable epilepsy syndrome with autosomal dominant inheritance found around the world. Here, we trace the history of this syndrome. Initially, it was likely conflated with other familial myoclonus epilepsies, especially the progressive myoclonus epilepsies. As the progressive myoclonus epilepsies became better understood clinically and genetically, this group began to stand out and was first recognized as such in Japan. Subsequently, families were recognized around the world and there was debate as to whether they represented one or multiple disorders. Clarification came with the identification of pentanucleotide repeats in Japanese families, and FAME/BAFME was quickly shown to be due to pentanucleotide expansions in at least six genes. These have geographic predilections and appear to have been caused by historically ancient initial mutations. Within and between families, there is some variation in the phenotype, explained in large part by expansion size, but whether there are features specific to individual genes remains uncertain.
Preclinical pharmacokinetics and tolerability of a novel meglumine‐based parenteral solution of topiramate and topiramate combinations for treatment of status epilepticus
Authors: Rundfeldt Chris , Klein Pavel , Boison Detlev , Rotenberg Alexander , D'Ambrosio Raimondo , Eastman Cliff , Purnell Benton , Murugan Madhuvika , Goodkin Howard P. , Löscher Wolfgang
Published: January 2023

Objective

For an antiseizure medication (ASM) to be effective in status epilepticus (SE), the drug should be administered intravenously (i.v.) to provide quick access to the brain. However, poor aqueous solubility is a major problem in the development of parenteral drug solutions. Given its multiple mechanisms of action, topiramate (TPM) is a promising candidate for the treatment of established or refractory SE, as supported by clinical studies using nasogastric tube TPM administration. However, TPM is not clinically available as a solution for i.v. administration, which hampers its use in the treatment of SE. Here, we describe a novel easy‐to‐use and easy‐to‐prepare i.v. TPM formulation using the U.S. Food and Drug Administration (FDA)–approved excipient meglumine.

Methods

During formulation development, we compared the solubility of TPM in bi‐distilled water with vs without a range of meglumine concentrations. Furthermore, the solubility of combinations of TPM and levetiracetam and TPM, levetiracetam, and atorvastatin in aqueous meglumine concentrations was determined. Subsequently, the pharmacokinetics and tolerability of meglumine‐based solutions of TPM and TPM combinations were evaluated in rats, including animals following fluid percussion injury or pilocarpine‐induced SE.

Results

The amino sugar meglumine markedly enhances the aqueous solubility of TPM. A comparison with data on dissolving TPM using sulfobutylether‐β‐cyclodextrin (Captisol) demonstrates that meglumine is much more effective for dissolving TPM. Furthermore, meglumine can be used to prepare drug cocktails where TPM is co‐administered with another ASM for SE treatment. The tolerability studies of the meglumine‐based TPM solution and meglumine‐based TPM combinations in normal rats and the rat fluid percussion injury and pilocarpine‐induced SE models demonstrate excellent tolerability of the novel drug solutions. Preclinical studies on antiseizure efficacy in the SE model are underway.

Significance

In conclusion, the novel meglumine‐based solution of TPM presented here may be well suited for clinical development.
Some novel q‐rung orthopair fuzzy similarity measures and entropy measures with their applications
Authors: Ganie Abdul Haseeb , Singh Surender
Published: January 2023

In this paper, we have introduced some new similarity measures for ‐rung orthopair fuzzy sets and discussed their various features. These similarity measures have been constructed with the help of t‐conorms. The suggested similarity measures are more effective than the available ones in computing the similarity between distinct ‐rung orthopair fuzzy sets. With the help of these suggested similarity measures, we have also developed some novel entropy measures for ‐rung orthopair fuzzy sets. The newly proposed entropy measures are more effective than the existing ones in handling linguistic hedges. The applicability of the suggested similarity measures has been demonstrated in pattern analysis and the findings have been found to be better than due to existing ones. The traditional decision‐making method namely, the technique for order preference by similarity to the ideal solution gives us a compromise solution that is either closest to the positive ideal solution and farthest from the negative ideal solution but not both. So, to overcome this major drawback, we suggest a novel multi‐attribute decision‐making method in the ‐rung orthopair fuzzy environment and apply it to a decision‐making problem.
Synthetic cannabinoid receptor agonists are monoamine oxidase‐A selective inhibitors
Authors: Hindson Sarah A. , Andrews Rachael C. , Danson Michael J. , van der Kamp Marc W. , Manley Amy E. , Sutcliffe Oliver B. , Haines Tom S. F. , Freeman Tom P. , Scott Jennifer , Husbands Stephen M. , Blagbrough Ian S. , Anderson J. L. Ross , Carbery David R. , Pudney Christopher R.
Published: January 2023

Synthetic cannabinoid receptor agonists (SCRAs) are one of the fastest growing classes of recreational drugs. Despite their growth in use, their vast chemical diversity and rapidly changing landscape of structures make understanding their effects challenging. In particular, the side effects for SCRA use are extremely diverse, but notably include severe outcomes such as cardiac arrest. These side effects appear at odds with the main putative mode of action, as full agonists of cannabinoid receptors. We have hypothesized that SCRAs may act as MAO inhibitors, owing to their structural similarity to known monoamine oxidase inhibitors (MAOI's) as well as matching clinical outcomes (hypertensive crisis) of ‘monoaminergic toxicity’ for users of MAOIs and some SCRA use. We have studied the potential for SCRA‐mediated inhibition of MAO‐A and MAO‐B via a range of SCRAs used commonly in the UK, as well as structural analogues to prove the atomistic determinants of inhibition. By combining in silico and experimental kinetic studies we demonstrate that SCRAs are MAO‐A‐specific inhibitors and their affinity can vary significantly between SCRAs, most notably affected by the nature of the SCRA ‘head’ group. Our data allow us to posit a putative mechanism of inhibition. Crucially our data demonstrate that SCRA activity is not limited to just cannabinoid receptor agonism and that alternative interactions might account for some of the diversity of the observed side effects and that these effects can be SCRA‐specific.
Flexible species distribution modelling methods perform well on spatially separated testing data
Authors: Valavi Roozbeh , Elith Jane , Lahoz‐Monfort José J. , Guillera‐Arroita Gurutzeta
Published: January 2023

Aim

To assess whether flexible species distribution models that perform well at nearby testing locations still perform strongly when evaluated on spatially separated testing data.

Location

Australian Wet Tropics (AWT), Ontario, Canada (CAN), north‐east New South Wales, Australia (NSW), New Zealand (NZ), five countries of South America (SA), and Switzerland (SWI).

Time period

Most species data were collected between 1950 and 2000.

Major taxa studied

Birds, mammals, plants and reptiles.

Methods

We compared 10 species distribution modelling methods with varying flexibility in terms of the allowed complexity of their fitted functions [boosted regression trees (BRT), generalized additive model (GAM), multivariate adaptive regression splines (MARS), maximum entropy (MaxEnt), support vector machine (SVM), variants of generalized linear model (GLM) and random forest (RF), and an Ensemble model]. We used established practices for model selection to avoid overfitting, including parameter tuning in learning methods. Models were trained on presence–background data for 171 species and tested on presence–absence data. Training and testing data were separated using both random and spatial partitioning, the latter based on 75‐km blocks. We calculated the average performance and mean rank of the methods (focussing on the area under the receiver operating characteristic and precision‐recall gain curves, and correlation) and assessed the statistical significance of the differences between them.

Results

The ranking of methods did not change when evaluated on spatially separated testing data. Methods with the strongest predictive performance were nonparametric methods known to be flexible. An ensemble formed by averaging predictions of five pre‐selected modelling methods was the best model in both random and spatial partitioning, followed by MaxEnt and a variant of random forest.

Main conclusions

Whilst some modellers expect methods limited to simple smooth functions to predict better spatially separated data, we found no evidence of that using blocks of 75 km. We conclude that flexible models that are tuned well enough to avoid overfitting are effective at predicting to spatially distinct areas.
Incident edentulism and number of comorbidities among middle‐aged and older Americans
Authors: Tung Ho‐Jui , Ford Randall
Published: January 2023

Backgrounds

Certain chronic non‐communicable diseases have been associated with the loss of all natural permanent teeth, referred to as edentulism. It has been suggested that edentulism, a chronic dental state, involving the loss of all teeth and poorer masticatory efficiency, could be associated with multiple chronic conditions as people age. In this study, we describe the association between the number of comorbidities and incident edentulism in a representative sample of older Americans.

Methods

We took data from the Health and Retirement Study (HRS). Dentate participants aged 50 or older at the baseline of 2006 (N = 13 221) and 2012 (N = 13 938) were linked to their dentate and survival status at the follow‐up interviews in 2012 and 2018, respectively. The association between the number of comorbidities and incident edentulism was investigated by using multinomial logistic regression models.

Results

Over the two observation periods, the number of selected chronic conditions was predictive of edentulism 6 years later. A 10% higher chance of becoming edentulous by 2012 (OR = 1.10, 95% CI = 1.01, 1.20) was found for every additional comorbid condition to those who remained dentate in 2012. A similar association was identified for the 2012–2018 period.

Conclusion

Among older adults, the number of comorbidities was predictive of incident edentulism, and the same association pattern was found across two longitudinal study periods. Older adults with an increase in the number of comorbidities may experience a higher chance of tooth loss later in time.
The role of university leaders in a political crisis: Students' perspectives from Hong Kong
Authors: Lo William Yat Wai , Auld Euan
Published: January 2023

University students actively participated in the 2019 Hong Kong protests. In this context, the students expected that their universities would support their political stance. Drawing on data from interviews with student leaders, this article documents and examines students' expectations for their university heads, how they interacted and negotiated with university management and how university leaders variously responded to the students' expectations during the social movement. Noting the difficulties in reconciling conflicts over the positioning of the university amid strong political polarisation and social divisions in the society, this article argues that university leaders can only passively adapt to political unrest, and that such passive adaptation exemplifies university's vulnerability to political crises.
Stories for Change: The impact of Public Narrative on the co‐production process
Authors: Moniz Sophie , Karia Amelia , Khalid Ahmad Firas , Vindrola‐Padros Cecilia
Published: January 2023

Introduction

Involving service users in health service design and delivery is considered important to improve the quality of healthcare because it ensures that the delivery of healthcare is adapted to the needs of the users. Co‐production is a process used to involve service users, but multiple papers have highlighted the need for the mechanisms and values guiding co‐production to be more clearly stated. The aim of this paper was to evaluate the mechanisms and values that guided the co‐production approach of the Stories for Change project, which used Public Narrative as part of the co‐design process to create change in National Health Service maternity services.

Methods

This study was conducted using a rapid feedback evaluation approach. Semistructured interviews (n = 16) were the main source of data, six of which were maternity service users, with observations (5 h) and documentary analysis also carried out in parallel. RREAL sheets were used for data analysis to organize data based on key topics of interest.

Results

This study identified three broad mechanisms and values underpinning the co‐production approach: creating an open and safe space to share ideas, learning how to tell stories using Public Narrative and having service providers who play a key role in strengthening the health system listen to stories compelling them to action. This study identified the main areas for improvement of the Stories for Change project related to recruitment, the inclusion of participants, the co‐design process, the Skills Session and the Learning Event.

Conclusion

Our study provided a deeper understanding of the co‐production approach that addresses the need to uncover the mechanism and values underlying co‐production and co‐design approaches. This study expands on the literature pertaining to the influence of storytelling in creating meaningful change in health care. We propose a co‐design methodology that uses Public Narrative as a model for service user engagement to help inform future healthcare development processes.

Patient or Public Contribution

The experiences and perceptions of maternity service users and health professionals informed this evaluation. The project organizers were involved in the manuscript preparation stage by providing feedback, and service users wrote a commentary on the project from the lived experience perspective.
Self‐management and illness perception among cervical cancer patients: A cross‐sectional study
Authors: Xiong Chenxia , Jiang Chaonan , Zhang Huiling , Chen Jing , Zhao Meng , Xiong Chuyan , Luo Xia , Zhang Yue , Li Mingfang , Guo Zijun , Yan Jun
Published: January 2023

Aim

This study aimed to describe self‐management among cervical cancer patients and to elucidate the relationship between illness perception and self‐management in patients with cervical cancer.

Methods

This was a cross‐sectional study. A convenience sample of 220 cervical cancer patients was recruited from the gynaecology outpatient department of a cancer hospital. Data were collected from September 2018 to February 2019. Self‐management and illness perception were assessed using the Cancer Self‐Management Assessment Scale and the Revised Illness Perception Questionnaire for cervical cancer, respectively. Data were analysed using Pearson correlation analysis, univariate analysis and hierarchical linear regression analysis.

Results

The mean score of self‐management was 3.87 ± 0.53, and daily life management showed the highest score (4.18 ± 0.58), while symptom management was the lowest (3.11 ± 082). Hierarchical linear regression analysis showed that family monthly income per person, types of surgery and personal control were factors that significantly influenced self‐management.

Conclusions

The results demonstrate that self‐management among patients with cervical cancer needs to be improved. The significant influence of illness perception offers an opportunity for nurses to improve self‐management behaviours of patients with cervical cancer.
Inactivation of mitochondrial pyruvate carrier promotes NLRP3 inflammasome activation and gout development via metabolic reprogramming
Authors: Chen Lih‐Chyang , Chen Yu‐Jen , Lin Hsin‐An , Chien Wu‐Chien , Tsai Kuen‐Jou , Chung Chi‐Hsiang , Wang Jui‐Yang , Chen Chien‐Chou , Liao Nan‐Shih , Shih Chieh‐Tien , Lin Yi‐Ying , Huang Chi‐Ning , Ojcius David M. , Huang Kuo‐Yang , Lin Hsin‐Chung
Published: January 2023

The nucleotide‐binding and oligomerization domain, leucine‐rich repeats, and pyrin domain‐containing protein 3 (NLRP3) inflammasome plays a crucial role in innate immunity and is involved in the pathogenesis of autoinflammatory diseases. Glycolysis regulates NLRP3 inflammasome activation in macrophages. However, how lactic acid fermentation and pyruvate oxidation controlled by the mitochondrial pyruvate carrier (MPC) affect NLRP3 inflammasome activation and autoinflammatory disease remains elusive. We found that the inactivation of MPC with genetic depletion or pharmacological inhibitors, MSDC‐0160 or pioglitazone, increased NLRP3 inflammasome activation and IL‐1β secretion in macrophages. Glycolytic reprogramming induced by MPC inhibition skewed mitochondrial ATP‐associated oxygen consumption into cytosolic lactate production, which enhanced NLRP3 inflammasome activation in response to monosodium urate (MSU) crystals. As pioglitazone is an insulin sens MSDC‐itizer used for diabetes, its MPC inhibitory effect in diabetic individuals was investigated. The results showed that MPC inhibition exacerbated MSU‐induced peritonitis in diabetic mice and increased the risk of gout in patients with diabetes. Altogether, we found that glycolysis controlled by MPC regulated NLRP3 inflammasome activation and gout development. Accordingly, prescriptions for medications targeting MPC should consider the increased risk of NLRP3‐related autoinflammatory diseases.
Characteristics and aetiology of low‐temperature burns in Beijing of China
Authors: Xie Xiaoye , Liu Xinzhu , Cai Jianhua , Zhang Bohan , Sun Tianjun , Luo Peng , An Dai , Deng Yurong , Shen Chuan'an
Published: January 2023

This study was designed to analyse the characteristics and aetiology of low‐temperature burns and explore the prevention and treatment strategies. In total, 206 patients hospitalised with low‐temperature burns in a major burn center in Beijing from 2017 to 2021 were included. There were 35–49 cases per year, with an average of 41 ± 4.5 cases. The prevalence of low‐temperature burns was higher in female than in male and are mainly resulted from two kinds of incidents: unintended burns from heat treatment (50.97%, 105/206) and improper use of heating devices to keep warm (43.69%, 90/206). Most cases occurred in autumn (33.01%, 68/206) and the least in spring (17.96%, 37/206); cases in summer (24.27%, 50/206) and winter (24.76%, 51/206) accounted for nearly a quadrant respectively. Low‐temperature burns in summer were mainly unintended burns from heat treatment (80%, 40/50), whereas in autumn were mainly resulted from improper use of heating devices to keep warm (55.88%, 38/68), the difference was statistically significant (χ2 = 42.801, P < .001). Of all the cases, the burn size ranged from 0.2% to 5% TBSA, mostly less than 1% (85.92%, 177/206); third‐degree burns accounted for 98.54% (203/206). Patients admitted after 3 weeks post‐injury accounted for 42.23% (87/206). All patients were cured, and most of them were by surgeries (70.87%, 146/206). The results of the study show that low‐temperature burn injury features a predictable morbidity among different seasons, a higher prevalence in adult women and a frequent occurrence at home. The wounds of low‐temperature burns are often small in size but deep in depth, and can be easily misdiagnosed as superficial burns. However, most low‐temperature burn wounds require surgical treatment. The study also suggests that based on the characteristics and aetiology of low‐temperature burns, targeted prevention and treatment measures should be mapped out.
Synthesis, crystal structure, and characterization of Na2SrV4O12: A low‐firing dielectric vanadate
Authors: Li Chunchun , Meng Yingzhi , Hou Hongping , Zhang Amei , Khaliq Jibran , Liao Na , Fu Caixia , Liu Laijun , Du Hongliang
Published: January 2023

In this work, cyclotetravanadate Na2SrV4O12 was synthesized at a relatively low sintering temperature of ∼500°C using a solid‐state reaction method. X‐ray diffraction and a transmission electron microscope characterization featured a tetragonal structure that was built by a 3D frame of isolated tetracyclic (V4O12)4−. Dielectric measurements demonstrated strong dependence on frequency and temperature. A low relative permittivity of εr ∼ 8 ± 0.2 and a dielectric (loss tanδ) ∼ 0.4 ± 0.01 was achieved at a frequency of 10 kHz and room temperature. ac impedance and conductivity analysis revealed a thermally activated migration behavior of charge carriers with a short‐range hopping feature. XPS analysis validated the existence of oxygen vacancy and reduction in vanadium (from V5+ to V4+), which gave rise to charged lattice defects. The migration or hopping of such charged defects was responsible for the observed electrical behaviors. Owing to the simple composition, inexpensive raw materials and low density (2.99 g/cm3) make Na2SrV4O12 ceramic a potential candidate for lightweight devices and in photocatalytic degradation and all‐solid‐state ion batteries.